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Effects of Swallowing Effort on Bolus Accommodation in Healthy Elderly Individuals

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Title:
Effects of Swallowing Effort on Bolus Accommodation in Healthy Elderly Individuals
Creator:
LaGorio, Lisa A.
Place of Publication:
[Gainesville, Fla.]
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University of Florida
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english
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1 online resource (120 p.)

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Rehabilitation Science
Committee Chair:
Crary, Michael A
Committee Members:
Carnaby, Giselle Denya
Fuller, David D
Striley, Catherine L
Graduation Date:
12/15/2012

Subjects

Subjects / Keywords:
Age groups ( jstor )
Deglutition disorders ( jstor )
Liquids ( jstor )
Nectar ( jstor )
Palatal consonants ( jstor )
Puddings ( jstor )
Sensors ( jstor )
Swallowing ( jstor )
Tongue ( jstor )
Viscosity ( jstor )
Rehabilitation Science -- Dissertations, Academic -- UF
accommodation -- age -- aging -- biokinematic -- bolus -- effort -- hyoid -- larynx -- lingual -- palatal -- pharyngeal -- pressure -- swallowing -- typical -- viscosity -- volume
Genre:
Electronic Thesis or Dissertation
bibliography ( marcgt )
theses ( marcgt )
government publication (state, provincial, terriorial, dependent) ( marcgt )
Rehabilitation Science thesis, Ph.D.

Notes

Abstract:
Bolus accommodation is the involuntary process of physiologic adjustment to varying bolus characteristics during swallowing. These adjustments facilitate precisely coordinated timing and sufficient contractile force to safely propel different materials through the upper aerodigestive tract. Bolus accommodation may change with advancing age. Age-related changes may reflect reduced physiologic swallowing efficiency and relate to increased risk of swallow-related morbidity. As such, bolus accommodation may serve as a surrogate for sub-clinical dysphagia in the elderly. To develop this potential marker of dysphagia, comprehensive knowledge of aging-related effects on bolus accommodation is needed. Prior studies of bolus accommodation in the elderly have focused primarily on swallow timing and movement parameters. Few studies have investigated bolus accommodation effect on swallow pressures. This cross-sectional study improved upon previous studies by simultaneously evaluating change in lingual-palatal pressures, pharyngeal pressures, and swallow biokinematics as a function of increased swallowing effort, bolus volume and viscosity, and age. Thirty-one adults between 60-88 years of age participated. Each underwent videomanofluoroscopic swallowing evaluation that simultaneously captured seven oropharyngeal pressures and two kinematic measures during each swallow. Participants swallowed a series of 32 boluses, systematically varying in volume and viscosity, under two conditions (typical and effortful swallowing). A 4-way repeated measures ANOVA (swallowing condition x volume x viscosity x age group) was conducted for each physiologic parameter investigated. Significant main and interaction effects were identified for several physiologic measures. Swallowing condition effects demonstrated greater pressure generation during effortful swallowing. Volume effects showed greater laryngeal movement with larger volumes. Viscosity effects demonstrated linear trend of greater pressure generation with increased viscosity. Age group effects demonstrated that the 80 year old group generated lower pressures than younger participants. Overall, the oldest adults produced lower pressures than their younger counterparts. However, swallow pressures were modulated by bolus characteristics and by volitionally increasing swallowing effort. Moreover, by volitionally increasing swallowing effort, the oldest adults produced pressures approximating those pressures produced by younger adults during typical swallowing. When taken as a whole, these results support the notion that volitionally increasing swallowing effort and manipulating bolus characteristics may serve to over-ride automatic aspects of bolus accommodation. ( en )
General Note:
In the series University of Florida Digital Collections.
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Includes vita.
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Includes bibliographical references.
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Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Thesis:
Thesis (Ph.D.)--University of Florida, 2012.
Local:
Adviser: Crary, Michael A.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2014-12-31
Statement of Responsibility:
by Lisa A. LaGorio.

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UFRGP
Rights Management:
Applicable rights reserved.
Embargo Date:
12/31/2014
Classification:
LD1780 2012 ( lcc )

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1 EFFECTS OF SWALLOWING EFFORT ON BOLUS ACCOMMODATION IN HEALTHY ELDERLY INDIVIDUALS By LISA A LAGORIO A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2012

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2 2012 Lisa Allison LaGorio

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3 To all of the teachers throughout my life; you ha ve taught me to love learning. I hope that I can instill som e of that love in my own students.

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4 ACKNOWLEDGMENTS I would like to thank my parents w ithout whose love and support I would not have had the perseverance to fulfill this dream of earning my PhD and becoming a college professor I would like to tha nk my cousin Anne Adams for her emotional and financial support throughout this endeavor. She was first to affirm that starting a PhD in my mid be. Without her encouragem ent I may not have made this life change. I also want to sincerely thank my official mentor and committee chair, Michael Crary. He took a chance on me in the beginning, and since then has provided intellectual guidance, moral and financial support, and a k ick in the butt when needed. As a result of his mentorship I am a better clinician, teacher, public speaker, writer and critical thinker than when I first started this program. And, now, because of him, I have become a scientist. I want to ex press my utm ost gratitude to my comm ittee co chair Giselle Carnaby. Throughout my tenure at UF she has inspired me both personally and professionally, and challenged me to think beyond what I thought was possible As a result, I have g rown in more ways than I ever anticipated when I started this program. Lastly, in addition to everything else, she served as my NIH F31 during the grant writing process, I wo uld never have been awarded the grant. I would also like to thank the other members of my committee, David Fuller who has been with me from the beginning and who continues to pique my intellectual curiosity regardi ng neurology and rehabilitation; Catherin e Striley who judg ed my final

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5 MPH project and graciously accepted my invitation t o join my dissertation committee after previous members left UF ; and C ynthia Prins, Elena Andresen and Nabih Asal who guided me through the MPH degree and PhD qualification pr ocess es I would like to thank the physician mentors on my NIH F31 fellowship team Dr. Neal Chheda ENT and Dr. Baharak Moshiree GI. Without their willingness to be included on the project, I would not have received the grant. I also want to thank Dr. M oshiree for serving as my physician mentor during my MPH internship. I want to thank my many wonderful friends and colleagues who encouraged and assisted me t h roughout my tenure here at UF. These include Yvonne Rogalski who introduced herself to me on the first day of cla ss and who served as my Gainesville guide; Jill McClung with whom I shared many pe aks and valleys over the years; and the numerous post doc, graduate and undergraduate students who have worked in the UF Swallowing Research Lab over the year s especially C atie Ohme, Pam Carvajal, Giedre Berretin Felix, Lan Yue, and Livia Sura I also want to thank clinic supervisor Sara Plager and department chair Christine Sapienza for their moral and financial support. For supporting the exe cution of my di ssertation study, I would like to first thank the UF College of Public Health and Health Professions (PHHP) Research Committee for the generous grant that paid for the tongue bulbs ; and the UF PHHP Department of Speech, Language and Hearing Sciences for pa ying for all project related items that exceeded the funds av ailable through the NIH grant. Next, I would like to thank the other clinicians in the department for working with and around me as I tested subjects; I know that this project often inconvenience d them I the radiology residents and staff, especially Tom Kennedy, Pat Dickerson and Nancy LeVake.

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6 Additionally I am indebted to Victor Binzari for analyzing my biokinematic data, to Aarthi Madhavan for being an independent judge for mea suring the lingual palatal and pharyngeal pressure data, and to Isaac Sia for being an independent judge for measuring the biokinematic data I also want to thank Isaac each subject testing session H is willin gness to participate in each of these testing sessions made this project manageable and fun Finally, I am forever grateful to the senior citizens who volunteered to participate in this study. Had they not been willing to permit me to insert the endoscope and catheter through their noses I would never have been able to do this project.

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7 TABLE OF CONTENTS page ACKNOWLEDGMENTS ................................ ................................ ................................ .. 4 LIST OF TABLES ................................ ................................ ................................ .......... 10 LIST OF FIGURES ................................ ................................ ................................ ........ 11 LIST OF ABBREVIATIONS ................................ ................................ ........................... 12 ABSTRACT ................................ ................................ ................................ ................... 13 CHAPTER 1 INTRODUCTION ................................ ................................ ................................ .... 15 Statement of the Problem ................................ ................................ ....................... 15 Study Purpose ................................ ................................ ................................ ........ 16 Study Aims ................................ ................................ ................................ .............. 16 Primary Aim ................................ ................................ ................................ ...... 17 Exploratory Aim ................................ ................................ ................................ 17 2 LITERATURE REVIEW ................................ ................................ .......................... 18 Chapter Overview ................................ ................................ ................................ ... 18 Studies of Bolus Accommodation ................................ ................................ ........... 18 Bolus Accommodation Effects on Timing Parameters ................................ ...... 18 Volume effects ................................ ................................ ........................... 18 Viscosity effects ................................ ................................ ......................... 19 Bolus Accom modation Effects on Biokinematic Distance Parameters ............. 19 Volume effects ................................ ................................ ........................... 19 Viscosity effects ................................ ................................ ......................... 20 Bolus Accommodation Effects on Pressure Parameters ................................ .. 21 Volume effects on lingual pressure ................................ ............................ 21 Visco sity effects on lingual pressure ................................ .......................... 22 Volume effects on pharyngeal pressure ................................ ..................... 22 Viscosity effects on pharyngeal pressure ................................ ................... 23 Summary ................................ ................................ ................................ .......... 23 Aging Effects on Bolus Accommodation ................................ ................................ 23 Lingual Palatal Pres sure ................................ ................................ .................. 25 Pharyngeal Pressures ................................ ................................ ...................... 26 ................................ ................. 27 Limitations in the Literature ................................ ................................ ..................... 30 Significance of the Proposed Study ................................ ................................ ........ 32

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8 3 METHODS AND MATERIALS ................................ ................................ ................ 35 Study Overview and Design ................................ ................................ .................... 35 Participants ................................ ................................ ................................ ............. 35 Inclusion Criteria ................................ ................................ ............................... 36 Exclusion Criteria ................................ ................................ ............................. 36 Study Protocol ................................ ................................ ................................ ........ 36 Clinical Swallowing Examination ................................ ................................ ...... 37 Mental status examination ................................ ................................ ......... 37 Reflux symptom survey ................................ ................................ .............. 37 Clinic al assessment of swallowing function ................................ ............... 37 Oral intake documentation ................................ ................................ ................ 38 Endoscopic Swallowing Evaluation ................................ ................................ .. 38 Effortful Swallow Training Session ................................ ................................ ... 38 Fluoroscopic Swallowing Evaluation ................................ ................................ 39 Equipment u sed during the fluoroscopic swallowing assessment .............. 40 Fluoroscopic examination procedure ................................ ......................... 43 Bolus randomization ................................ ................................ .................. 44 Data Measurement ................................ ................................ ................................ 44 Lingual Palatal Peak Pressures ................................ ................................ ....... 45 Pharyngeal Manometric Pe ak Pressures ................................ ......................... 45 Base of tongue (BOT) ................................ ................................ ................ 45 Hypopharynx (HYPO) ................................ ................................ ................ 46 Up per esophageal sphincter relaxation nadir (UES nadir) ......................... 46 Clearing wave (C Pk) ................................ ................................ ................. 47 Hyoid and Laryngeal Excursion ................................ ................................ ........ 47 Reliability ................................ ................................ ................................ .......... 49 Inter rater agreement ................................ ................................ ................. 49 Intra rater agreement ................................ ................................ ................. 49 Data Management ................................ ................................ ................................ .. 49 Sample Size and Power Considerations ................................ ................................ 50 Statistical Analys is Plan ................................ ................................ .......................... 50 Primary Aim ................................ ................................ ................................ ...... 51 Exploratory Aim ................................ ................................ ................................ 51 4 RESULTS ................................ ................................ ................................ ............... 58 Participant Characteristics ................................ ................................ ...................... 58 Preliminary Data Analysis ................................ ................................ ....................... 59 Data Distr ibution Characteristics ................................ ................................ ...... 59 Bolus Trial Analysis ................................ ................................ .......................... 60 Primary Aim ................................ ................................ ................................ ............ 60 Lingual Palatal Pressures ................................ ................................ ................. 60 Anterior tongue peak ................................ ................................ .................. 60 Middle tongue peak ................................ ................................ .................... 61 Posterior tongue peak ................................ ................................ ................ 62 Pharyngeal Manometric Pressures ................................ ................................ .. 64

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9 Base of tongue peak (BOT) ................................ ................................ ....... 64 Hypopharyngeal peak (HYPO) ................................ ................................ ... 64 UES nadir peak ................................ ................................ .......................... 65 Clearing wave peak (C Pk) ................................ ................................ ........ 66 Biokinematic Measures ................................ ................................ .................... 70 Hyoid excursion ................................ ................................ ......................... 70 Laryngeal excursion ................................ ................................ ................... 71 Exploratory Aim ................................ ................................ ................................ ...... 71 Typical Swallow ................................ ................................ ................................ 71 Effortful Swallow ................................ ................................ ............................... 71 Reliability Analysis ................................ ................................ ................................ .. 72 Lingual Palatal Pressures ................................ ................................ ................. 72 Pharyngeal Pressures ................................ ................................ ...................... 72 Biokinematic Measures ................................ ................................ .................... 72 Reliability Summary ................................ ................................ .......................... 73 5 DISCUSSION ................................ ................................ ................................ ......... 95 Primary Aim ................................ ................................ ................................ ............ 95 Lingual Palatal Pressures ................................ ................................ ................. 95 Pharyngeal Pressures ................................ ................................ ...................... 98 Biokinematic Measures ................................ ................................ .................. 100 Exploratory Aim ................................ ................................ ................................ .... 102 Study Strengths ................................ ................................ ................................ .... 104 Multiple Simultaneous Measures ................................ ................................ .... 104 Participant Sample ................................ ................................ ......................... 105 St udy Limitations ................................ ................................ ................................ .. 105 Measurement Error ................................ ................................ ........................ 105 Catheter placement ................................ ................................ .................. 105 Missing data ................................ ................................ ............................. 105 Power ................................ ................................ ................................ ............. 106 Directions for Future Research ................................ ................................ ............. 106 C onclusion ................................ ................................ ................................ ............ 107 LIST OF REFERENCES ................................ ................................ ............................. 110 BIOGRAPHICAL SKETCH ................................ ................................ .......................... 120

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10 LIST OF TABLES Table page 2 1 Summary of the key effects of increasing volume and viscosity on bolus accommodation ................................ ................................ ................................ .. 34 3 1 Sample size and power calcula tions ................................ ................................ ... 52 4 1 Participant characteristics with data presented as proportions with 95% confidence intervals, except where indicated. ................................ .................... 74 4 2 Pearson correlation coefficients for trial 1 and trial 2 of each bolus .................... 75 4 3 Mean (SD) peak lingual palatal pressures ( mm Hg ) produced during typical and effortful swallows of each bolus, by age group ................................ ............ 76 4 4 Mean (SD) peak pharyngeal pressures ( mm Hg ) produced during typical and effortful swallows of each bolus, by age group ................................ ................... 78 4 5 Mean (SD) hyoid and laryngeal excursion in mm produced during typical and effortful swallows of each bolus, by age group ................................ ................... 80 4 6 Repeated measures main effects for all factors ................................ .................. 81 4 7 Repeated measures 2 way interaction effects ................................ .................... 82 4 8 Repeated measures 3 way and 4 way interaction effects ................................ .. 83 4 9 Relationship between pressure and movement parameters ............................... 84

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11 LIST OF FIGURES Figure page 3 1 Study equipment set up in the fluoroscopy suite. Photo courtesy of the author. ................................ ................................ ................................ ................ 54 3 2 Close up of tongue bulb placement inside the mouth. Photo courtesy of the author. ................................ ................................ ................................ ................ 54 3 3 Manometric catheter with three transducers used for pharyngeal measurements. Photo courtesy of the author. ................................ .................... 55 3 4 Example of integrated fluo roscopy, lingual palatal pressures, and pharyngeal manometry. Photo courtesy of the author. ................................ .......................... 56 3 5 Videofluoroscopic still image showing measurements made for biokinematic analysis. Photo cour tesy of the author. ................................ ............................... 57 4 1 Within group main effects for swallowing condition by physiologic parameter. Asterisk denotes significant effect. ................................ ................................ ..... 85 4 2 Within group main effects for volume by physiologic parameter. Asterisk denotes significant effect ................................ ................................ .................... 86 4 3 Within group main effects for viscosity for the three lingual pala tal pressure parameters. Brackets with asterisks denote significant effect between the two viscosities. ................................ ................................ ................................ .......... 87 4 4 Within group main effects for viscosity by physiologic parameter. Brackets with a sterisks denote significant effect between the two viscosities. .................. 88 4 5 Between groups main effects for age by physiologic parameter. Brackets with asterisks denote post hoc signficant differen ces between the age groups. ................................ ................................ ................................ ............... 89 4 6 Middle lingual palatal pressure 3 way interaction for swallowing condition, viscosity, and age group ................................ ................................ ..................... 90 4 7 Middle lingual palatal pressure 2 way interaction for volume x viscosity ............ 91 4 8 Posterior lingual palatal pressure 3 way interaction for volume, viscosity, and age. ................................ ................................ ................................ .................... 92 4 9 Posterior lingual palatal pressure 2 way interaction for volume and viscosity .... 93 4 10 Pharyngeal clearing wave peak pressure (C Pk) 4 way interaction between swallowing condition, volume, viscosity, and age. ................................ .............. 94

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12 LIST OF ABBREVIATION S ANOVA Analysis of Variance BA B olus accommodation BMI Body Mass Index BOT B ase of tongue C Pk C learing wave peak Digi tal Swallowing Workstation FOIS Functional Oral Intake Scale HRM High resolution manometry HYPO Hypopharynx HURRC Human Use of Radioisotopes and Radiation Committee IRB Institutional Review Board MASA Mann Assessment of Swallowing Ability NIH National Inst itutes of Health m L m illiliters mm Hg millimeters of mercury MMSE Mini Mental Status Examination ns n ot significant PES Pharyngeal e sophageal segment RFS Reflux Finding Scale RSI Reflux Symptom Index SD Standard deviation UF University of Florida UES Upper esophageal sphincter

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13 Abstract of Dissertation Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy EFFECTS OF SWALLOWING EFFORT ON BOLUS ACCOMMODAT ION IN HEALTHY ELDERLY INDIVIDUALS By Lisa A. LaGorio December 2012 Chair: Michael A. Crary Major: Rehabilitation Science Bolus a ccommodation is the involuntary process of physiologic adjustment to varying bolus characteristics during swallowing. The se adjustments facilitate precisely coordinated timing and sufficient contractile force to safely propel different materials through the upper aerodigestive tract. Bolus accommodation may change with advancing age. Age related changes may reflect reduced p hysiologic swallowing efficiency and relate to increased risk of swallow related morbidity. As such, bolus accommodation may serve as a surrogate for sub clinical dysphagia in the elderly. To develop this potential marker of dysphagia, comprehensive knowle dge of aging related effects on bolus accommodation is needed P rior studies of bolus accommodation in the elderly have focused primarily on swallow timing and movement parameters Few studies have investigated bolus accommodation effect on swallow pressu res This cross sectional study improved upon previous studies by simultaneously evaluating change in lingual palatal pressures, pharyngeal pressures, and swallow bio kinematics as a function of increased swallowing effort, bolus volume and viscosity and a ge.

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14 Thirty one adults between 60 88 years of ag e participated. Each underwent video manofluoro scopic swallowing evaluation that simultaneously captured seven oropharyngeal pressures and two kinematic measures during each swallow. Participants swallowed a se ries of 32 boluses, systematically varying in volume and viscosity under two conditions (typical and effortful swallowing). A 4 way repeated measures ANOVA ( swallowing condition x volume x viscosity x age group ) w as conducted for each physiologic paramete r investigated. Significant main and interaction effects were identified for several physiologic measures. Swallowing condition effects demonstrated greater pressure generation during effortful swallowing. Volume effects showed greater laryngeal movement w ith larger volumes. Viscosity effects demonstrated linear trend of greater pressure generation with increased viscosity Age group effects demonstrated that the 80 year old group generat ed lower pressures than younger participants O verall, the oldest adults produce d lower pressures than their younger counterparts. H owever, swallow p ressures were modulated by bolus characteristics and by volitionally increasing swallowing effort Moreover, by volitionally increasing swallowing effort, the oldest adults produced pressures approximating those pressures produced by younger adults during typical swallowin g. When taken as a whole, these results support the notion that volitionally increasing swallowing effort and manipulating bol us characte ristics may serve to over ride a utomatic aspect s of bolus accommodation

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15 CHAPTER 1 INTRODUCTION Statement of the Problem Bolus accommodation is the process of involuntary ph ysiologic adjustment to varying bolus characteristics during swallowing. These adjustments facilitate precisely coordinated timing and enough contractile force to safely propel different materials through the upper aerodigestive tract. Bolus accommodation may become altered as a result of underlying disease or advancing age. Alterations imply impaired swallowing physiology which in turn may result in increased morbidity and mortality, especially among elderly individuals. 1 As such, bolus accommodation may serve as a surrogate indicator for sub clinical swallowing dysfunction, or dysphagia. To develop this potential marker of dysphagia, comprehensiv e knowledge of aging related effects on bolus accommodation is needed. Several gaps within the bolus accommodation literature limit the knowledge base of the effects of advancing age, volitionally increasing effort, and manipulating bolus characteristics l ike volume and viscosity, on swallowing physiology. First, many prior studies have been conducted with younger participants; few studies have looked at bolus accommodation in older individuals. Second, vari ous methods have been employed precluding seamless comparison of results across studies. Third, studies have predominately evaluated the effects of one volume across multiple viscosities, or multiple volumes of a single viscosity. Therefore, identifying potential interactions between volume, viscosity, an d age, has not been possible. Fourth, tendency to use standalone, non integrated technologies has limited prior study to single physiologic measures Fifth, studies have primarily focused on swallow timing or biokinematic

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16 measures 2 9 Few studies have evaluated bolus accommodation effects on p ressure generation during swallowing. Last, volitionally increasing swallowing effort or the is a frequently prescribed technique for increasing swallow pressures, bolus driv ing force, and pharyngeal clearing force in persons with dysphagia. As such, volitionally increasing swallowing effort may serve as a means of over riding a utomatic bolus accommodation patterns; but, study of the effect of this technique on bolus accommoda tion is limited. In summary, f rom those few studies that investigated bolus accommodation and aging, variability in inst rumentation, measurement method bolus evaluated, component of physiology studied and lack of integrated assessment have made it diffi cult to draw conclusions. Furthermore, e xamination of swallowing pressure parameters is limited, and the combined effects of advancing age and volitionally increasing swallowing effort on bolus accommodation and swallow pressure generation is unknown. Stu dy Purpose T h is project incorporated a novel approach to evaluate the impact of age and volitional swallow effort on bolus accommodation characteristics. I ntegrated video manofluorography was used to simultaneously examine change in lingual palatal pressure s, pharyngeal pressures, and swallow bio kinematics as a function of increased swallowing effort, bolus volume and viscosity, and age in healthy older adults. S tudy Aim s This study had one omnibus primary aim with multiple hypotheses and one exploratory ai m.

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17 Primary Aim To i dentify and describe changes in pressure and biokinematic parameters during swallowing as a function of systematically increasing volitional swallowing effort bolus volume, bolus viscosity, and participant age in a sample of healthy old er individuals. Hypotheses: 1. Volitionally increasing swallow effort will result in increased pressure and hyolaryngeal movement within each age group 2. As bolus volume systematically increase s swallow pressures and hyolaryngeal movement will increase across all physiologic measures within each age group 3. As bolus viscosity systematically increase s swallow pressures and hyolaryngeal movement will increase across all physiologic measures within each age group 4. Older participants will demonstrate lower pressu re s and shorter hyolaryngeal movement distance than younger participants Exploratory Aim To explore potential relationships between swallowing pressure and movement during both typical and effortful swallowing tasks. Hypothesis : T ongue and pharyngea l pres sure parameters will be strongly correlated with change in hyoid and laryngeal excursion during both the typical and effortful swallowing conditions.

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18 CHAPTER 2 LITERATURE REVIEW Chapter Overview This chapter reviews the literature on bolus accommodation to support the rationale for this study. This review includes a discussion of what is known regarding bolus accommodation, age effects on bolus accommodation, the effect of the effortful swallow technique on bolus accommodation, and limitations in the lite rature. Studies of Bolus Accommodation B olus accommodation is the process of involuntary physiologic adjustment to varying bolus ch aracteristics during swallowing. Evidence of bolus accommodation is seen neurologically via change in muscle fiber activity 10 11 and cortical representation ; 12 13 and functionally via change in swallow timing, movement, and pressure generation parameters observed while swallowing boluses with different sensory characteristics 14 19 Prior studies of bolus accommodation may be separated into those that focus on swallow timing, those that focus on swallow biokinematic distance, and tho se that focus on swallow pressure generation. Further delineation is based on manipulation of bolus volume and viscosity. Bolus Accommodati on Effects on Timing Parameters Volume effects Studies of bolus accommodation on swallowing timing suggest that incr eased bolus volume results in earlier onset of lingual, pharyngeal, and hyo laryngeal movement; and upper esophageal sphincter (UES) relaxation Larger volumes have also been associated with shorter oral and pharyngeal transit times, 20 21 and longer UES

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19 relaxation time. 22 For example, Dantas reported a trend toward shorter (i.e. faster) oral and pharyngeal transit times w/ increased volume. 12 finding that larger boluses traversed the oropharynx more rapidly than smaller boluses. 23 Perlman showed faster swallowing onset with increased volumes, but observed increased duration of laryngeal muscle activity, i.e. longer swallow duration as volume increased. 24 Similarly, Ertekin, found that total duration of submental electromyographic (sEMG) muscle activity, laryngeal elevatio n time, and cricopharyngeal EMG pause all increased significantly with increasing bolus volume. 25 In summary, increasing bolus volume results in faster onset of key swallowing events, and prolonged duration of muscle activity during the swallow. Viscosity effects Viscosity related timing results suggest that i ncreas ing viscosity resu lt s in slower oral and pharyngeal swallow onset longer swallow duration, and longer UES opening, but published results are conflicted. For example, both Bisch 26 and Reimers Nels 27 found that increasing viscosity resulted in faster pharyngeal swallow onset, longer pharyngeal swallow duration, faster pharyngeal bolus transit, earlier airway closure, and longer UES opening. Conversely, Kendall found no significant viscosity effect on oral or pharyngeal timing. 28 Likewise, Butler found no visco sity effects on pharyngeal timing. 29 Inconsistency in viscosity investigated, instrumentation, and measurement definitions may have factored into the contradictor y findings. Bolus Accommodation Effects on Biokinematic Distance Parameters Volume effects S tudies of volume effects on h yo laryngeal movement distances have consistently found that i ncreasing volume results in increasing maximum hyoid and

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20 laryngeal excurs ion, until such point as a physiologic volume threshold is reached where subsequent volume increases do not influence hyo laryngeal movement distance. 14 30 33 Variability in study volumes and participant age has precluded identification of an exact volume threshold ; however, younger participants have demonstrated higher physiologic volume thresholds than older p articipants. Viscosity effects S tudies evaluating viscosity effects on hyolaryngeal movement in either healthy or patient populations have produced contradictory results Among these, Chi Fishman and Sonies compared the effects of four different liquid v iscosities, thin, nectar, honey, and pudding thick, on both hyoid movement duration and maximal distance. 33 Results indicated significa ntly longer movement duration for the pudding thick viscosity, but no viscosity effect for maximum distance. Similarly, Kendall found no viscosity differences in hyoid movement between a 3 mL liquid bolus and a 3mL pudding bolus. 28 Conversely, Ishida, Palmer and Hiiemae found a significant difference in hyoid maximum elevation as a function of viscosity. 34 They found that the more viscous materials resulted in greater hyoid displacement. Variation in instrumentation and measurement technique, volume of the material being evaluated, and degree of viscosity being compared have all made it difficult to fully characterize viscosity effects on hyo laryngeal movement. Furthermore, studies have focused on movement of the hyoid bone, or the movement of the hyo laryngeal complex as a whole. No st udy has investigated viscosity effects on laryngeal movement distance separately from hyoid movement distance. But, as each reflects a different physiologic swallowing parameter, the hyoid and larynx may react differently as a result of bolus accommodation

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21 Bolus Accommodation Effects on Pressure Parameters Study of bolus accommodation effects on swallowing pressure parameters can be separated into studies of lingual pressure and studies of pharyngeal pressure. Each will be discussed in terms of volume and viscosity effects. Volume effects on lingual pressure Investigation of volume effects on lingual propulsive pressures generated during swallowing has produced contradictory results. Kahrilas found that tongue driving force and bolus propulsion rate from t he oral cavity into the pharynx varied with volume. 35 Propulsion was more vigorous with large volumes but relatively delayed, and sluggish with smaller volumes. Similarly, Pouderoux and Kahrilas found that as volume increased, lingual propulsive force increased. 36 Conversely, Miller and identified no volume effect on maximal lingual propulsive force. Differences in site of measure ment may have produced this contradictory data. Pouderoux and Kahrilas measured tongue force in the center of the tongue, whereas Miller and Watkins measured force on the lateral tongue. Given that normal swallowing involves whole tongue to palate contact to generate a sufficient stripping wave and propel the bolus into the pharynx, measuring midline force has more clinical relevance. Furthermore, both studies used the Iowa Oral Pressure Instrument (IOPI ; IOPI Medical, Carnation WA ) device to measure lingu al pressure, which may have influenced their results. The IOPI measures lingual palatal pressure via a free floating air bulb that lies on the top of the tongue. In this position, simultaneous manipulation of both the air bulb and the bolus may have interf ered with volume accommodation, thereby obscuring any volume effect. Use of a measurement device affixed to the palate may identify a volume effect.

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22 Viscosity effects on lingual pressure Studies of viscosity effects on lingual pressure generation have sho wn that increasing viscosity results in increased lingual propulsion pressure during swallowing in healthy subjects. But like studies of volume effects, results have been contradictory depending on the specific viscosities investigated. For example, in com paring pressures generated during swallowing of water or other thin liquids against pressures generated with swallowing more viscous materials, many studies have reported greater pressure generation with increased viscosity. 36 39 However, one study reported no significant viscosity related lingual pressure differences between nectar thick and honey thick liquids 38 But, these two viscosities may not have been different enough to produce different pressures. Furthermore, the range of evaluated viscosities studied has been primarily limited to liquids; and, no study has investigated viscosity related pressure generation for semi solid boluses. Volume effects on pharyngeal pressure Among the few studies investigating pharyngeal pressure generation as a function of increasing volume, results ha ve been contradictory. For example, Shaker reported no volume effects on hypopharynx contraction pressure or UES resting pressure amplitudes as volume of water increased. 40 Similarly, Butler found no significant main effects of volume on either upper (base of tongue ), lower (hypopharynx) or UES relaxation pressures. 29 Consistent with Shaker and Butler, Gumbley reported no volume effects in the upper pharynx; but, contrary to them, did find volume driven effects in UES relaxation pressure. 41 Higher pressures indicating less relaxation were observed as volume increased Finally, Hoffman identified volume related pressure differences across the entire pharynx from the most upper portion at the velopharynx,

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23 through the middle base of tongue and hypopharyngeal regions, to the UES relaxation pressure in the lower pharynx. 42 These different findings may be due to technology utilized, as the Hoffman study is the only study that used high resolution manometry (HRM). HRM simultaneously measures pressures in a continuous manner from multiple anatomi c sites. Pressures are reported for a region and not just from a fixed sensor location. Consequently, this more sophisticated technology may identify pressure variations that simpler catheters do not. Viscosity effects on pharyngeal pressure Like studies of volume effects on pharyngeal pressure, studies investigating pharyngeal pressures as a function of increasing viscosity, have reported contradictory results. Some investigations have supported a viscosity effect in which increased viscosity resulted in greater pharyngeal pressures in the hypopharynx and lower relaxation pressures in the UES. 29 43 46 But, others h ave not. 47 26 48 49 Summary Prior studies of bolus accommodation have focused primarily on the effects of manipulating volume and viscosity on swallow timing parameters. A few studies have evaluated the effects of manipulating vo lume and viscosity on swallow pressure and movement parameters. When results are taken as a whole, patterns of volume and viscosity effects are beginning to emerge; but, contradictory results prevent making definitive conclusions. Table 2 1 summarizes key volume and viscosity effects. Aging Effects on Bolus Accommodation Aging related changes have been identified in all aspects of swallowing, from changes in head and neck anatomy to changes underlying physiologic and neurologic

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24 swallowing mechanisms 1 For example, in the aged tongue, fatty infiltration has been observed, 50 51 which is believed to reduce tongue mobility, slow swallow timing measures, 52 54 and r educe isometric pressure generation. 50 Additionally, in the aged pharynx, the distance between the hyoid bone and larynx at rest is greater, the anterior posterior maxim um pharyngeal width during swallowing is greater, and the posterior pharyngeal wall is thinner. 55 Together, these anatomical changes are associated with restricted hyolaryngeal elevation, shorter UES relaxation duration and smaller UES opening, 50 slower bolus transit times, and decreased pharyngeal co nstriction. Lastly, in the aged larynx, connective tissue change results in the larynx being more inferiorly positioned in the pharynx. This lower position results in the larynx having to travel greater distance during a swallow. This in turn may influence glottal closure, airway protection, and UES relaxation. 56 57 In healthy seniors, these changes, termed pres byphagia, appear to be a function of overall progressive decline in resiliency, or functional reserve. In seniors with significant health morbidities, the interaction of presbyphagia with disease related effects, places them at increased risk of dysphagia. Sarcopenia, or age related loss of muscle mass and conc omitant reduced muscle strength, 58 60 is known to impact the structure and function of muscles of the swa llowing system. These age related musculature changes have been shown to impact timing and movement parameters of bolus accommodation 40 49 54 but impact on pressure parameters has been relatively unstudied. The few studies of bolus accommodation effects on swallowing pressure parameters in older adults can be s eparated into studies of lingual pressure and studies of pharyngeal pressure.

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25 Lingual Palatal Pressure Numerous studies have documented an age related reduction in maximal isometric tongue pressure, 8 53 61 62 but, few have investigated lingual propulsion pressure during functional swallowing. Fewer still have investigated bolus accommodation and its effects on lingual pressure generation. Nicosia 37 and Youmans and Stierwalt 63 studied age related differences in both isometric tongue pressures during a static tongue hold t ask and functional tongue propulsion pressures as a function of swallowing boluses of different volumes and viscosities. Congruent with previous studies of isometric tongue pressure in older adults, Nicosia found that older participants generated lower max imum isometric pressure than the younger participants. But, no age or volume related differences in lingual palatal propulsion pressures during swallowing were identified. Only a viscosity effect was observed; swallowing the semi solid bolus resulted in gr eater pressure than swallowing either of the volumes of the liquid boluses, in both participant groups. Y oumans and Stierwalt expanded on the Nicosia study by increasing sample size, age range of participants, and volume and viscosity range of boluses. The ir results maximum tongue pressure during the isometric task, but no significant age differences or volume related effects were identified in lingual palatal propulsion press ures during the swallowing task. The only observed differences were viscosity related; nectar, honey, and pudding viscosities differed significantly from thin liquids, but, did not differ from each other. They concluded that maximal tongue pressure generat ed during swallowing differed as a function of bolus viscosity, and not as a function of age

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26 Butler investigated the relationship between tongue adiposity, isometric tongue strength, and lingual pressures generated during swallowing as a function of acco mmodating to different volumes and viscosities in older individuals. 64 Unique to this study, participants underwent computerized to mography scan of the tongue to obtain a measure of tongue adiposity. Furthermore, so as to not interfere with tongue movement during swallowing, tongue pressures were measured via a 3 bulb array affixed to the roof of the mouth. Results showed that while i ncreased tongue adiposity resulted in lower posterior tongue maximum isometric strength, this fatty infiltration did not affect lingual pressure generation during a swallow. This study further clarified the relationship between isometric and functional ton gue pressures, however did little to clarify bolus accommodation effect. In summary, with advancing age the tongue undergoes structural change like fat infiltration ; but the functional impact of this on pressure generation during swallowing is not fully understood. What is apparent is that bolus accommodation effects on lingual pressure generation appear to be driven by bolus viscosity, and not by age or volume. Pharyngeal Pressures Studies of age effects on pharyngeal pressure amplitude are few in numbe r, and results are contradictory. For example, three separate studies investigated age effects on both pharyngeal contractile pressures and UES relaxation pressures simultaneously. Results both supported and contradicted each other. V an Herwaarden found th at as viscosity increased from liquid to pudding, pharyngeal contractile pressures did not change in younger people, but, increased in older people. 45 And, mean upper pharyngeal pressure (base of tongue and hypopharyngeal pressure combined) was significantly higher in the older participants for each viscosity. However, neither Butler 29

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27 nor Meier Ewert 65 found viscosity related or age related differences in pha ryngeal contractile pressures. For UES relaxation pressures, both van Herwaar den and Butler found that as viscosity increased, UES relaxation pressure increased and was consistently highest, i.e. less relaxed, in the older participants. But, Meier Ewert did not find a consistent viscosity related UES pressure in his older participa nts. Rather, he found an age effect for UES relaxation pressure for the solid viscosity only; older subjects demonstrated higher UES pressure when swallowing a cookie In summary, the pharynx undergoes structural changes with advancing age; but, like the tongue, the functional impact of these on pressure generation during swallowing is not fully understood. Bolus accommodation effects on pharyngeal contractile pressures and UES relaxation pressures appear to be driven by both age and viscosity, but, no con sensus regarding the pattern of these effects has been reached. Difference between maximal isometric pressure and sub maximal functional swallowing pressure has led to the notion of functional or physiologic reserve in the swallowing system. 53 66 Functional reserve is a measure of physiologic resiliency. 67 68 Loss of functional reserve is considered to be a contributor to frailty and disability in older individuals. 83 As such, reduced functional reserve may limit the degree of bolus accommodation effects such that greater differences in bolus characteristics may be requir e d before differences in pressure and movement can be produ ced in older individuals Converging evidence from the exercise science, physical therapy, and gerontology literature indicates that voluntary increase in muscle effort helps older adults accomplish motor tasks that they are unable to complete with normal effort

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28 levels. 69 Applied to swallowing, voluntarily increasing swallowing effort may help to over ride the involuntary aspect of bolus accommodation, thereby helping the older adult pro duce sufficient pressure for safe swallowing. In fact, v olitional ly increasing frequently prescribed for increasing swallow pressures, i.e. tongue driving force, and pharyngeal cleari ng force in persons with dysphagia. 70 72 As such, the effortful swallow technique may expose upper limits to bolus accommodation based on reduced physiologic re serve specific to older adults. N umerous investigations into the effect of the effortful swallow technique on swallowing physiology have been completed. Results indicate that effortful swallowing generated greater surface electromyographic amplitudes, 70 higher velocity bolus driving force, 73 greater pharyngeal contraction duration, 74 increased hyoid vertical displacement, 75 76 decreased pharyngeal residue implying increased pharyngeal clearing force, 54 and improved esophageal bolus flow 77 78 than typical swallowing in healthy younger adults. Given this confluence of positive effects on swallowing that use of the effortful swallow technique will impact bolus accommodation in a similar fashion. No study has directly investigated the effect of the effortful swallow on bolus accommodation in older adults. Rather, effects must be inferred from studies of the constant, integrated with studies of its effect on bolus accommodation in younger adults. Study of effortful swallowing effect in older healthy adults has been limited to two investigations. Hind and Nicosia investigated typical versus effortful swallowing on

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29 temporal swallowing measures, lingual palatal pressure generation, and hyolaryngeal maximal movement in healthy middle aged and older adults 79 They reported an age x swallow condition interaction for lingual palatal pressure generation. All participants generated greater lingual palatal pressures during the effortful swallow regardless of age, with younger participants demonstrating significantly higher pressures than older participants. They also reported that effortful swallowing resulted in significantly longer swallow durations and gr eater hyoid anterior movement than typical swallowing, regardless of age. Similarly, Yeates, Steele, and Pelletier compared swallow condition effect between younger (age 18 25 years) and older (age 60 years) women. 80 Like Hind and Nicosia, they reported inc reased lingual palatal pressure with the effortful swallow regardless of age. But, they did not observe the same age x swallowing condition interaction. Rather, they observed no pressure differences between the younger and older participants for either swa llowing condition. No study has investigated effortful swallowing effects on bolus accommodation for lingual palatal or pharyngeal pressures in any population. Two studies have investigated the effects of the effortful swallow on bolus accommodation for U ES relaxation pressure. Witte 74 and Takasaki 81 compared typical and effortful swallow ing o f saliva and water in healthy youn ger adults. Results of the two studies were equivalent. They found that volitionally increasing swallowing effort resulted in lower UES relaxation pressure, i.e. more relaxation, for both viscositie s, with less pressure, i.e. less relaxation, demonstrated during the saliva swallow than the water swallow. Neither study was able to determine which bolus characteristic, volume or viscosity, resulted in

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30 the decreased UES relaxation pressure. Furthermore, neither study evaluated more viscous materials In summar y, limited data regarding effects of the effortful swallow on bol us accommodation in healthy older adults underscore the need for more study into the technique Such information may help determine the merit of volitionally increasing swallowing effort as a means of over riding the involuntary bolus accommodation process. If this is possible, then, use of the effortful swallow in conjunction with manipulating bolus characteristics may serve as one component in a dysphagia rehabilitation protocol. Limitations in the Literature Prior studies of bolus accommodation in younger individuals have demonstrated both volume and viscosity related effects on swallow timing and pressure. Increasing volume results in faster swallowing timing measures and may or may not res ult in higher lingual palatal and pharyngeal pressures. Increasing viscosity results in longer timing measures, higher lingual palatal pressure, and possibly higher pharyngeal pressures. Studies of bolus accommodation in healthy older individuals have been inconclusive; but, lingual palatal and pharyngeal pressures appear to be viscosity driven. Furthermore, while use of the effortful swallow is an accepted clinical technique to improve swallow pressure and movement parameters in patient populations, effect on bolus accommodation in healthy older individuals has not been studied. Therefore, evaluation of the effect of this technique on bolus accommodation in an older population is warranted. Results may illuminate the potential of volitionally increasing swa llowing effort and manipulating bolus characteristics as a means of over riding the voluntary

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31 aspects of bolus accommodation. If this is possible, the n this may become a strategy as one component of a dysphagia rehabilitation protocol. This paucity of data emphasizes that several gaps exist in the bolus accommodation literature. D ifferences in instrumentation, measurement methods, and component of physiology studied have made it difficult to draw conclusions about age effects on bolus accommodation in healt hy swallowing. For example, c ommon instrumentation includes rectified surface electromyography (sEMG), 82 both free floating 38 39 79 and affixed lingual palatal pressure bulbs, 29 83 pharyngeal manometry using solid state, 29 64 water perfused, 3 20 84 or high resolution catheters, 42 and isolated videofluoroscopy. 29 33 85 Although each technology provide d useful information, failure to standardize instrumentation or capture simultaneous oral and pharyngeal measures does not allow for seamless com p arison of data between studies. Similarly, while early met hod studies identified the advantages of integrating pharyngeal manometry with fluoroscopy, 86 studies of bolus accommodation utilizing pharyngeal manometry have not consistently integrated manometry and fluoroscopy. 63 C onsequently consistency of pharyngeal sensor pl acement can not be guaranteed throughout the study and biokinematic measures can not be obtained. S tudies of bolus accommodation effects us ing simultaneous integrated technologies will provide a more comprehensive perspective on physiologic alterations re lated to changing bolus characteristics. Variability among boluses studied and small sample sizes 36 87 further complicate characterization of bolus accommodation with advancing age. Conclusions regarding volume and viscosity effects on normal swallowing pressures and

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32 biokinematic parameters in this population are difficult to make from these small samples. M ost studies of age effects on bolus accommodation have studied swallowing timing characte ristics or bio kinematic parameters. E xamination of swallowing pressure parameters is limited. However, bolus accommodation effects on p ressure generation required to swallow a bolus should also be considered an important component of physiology that may ch ange with age. But, only a few studies have systematically investigated bolus accommodation effects on swallowing pressure parameters in older adults Their results have laid the foundation for two disti nct areas of physiologic study: 1) aging effects on tongue pressure as an indicator o f change in bolus driving force; and 2) aging effects on pharyngeal pressure and biokinematic movement as indicators of change in bolus clearing forces. Lastly, v olitionally increasing swallowing effort is a technique rou tinely used to improve inadequate swallowing pressure and force in patients with dysphagia. But, its effect on bolus accommodation in older adults is relatively unstudied. Investigation into may help illuminate the value of using thi s technique to over ride volitional patterns of bolus accommodation and as such may serve as a strategy in dysphagia rehabilitation. Significance of the Proposed Study Bolus accommodation facilitate s precisely coordinated timing and sufficient contractile force to safely propel different materials through the upper aerodigestive tract. Presence of sarcopenia related sub clinical pressure or movement alterations in asymptomatic older individuals may be indicative of risk for developing swallowing problems. I dentifying and describing these sub clinical alterations should serve to fill

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33 critical research gaps and provide additional age referenced information for comparison to abnormal swallowing functions in patient populations. Furthermore, i ncreasing th is know ledge base may provide information regarding the value of manipulating bolus characteristics, or volitionally increasing swallowing effort, as potential strategies to assist in the rehabilitation of swallowing disorde rs.

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34 Table 2 1. Summary of the key eff ects of increasing volume and viscosity on bolus accommodation Volume Viscosity Timing Effects Faster onset of key swallowing events Slower onset of key swallowing events Prolonged muscle activity Prolonged muscle activity Movement Effects Longer hyolaryngeal maximal distance until physiologic volume threshold reached Longer hyolaryngeal maximal distance Pressure Effects Lingual Palatal Unclear; some studies report increased pressure; others report no increase Increased pressure for more vi scous materials Pharyngeal Unclear; early studies report no change; recent study reports increased pressure Unclear; some studies report increased pressure; others report no increase UES Relaxation Unclear; some studies report increased pressure; others report no effect Unclear; some studies report increased pressure; others report no increase

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35 CHAPTER 3 METHODS AND MATERIALS Study Overview and Design A prospective, cross sectional study with repeated measures design was employed to investigate the eff ects of age and swallowing effort on bolus accommodation in a sample of healthy older individuals Bolus accommodation effect was measured for t he physiologic parameters of lingual palatal pressure, pharyngeal manometric pressure, and hyoid and laryngeal e xcursion during typical and effortful swallowing. A ge effects were analyzed by age group with participants categorized by of materials that increased in volume and visco sity. Swallowing examination was conducted via radiologic videofluoroscopy with integrated manometry or videomanofluorography (VMF) Materials to be swallowed were presented in a pre determined, randomized order. Swallowing condition ( typical versus effor tful ) was also presented in a pre determined randomized order. This study was approved by both the Institutional Review Board (IRB) and the Human Use of Radioisotopes and Radiation Committee (HURRC ) at the University of Florida. Participants Healthy elderl y adults between 60 90 years of age were recruited from the local community Targeted sample size was 32 participants. Recruitment goal was at least 10 participants in each age decade group (e.g. 60 69, 70 79, 80 90) with balanced gender distribution per d ecade group. Sampling frame in cluded word of mouth referrals program that links medically underserved individuals to research opportunities, and

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36 respondents to newspaper and web based advertisements. All potential participants were pre screened via telephone review utilizing an IRB approved script to ensure inclusion criteria. The study was explained in detail to all participants during this phone screening and again during the s tudy visit, prior to enrollment. All participants signed the University of Florida IRB approved informed consent document prior to inclusion in the st udy Subject inclusion and exclusion criteria were as follows: Inclusion Criteria Self reported healthy a dults 60 years of age and older with no diet restrictions due to diagnosed dysphagia (Functional Oral Intake Scale of 6 or higher). 88 Normal Mini Mental Status Examination score (score equal to 24 or greater). 89 Adequate dentition, either natural or artificial (dentures), to be able to masti cate semi solid boluses. Exclusion Criteria Previous or concurrent diagnosis of oral pharyngeal dysphagia. Concurrent diagnosis of neurodegenerative disease, strok e, acquired brain injury, brain tumor, head and neck cancer, tracheotomy, or any other morbi dity known to adversely affect oral pharyngeal swallowing function. Diagnosed or suspected acid reflux meeting any one of the following criteria: current reflux medication prescription (proton pump inhibitors like Nexium Protonix etc., or hydrogen ion acid blockers like Zantac ), Reflux Symptom Index score >13 90 Reflux Findi ng Score> 7 91 Study Protocol All enrolled participants underwent a clinical swallowi ng assessment, an endoscopic evaluation, an effortful swallowing training session, and a fluoroscopic swallowing assessment with integrated manometry. The clinical evaluation was used to ensure that participants m et al l inclusion requirements. The endoscop ic evaluation was completed to ensure normalcy of subject anatomy, and to identify any potential

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37 anatomical variants that may have precluded manometer placement or possibly altered bolus accommodation. The effortful swallowing training session was used to ensure that all participants were able to adequately differentiate and produce both a typical and an effortful swallow. Detailed lingual palatal, pharyngeal manometric, and hyolaryngeal excursion data was collected during the fluoroscopic evaluation and us ed as measures of bolus accommodation. Clinical Swallowing Examination A clinical swallowing examination was conducted prior to the fluoroscopic evaluation. This clinical examination consisted of four components: a mental status examination, subject reflu x symptom survey, a clinical assessment of swallowing function, and documentation of current oral intake. Mental status examination T he Mini Mental Status Examination 75 was used to ensure that participants had adequate ability to provide informed consent, follow directions, and participate in the study. Participants scoring 23 or less were excluded. Reflux symptom survey The Reflux Symptom Index 90 is a standardized method of quantifying symptoms commonly associated with acid reflux Participants scoring greater than 13 were excluded Clinical assessment of swallowing function Th e Mann Assessment of Swallowing Function (MASA) 92 is a psychometrically vali dated tool to evaluate swallowing ability. In this study, t h e MASA served as a screening tool to identify any overt, previously undiagnosed dysphagia. A score of less

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38 than 178 out of 200 identifies patients with clinical signs and symptoms of dysphagia. Pa rticipants with scores indicating dysphagia were excluded from this study. Oral intake documentation The Functional Oral Intake Scale (FOIS) 88 is a psychometrically validated 7 point ordinal rating scale d escribing the type of oral diet consumed. A score of 5 or less out of a maximum of 7 was used to reflect limitat ions in functional o ral intake. Endoscopic Swallowing Evaluation Following completion of the clinical swallowing assessment, an endoscopic assessment was conducted. To complete this examination a fiberoptic laryngeal endoscope was passed transnasally into the oropharynx. Fro m this position, the clinician is able to visually examine velopharyngeal closure and the structure and function of nasopharynx, hypopharynx, and larynx during phonation and swallowing. Participants with anatomical variants that may have precluded catheter insertion or inte rfered with bolus accommodation were withdrawn from the study. Also, t he Reflux Finding Score (RFS), 91 a visual/perceptual measure of anatomic change associated with uncontrolled acid irritation, was completed during the endoscopic exam. Participants with RFS score greater than 7 were withdrawn from the study. Effortful S wallow Training Session Prior to the fluoroscopic swallowing assessments, participants were taught to produce a swallow using increased volitional effort. To train this effortful swallow ability, submental surface electromyography (sEMG) with a visual wave form display of muscle activity during swallowing was used to provide the biofeedback. The Pathway MR 15 surface biofeedback device with integrated Synergy Plus software (The Prometheus Group, Dover, New Hampshire) was used to provide the biofeedback. The electrode

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39 was placed on the skin surface under the chin, over the submental muscles and position ed with the anode sensors placed vertically superior to the ground sensor. Once the electrode was placed and adequate recording verified, participants were instructed to swallow their saliva normally. A mean of three separate saliva swallows was generated Success was defined as doubling of sEMG amplitude from typical swallow effort. 70 Successful performance criterion was demonstrated ability to swall ow hard on 4 of 5 (80%) trials. Fluoroscopic Swallowing Evaluation The fluoroscopic swallowing evaluation consisted of simultaneous lingual palatal and pharyngeal manometry conducted under videofluoroscopy. During videofluoroscopy, radiographic moving imag es of the swallow are captured, allowing the clinician to examine oropharyngeal and esophageal movements and bolus flow through all stages of the swallow. Video fluoroscopic evaluation was conducted in a fluoroscopy suite within the Shands at UF Department of Radiology. Participants wore a radiation shielding lead vest around their torsos and were seated in a chair throughout the procedure Participants were asked to swallow a series of materials while wearing three different data collection sensors: a ling ual palatal pressure sensor, a pharyngeal manometric catheter, and a surface electromyography electrode placed under the chin over the submental muscles. All sensors were attached to the KayPentax Digital Swallowin g Workstation ( Model 7120, New Jersey) which was connected to the fluoroscopy equipment (Precision 500D R&F GE Healthcare, Worldwide ) ( Figure 3

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40 1). Prior to placement, both the lingual palatal pressure sensor and the manometric catheter were calibrated follow ing standardized procedures. 93 Two examiners were needed to place the senso rs and conduct the examination. Equipment used during the fluoroscopic swallowing assessment Specific equipment and data collection measures utilized during the study assessment were as follows: The digital swallowing workstation The with integrated digital v ideo r ecording and digital s wallowing s ignals l ab allows for time synchronized, simultaneous data capture from all sensors and fluoroscopy equ ipment 93 Lingual palatal pressures Three lingual palatal pressures, anterior, middle, and posterior, were collected using a three bulb tongue pressure array placed inside the mouth and affixed to the palate using Stomahesive (Product # 25542, ConvaTec inc. Princeton, NJ). The tongue bulb array was positioned approximately 1 mm posterior to the upper dentition, with the anterior bulb placed along the al veolar ridge and the middle and posterior bulb s positioned on the hard palate (Figure 3 2). Prior to affixing the tongue bulb array, the roof of the mouth was wiped with gauze in order to dry the tissue and promote optimal bulb to palate contact and adhesi on. Although influence of tongue bulb presence on tongue pressures generated while swallowing is unknown, Hind found that presence of this array did not alter swallowing pattern in healthy adults. 94 Pharyngeal manometric pressures Manometry is a technique for measuring pres sure. The manometric catheter measures pressure changes across a series of integrated pressure transducers or sensors. When used in swallowing assessment and depending on the type of catheter used, manometry can provide information regarding pharyngeal, ph aryngeal esophageal segment (PES), upper esophageal sphincter

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41 (UES), and/or esophageal pressure generation during a single swallowing event. Swallowing manometry can be utilized alone or in conjunction with videofluoroscopy (videomanofluorography, VMF). Th e combined VMF technique is preferred over manometry alone as it allows for radiologic confirmation of catheter position and bolus location during all phases of the swallow. In this study four pharyngeal pressure measures, i.e. base of tongue (BOT) hypoph arynx (HYPO), UES relaxation nadir and PES clearing wave peak (C Pk) pressures, were obtained using a 2.1 mm, solid state, triple sensor, catheter tip pressure transducer manometer (Model # CT O 3e Gaeltec Devices Ltd., Scotland, distributed by Medical Me asurements Incorporated, Hackensack, NJ) (Figure 3 3) This catheter was selected because it was supported for use with the KayPentax 93 and was similar to proposed pharyngeal manofluorography cathete r standards. 95 In order to minimize radiation exposure, the manometer was inserted trans nasally into the pharynx and positioned under endoscopic guidance following a published and com 96 Following this technique, the manometer was advanced until the most distal sensor was positioned in the proximal esophagus, the middle senso r in the hypopharynx, and the proximal sensor in the pharynx adjacent to the base of the tongue. Once thusly positioned, the catheter was slowly retracted until the distal sensor was located into the PES To ensure correct placement, presence of the charac 97 representing PES resting and nadir measurements was identified. When an m wave was not im mediately seen, subtle manometer placement adjustments (e.g. retracting or advancing ) were made as needed until the m wave was clearly noted. Once the m wave identified and corresponding

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42 pressure increases were noted in both the BOT and HYPO sensors, the m anometer position was verified fluoroscopically. When properly positioned sensor three is in the UES, sensor two 3.5 cm superior, resting in the hypopharynx, and sensor one 3.0 cm superior to sensor two, resting in the upper pharynx. These sensor location s are consistent with locations previously described. 29 98 Once placement was visually confirmed, the manomete tape. After taping, the participant was encouraged to dry swallow in order to adapt to the presence of the catheter. Although influence of manometer presence on pharyngeal pressure during swal lowing was unknown, Suiter and Moorhead demonstrated that the presence of a 3.5 mm transnasal endoscope did not alter swallowing physiology. 99 Therefore; presence of a 2.1 mm manometric catheter should not have altered swallowing physiology. Surface electromyography. Surface electromyo graphy served as a surrogate during typical and effortful swallows. A three sensor sEMG electrode (Uni Patch Disk # 7500, Covidien Corporation, Tyco Healthcare, Wabasha, MN) was placed on the skin surfa ce under the chin, over the submental muscles, and positioned with the cathode and anode sensors placed horizontally, superior to the ground sensor Hyoid anterior superior excursion and laryngeal excursion Hyoid and laryngeal biokinematic excursion dist ances were measured off line from recorded fl uoroscopic images The public domain, NIH developed ImageJ software 100 was used to make these measurements. Detailed description of the measurement technique is provided in the Data Measurement section of this paper.

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43 Fluoroscopic e xamination p rocedure Following in strument placement all participants performed a dry swallow to test instrumentation and to ensure all sensors were recording accurately. Once all equipment was deemed to be recording accurately, participants rested for 10 15 seconds to allow their swallow ing system to return to baseline; then baseline readings were recorded. Once a stable baseline was established for each sensor participants received a 5 mL thin liquid barium practice bolus followed by the study boluses, presented in pre determined rando mized order. Commerciall y available Varibar barium products ( E Z EM Inc. Lake Success, NY) were used for the liquid boluses, while differing volumes of fresh banana served as the semi solid boluses. Liquid boluses were measured into 5 and 10 mL samples o f thin, nectar, and pudding thick barium. Semi solid boluses were measured into 1 and 2 teaspoon slices and impregnated with nectar thick barium. To ensure that each subject received the correct bolus volume, all pre measured liquid boluses were delivered to the mouth via syringe, and all semi solid boluses via spoon. Participants were instructed to hold the bolus in the mouth until cued to swallow In order to mitigate any potential order effects on swallowing physiology, boluses were presented in a pre de termined randomized order. Participants completed 32 different swallows [2 bolus volumes x 4 viscosities (3 liquid and 1 semi solid viscosity) x 2 swallowing conditions (typical vs. effortful) x 2 trials per bolus]. After each bolus was swallowed, particip given the subsequent bolus. Due to potential for significant performance variability during trials of discrete swallowing, 101 stimulus repetition, i.e. swallowing more tha n one bolus trial per bolus condition, was considered necessary to assess inter trial variability

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44 As such, previous studies have involved 3 or more repetitions of each bolus. 71 102 104 However, these studies did not involve fluoroscopy, so participants were not exposed to radiation. Consequently, in order to balance the need for scientific rigor with minimizing radiation exposure, two trials of each bolus were deemed an acceptable compromise; a compromise that appears to have been made in similar investigations. 18 99 105 Approximately 90 minutes of time was needed to complete the clinical assessment, endoscopic assessment, train participants in the effortful swall ow, attach all of the data collection sensors, and c omplete the VMF assessment. Bolus randomization S wallowing condition order and bolus viscosity presentation order were randomized. Bolus volume was not randomized; rather, all participants swallowed a 5 m L bolus first, followed by a 10 mL bolus of the same viscosity. An on line computer generated random number generator, http://www.random.org/integer sets/ was used to produce two randomization lists; the f irst list contained 40 pairs of randomly ordered nectar, 3 = pudding, 4 = banana). Randomization was assigned sequentially based on subject enrollment order; randomizatio n was not blocked by age group. Data Measurement Primary outcomes included change in swallowing pressures and movement parameters as a functio n of swallowing c ondition bolus volume and viscosity, and age group. All data measu rements were collected off line. Specifi c dependent variables included: Difference in peak anterior, middle, and posterior lingual palatal pressures.

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45 Difference in peak base of tongue, hypo pharyngeal, UES relaxation nadir and pharyngeal esophageal segment (PES) clearing wave pressure s Difference in hyoi d maximum superior anterior excursion as measured by published biokinematic protocol. 32 106 Diff erence in laryngeal maximum excursion as measured by published biokinematic protocol. 32 106 Lingual P alatal Peak Pressures These were obtained for each tongue bulb (anterior, middle, and posterior) in the 3 bulb array by analyzing the individual graphic waveform s and pressure values produced by the software algorithm (Figure 3 4). Peak pressure was operationally defined as the highest pressure value obtained during the positive pressure wave produc ed during the primary swallow. T o ensure that the wave being measured corre sponded to the primary swallow, a ll waves were visually correlated with fluoroscopic image Pharyngeal Manometric Peak Pressures Peak pressures from the BOT, HYPO, nadir, and C Pk were obtained for each manometric sensor in the 3 sensor cath eter, by analyzing the individual graphic waveforms and pressure values produced by the software algorithm (Figure 3 4). Operational definitions, terms, and reference points are based on McConnel work. 107 Base of tongue (BOT) BOT peak pres sure was operationally defined as the highes t amplitude value identified in the BOT wave from sensor one When no obvious BOT wave was produced, inspection of the remaining manometric measures was completed to determine the correct score for this measure. When inspection revealed that the

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46 manometer was deemed to be working correctly but no obvious BO T wave was manometric or other error, or when participant neck length was sh ort thereby incorrectly positioning the sensor in the nasopharynx behind the palate, no peak was recorded Rather, data was entered as a missing value. Hypopharynx (HYPO) HYPO peak pressure was operationally defined as the highest amplitude value in the HY PO pressure wave identified at sensor two When no obvious HYPO wave was produced, inspection of the remaining manometric measures was completed to determine the correct score for this measure. When inspection revealed that the manometer was deemed to be w orking correctly but, no obvious HYPO wave was manometric or other error, no peak was recorded Rather, data was entered as a missing value. Upper e sophageal s phincter r elax ation n adir (UES nadir ) The UES nadir pressure was operationally defined as the lowest pressure during the relaxation of the pharyngeal esophageal segment (PES) on sensor three. W hen no obvious nadir was produced, inspection of the remaining manometric mea sures was completed to determine the correct score for this measure. When inspection revealed that the manometer was deemed to be working correctly but, no obvious nadir was manometric or other e rror, no peak was recorded Rather, data was entered as a missing value.

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47 Clearing wave (C Pk) Th e clearing wave peak was operationally defined as the highest pressure following the relaxation of the PES on sensor three. W hen no obviou s clearing wave was produced, inspection of the remaining manometric measures was completed to determine the correct score for this measure. When inspection revealed that the manometer was deemed to be working correctly but, no obvious clearing wave was pr manometric or other error, no peak was recorded Rather, data was entered as a missing value. Hyoid and Laryngeal Excursion Biokinematic measure s of both hyoid and laryngeal e xcursion during swallowing were measured from digitized still image frames obtained from the recorded fluoroscopic examinations. To obtain these images, the PI reviewed the digitally integrated recordings of each videofluoroscopic study frame by frame on the identified a pair of still frame images for each swallow, and saved the images on the as a digital image file in jpeg format. The first frame of each pair represented the resting, pre swallow position of both the hyoid bone and the laryn x before a bolus was placed in the mouth The second frame depicted the point during the swallow that corresponded to both maximum hyoid and maximal laryngeal excursion. Once captured, each of these files was digitally transferred from the to the Imag eJ analysis workstation via USB connected digital hard drive. Once transferred, an independent rater previously trained to the lab standard competency in ImageJ analysis procedures, analyzed each picture frame using the ImageJ software 100 via a standardized protocol. 32 106 In analyzing these images, first a line was drawn from the

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48 anterior inferior corner of the second cervical vertebra to the anterior inferior cor ner of the fourth cervical vertebra (C2 to C4). Then, each image was rotated as necessary so that this line and therefore the cervical spine were oriented in a true vertical position for more accurate measurement. Once vertically oriented, three points on the image were selected for measurement: 1) the anterior inferior corner of C4, which served as the anchor point; 2) the anterior inferior corner of the hyoid bone, and; 3) the anterior inf erior corner of the vocal folds at the point of the anterior superi or corner of the visible tracheal air column. The ImageJ program calculates values of each point as an x, y coordinate in a 2 dimensional plane. To measure both hyoid excursion and laryngeal excursion, the distance between the x coordinates and the y coor dinates for the anchor point and each structure in question was calculated for both the pre swallow and during swallow conditions. Then, the difference in distance from pre to swallow images was calculated a s a measure of total excursion (Figure 3 5). To e nsure accurate calibration between the two images, each subject wore a 20 mm calibration marker circumferentially around the neck during the fluoroscopic assessment. This marker is clearly visible on the fluoroscopic recordings (Figure 3 5). Prior to makin g distance measurements, the calibration marker was measured and a constant distance of 20 mm was set within the ImageJ software. All subsequent measures were considered relative to this calibration. With all swallows for all participants being calibrated using the same calibration marker, the mean and standard deviation of both hyoid and laryngeal excursion during swallowing for each individual bolus volu me and viscosity was calculated

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49 Reliability Inter rater reliability and intra rater reliability were a ssessed for each of the nine dependent variables and for selecting the fluoroscopy frame that represented maximum hyoid and laryngeal displacement. Raters were allowed to review the swallow video clips and sensor graphical waveforms as many times as necess ary. Intra class correlation (ICC) was used to analyze rater agreement for the continuous pressure and movement variables. Kappa was used to assess concordance of fluoroscopy frame choice Inter rater agreement Two independent raters served as reliability judges. Each was a doctoral student in the UF Swallowing Research Lab and each was trained to lab standard competency level prior to making independent measurements. The first rater was trained on analysis procedures and the second on ImageJ operatio ns. After the initial ratings were obtained, these two raters scored a randomly selected subset of swallows representing 5% of the original number of swallows to o btain a measure of reliability. Intra rater agreement Once all participants were measured, an d following a one month wash out period, the PI re scored this same randomly selected 5% subset of the recordings of the total number of swallows to obtain a measure of reliability. Data Management To ensure patient confidentiality, all participants were assigned a unique participant number. This number was used to identify all outcome measures. Furthe rmore, de identified data was entered into a password protected database (M icrosoft Excel 2010 ) in a central computer system.

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50 Sample Size and Po wer Considerations From both a preliminary study conducted in the UF Swallowing Research Laboratory and from data published by other authors, measures of effect size for 108 for group means and standard deviations. Results of these calculations are found in Table 3 1. Depending on the effort parameter considered, eff ect sizes ranged from .03 for G umbley work with young adults, 41 work comparing young and old adults. 29 These effect sizes demonstrate small to large effects, suggesting that some swallowing effort parameters may not appreciably change to accommodate boluses of different characteristics, while others may change greatly. C onsidering these calculations, a sample size of 32 elderly participants was deemed appropriate to achieve statistical power (1 tailed test to detect ch ange due to bolus accommodation. Statistical Analysis Plan This study was descriptive and relational in nature. Therefore, data w ere characterized using summary statistic s and graphic methods. Study population demographics were described using means, standard deviations and ranges for continuous variables (age, MMSE, MASA FOIS, Body Mass Index (BMI), RSI, RFS ) ; and proportions for categorical variables (gender, race, teet h type, presence/absence of cardiovascular disease, presence/absence of diabetes ). Inter trial variability between trials 1 and 2 was estimated using bi variate correlation analysis. If correlations were large ( r .5) 108 then, trial 2 of each bolus was to be used in the p rimary and exploratory analyses. Trial 2 was chosen for these analyses t o mitigate any participant test anxiety or anticipatory effects. If correlations were small ( r < .5), 108 then the two trials were to be

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51 averaged and average score was to be used in all analyses. All descriptive and inferential analyses were com pleted using IBM SPSS Statistics version 20 (IBM Corporation Somers, NY ). Primary Aim Multiple four factor r epeated m easures ANOVA w ere used to explore within group effects for swallowing condition, volume, and viscosity, and between group effects for a ge group, for each physiologic parameter. Statistical significance for the primary outcome was determined using a two tailed preset level of = .05. test of equality of error variance was used to examine potential ANOVA assumption violat ions. When stringent significance level of = .01 was adopted. 109 used to examine re peated measures effects. When violations, then the appropriate correction, either Greenhouse Geisser or Huyhn Feldt, was applied. 110 Descriptive and inferential results for volume and viscosity, as well as m easures of effect size where indicated, are reported for each physiologic parameter. Effect size is reported as partial eta squared ( p 2 ) Previous behavioral science literature has interpreted effect size measures as being small ( p 2 = .01 ), medium ( p 2 = 06 ), or large ( p 2 = .14). 109 Exploratory Aim Pearson product moment correlations were calculated to explore relationships between lingual palatal and pharyngeal manometri c pressure measure with hyoid and laryngeal movement for each swallowing condition Statistical significance for the exploratory outcome was determined using a two tailed preset alpha level of .05.

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52 Table 3 1. Sample size and power calculations Reference Study Measure Reference Study Bolus Reference Study n Reference Study Effect Size Reference Study Achieved Power Calculated n for This S tudy Lingual Palatal Pressure (anterior) 5 ml thick vs. 10 ml thick liquid 11 patients .35 .22 24 Lingu al Palatal Pressure (anterior) 10 ml thin vs. 10 ml thick liquid 11 patients .38 .20 24 Lingual Palatal Pressure (anterior) 10 ml thin vs. 10 ml pudding 11 patients .65 .49 16 Base of Tongue Peak Manometric Pressure 41 5 ml vs. 10 ml water 40 young .03 .05 2184 Hypopharynx Peak Manometric Pressure 41 5 ml vs. 10 ml water 40 young .06 .07 552 PES Nadir Peak 41 5 ml vs. 10 ml water 40 young 0.30 .05 2184 Phary ngeal Nadir 96 Saliva 23 young; 21 older 2.33 1.00 16 Hyo laryngeal Excursion 106 5 ml vs. 10 ml thin barium 20 elderly 0.36 .33 24

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53 T able 3 1 C ontinued Reference Study Measure Reference Study Bolus Reference Study n Reference Study Effe ct Size Reference Study Achieved Power Calculated n for T his Study Effortful Swallowing BOT Peak Pressure 74 10 ml water; normal vs. effortful swallow 40 young adults .44 .77 32 Hypopharyngeal Peak 74 10 ml water; normal vs. effortful swallow 40 young adults .50 .87 32 PES Nadir 74 10 ml water; normal vs. effortful swallow 40 young adults .06 .07 560

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54 Figure 3 1. Study equipment set up in the fluoroscopy suite Photo courtesy of the author. Figure 3 2 Close up of tongue bulb placement inside the mouth Photo courtesy of the author.

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55 Figure 3 3 Manometric catheter with three transducers used for pharyngeal measurements Photo courtes y of the author.

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56 Figure 3 4 Example of integrated fluoroscopy, lingual palatal pressures, and pharyngeal manometry Photo courtesy of the author.

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57 Figure 3 5 Videofluoroscopic still image showing measurements made for biokinematic analysis Ph oto courtesy of the author.

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58 CHAPTER 4 RESULTS Participant Characteristics Thirty eight self reported healthy volunteers between the ages of 60 and 88 were enrolled in this study over a 12 month period. Four participants failed the screening procedures an either failing the Reflux Symptom Ind ex or the Reflux Finding Score tests, and one endoscopic evaluation revealed a paralyzed vocal fold Two participants were unable to tolerate the complete manofluorography procedures (tongue pressure and pharyngeal manometry), and were also withdrawn. Additionally, one participant error. Thus, final sample size for data collection and analysis was 31 participants. Among these 31 participants, 7 were unable to tolerate the pharyngeal manometric catheter; therefore, only tongue pressure and biokinematic data were available from these subjects. Chi square analysis revealed no age group bias among the participants who did not tolerate the catheter ( 2 = .079, p = .961). All participants demonstrated adequate cognition to participate in this study [MMSE = 29.10 (SD = 1.08, range 27 30)], reported eating a regular diet [FOIS = 6.84 ( SD = 0.37)], denied reflux symptoms [RSI = 4.32 ( SD = 3.73, range 1 12)], and denied current or previous history of dysphagia or any disease known to be associated with dysphagia. Clinical and endoscopic swallowing evaluations revealed that participants had adequate dentition to support chewing the banana boluses, no clinical dysphagia [MASA =195.13 ( SD = 5.40, range 178 200)], no anatomic variants that might alter bolus accommodation, and no laryngeal anatomic findings to indicate reflux [RF S = 2.63

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59 ( SD = 2.53, range 0 7)]. Table 4 1 provides additional participant characteristic information. Analyses of patient characteristic variables were completed to identify any possible age group differences that might influence the analyses. Chi squar e analysis was run for the categorical variables obtained [ gender, race, teeth type (natural or denture), presence of cardia c disease, presence of diabetes] Results were not significant for any variable except race ( 2 = .9.439, p = .009), as only 5 non Caucasian individuals participated. All non Caucasians were in the 60 year old age group. As so few participants were not Caucasian, race was not used as a co variant. Univariate ANOVA was run for the only continuous v ariable obtained that was not used for participant screening [Body Mass Index (BMI)] This r esult was not significant. Given these results, no co variates were included in the ANOVA analyses. Preliminary Data Analysis Data Distribution Characteristics Data for the 14 dep endent pressure variables (i.e., 2 trials for each of the 3 tongue pressure and 4 pharyngeal pressures) and the 4 dependent movement variables (2 trials each for both hyoid and laryngeal excursion) were first examined for distribution normal cy characteristics. Box plots, histograms, and the SPSS outlier analysis were used to identify outliers. No extreme outliers were identified for any of the tongue pressure measures; however, at least one extreme outlier was identified for each of the phary ngeal manometry measures and both of the hyoid and laryngeal excursion measures. These were further analyzed for inclusion/exclusion in the final dataset. After inspection, all were included as they were felt to be representative of the heterogeneity in th e population. Normalcy assessment was conducted by visual examination of

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60 histograms with a superimposed normal distribution curve, and by measures of skewness and kurtosis. All variables had a normal distribution. Bolus Trial Analysis Pearson product momen t correlations for inter trial variability ranged from .66 for the UES nadir to .85 for the posterior tongue (Table 4 2). As all correlations were large 108 and statistically significant, trial #2 was used in all analyses. Primary Aim The primary aim of this study was to identify and describe changes in swallowing pressures and biokinematics as a function of increasing swallowing effort, and accommodation to boluses of increasing volume and viscosity, across age groups. Lingual Palatal Pressures Three separate 4 factor for swallowing condi tion x volume x viscosity x age group were conducted. Descriptive results for the three lingual palatal pressures are given in Table 4 3. Inferential results are as follows: Anterior tongue peak Interaction s No significant interactions were identified; therefore, main effects for each factor were evaluated. Swallowing c ondition. Results revealed a significant within group main effect for swallowing condition [F(1, 25) = 47.546, p p 2 = .655] with greater pressure observed in the effortful swallow than in the typical swallow (Table 4 6; Figure 4 1). Volume. No significant within group main effects for volume were identified. Viscosity. Results revealed a significant wit hin group main effect for viscosity p 2 = .524]. Review of the viscosity graph revealed a linear trend with pressure increasing as viscosity increased. Tests of within group

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61 contrasts revealed that pressures were significantl y greater when swallowing the pudding than when swallowing the thin liquid stimuli p 2 = .246 ], and pressures were greater when swallowing the banana stimulus than when swallowing any other viscosity {thin: [F(1, 25) = 71.062, p p 2 = .740], nectar: p 2 p 2 = .519]} (Table 4 6; Figure 4 3). No significant differences in pressure were observed when swallowing the thin and nectar thick liquid s timuli, or when swallowing the nectar thick liquid and pudding stimuli. Age group. Results revealed a significant between group main effect for age p 2 = .207]. Post hoc analysis revealed that the 80 year old age group produce d significantly lower pressures than the 70 year old age group (p = .0 17 ) (Table 4 6; Figure 4 4). No significant differences were noted between the 60 and 70 year old age groups, or between the 60 and 80 year old age groups. Middle tongue peak Interaction s. Results revealed two significant interactions. First, a significant 3 way interaction for swallowing condition x viscosity x age group was identified [F(6, 75) p 2 = .184]. To further analyze this interaction, two separate 2 factor ANOVAs for viscosity x age were run for each swallowing condition. Tests of contrasts were performed comparing swallowing condition to each level of visco sity across the three age groups. Contrast results revealed that during typical swallowing, the 70 year old age group produced significantly greater pressures when swallowing the banana than when swallowing the pudding stimuli [F(1, 25) = 4.484, p = .022, p 2 =.264]. And, during effortful swallowing, the 70 year old age group generated significantly greater

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62 pressure when swallowing the pudding than when swallowing the thin liquid stimuli [F(1, 25) = 5.979, p = .008, p 2 =.324] (p = .008) (Table 4 8; Figure 4 6). Additionally, results revealed significant 2 way interaction for volume x viscosity p 2 = .132]. Review of the interaction graph revealed that for both thin and nectar thick liquid stimuli, higher pressures were generated when swallowing the 5 mL volume than when swallowing the 10 mL volume. For pudding and banana stimuli, this was reversed with higher pressures generated when swallowing the 10 mL volume than when swallowing the 5 mL volume. Tests of contrasts revealed tha t pressures were significantly higher when swallowing the 10 mL volume of pudding than p 2 = .185]. Also, pressures were significantly higher when swallowing the 10 mL volume of b anana p 2 = .265] or nectar p 2 = .202] (Table 4 7; Figure 4 5) Swallowing condition. R esults revealed a significant within group main effect for swallowing condition [F(1, 25) = 36.772, p p 2 = .595] with greater pressure observed in the effortful swallow than in the typical swallow (Table 4 6, Figure 4 1). Posterior tongue peak Interactions Results revealed two signific ant interactions. First, a significant 3 way interaction for volume x viscosity x age group was identified [F(6, 75) = 2.604, p = p 2 = .172]. To evaluate this interaction, contrasts were performed comparing each viscosity to the 5 mL volume first, and then to the 10 mL volume, across the three age groups. Contrasts revealed two significant relationships. The first was observed when comparing pressures generated while swallowing nectar thick liquid to those generated

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63 while swallowing banana stimuli [ F(2, 25) p 2 = .269]; the second when comparing pressures generated while swallowing pudding to those generated while swallowing p 2 = .271]. Review of the interaction graph reveals that the 80 year ol d age group generated lower pressures for both volumes across all viscosities than those generated by either the 60 or 70 year old age groups. Also, both the nectar to banana and pudding to banana contrasts appear to be most pronounced in the 60 year old a ge group (Table 4 8; Figure 4 8). Next, initial results revealed a significant 2 way interaction between volume x for the interaction [W = .629, 2 (5) = 10.990, p = .052)], and the Greenhouse Geisser 110 therefore, degrees of freedom were corrected using the Huyhn Corrected results revealed a significant 2 way interaction between volume x viscosity p 2 = .168 ]. For both liquid stimuli, greater pressures were generated when swallowing the 5 mL volume than when swallowing the 10 mL volume. Conversely, for pudding and banana stimuli, greater pressures were generated when swallowing the 10 mL volume than when swallowing the 5 mL volu me. Tests of contrasts revealed that pressures produced when swallowing 10 mL of pudding were significantly greater than pressures produced when swallowing either 5 or 10 mL p 2 = .346] or nectar thick liquid stimuli [ F(1, 25) = p 2 = .222]. Posterior lingual palatal pressures generated when swallowing 10 mL of banana were also greater than those generated when swallowing

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64 p 2 = .155] or nectar thick liquid p 2 = .155]. (Table 4 7; Figure 4 7) Swallowing c ondition. Results revealed a significant within group main effect for swallowing condition [F(1, 25) = 46.300, p p 2 = .649] with greater pressure obse rved in the effortful swallow than in the typical swallow (Table 4 6; Figure 4 1). Pharyngeal Manometric Pressures Three separate 4 factor repeated measures ANOVAs for swallowing condition x volume x viscosity x age group were conducted. Descriptive result s for the 4 pharyngeal pressures are depicted in Table 4 4. Inferential results are as follows: Base of tongue peak (BOT) Interactions No significant interactions were identified; therefore, main effects for each factor were evaluated. Swallowing c onditi on. Results revealed a significant within group main effect for swallowing condition [F(1, 19) = 20.947, p p 2 = .524], with greater pressure observed in the effortful swallow than in the typical swallow (Table 4 6; Figure 4 1). Volume. No signi ficant within group main effect for volume was found. Viscosity. No significant within group main effect for viscosity was found. Age group. No significant between group main effect for age group was found. Hypopharyngeal peak (HYPO) Interaction s. No si gnificant interactions were identified; therefore, main effects for each factor were explored. Swallowing c ondition. No significant within group main effect for swallowing condition was found. Volume. No significant within group main effect for volume wa s found.

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65 Viscosity. Results revealed a significant within group main effect for viscosity [F(3, 54) = 3.387, p p 2 = .158]. Review of the viscosity graph revealed a linear trend with pressure increasing as viscosity increased. Tests of within grou p contrasts revealed that pressures generated when swallowing pudding were significantly higher than when swallowing nectar thick liquids [F(1, 18) = 12.069, p p 2 = .401] (Table 4 6; Figure 4 3) No other significant viscosity related differences were observed. Age group. No significant between groups main effect for age was found. UES n adir peak Interactions No significant interactions were identified; therefore, main effects for each factor were evaluated. Swallowing c ondition. Results revea led a significant main effect for swallowing condition [F(1, 13) = 7.185, p p 2 = .356] with the higher pressure values indicating that the PES relaxe d less during effortful swallowing than during typical swallowing (Table 4 6; Figure 4 1). Volume. Results revealed a significant main effect for volume [F(1, 15) = 12.127, p p 2 = .447] with higher pressures generated when swallowing the 10 mL bolus than when swallowing the 5 mL bolus volume indicating that the PES relaxed less as volume increased (Table 4 6; Figure 4 2). Viscosity. Initial results revealed that M sphericity had been violated for the viscosity main viscosity effect [W = .436, 2 (5) = 11.401, p = .044)], and that the Greenfield Geisser correction met criterion for being too 110 therefore, degrees of freedom were corrected using the Huyhn orrected results revealed a significant within p 2 = .170].

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66 Review of the viscosity graph revealed a negative linear trend with less UES nadir pressure generated as viscosity increased in dicating more relaxation as viscosity increased Tests of contrasts revealed that significantly less nadir pressure was generated when swallowing the pudding stimulus than when swallowing either the nectar p 2 = .324] or th in liquid stimuli [F(1, 25) = 7.949, p 2 = .346] (Table 4 6; Figure 4 3). No significant difference was observed for relaxation pressures generated when swallowing the pudding and banana stimuli. Age group. No significant between group s main effe ct for age was found. Clearing wave peak (C Pk) Results revealed a significant 4 way interaction for swallowing condition x volume p 2 = .235]. To further analyze this interaction, a series of 3 way repea ted measures each level of one variable and comparing it to all levels of the other variables. Swallowing condition was analyzed first, followed by volume, viscosity, and age. Typical swallowing condition, 3 factor ANOVA. Results of a 3 way repeated measures ANOVA for volume x viscosity x age revealed a significant 3 way interaction [F(6, 63) = 2.599, p = .026]. To further analyze this 3 way i nteraction, a series of 2 way repeated measures t each level of one variable and comparing it to all levels of the remaining two variables. Volume was analyzed first. For 5 mL, results of a 2 way ANOVA for viscosity x age revealed no significant main or interaction effects. For 10 mL, results of a 2 way ANOVA for viscosity by age revealed a significant interaction [F(6, 63) = 2.426, p = .036, p 2 = .188]. Tests of contrasts revealed that pressures generated when swallowing the banana stimulus were greater

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67 p 2 = .254] or nectar p 2 = .255]. Next, viscosity was analyzed. For nectar thick liquids, results of a 2 way ANOVA for volume x age group revealed a significant 2 way interaction [F(2, 21) = 3.394, p = p 2 = .244] with the 60 year old age group generating greater pressure than either the 70 or 80 year old age groups. No significant main or interaction effects were observed for thin liquids, pudding, or banana stimuli. Last, age was analyzed by individual age group. For the 60 year old age group, results of a 2 way ANOVA for vo lume x viscosity revealed a significant interaction [F(3, p 2 = .324]. Tests of contrasts revealed that pressures generated when swallowing nectar thick liquids were greater than pressures generated when swallowing either the pudding p 2 = .616] or banana stimuli p 2 = .524]. No significant main or interaction effects were observed for either the 70 or 80 year old age groups. Effortful swallowing condition 3 factor ANOVA Results of a 3 way ANOVA for volume x viscosity x age revealed a significant 2 way interaction for volume x age p 2 = .274], with greater pressures generated when swallowing the 5mL volume than when swallowing the 10 mL volume stimuli across all age groups. No main effect for viscosity was observed. Volume 3 factor ANOVA For the 5 mL volume, results of a 3 way ANOVA for swallowing condition x viscosity x age revealed no significant main or interaction effects. Similarly, for the 1 0 mL volume, results of a 3 way ANOVA for swallowing condition x viscosity x age revealed no significant main or interaction effects.

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68 Viscosity thin liquid, 3 factor ANOVA Each viscosity was analyzed individually. For thin liquids, results of a 3 way A NOVA for swallowing condition x volume x age revealed no significant main or interaction effects. Viscosity nectar thick liquid, 3 factor ANOVA. For nectar thick liquids, results of a 3 way ANOVA for swallowing condition x volume x age revealed a signifi cant 2 p 2 = .273]. Pairwise comparisons revealed that for the 5 mL volume, pressures generated by the 60 and 80 year old age groups were greater than pressures generated by the 70 year old age group, whereas for the 10 mL volume pressures generated by the 70 and 80 year old age groups were greater than pressures generated by the 60 year old age group. However, none of these comparisons reached statistical significance. Viscosity pudding, 3 fact or ANOVA. For pudding, results of a 3 way ANOVA for swallowing condition x volume x age revealed a significant 3 way interaction [F(2 p 2 = .238]. To further analyze this interaction, a series of 2 way repeated measures comparing it to all levels of the remaining two variables. Swallowing condition w as analyzed first. For typical swallowing, results of a 2 way ANOVA for volume x age revealed no significant interaction or main effects. For effortful swallowing, results of a 2 way ANOVA for volume x age revealed a significant volume x age interaction [F(2, 21) = 3.637, p = .044, p 2 = .257]. Tests of contrasts revealed that pressures were more variable for the 10 mL volume than for the 5 mL volume, with the 60 and 80 year old groups generating higher pressure for the 10 mL volume and the 70 year old group generating lower pressur e for the 10 mL volume of pudding.

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69 Next, volume was analyzed. Results of two separate 2 way ANOVAs for swallowing condition x age revealed no significant main or interaction effects for either the 5 mL or the 10 mL volumes. Last, age was analyzed by in dividual age group. No significant main or interaction effects were observed for any of the age groups. Viscosity banana, 3 factor ANOVA. For the banana stimulus results of a 3 way ANOVA for swallowing condition x volume x age revealed a significant 3 w ay p 2 = .347]. To further analyze this i nteraction, a series of 2 way repeated measures one variable and comparing it to all levels of the remaining two variables. Sw allowing condition was analyzed first. Results of a 2 way ANOVA for volume x age revealed no significant main or interaction effects for either swallowing condition. Next volume was analyzed. For 5 mL, results of a 2 way ANOVA for swallowing condition x age revealed no significant main or interaction effects. For 1 0 mL, results of a 2 way ANOVA revealed a significant main effect for swallowing condition [F(1, 19) = p 2 = .204], with higher pressures generated during the typical swallow than during the effortful swallow. Last, age was analyzed by ind ividual age group. No significant main or interaction effects were observed for any of the age groups. Age group analysis, 3 factor ANOVA A separate 3 factor repeated measures ANOVA of swallowing condition x volume x viscosity was conducted for each age group individually. No significant interactions or main effects were identified for any of the age groups.

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70 Biokinematic Measures Two separate 4 factor repeated measures ANOVAs for swallowing condition x volume x viscosity x age group were conducted. Descri ptive results for the two biokinematic measures are given in Table 4 5. Inferential results are as follows: Hyoid excursion Interaction s. No significant interactions were identified; therefore, main effects for each factor were evaluated. Swallowing c ondi tion. Results revealed a significant main effect for swallowing condition [F(1, 21) = 4.517, p p 2 = .177] with hyoid excursion distance greater during effortful swallowing than during typical swallowing (Table 4 6; Figure 4 1). Volume. No significant within group main effect for volume was found. Viscosity. Results indicated that Mauchle sphericity had been violated for the viscosity main effect, [ W = .411 2 (5) = 17.514, p = .004 ) ] therefore, degrees of freedom were corrected using the Greenhouse Geisser estimate 6 1 5). Corrected results revealed a significant main effect for viscosity [F(1.846, 38.770) = 4.288, p p 2 = .170]. Review of the viscosity graph revealed a positive relationship in that mean hyoid excursion increased as viscosity increased Tests of contrasts revealed th at hyoid maximal distance was significantly longer when swallowing banana than when swallowing both the thin F(1, 21) = 8.469, p p 2 = .287] and the nectar thick liquids [F(1, 21) = 5.605, p p 2 = .211] (Table 4 6; Figure 4 3) No significa nt difference was observed between the banana and pudding hyoid excursion distance, or between any other viscosities. Age group. No significant between groups main effect for age was found.

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71 Laryngeal excursion Interaction s. Results revealed no significan t interactions; therefore, main effects for each factor were evaluated. Swallowing c ondition. No significant within group main effect for swallowing condition was found. Volume. Results revealed a significant main effect for volume [F(1, 20) = 13.649, p p 2 = .460] with laryngeal excursion greater for the 10 mL volumes (Table 4 6; Figure 4 2). Viscosity. No significant within group main effect for viscosity was found. Age group. No significant between group main effect for age group was found. E xploratory Aim relationships between pressures and movement for each of the swallowing conditions. Typical Swallow Hyoid excursion was not significantly correlated with any of the pressure parameters. Laryngeal excursion was significantly correlated with anterior and posterior lingual palatal pressure, and with hypopharyngeal (HYPO) pressure (Table 4 9 ) Effortful Swallow Hyoid excursion was significantly correlated with all three lingual palatal pressures and with UES relaxation nadir pressure (Table 4 9). Laryngeal excursion was significantly correlated with anterior and posterior lingual palatal pressures, and with UES relaxation nadir pressure (Table 4 9).

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72 Reliability Analysis Participants completed a total of 992 swallows. Five percent of these (50 swallows) were randomly selected and analyzed for concordance. Lingual Palatal Pressures Homogeneity of tongue pressure measurements between the 2 raters was demonstrated by ICC mea sures ranging from .918 to .994, depending on the variable of interest [(Anterior: ICC = .979, 95% CI, .963 to 988); (Middle: ICC = .994, 95% CI, .990 to .997); (Posterior: .ICC = .918, 95% CI, .859 to .953)]. Consistency of tongue pressure measurements by the primary rater was demonstrated by ICC measures ranging from .995 to 1.00 depending on the variable of interest [(Anterior: ICC = .999, 95% CI, .9999 to 1.00); (Middle: ICC = .998, 95% CI, .996 to .999); (Posterior: ICC = .995, 95% CI, .989 to .997 )]. Pharyngeal Pressures Homogeneity of pharyngeal pressure measurement between the 2 raters was demonstrated by ICC measures ranging from .893 to 1.0, depending on the variable of interest [(BOT: ICC = 1.0, 95% CI, 1.0 to 1.0); (HYPO: ICC = .893, 95% CI, .79 3 to .946); (Nadir: ICC = .980, 95% CI, .959 to .990); (UES Nadir: .997, 95% CI, .986 to .997)]. Consistency of pharyngeal pressure measurements by the primary rater was demonstrated by ICC measures ranging from .973 to 1.00 [(BOT: ICC = 1.00, 95% CI, 1.00 to 1.00); (HYPO: ICC = .973, 95% CI, .937 to .988); (Nadir: ICC = .989 95% CI, .972 to .005); (PES: 1.00, 95% CI, .999 to 1.00)]. Biokinematic Measures Initial agreement between the 2 raters for selecting the single frame representing the point of maximum hyo laryngeal excursion during the swallow was 26.92% (Kappa

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73 could not be computed as there was not a symmetric 2x2 table). However, when acceptable response was widened to include 1 fluoroscopy frame in either direction, agreement improved to 77.8%. When acceptable response was widened to include 2 fluoroscopy frames in either direction, agreement reached 97.7%. This was considered acceptable agreement as each frame represented .0 3 seconds of the swallow. Homogeneity of measuring hyoid excursion distance between the 2 raters was demonstrated by ICC = .926 (95% CI = .872 .957, p < .0001). Homogeneity of measuring laryngeal excursion distance between the 2 raters was demonstrated by ICC = .765 (95% CI: .605 .865, p < .0001). A greement was within acceptab le levels and similar to biokinematic measurement agreement in other studies. 106 111 Reliability S ummary Overall these reliability values suggest that the less variable and computer generated swallow pressure measures were highly rel ia ble between and within raters. However, the more variable and subjective movement distance measures were less reliable between and w ithin raters.

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74 Table 4 1. Participant characteristics with data presented as proportion s with 95% confidence intervals except where indicated. Characteristic 60 year olds (n =12) 70 year olds (n = 10) 80 year olds (n = 9) Demographics Age in years [ mean (SD) ] 63.17 (2.52) 75.40 (7.68) 82.11 (2.37) Gender Male .50 (.26 .75) .50 (.24 .76) .78 (.45 .94) Female .50 (.26 .75) .50 (.24 .76) .22 (.06 .55) Race White .58 (.32 .81) 1.0 (.73 1.0) 1.0 (.70 1.0) Black .42 (.19 .68) 0.0 ( .0 .28) 0. 0 ( .0 .30) Swallowing Characteristics* MASA mean score (SD) 198.42 (1.08) 195.60 (3.60) 190.22 (7.03) FOIS mean score (SD) 6.92 (.29) 6.9 0 (.32) 6.67 (.50) Dentition Teeth .83 (.55 .95) .80 (.49 .94) 1.0 (.70 1.0) Dentures .17 (.05 .45) .20 (.06 .51) 0.0 ( .0 .30) Health Characteristics* MMSE score [mean (SD) ] 29.17 (1.12) 29.20 (1.03) 28.89 (1.17) BMI [mean (SD) ] 27.11 (4.70) 24.07 (2.82) 25.63 (4.79) Reflux RSI score [mean (SD) ] 2.17 (2.76) 6.50 (3.69) 4.78 (3.63) RFS score [mean (SD) ] 1.58 (1.93) 3.00 (2.79) 3.75 (2.66) Cardiac Disease .17 (.05 .45) .40 (.17 .69) .44 (.19 .73) Diabetes .25 (.09 .53) .20 (.06 .51) 0.0 (.0 .23) All confidence intervals were calculated using the Wilson method. 112

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75 Table 4 2. Pearson correlation coefficients for t rial 1 and t rial 2 of each bolus r df p* Anterior T ongue .825 470 <.0001 Middle T ongue .825 470 <.0001 Posterior Tongue .850 470 <.0001 BO T .780 362 <.0001 HYPO .702 351 <.0001 Nadir .656 353 <.0001 Clearing Wave .749 378 <.0001 Hyoid Excursion .788 470 <.0001 Larynx Excursion .809 419 <.0001 *Significance for 2 tailed test

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76 Table 4 3. Mean (S D ) peak lingual palatal pressures ( mm Hg ) produced during typical and effortful swallows of each bolus by age group Typical Swallowing Effortful Swallowing Anterior Tongue 5 mL Thin 110.76 ( 71.67 ) 145.15 (104.87) 50.64 (40.48) 184.46 (121.88) 23 1.40 (100.26) 145.18 (76.07) Nectar 132.81 (86.73) 150.25 (117.64) 79.80 (73.53) 161.91 (87.78) 255.71 (138.97) 149.64 (60.74) Pudding 135.62 (67.95) 159.90 (118.36) 99.36 (113.03) 184.06 (119.33) 256.05 (85.670 162.22 (85.54) Banana 198.18 (84.27) 238.59 (86.96) 117.21 (84.91) 216.74 (138.89) 304.18 (83.31) 216.27 (129.45) 10 mL Thin 103.24 (75.14) 135.04 (86.38) 49.17 (43.94) 172.14 (118.15) 215.99 (152.73) 154.33 (73.10) Nectar 122.22 (76.70) 153.31 (105.14) 56.75 (48.95) 164.73 (104. 05) 248.53 (140.32) 135.29 (64.14) Pudding 174.29 (110.04) 169.35 (77.22) 90.82 (67.24) 221.99 (104.03) 262.91 (109.28) 123.77 (62.14) Banana 205.12 (85.95) 253.68 (85.05) 138.33 (83.51) 252.79 (79.62) 294.77 (122.61) 184.77 (82.56) Middle Tongue 5 mL Thin 126.91 (82.69) 155.71 (64.88) 71.58 (45.46) 176.41 994.73) 227.06 (63.19) 162.71 (78.24) Nectar 139.08 (94.61) 143.36 (62.63) 112.46 (67.58) 158.64 (93.220 236.99 (75.32) 168.44 (73.31) Pudding 156.29 (107.26) 186.98 (86.64) 128.39 (127.03) 183.24 (121.67) 282.07 (85.21) 169.89 (107.86) Banana 182.98 (91.95) 261.14 (60.45) 148.25 (94.18) 215.76 (113.00) 296.78 (75.55) 191.29 (92.97) 10 mL Thin 119.19 (80.86) 128.17 (50.51) 73.88 (42.39) 171.79 (94.99) 186.27 (74.13) 153.2 7 (62.90) Nectar 134.99 (87.96) 141.78 (56.29) 78.24 (45.73) 156.47 (96.61) 207.00 (70.19) 145.16 (50.84) Pudding 152.72 (92.32) 204.36 (65.49) 137.68 (95.96) 183.91 (98.76) 316.77 (119.41) 171.93 (85.34) Banana 174.52 (85.22) 258.64 (59.32) 190.28 (9 8.97) 237.89 (78.79) 297.70 (100.08) 218.43 (141.91)

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77 Table 4 3 C ontinued Typical Swallowing Effortful Swallowing Posterior Tongue 5 mL Thin 180.13 (59.57) 210.47 (62.46) 115.92 (54.40) 229.38 (65.91) 306. 55 (79.42) 161.79 (99.35) Nectar 189.32 (81.57) 214.86 (80.03) 137.90 (41.51) 235.74 (84.28) 298.55 (75.01) 163.82 (82.61) Pudding 243.03 (101.31) 243.25 (50.72) 141.14 (64.31) 271.08 (84.35) 343.91 (61.20) 199.87 (101.96) Banana 212.29 (102.18) 286.49 (42.96) 155.02 (58.49) 265.16 (79.89) 365.98 (51.31) 221.14 (91.78) 10 mL Thin 163.22 (56.46) 196.00 (60.87) 108.55 (31.93) 231.39 (67.93) 283.34 (83.60) 147.39 (73.81 Nectar 175.40 (57.29) 225.94 (64.60) 114.35 (38.16) 221.79 (87.12) 273.15 (63. 98) 168.68 (67.39) Pudding 240.09 (85.95) 272.79 (47.19) 172.95 (52.72) 283.59 (91.49) 347.03 (84.71) 212.42 (94.31) Banana 264.56 (74.59) 286.48 (63.76) 176.14 949.25) 292.65 (69.54) 337.02 (60.28) 201.97 (98.47)

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78 Table 4 4 Mean (S D ) peak pharyngea l pressures ( mm Hg ) produced during typical and effortful swallows of each bolus by age group Typical Swallowing Effortful Swallowing BOT 5 mL Thin 77.62 (27.40) 83.43 (40.310 74.61 (28.31) 89.72 (17.4 2) 115.10 (47.96) 101.64 (46.93) Nectar 73.69 (21.08) 79.60 (28.75) 83.85 (38.27) 92.25 (19.16) 113.18 (44.16) 84.65 (37.40) Pudding 81.72 (20.32) 78.27 (31.94) 86.37 (48.92) 98.03 (21.25) 103.36 (32.72) 84.69 (41.29) Banana 74.22 (17. 14) 90.07 (36.64) 82.61 (29.21) 99.50 (18.07) 114.01 (36.53) 94.76 (33.13) 10 mL Thin 72.64 (14.88) 68.80 (32.58) 59.40 (27.35) 90.41 (19.56) 120.19 (48.04) 84.12 (39.45) Nectar 70.16 (17.03) 81.79 (29.01) 68.43 (26.88) 90.57 ( 18.10) 106.85 (45.20) 90.99 (42.08) Pudding 76.42 (20.15) 84.85 (25.64) 74.53 (23.85) 92.54 (17.34) 106.31 (49.27) 85.06 (31.71) Banana 74.14 (15.33) 85.07 (39.24) 79.76 (28.20) 97.43 (20.84) 112.18 (30.60) 99.87 (40.38) HYPO 5 mL Thin 85.36 (46.86) 102.93 (62.92) 58.58 (20.42) 91.39 (35.11) 83.59 (26.07) 67.35 (15.46) Nectar 90.91 (49.14) 84.74 (33.63) 56.64 (22.43) 93.56 (49.68) 89.78 (37.23) 67.72 (17.08) Pudding 93.52 (44.55) 97.96 (49.3 4) 62.01 (29.67) 91.77 (39.29) 87.84 (40.98) 77.36 (26.53) Banana 96.63 (44.14) 85.60 (31.65) 64.25 (33.34) 114.59 (31.61) 91.54 (30.12) 70.45 (14.85) 10 mL Thin 85.18 (35.78) 100.23 (65.17) 64.05 (21.63) 86.58 (34.21) 89.86 (3 5.02) 62.83 (18.76) Nectar 90.87 (53.25) 74.25 (37.88) 56.08 (21.01) 87.64 (38.74) 85.19 (37.06) 64.89 (16.08) Pudding 92.26 (40.45) 100.66 (36.71) 70.87 (21.10) 106.47 (44.54) 104.32 (29.60) 75.88 (16.96) Banana 90.52 (32.33) 85.10 (37.55) 66.37 (21.23) 118.27 (40.52) 102.00 (56.35) 70.64 (20.77)

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79 Table 4 4. Continued Typical Swallowing Effortful Swallowing Nadir 5 mL Thin 4.38 (7.23) 1.98 (6.18) 1.79 (4.14) 1.65 (4.20) 10.25 (12.44) .27 (6.33) Nectar 3.38 (4.23) 6.38 (5.45) 3.04 (6.92) 2.92 (3.32) 10.59 (18.07) 95 (6.28) Pudding 5.69 (5.18) 3.65 (4.26) 2.79 (6.03) .79 (5.23) 7.51 (15.87) 3.40 (7.98) Banana 3.64 (5.17) 2.79 (5.03) 2.65 (15.97) 4.71 (6.92 ) 19.07 (28.96) 2.99 (13.09) 10 mL Thin 1.13 (4.50) .71 (4.46) 5.07 (5.58) 4.71 (6.92) 19.07 (28.96) 2.99 (13.09) Nectar 4.45 (10.70) 2.07 (7.24) 2.55 (8.53) 4.55 (4.15) 12.63 (12.40) 3.89 (7.43) Pudding 2.34 (4.50) 7.33 (5.42) 3.15 (8.43) 3.23 (3.54) 7.47 (20.71) 2.20 (8.95) Banana 3.95 (5.40) 1.92 (4.84) 1.98 (14.11) 4.25 (5.460 6.79 (16.61) 1.93 (11.55) C Peak 5 mL Thin 135.53 (47.86) 137.03 (36.88) 142.89 (32.66) 136.22 (49.37) 123.26 (26.50) 136. 59 (36.98) Nectar 137.82 (50.92) 137.71 (40.55) 150.69 (40.80) 151.78 (55.67) 146.43 (32.18) 138.20 (38.22) Pudding 144.35 (59.83) 136.94 (39.09) 148.64 (40.36) 143.61 (54.77) 152.28 (44.95) 144.92 (40.63) Banana 143.24 (52.22) 138.46 (22.14) 145.99 (36 .58) 134.85 (36.67) 157.97 (41.17) 134.81 (38.97) 10 mL Thin 149.40 (79.19) 126.98 (46.49) 138.81 (33.41) 140.93 (70.52) 134.27 (53.01) 140.65 (20.22) Nectar 154.25 (58.78) 134.63 (33.19) 134.47 (29.20) 155.36 (62.43) 143.17 (36.89) 112.45 (56.49) Pudding 132.99 (59.28) 143.51 (51.11) 143.84 (42.96) 148.61 (59.87) 112.45 (56.49) 157.84 (39.93) Banana 140.32 (55.80) 155.42 (41.63) 153.65 (38.74) 135.57 (56.72) 129.77 (36.87) 140.92 (40.80)

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80 Table 4 5 Mean (SD) hyoid and laryngeal excursion in mm produced during typical and effortful swallows of each bolus, by age group Typical Swallowing Effortful Swallowing Hyoid 5 mL Thin 29.77 (9.30) 30.02 (6.93) 32.85 (9.24) 33.30 (7.34) 32.44 (5.44) 32.91 (7 .89) Nectar 30.43 (8.09) 33.21 (5.65) 31.74 (11.32) 32.75 (9.47) 33.39 (4.75) 33.22 (6.61) Pudding 29.49 (9.86) 34.18 (3.53) 33.11 (9.85) 31.23 (9.35) 35.16 (6.18) 33.69 (9.03) Banana 32.09 (9.37) 34.02 (4.52) 34.26 (9.64) 33.48 (8.95) 34.49 (5.65) 32.5 7 (9.51) 10 mL Thin 30.41 (9.40) 33.79 (5.32) 32.58 (8.84) 31.84 (7.96) 33.23 (5.59) 31.77 (9.08) Nectar 31.34 (10.09) 33.71 (5.49) 33.38 (9.35) 30.42 (10.44) 34.19 (4.59) 32.97 (9.60) Pudding 29.21 (12.44) 34.13 (5.51) 32.91 (9.47) 31.35 (10.47) 36.39 (4.82) 32.99 (8.59) Banana 33.54 (9.49) 33.56 (5.36) 34.93 (10.11) 35.01 (8.81) 37.98 (10.78) 35.22 (9.77) Larynx 5 mL Thin 31.84 (8.18) 34.15 (3.64) 30.50 (7.34) 31.78 (7.90) 32.85 (5.45) 31.11 (7.35) Nectar 30.43 (8.94) 32.90 (5. 13) 30.55 (8.25) 33.32 (9.26) 34.88 (5.35) 30.73 (9.08) Pudding 32.69 (9.85) 32.85 (5.24) 33.38 (9.67) 33.06 (8.56) 34.51 (5.39) 31.52 (9.02) Banana 34.06 (9.02) 33.58 (3.79) 32.09 (13.75) 34.86 (9.58) 33.87 (5.89) 30.12 (11.36) 10 mL Thin 32.64 (9.77) 34.95 (5.15) 31.73 (9.00) 32.28 (9.48) 34.63 (5.25) 30.68 (8.14) Nectar 33.01 (9.27) 34.57 (3.76) 31.84 (10.02) 32.27 (9.04) 34.02 (6.78) 30.45 (7.41) Pudding 33.94 (8.95) 36.70 (6.03) 32.27 (11.55) 33.63 (8.94) 36.14 (4.89) 33.18 (9.71) Banana 3 7.49 (8.41) 34.95 (6.29) 31.99 (9.65) 34.44 (9.47) 34.76 (9.42) 34.67 (9.42)

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81 Table 4 6. Repeated measures main effects for all factors Within Group Between Group s Swallowing Condition Volume Viscosity Age Group F p F p F p F p Anterior Ton gue 47.546 < .0001 -n s a 27.565 < .0001 3.256 .05 Middle Tongue 36.772 < .0001 -ns 31.924 < .0001 b -ns Posterior Tongue 46.300 < .0001 -ns 31.967 < .0001 b 5.650 .001 Base of Tongue 20.947 .003 -ns -ns -ns Hypopharynx -ns -ns 3.38 7 .051 -ns Nadir 7.185 001 12.127 .0 03 3.070 .038 b -ns Clearing Wave -ns -ns -ns -ns Hyoid Excursion 4.517 .046 -ns 4.288 .017 -ns Larynx Excursion -ns 13.649 .001 -ns -ns a ns = not sign i ficant b Greenhouse Geisser spheric ity correction applied

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82 Table 4 7 Repeated measures 2 way interaction effects Condition x Volume Condition x Viscosity Condition x AgeGroup Volume x Viscosity Volume x AgeGroup Viscosity x AgeGroup F p F p F p F p F p F p Anterior Tongue -ns a -ns -ns -ns -ns -ns Middle Tongue -ns -ns -ns 3.788 .014 -ns -ns Posterior Tongue -ns -ns -ns 2.472 .0 03 b -ns -ns Base of Tongue -ns -ns -ns -ns -ns -ns Hypopharynx -ns -ns -ns -ns -ns -ns Nadir ns -ns -ns -ns -ns -ns Clearing Wave -ns -ns -ns -ns -ns -ns Hyoid Excursion -ns -ns -ns -ns -ns -ns Larynx Excursion -ns -ns -ns -ns -ns -ns a ns = not sign i ficant b Huynh Feldt sphericity correction app lied

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83 Table 4 8 Repeated measures 3 way and 4 way interaction effects Condition x Volume x Viscosity Condition x Volume x AgeGroup Condition x Viscosity x AgeGroup Volume x Viscosity x AgeGroup Condition x Volume x Viscosity x AgeGroup F p F p F p F p F p Anterior Tongue -n s a -ns -ns -ns -ns Middle Tongue -ns -ns 2.823 .016 -ns -ns Posterior Tongue -ns -ns -ns 2.604 .024 -ns Base of Tongue -ns -ns -ns -ns -ns Hypopharynx -ns -ns -ns -ns -ns Nadi r -ns -ns -ns -ns -ns Clearing Wave -ns -ns -ns -ns 2.911 .015 Hyoid Excursion -ns -ns -ns -ns -ns Larynx Excursion -ns -ns -ns -ns -ns a ns = not sign i ficant

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84 Table 4 9. Relationship between pressure and moveme nt parameters Typical Swallow Effortful Swallow Hyoid Larynx Hyoid Larynx r df p r df p r df p r df p Lingual Palatal Pressure Anterior .115 205 ns .252 197 <.0001 .246 212 <.0001 .183 205 .008 Middle .010 205 ns .066 197 ns .135 212 .0 49 .034 205 ns Posterior .127 205 ns .229 197 .001 .208 212 .002 .157 205 .023 Pharyngeal Pressure BOT .017 173 ns .053 165 ns .068 172 ns .111 165 ns HYPO .076 165 ns .346 157 <.0001 .095 162 ns .141 155 ns Nadir .009 167 ns .031 159 ns .172 160 .028 .245 153 .002 C Pk .035 173 ns .066 165 ns .020 170 ns .023 163 ns *ns = not significant

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85 Figure 4 1. Within group main effects for swallowing condition by physiologic parameter. Asterisk denotes significant effect.

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86 Figure 4 2. Within group main effects for volume by physiologic parameter. Asterisk denotes significant effect

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87 Figure 4 3. Within group main effects for viscosity for the three lingual palat al pressure parameters. Brackets with asterisk s denote signif icant effect between the two viscosities

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88 Figure 4 4. Within group main effects for viscosity by physiologic parameter. Brackets with asterisks denote significant effect between the two viscosities.

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89 Figure 4 5 Between groups main effect s for age by physiologic parameter. Brackets with a sterisks denote post hoc signficant differences between the age groups.

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90 Figure 4 6. Middle lingual palatal pressure 3 way interaction for swallowing condition, viscosity, and age group

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91 Figure 4 7. Middle lingua l palatal pressure 2 way interaction for volume x viscosity

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92 Figure 4 8. Posterior lingual palatal pressure 3 way interaction for volume, viscosity, and age.

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93 Figure 4 9. Posterior lingual palatal pressure 2 way interaction for volume and viscosity

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94 Figure 4 10. Pharyngeal clearing wave peak pressure (C Pk) 4 way interaction between swallowing condition, volume, viscosity, and age.

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95 CHAPTER 5 DISCUSSION Primary Aim Measures of peak swallowing pressure and maximal hyo laryngeal movement as a functio n of swallowing condition, bolus volume and viscosity, and age were simultaneously evaluated in healthy older adults between 60 and 88 years of age, using a novel, integrated videomanofluoroscopic approach. Results demonstrated that each of these factors i nfluenced the nine physiologic parameters studied, but, to varying degrees. Lingual Palatal P ressures Lingual palatal pressures demonstrated the most consistent response to varying swallowing conditions and bolus characteristics, across all age groups. F or example, volitionally increasing swallowing effort resulted in significantly higher lingual palatal pressures at all 3 tongue bulb locations. This observation is consistent with prior findings. For example, both Hind 94 and Huckabee and Steele 71 reported that effortful swallowing resulted in increased lingual palatal pressures for all participants, regardless of age. Additionally, Hind reported a swallowing effort x age interaction, which was not observed in this study. She reported that younger individuals produced higher lingual pressures at all 3 tongue bulb locations than pressures produced by older participants. However, she included participants from ag e 45 to 90, dividing them into two groups, those younger and older than 60 years. Inclusion of participants younger than 60 years of age may have resulted in this interaction. A significant main effect for viscosity was noted at all three lingual palatal pressures, with linear trend of increasing pressure with increasing viscosity. Significant

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96 differences in pressures were identified between the pudding and two liquid stimuli, and between the banana and two liquid stimuli, but no differences were observed between the two liquids. This observation was consistent with prior literature ; 62 66 a nd, by including the semi solid bolus, expands upon prior investigations. Given consistency of results across multiple studies the observation that additional tongue force is required to propel boluses of increasing viscosity may be a robust finding. A significant 3 way inter action of swallowing condition x viscosity x age was noted, but only for the middle tongue lingual palatal pressure. Analysis of the swallowing condition and viscosity components of the interaction revealed that the pudding and banana viscosities yielded s ignificantly greater pressures than either of the liquids, for both swallowing conditions. This is a new finding in the literature as no other investigators have evaluated the effect of effortful swallowing f or these more viscous materials Investigation i nto the role of age in this interaction revealed the more interesting findings. First, during typical swallowing, the 70 year old group generated significantly higher middle tongue pressure while swallowing the semi solid banana in comparison to the puddin g stimulus, indicating a viscosity driven bolus accommodation effect. But, during effortful swallowing, the 70 year old group generated equivalent pressures for these two boluses, indicating a limited accommodation effect. One potential explanation of this apparent over ride of the bolus accommodation effect may be that the 70 year old group reached a physiologic ceiling at which no higher lingual palatal pressures could be generated. Last, no significant differences in pressure generation were observed bet ween the 60 and 80 year old groups, for either typical or effortful swallowing conditions. Lower pressures for the 80 year old group when

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97 compared to the 70 year old group was expected and hypothesized a priori, but, equivalent pressures between the 60 and 80 year old groups were unexpected, and may represent a bias toward sicker 60 year old participants, or healthier 70 year old participants in our sample A significant 3 way interaction for volume x viscosity x age was observed for posterior lingual pala tal pressures. Analysis of the interaction revealed a linear trend of increased pressure with increasing viscosity across all age groups, for the 5 mL volume. This linear trend persisted in the 60 year old age group for the 10 mL volume, but was not demons trated in the 70 and 80 year old groups. Instead, no bolus accommodation effect was observed between the pudding and banana stimuli at the 10 mL volume. Like the lack of accommodation observed in the 70 year old group for the 3 way swallowing condition x v iscosity x age interaction, this apparent over ride of the bolus accommodation effect may represent a physiologic ceiling at which no higher lingual palatal pressures could be generated. Another possibility for the lack of bolus accommodation in these two age groups may be presence of an underlying volume x viscosity modulated sensory threshold precluding discrimination between these boluses. Evidence for such a volume threshold has been observed for hyo laryngeal movement, 14 30 33 generation. Also, prior studies showing no volume effect on ling ual palatal pressure further support this idea 62 66 While no direct evidence for an equivalent viscosity t hreshold exits, extrapolation from prior studies identifying an age related increase in lingual sensory threshold for touch, 113 114 115 may imply existence of a bolus accommodation viscosity threshold.

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98 A main effect for age was demonstrated for the anterior and pos terior lingual palatal pressures with the 80 year old group generating significantly lower pressures than the 70 year old group. This observation contradicts prior studies that failed to show an age effect for these pressures. 62 66 D ifferences in sampling and age analysis method s may explain these different findings. Both of these prior studies investigated age differences between one younger and one older group, whereas the present study included only older participants. Furthermore, the present study analyzed age by decade, which allowed for identification of possible differences due to advancing age. In conc lusion, evidence for a bolus accommodation effect from manipulating swallowing effort, volume and viscosity is seen in changing lingual palatal pressures in older adults regardless of age. W hile oldest participants demonstrated lower lingual pressures than the younger participants, manipulating these factors continued to modulate lingual palatal pressures implying that even the oldest participants may be able to volitionally over ride the more automatic aspects of bolus accommodation. Pharyngeal P ressures Pharyngeal pressures demonstrated bolus accommodation effects from each of the factors examined, across all age groups, but responses were more variable than those observed for lingual palatal pressures. For example, volitionally increasing swallowing eff ort resulted in greater base of tongue and hypopharyngeal pressures. This observation is consistent with results from prior studies. 74 81 However, volitionally increasing swallowing effort also resulted in higher UES nadir relaxation pressures indicating less relaxation an observation that contradicts prior studies. 70 For example, Huckabee demonstrated lower UES nadir relaxation pressures and greater r elaxation with the effortful swallow. However her study was conducted with younger participants

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99 under the age of 30. The combined effects of the effortful swallow with age related reduction in UES sphincter opening, 54 may have led to the higher UES n adir pressures observed in this study. The UES nadir relaxation pressure was the only pharyngeal pressure significantly influenced by volume. Increased volume resulted in higher nadir pressure i.e. less relaxation This observation has been observed in a p revious study of younger participants, 41 but was not participants. 29 Instead, Butler observed a volume x viscosity x age interaction for UES nadir pressure with pressures from the younger participants driving the interaction Among the older participan ts, Butler reported a non significant linear trend of increased UES nadi r pressures as volume increased. A l inear trend of increasing pressure with increasing viscosity was consistently observed in the BOT and HYPO pressures. Pressure increases trended tow ard significance for the BOT pressures and were significant for the HYPO pressure. Both of these observations are consistent with previous findings. 29 116 Additionally, increased viscosity resulted in decreased UES nadir relaxation pressure, with significant differences observed between the pudding and the two liqui d stimuli. This observation is both consistent with 116 and contradictory to 29 previous findings. While Raut observed equivalent results, Butler did not. Variability in bolus volume and viscosity, catheter technology, participant age, and effects of the effortful swallow technique may have resulted in the differences between the studies. A significant 4 wa y interaction for swallowing condition x volume x viscosity x age was observed for the pharyngeal clearing wave peak pressure. This observation is new

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100 in the literature. No prior study has reported bolus accommodation effects of the effortful swallow on ph aryngeal clearing wave pressures; however a recent study has suggested that this behavioral technique may influence esophageal transport. 77 78 Given that the effortful swallow appears to influence BOT and HYPO pharyngeal pressures and UES nadir relaxation pressure, and may influence esophageal transport pressure, it is plausible that this technique would also influ ence pharyngeal clearing wave pressure. Volume, viscosity, and age factors may then serve to modulate the effortful swallow effect on bolus accommodation for this clearing wave. One implication of this complex interaction may be that volitionally increasin g effort in conjunction with manipulating volume and viscosity may help healthy older adults propel materials through the proximal esophageal via a higher amplitude UES clearing pressure. Biokinematic Measures Volitionally increasing swallow effort resulte d in greater hyoid movement. This observation is consistent with prior literature. 76 79 For example, H ind evaluated effect of effortful swallowing of a 3 mL thin liquid bolus in group of middle age and older adults. They reported that both superior and anterior hyoid displacement were greater for the effortful swallow. Contrarily, v olitionally increasing s wallowing effort di d not affect laryngeal movement, a finding that is also consistent with prior literature. 75 Inability to affect laryngeal movement distance by manipulating swallowing parameters may represent a physiologic fail safe mechanis m that maintains laryngeal closure during the swallow I healthy individuals. A significant volume effect was identified for laryngeal but not for hyoid excursion. One explanation for this may be measurement error in that point to point reliability for sel ecting the fluoroscopy frame representing maximum hyoid excursion

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101 was only 27%. Although failure to find significant volume effect for hyoid movement was unexpected, the variability in these results is not incongruent with prior literature. For example, Mo lfenter and Steele recently completed a meta analysis of studies of hyo laryngeal movement during swallowing. 117 Their overarching conclusion regarding volume effect was that results show great variability; but, generally, increase in volume results in increase in both mean anterior and superior hyoid displacement. Mean displacement ranged from 5.8 mm to 25 mm in either direction. Given this, our results of mean total movements ranging from 25 to 31 mm are c onsistent with the literature. A significant viscosity main effect for hyoid movement was identified; maximum distance was significantly longer for the banana viscosity when compared to either of the liquid viscosities. This observation is both consistent with and contrary to prior literature. For example, Dantas 3 84 and Ishida 34 identified that swallowing higher density barium or higher viscosity materials produced increased hyoid movement. However neither Chi Fishman, 33 or Kendall 118 identified a viscosity effect. One explanation for these discrepancies may be in the techniqu e employed to capture hyoid movement. Chi Fishman and Sonies used ultrasonography, while Dantas, Ishida and this study used videofluoroscopy. Another explanation may be in bolus size. Both Ishida and this study used 5 and 10 mL bolus volumes of each visco sity, while Kendall evaluated a 3 mL bolus. Given the presence of a proposed volume related c eiling effect on hyoid movement distance, 14 30 33 Smaller bolus volumes may have been insufficient to stimulate a viscosity response in the biokinematic system.

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102 No significant age effects were observed for either biokinem atic measure. This was contradictory to the literature. 3 84 Prior work has indicated increased hyo laryngeal e xcursion in older adults, when compared to younger adults. One explanation for lack of significant age effect in this study may be that by age 60, anatomic change underlying increased hyo laryngeal excursion may have reached a physiologic ceiling in which no further age related hyolaryngeal movement differences may be observed. Another explanation may be that by analyzing age by decade, potential age differences between the 60 and 80 year old age groups may have regressed to the mean, washing out any age ef fect. Lastly, interplay between age, volume and viscosity may have resulted in lack of an age effect. Exploratory Aim This study investigated potential relationships between swallowing pressures and hyoid and laryngeal excursion during both typical and ef fortful swallowing. It was hypothesized that strong correlations would be found between pressures and movement for each swallowing condition. However, results did not support this. During typical swallowing, no pressures were correlated with hyoid movement ; while anterior lingual palatal, posterior lingual palatal, and HYPO pharyngeal pressures were correlated with laryngeal movement. During effortful swallowing, the three lingual palatal pressures and the UES nadir relaxation pressure were correlated with hyoid movement; while no change was observed in laryngeal correlations. Furthermore, all identified correlations, while significant for the study sample size, were weak, irrespective of swallowing condition. Failure to identify strong correlations between swallow pressure and movement parameters questions the underlying premise that these physiologic parameters are

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103 related. While seemingly implausible evidence for lack of a relationship between these two parameters exists. Patients who have undergone total laryngectomy with radical neck dissection have had the hyoid, larynx, and much of the pharyngeal musculature surgically excised. While prevalence of dysphagia may be as high as 70% in this population, 119 patients are able to eat and drink orally without these pharyngeal s tructrues Manofluoroscopic analysis of swallowing in these patients reveals th at lingual propulsion pressures are the primary driving force behind bolus transit 120 121 Failure to identify significant correlations for hyoid movement during the typical swallow condition, contrasted with presence of significant correlations during the effortful swallowing co ndition suggests that something intrinsic within the effortful swallow technique drives a stronger lingual palatal and hyoid physiologic relationship. One possible explanation may be that the effortful swallow produced an anticipatory priming effect in the system. Evidence for this potential priming effect has been observed in prior studies of hyoid movement during effortful swallowing. 75 Bulow identified that when a bolus was in the mouth, baseline hyoid position was higher in the pharynx duri ng the effortful swallow. This resulted in shorter hyoid movement distance during effortful swallowing than during typical swallowing. However, this study attempted to control for this priming effect by selecting a baseline hyoid position from a video stil l captured prior t o placing a bolus in the mouth. This same baseline picture was used for all biokinematic distance measures. Lastly, this exploratory analysis was run with aggregate data without regard to bolus accommodation or age effects Perhaps explor ing potential relationships by volume, viscosity, age, or any combination thereof would have yielded stronger

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104 correlations. For example, analyzing by age may have revealed presence of strong relationships between pressures and hyoid movement, within the yo unger age groups. Study Strengths Multiple Simultaneous Measures This study used a unique integrated videomanofluoroscopic approach which allowed for simultaneous data capture of multiple physiologic parameters, an approach heretofore not taken. Additiona lly, use of videomanofluoroscopy improved measurement accuracy through verification of catheter placement. Catheter verification was most important for identifying the exact position of the BOT sensor within the pharynx. Since catheter placement was determ ined based on the most distal sensor, the two proximal sensors individuals with short necks, this resulted in the BOT sensor being mis positioned in the nasopharynx superior to the soft palate. When this occurred, pressure information from this sensor was discarded. Without videofluoroscopy, this sensor location issue would not have been identified and some data would have been recorded erroneously. Another advantag e of the integrated manofluoroscopy approach is that by visualizing the swallow, the examiner can confirm when the target swallow actually occurs. This was most important for analyzing the pudding and banana swallows. Often, as participants manipulated tho se boluses in their mouths, a small saliva bolus was spontaneously swallowed first, producing pressure waves on the graphic display. Had the examiner not been able to visualize the swallow fluoroscopically, these incorrect pressure waves would have been me asured instead. But, by confirming that this was not the target bolus being swallowed these pressures were not analyzed.

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105 Participant Sample Prior studies of swallowing pressures in older subjects have been limited by small sample size (n < 20), or, in the subjects in to one group (age 65 years). By expanding the sample size to 31 and by dividing participants by age decade, this study was able expand on prior studies, and identify variability in bolus accomm odation as a function of advancing age. Study Limitations Measurement Error Catheter placement Despite following standard procedures for catheter placement, catheter position changed during some of the effortful swallows. This movement meant that some of t he sensors were temporarily mis positioned into different pharyngeal regions during a particular swallow. Consequently, when analyzing all graphical waveforms, care was taken to ensure that peak pressure values were recorded in the dataset for the correct pharyngeal region of the pressure and not just for the sensor. Doing this ensured more accuracy of the data, but also resulted in missing data for some individual swallows. Missing data Seven of the subjects were not able to tolerate the catheter insertion Consequently, no pharyngeal measurements were obtained for these individuals. In a sample of 31 participants, this equaled a 22.5% loss of data for these measures. Furthermore, some participants were too large to be positioned easily in the fluoroscopy s uite so that that the pre swallow position of the larynx was unable to be visualized. This precluded accurate measurement of laryngeal excursion in 4 subjects resulting in a 14% loss of data for this measure. Loss of data may have influenced type II error rate.

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106 Power P ower calculations determined that sample size of 32 was necessary to identify bolus accommodation effects in some of the physiologic parameters being investigated. But, with 9 different physiologic parameters evaluated, 31 subjects, and missin g data, the study was still underpowered. As a result, this study suffers from Type II error in that analysis may have revealed some significant effects that trended toward significance, but did not reach the prescribed alpha level. Directions for Future Research Experience with this project has suggested many areas of future investigation. For example, this study did not explore the effect of volitionally improving swallowing effort, bolus volume and viscosity, or advancing age on bolus accommodation for esophageal pressures. But, two recent pilot studies have shown that using the effortful swallow technique increased distal esophageal contraction pressure in healthy youn g adults. 77 78 This raises the possibility that this behavioral technique for improving pressures and movement during the volitional stages of the swallow may help improve pressure and bolus motilit y during the involuntary stage of the swallow. Future investigation into this new role for the effortful swallow technique is warranted. Additionally, this study excluded persons with known gastroesophageal reflux disease (GERD) under the assumption that G ERD might influence bolus accommodation. But, to our knowledge this assumption has not been tested. Therefore, replicating this study in participants with known reflux disease may be beneficial. Study of bolus accommodation in patient populations is limit ed. Replication of this study in different patient populations should provide more insight into the effect of manipulating bolus characteristics as a dysphagia rehabilitation strategy.

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107 This study focused on effects of volume and viscosity manipulation on p ressure and movement, but, other bolus characteristics like taste should also be investigated for their effects on pressure and movement in older populations. For example, swallowing a sour bolus improves speed of the swallow, 122 126 but, little is known about its effect on swallowing pressure generation. Neurophysiology studies of age, bolus characteristics, and swallow task effects are in t heir infancy. Future studies should investigate the effects of these factors on bolus accommodation for neurophysiologic change in older populations. Additionally, future studies could study the reciprocal of this, i.e. the effects of underlying neurology on bolus accommodation. Manini and Clark posited that age related changes in structure and function of the nervous system necessarily precede observed loss of skeletal muscle functional force. 127 For bolus accommodation, this loss of functional force translates to decline in swallow pressure generation. Together, results of these two types of studies will grow the knowledge base regarding the underpinnings of swallowing neurophysiology. This knowledge should provide insight into the value of manipulating swallowing effort and bolus characteristics for inducing neural plasticity and cortical re organization as an outcome in dyspha gia rehabilitation paradigms. Conclusion Historically, studies of bolus accommodation effects on swallowing physiology have focused primarily on temporal aspects of the swallow. Few studies of swallowing pressure and movement have been completed. Among th ose that have, small sample sizes, studying only one component of the swallowing mechanism, lack of integrated technologies, and predominance of using younger subjects, have made it difficult to

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108 draw any conclusions about bolus accommodation on swallowing pressures or movement in older individuals. This study helped to fill some of the gaps in the knowledge base on bolus accommodation in older adults. By using a novel approach that integrated lingual palatal pressure, pharyngeal m anometry, and videofluoros copy effects of swallowing condition, bolus volume, bolus viscosity, and advancing age on pressure and movement during the swallow were able to be simultaneously studied Results indicated a consistent swallowing condition effect and a consistent viscosity effect, both as main and interaction effects. These were most pronounced with lingual pressures, as very few pharyngeal effects were identified. Explanation for predominance of lingual effects may be that lingual pressures are more amenable to sensory inf luences than pharyngeal pressures. Or, as the more volitional aspect of swallowing, lingual pressures may have more opportunity for bolus accommodation than the more involuntary, neurologically patterned pharyngeal pressures. Volitionally increasing swall owing effort resulted in increased pressures, but not necessarily movement, across all age groups. The fact that this impact on pressures occurred and did not diminish with age is an important observation to note. It supports the premise that use of the ef fortful swallow technique may help older adults over ride involuntary bolus accommodation pressure patterns, in order to swallow more safely. Additionally, the observation that lingual palatal pressures systematically increased as viscosity increased suppo rts the concept that manipulating bolus characteristics like viscosity, may facilitate increased motor unit recruitment to produce a stronger swallowing pressure response. When taken as a whole, one implication of these

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109 findings may be that combining the e ffortful swallow technique with viscosity manipulation can serve as an effective means of increasing functional swallowing reserve in healthy older adults. If so, this combination may prove effective in dysphagia rehabilitation paradigms.

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120 BIOGRAPHICAL SKETCH Lisa A. LaGorio completed a Bachelor of Arts degree in Spanish with a minor in chemistry at the University of Minnesota, and a Master of Science degree in communication disorders at St. Cloud State University in Minnesota She is a licensed medical speech language pathologist, and is skilled in the rehabilitation of communication and swallowing disorders (dysphagia). T hroughout her career she has served in various clinical and management positions. Ms. LaGorio overarching career interest is in dysphagia prevention and rehabilitation, p rimarily in older adults Given that, s he began doctoral tra ining in the rehabilitation science program at the University of Florida (UF) in 2006 I n an effort to strengthen he r ability to conduct population based research, in 2007 she amended her original doctoral program to include a Master of Public Health, epid emiology concentration This MPH degree was confer red in August, 2012. During this non traditional joint degree program Ms. LaGorio has won many prestigious scholarships, awards and grants including the American Speech La nguage and Hearing Association Fou ndation New Century Scholars Doctoral Scholarship, the UF Leighton E. Cluff Award for Aging Research, the UF Sam & Connie Holloway Scholarship, and a 2 year NIH Kirschstein NRSA F31 Pre Doctoral Fellowship from the National Institute on Dea fness and other Communication Disorders. Currently, Ms. LaGorio works in the UF Swallowing Research Lab where she is pursuing a line of research investigating swallowing changes in healthy aging and in disordered populations Her goal is to develop better dysphagia prevention and rehabilitation strategies