|UFDC Home||myUFDC Home | Help|
This item has the following downloads:
EXAMINIG APATHY AND DEPRESSION IN PARKINSON'S DISEASE
LINDSEY ELIZABETH KIRSCH
A THESIS PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
MASTER OF SCIENCE
UNIVERSITY OF FLORIDA
I would like to thank my mentor, Dawn Bowers, for her generous time,
encouragement, and constant support. I would like to thank Michael Okun, Hubert
Fernandez, and their colleagues at the Movement Disorders Center for providing access
to patients and for their insightful comments on the study. I would also like to thank my
husband, Adam Darrow, for his unwavering devotion, love, patience, and support for all
of my endeavors.
TABLE OF CONTENTS
A C K N O W L E D G M E N T S .................................................................................................. ii
L IST O F TA B LE S ............... .. ........................ ........ ........ .. ............... v
LIST O F FIG U RE S .... .............................. ....................... ........ .. ............... vi
1. IN TR OD U CTION ............................................... .. ......................... ..
Motor Symptoms in Parkinson's Disease ............................................ ...............2
Em otional Sym ptom s in Parkinson's D isease........................................ ...................4
A pathy Syndrom es and Sym ptom s.......................................................... ............... 5
Apathy and D expression: Are They Dissociable? ........................................ ...............6
2. STATEMENT OF THE PROBLEM................................................................. 9
3 M E T H O D S .......................................................................................................14
P articip an ts ................. ....... .. .................................. ................14
Procedures and Assessment Instruments ............ .............................................17
Depression A ssessm ent Instrum ents ....................................... ............... 17
A pathy Instrum ent ................................................ ........ .. ............ 19
Statistical A naly ses........... ........................................................ .. ... .... .... 20
4 R E S U L T S .......................................................................... 2 3
A pathy Prevalence and Severity...................................................... .... ........... 23
Depression Prevalence and Severity .... ................. ..... ........................ ............. 24
Relationship between Apathy and Depression Prevalence.............................27
Relationship with Severity of Parkinson's Disease.................................................29
5. DISCU SSION ............. ........................................... .......................... 31
Summary and Interpretation of the Findings................................................... .....32
Comparing Prevalence and Severity Across Current Literature..............................35
Limitations of the Present Study.......... ....................................... 38
Directions for Future Research.......... ..... .................................... 39
L IST O F R E F E R E N C E S ...................................... .................................... ....................4 1
BIOGRAPH ICAL SKETCH ...................................................... 46
LIST OF TABLES
3-1 Parkinson and Dystonia Patient Characteristics.................... .................16
4-1 Means and Standard Deviations for Depression Scales.................... ...............26
4-2 Means and Standard Deviations for Patients Not Using Anti-Depressants .............27
4-3 Intercorrelations Between PD Apathy Scores, Depression Scores, and Disease
V a riab le s ...................................................... ............... 3 0
LIST OF FIGURES
1-1 Simplified pathophysiological model of motor dysfunction in PD..........................4
4-1 Prevalence of apathy in Parkinson's disease and Dystonia controls.....................23
4-2 Prevalence of BDI depression in Parkinson's disease and Dystonia controls. ........25
4-3 Overlap between apathy and depression, apathy alone, and depression alone
betw een groups....................................................... ........ ........ ............28
Abstract of Thesis Presented to the Graduate School
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Master of Science
EXAMINING APATHY AND DEPRESSION IN PARKINSON'S DISEASE
Lindsey Elizabeth Kirsch
Chair: Dawn Bowers
Major Department: Clinical and Health Psychology
Purpose: The purpose of the present study was to examine the hypothesis that
apathy is a core feature of Parkinson's disease (PD) and that apathy can be dissociated
Background and Hypotheses: Emotional changes frequently accompany PD,
and a high proportion of patients experience anxiety and depression. Recently, attention
has focused on the occurrence of a "syndrome of apathy," reflecting a primary loss of
motivation, loss of interest, and loss of effortful behavior. It has been argued that
"apathy" is distinct from depression, and reflects dysfunction of connections between
basal ganglia and anterior cingulate cortex in PD patients. Therefore, we hypothesized
that a) PD patients would have significantly more apathy than a clinical control group
(Dystonia), b) apathy is not simply a symptom of depression and thus a large proportion
of PD patients would exhibit apathy in the absence of depression, and c) apathy
symptoms would be significantly increased in more severe stages of Parkinson's disease.
Methods: Eighty patients with PD and twenty patients with Dystonia completed
a variety of depression and apathy measures including the Marin Apathy Evaluation
Scale (AES), the Beck Depression Inventory (BDI), the Centers for Epidemiological
Studies-Depression Scale (CES-D), and the Beck Hopelessness Scale (BHS). Data were
analyzed using chi squared tests for independence, independent samples t-tests, and one-
way Analyses of Variance.
Results: There was a significantly higher prevalence of apathy in PD patients
(freq. = 51%, 41/80) than in Dystonia patients (freq. = 20%, 4/20). The prevalence of
apathy in the absence of depression was substantial in PD patients and nonexistent in
Dystonia patients (PD = 28.8%, Dystonia = 0%). Further, there was a significantly
higher severity of apathy in PD patients than in Dystonia patients. When PD patients
were examined based on mild, moderate, and severe stages of disease (based on the
Hoehn-Yahr Staging criteria for PD), apathy had a tendency to increase as severity of
Conclusions: The present study found that there were a significantly higher
prevalence and an increased severity of apathy in PD when compared to a clinical control
group of Dystonia patients. Further, approximately thirty percent of PD patients showed
apathy in the absence of depression. It appears that apathy is a "core" feature of PD and
is not limited to co-occur within depression. The distinction between apathy and
depression may become increasingly important as more is discovered about the
differential pathophysiology, clinical correlates, and potential treatments for these mood
disturbances in PD.
Parkinson's disease (PD) is one of the most common late life neurodegenerative
diseases. PD produces substantial morbidity and mortality; over one million Americans
have Parkinson's disease, and approximately 60,000 new cases are diagnosed every year
(Okun & Vitek, 2002). Additionally, the incidence of Parkinson's disease increases with
age, and this incidence is predicted to triple over the next 50 years as the aging
population increases (Tanner et al., 2002). PD typically onsets in a patient's 50s or 60s
and is notable for a slow, insidious onset and a chronic progression over time. The
majority of PD cases are idiopathic (of unknown cause), and are 1.5 to 2 times more
likely to occur in males (Mayeau et al., 1995; Tanner et al., 2002).
Historically, Parkinson's disease has been thought of as primarily a motor
disease-producing symptoms such as tremor, rigidity, and bradykinesia (slowness of
movement). However, there are salient emotional changes that have been increasingly
recognized in Parkinson's disease in addition to motor symptoms. One salient emotional
change that has received recent attention is the occurrence of a "syndrome of apathy,"
reflecting a primary loss of motivation, loss of interest, and loss of effortful behavior.
This "syndrome of apathy" has potential clinical and theoretical importance. However,
there are relatively few studies examining this aspect of PD. The goal of the present
study was to examine the occurrence of apathy and whether it presents as a "core" feature
of Parkinson's disease distinct from depression. To do this, Parkinson's disease patients
and a group of clinical control patients completed a battery of apathy and depression
scales. Apathy and depression symptoms were then compared on their prevalence,
severity, and relationship to disease variables. Before turning to specific hypotheses and
predictions of the present study, a review of pertinent literature will be presented as
follows: 1) the hallmark motor symptoms of Parkinson's disease will be presented, 2) the
emotional symptoms of Parkinson's disease will be presented, and 3) the term apathy will
be defined and discussed.
Motor Symptoms in Parkinson's Disease
The hallmark motor symptoms of Parkinson's disease include a resting tremor,
bradykinesia, akinesia, muscular rigidity, and a gait disturbance. Resting tremor is the
most recognizable symptom of PD. However, only about 50% of patients show tremor as
their presenting symptom and approximately 15% of patients never show tremor during
the course of the disease (Martin et al., 1983). Other patients experience a postural
tremor in addition to a resting tremor. Postural tremors occur during activity and thus
may be more disabling than the resting tremor since they interfere with the use of the
limb (Jankovic, 1992). Bradykinesia and akinesia are distinctive features of PD.
Bradykinesia is slowness in execution of a movement, while akinesia is difficulty
initiating a movement. Akinesia can be observed when a patient has difficulty arising
from a chair or difficulty initiating the onset of gate ("gait hesitation"). Rigidity is also a
common complaint in PD, and is experienced by patients as a tightness of the muscles.
Rigidity in PD has been termed as "cogwheel" or "ratcheting" rigidity because of the
increasing resistance when an examiner moves patients' arms and legs (Lieberman,
1995). Tremor, rigidity, and bradykinesia onset unilaterally, but as the disorder
progresses they become bilateral, though the severity often remains asymmetrical. Gait
in PD is characterized by stooped posture, shuffling steps, destination (short steps that
become quicker and quicker as if the patient were about to run) and propulsion (forward
inclination of the body as if the patient were about to fall forward) (Lieberman, 1995;
Tyler, 1992). In addition, patients may experience motoric "freezing," where they halt
mid-gait and are unable to take any steps forward. Parkinson's patients may also
experience diminished facial expressivity ("masked facies"), reduced speech volume, and
small, illegible handwriting ("micrographia").
Motoric symptoms of PD are caused by the loss of dopaminergic neurons in the
substantial nigra pars compact. The substantial nigra (translated "black substance") are a
pair of small darkly pigmented bodies below the basal ganglia that synthesize dopamine.
It is estimated that motor signs begin occurring in PD when approximately 70% of the
dopamine producing cells in the substantial nigra pars compact have been lost (Feamley
& Lees, 1991; Halliday et al., 1996). Dopamine depletion in the substantial nigra affects a
cascade of other structures including the basal ganglia and feedback loops
communicating between the basal ganglia and frontal circuits (see Figure 1-1).
Medications that replace dopamine (e.g., levodopa, dopamine agonists) are the treatment
of choice for Parkinson's disease. Dopaminergic medication treatment is associated with
fluctuations in motor symptom severity. "On" periods are characterized by good clinical
control of symptoms by the medications, where as "off" period are marked by poor
symptom control. Both "on" and "off" periods can be complicated by dyskinesias,
excessive involuntary movements resulting from levodopa usage over time.
@i caudatee and putamen)
Figure 1-1. Simplified pathophysiological model of motor dysfunction in PD. Steps are
as follows: 1) the substantial nigra has reduced excitatory influence on the
striatum, 2) the striatum has reduced inhibition influence on the globus
pallidus disinhibitionn), 3) the globus pallidus is now disinhibited and exerts
stronger inhibitory influence on the thalamus, 4) the thalamus has reduced
excitatory influence on the cortex-leading to poverty of movement.
(SNpc=substantia nigra pars compacta.
Emotional Symptoms in Parkinson's Disease
Psychiatric symptoms and syndromes are highly prevalent in PD. Depression,
anxiety, and apathy are all common in PD (Brown & Pluck, 2000; Isella et al., 2002;
Poewe & Seppi, 2001). Prevalence rates of depression have been approximated at 40%
(Zgaljardic et al., 2003). Breaking this figure down into DSM diagnostic classification, a
recent meta-analysis reported that 10 studies using DSM-III or DSM-III-R criteria
classified approximately 25% of their PD patients with major depression, and 23% as
having dysthymia (Slaughter JR, Slaughter KA, Nichols, Holmes, & Martens, 2001). In
addition, 21 studies that used depression rating instrument such as the Beck Depression
Inventory (BDI), or Hamilton Rating Scale for Depression (Ham-D) classified 38% of
PD patients as depressed. Thus, depression is highly common in PD. It is thought that
depression may occur in high levels as a reaction to disability.
Clearly, adjusting to a having a medical illness, especially one that does not have a "cure"
but treatments that are temporary and lessen in effectiveness over time can cause reactive
depression. The early stages in which the patient is initially diagnosed may be the most
vulnerable to this reaction (McDonald, Richard, & DeLong, 2003). However, depression
in PD is also considered a primary consequence of brain pathophysiology of the disorder.
Depression in PD is proposed to be associated with decreased activation of the
orbitofrontal cortex (Cummings, 1993; Masterman & Cummings, 1997).
Apathy Syndromes and Symptoms
Apathy is an important but often overlooked feature of many psychiatric and
neurological disorders. Apathy refers to a cluster of behavioral, cognitive, and emotional
features such as lack of effort, loss of interest, and flattened emotions. The root of the
word "apathy" derives from the Greek "a" "pathos," meaning lack of passions. In the
psychological literature, the concept of apathy began with the use of a broader term-
negative symptoms. Descriptions of negative symptoms first appeared in the writings of
Hughlings-Jackson in the 1930s (Hughlings-Jackson, 1931). He distinguished the florid
or positive symptoms in schizophrenia from the deficit or negative symptoms. Positive
symptoms, such as hallucinations and delusions, were seen as an excess or distortion of
normal function, whereas negative symptoms, such as alogia, apathy, and poverty of
speech, were seen as a reduction or loss of normal function. Yet, this loss of normal
function is seen in disorders beyond schizophrenia. Robert Marin highlighted this fact in
the early 1990s. He proposed that apathy could manifest in neurological disorders as
both a symptom and a syndrome. His key paper in 1991 proposed diagnostic criteria for
a syndrome of apathy (Marin 1991). Apathy includes a primary lack of motivation that
manifests itself in 3 domains of symptoms: behavioral, cognitive, and affective. The
behavioral domain includes symptoms such as lack of effort, lack of productivity, and
dependence on others to structure one's activities. The cognitive domain includes
symptoms such as loss of interest in new experience and lack of concern about one's
personal problems. The affective domain includes symptoms such as flattened affect and
lack of response to positive or negative events. Marin emphasized that the lack of
motivation in a syndrome of apathy is primary, and not purely accounted for by
intellectual impairment, emotional distress, or diminished consciousness such as
drowsiness or delirium.
Apathy and Depression: Are They Dissociable?
Despite Marin's delineation of criteria for apathy, doubts have been raised about
whether apathy is a unique syndrome, or whether it is purely a symptom of depression.
Marin uses the term apathy as a symptom of other syndromes and as a syndrome all to
itself. Depressed patients will often present with the symptom of apathy-specifically
manifesting as loss of interest and decreased pleasure in activities they would normally
find enjoyable. In fact, diagnostic criteria for a Major Depressive Episode requires at
least 5 symptoms, with one symptom necessarily being either (1) depressed mood, or (2)
markedly diminished interest or pleasure in all or most all activities. Yet, this latter
symptom is also a cognitive symptom of a syndrome of apathy. Therefore, a syndrome
of depression can include symptoms of apathy. However, it can be argued (and will be
discussed further) that apathy can occur in the absence of depression and depression can
occur in the absence of apathy. One important difference between apathy and depression
is the notable lack of sadness, depressed mood, and dysphoria in apathy. Apathy presents
as blunted affect in both directions-neither happy nor sad.
Studies of frontal lobe disease and Alzheimer's disease have attempted to
disentangle apathy and depression syndromes. In frontal lobe disease, damage to the
mesial frontal lobe/anterior cingulate cortex and related subcortical feedback loops are
thought to produce a syndrome of apathy including lack of motivation, poverty of
behavior, reduced response initiation and creative thought, and emotional flattening. It
can also present with motoric slowness and deficits in sustained attention. Lesions in the
regions of the anterior cingulate cortex and supplemental motor area may produce a
syndrome of extremely severe apathy termed akinetic mutism. In this syndrome, the
patient makes no effort to communicate or initiate activities: they appear content to lie
silent and motionless. Patients may recover from this state, and after recovery one patient
reported that while she had exhibited these signs, she felt 'empty,' 'had nothing to say,'
and 'nothing mattered' (Damasio & Van Hoesen, 1983; Tranel, 1992). Akinetic mutism
is more clearly related to a syndrome of apathy than one of depression.
Apathy has been examined in Frontotemporal dementia (FTD). FTD is a
progressive cortical dementia affecting the frontal lobes and anterior temporal lobes; it is
associated with a profound alteration in personality and social conduct, often
characterized by lack of motivation or social disinhibition. In FTD, a syndrome of apathy
may manifest as emotional blunting, inappropriate emotional shallowness, unconcern,
and loss of empathy. It may include the behavior symptoms of reduced initiation of
speech and reduced personal hygiene and the cognitive symptoms of decreased mental
flexibility and loss of interest (Neary, Snowden, Gustafson, Passant, Stuss, Black et al.,
1998). Using a caregiver rating scale that includes questions in regards to apathy and
depression (the Neuropsychiatric Inventory), Neary and colleagues (1998) rated 28
patients with FTD in terms of their apathy and depression symptoms. A full sixty-one
percent of the patients showed apathy symptoms in the absence of depression symptoms,
while 29% showed both types of symptoms, and 11% showed depression symptoms
alone (Levy et al., 1998). Similar distinction has been made between apathy and
depression in Alzheimer's disease. Patients have been classified with the Marin Apathy
Evaluation Scale (AES; based on Marin's diagnostic apathy criteria) caregiver version
and the DSM-IV depression criteria (Starkstein, Petracca, Chemerinski & Kremer, 2001).
Results indicated that 13% of 319 Alzheimer's patients had apathy in the absence of
depression, 21.6% had depression alone, and 23.5% had both apathy and depression.
Thus, both of the above studies provide preliminary evidence that apathy and depression
can be dissociated in progressive neurological disorders.
STATEMENT OF THE PROBLEM
Depression is a common occurrence in PD and has been studied extensively. In
fact, there have been one hundred published English language studies specifically
examining depression in PD. Apathy, in contrast, is an understudied aspect of PD. Only
6 studies have investigated apathy in PD (Aarsland et al., 1999; Aarsland, Litvan, &
Larsen, 2001; Isella et al., 2002; Levy et al., 1998; Pluck & Brown, 2002; Starkstein et
al., 1992). There are several weaknesses and gaps left to be addressed by this small body
of literature. These weaknesses include the following: no control groups or inappropriate
control groups, inconsistency in method of reporting prevalence values, and
Two out of the 6 studies of apathy in Parkinson's disease had no control group
(Aarsland et al., 1999; Starkstein et al., 1992). This presents the problem of lack of an
appropriate comparison group. Apathy and depression can be examined in PD by itself,
but doing so does not provide a clear understanding of how aspects of apathy or
depression might be unique to PD. There is no way of knowing for example, whether
rates of apathy are comparable to those found in another movement disorder, or whether
rates of apathy are specifically higher in PD. Some studies have used a normal elderly
control group or an Osteoarthritis control group (Isella et al., 2002; Pluck & Brown,
2002). While these are important groups to consider, they still leave one wondering how
PD compares to other neurological disorders and specifically, other neurological
movement disorders. It is critical to examine apathy and depression in relation to another
movement disorder in order to understand whether apathy is, as we hypothesize, uniquely
present in high rates in PD. Thus, a control group that is a movement disorder with
similarly disabling motor symptoms and pathology will be the strongest test of whether
apathy is indeed a "core feature" of Parkinson's disease.
Methodologically, in order to clarify distinctions between apathy and depression
symptoms, it is important to separate groups into those with apathy symptoms in the
absence of depression, those with depression symptoms in the absence of apathy, and
those endorsing both types of symptoms. Not all studies break down their prevalence
figures into these groups. Thus, it is unknown whether their percent "depressed" also
includes those with apathy and their percent "apathetic" also includes those with
significant depressive symptoms. In addition to this methodological concern, there are
concerns with the measures used by previous studies to quantify apathy and depression.
In several studies, only one depression instrument was utilized. Furthermore, "cognitive"
symptoms of depression (e.g., hopelessness, guilt, worthlessness, anhedonia) have not
been examined separately from "somatic" symptoms of depression (e.g., sleep
disturbance, appetite disturbance, fatigue). Studies of depression in medical illness have
often been criticized for the potential overlap between somatic depression symptoms and
symptoms of the medical illness. Certainly in Parkinson's disease, there is such overlap
(examples from the BDI include: "It takes an extra effort to get started at doing
something," Item 15, "I get tired more easily than I used to," Item 17). It is important to
use more than one measure of depression to ensure that results are corroborated. In
addition, using measures of cognitive depression items only or analyzing total scores to
separate out somatic and cognitive components would be useful.
Three out of the six studies examining apathy in Parkinson's disease have used a
caregiver rating scale (the Neuropsychiatric Inventory) to document the occurrence and
severity of apathy and depression in the patient. The use of this scale poses interpretation
problems. While informant based information can be useful, it is questionable for the use
of assessing apathy. By definition, apathy is defined as a primary internal lack of
motivation that manifests in emotional, cognitive, and behavioral symptoms. Motivation,
emotions, and cognitions are all internal states, and as such may be difficult for others to
assess accurately. This is especially true in light of the fact that Parkinson's patients have
documented difficulties expressing and conveying emotions (e.g., "masked facies").
Therefore, misinterpretation of internal states is likely. It is more accurate (and arguably
simpler) to allow the patient themselves to answer questions about mood and motivation.
The present study attempted to address the issues cited above. To do this, several
self-report questionnaires (3 depression scales [Beck Depression Inventory, Centers for
Epidemiologic Studies-Depression scale, Beck Hopelessness Scale] and 1 apathy scale
[Marin's Apathy Evaluation Scale]) were administered to a group of 80 Parkinson's
disease patients and a group of 20 clinical control patients. Primary idiopathic adult-
onset Dystonia was chosen as a clinical control group for PD. Dystonia, like PD, is a
movement disorder that is progressive and disabling. It is characterized by involuntary,
sustained muscle contractions of opposing muscles, causing twisting movements and/or
abnormal postures. Dystonic movements can occur when the limbs are at rest, but most
often occur during voluntary movement. Like PD, it may occur with increased muscle
tone (rigidity), bradykinesia, and also may occur with tremor (Hallett, 1998; Jankovic &
The pathophysiology of Dystonia is not completely understood. However, studies
have shown that dystonic movements are associated with abnormal electromyographic
(EMG) activity (Cohen & Hallett, 1988; Farmer et al., 1998). Specifically on the level of
the muscles, co-contraction of antagonistic muscles and overflow into extraneous
muscles occurs. At the central nervous system level, studies have shown that there is
decreased amplitude of movement-related cortical potentials and decreased amplitude of
contingent negative variation (e.g., the electroencephalogram potential that appears
between a "warning" and a "go" stimulus in reaction time tasks). Further, decreased
blood flow has been shown to occur in the motor cortex and premotor cortex (specifically
in the caudal supplemental motor area and bilateral primary sensorimotor cortex,
Ceballos-Baumann et al., 1995). Current theory suggests that the pathology of Dystonia,
like Parkinson's disease, involves the basal ganglia circuitry. It is hypothesized that in
Dystonia there is overactivity in the direct pathway (e.g., globus pallidus intema ->
thalamus cortex, excitatory in nature) and underactivity in the indirect pathway (e.g.,
globus pallidus internal pedunculopontine nucleus brainstem and spinal cord,
inhibitory in nature). Both pathways result in overactivity of the cortex, causing the
excessive movements in dystonia. For the purposes of this study, of most importance is
the fact that both PD and Dystonia are progressive movement disorders involving basal
ganglia abnormalities. However, PD has been hypothesized to disrupt basal ganglia
connections to mesial frontal/anterior cingulate cortex putativelyy involved in apathy),
whereas Dystonia has been hypothesized to disrupt basal ganglia connections to
prefrontal cortex and the supplemental motor area.
The aims, hypotheses, and predictions of the present study are the following:
Aim 1: To determine the prevalence of apathy and depression in patients with PD
relative to that of a clinical control group of Dystonia patients. It is hypothesized that PD
patients will have a significantly higher apathy than Dystonia, and that this difference
may be due to differential involvement of frontal circuitry in PD (e.g., anterior
cingulated/mesial frontal cortex) versus Dystonia. Therefore, it is predicted that PD
patients will show a significantly higher prevalence of apathy (as defined by > 14 on the
Apathy Evaluation Scale) than Dystonia patients. It is further predicted that PD patients
will show significantly more severe apathy scores on the Apathy Evaluation Scale than
Aim 2: To investigate whether apathy is indeed a core feature of PD and not simply a
symptom of depression. It is hypothesized that a large proportion of PD patients will
have apathy in the absence of depression. It is predicted that a significantly greater
proportion of PD patients will exhibit apathy in the absence of depression (e.g., > 14 on
the Apathy Evaluation Scale without a > 14 on the Beck Depression Inventory) than
Aim 3: To examine the relationship between severity of PD and depression and apathy.
It is hypothesized that apathy will occur more severely in the later stages of PD and
depression will occur more severely in the earlier stages of illness. It is predicted that
Apathy Evaluation Scale scores will be significantly higher at increasing Hoehn-Yahr
Stages and that depression Beck Depression Inventory scores will be significantly higher
at earlier Hoehn-Yahr Stages.
Participants included eighty patients with idiopathic Parkinson's disease and a
clinical control group of twenty patients with idiopathic adult-onset Dystonia.
Participants were recruited through the Movement Disorders Center of the University of
Florida. They were invited to participate in the present study during their routine medical
appointment. As part of their routine workup with a movement disorders neurologist,
Parkinson's patients received standard measures for staging the severity of their motor
symptoms and the course of their disorder. These included the Unified Parkinson 's
Disease Rating Scale-motor examination (UPDRS [Fahn & Elton, 1987]), a modified
Hoehn-Yahr scale (Hoehn & Yahr, 1976), and the Schwab and EnglandActivities of
Daily Living Scale (Schwab & England, 1969). Additionally, Parkinson's patients
received a scale assessing "disease specific" quality of life (Parkinson's Disease Quality
ofLife Scale-39 [Peto, Jenkinson, & Fitzpatrick, 1995]). Dystonia patients received
standard measures for the staging of the severity of their motor symptoms (Unified
Dystonia Rating Scale [Comella et al., 2002; Dystonia Study Group, 1997]) and a scale
assessing quality of life (.\/,N t Form Health Survey 36 [Ware & Shelboume, 1992]).
To be included in the present study, Parkinson's (PD) and Dystonia (DYS)
patients had to be between 40 and 90 years of age, meet stringent diagnostic criteria for
their respective neurological disorders, be free of co-morbid neurological illness, and be
free from previous neurosurgical treatments such as deep brain stimulation or
pallidotomy. Patients in the present study were not selected for any known cognitive or
psychiatric state. The clinical diagnostic criteria for idiopathic PD was based on the
following: a) the presence of at least two of four cardinal motor signals (i.e., akinesia,
bradykinesia, resting tremor, rigidity), and b) a demonstrated therapeutic response to
dopamine replacement therapy defined by a sustained improvement of Parkinson's motor
symptoms (based on the Unified Parkinson's Disease Rating scale-motor subscale) after
administration of dopaminergic medication during their diagnostic neurological
examination. A positive response to dopaminergic therapy was necessary to exclude
patients with Parkinson's plus syndromes (e.g., Lewy body disease, corticobasal
degeneration, multiple systems atrophy). The clinical diagnostic criteria for idiopathic
adult-onset Dystonia was based on the following: a) an illness characterized by the
development of isolated dystonic movements and postures, b) a normal perinatal and
developmental history, and c) no antecedent illness or drug intake known to cause the
syndrome (Fahn, Bressman, & Marsden, 1998). All participants were adult onset, and
thus by definition were diagnosed after 20 years of age.
The PD patients included fifty-five men and twenty-five women who ranged in age
from 46 to 87 years (M= 68.9, SD = 9.5). Seventy-three (91.2%) patients were Tremor-
predominant PD subtype and seven (8.8%) were Akinetic-rigid PD subtype. (See Table
1-1). On average, the PD patients had been experiencing parkinsonian symptoms for six
years (M= 6.4, SD=5.7, range 1-34 years) and were in the middle stages of PD based on
the staging criteria from the Hoehn-Yahr scale. Approximately ninety-nine percent of
PD patients were taking dopaminergic medications (e.g., levodopa/carbidopa, dopamine
agonists, with one patient prescribed levodopa/carbidopa on the day of their evaluation)
and fifty-one percent were taking anti-depressant medication.
Adult-onset Dystonia patients included six men and fourteen women who ranged in
age from 43 to 87 years (M=60.9, SD= 1.9). For all patients in the present study,
symptoms began after age 30 (M= 53.5, range=31-87). Ten (50%) were Focal dystonia
subtype (i.e., affects a single body part) and ten (50%) were Segmental dystonia subtype
(i.e., affects one or more contiguous body parts). On average, they had been
experiencing symptoms of Dystonia for eight years (M=8.0, SD=7.8, range 0.5-30 years).
Twenty percent of Dystonia patients were prescribed anti-depressant medications.
Table 3-1. Parkinson and Dystonia Patient Characteristics
Characteristic PD patients DYS patients
(N 80) (N=20)
Disease Subtype 91.2% Tremor 50% Focal
8.8% Akinetic 50% Segmental
Age 68.9(9.5) 60.9(11.9) p <.01
Men: Women 55:25 6:14 p <.01
Yrs. Ed 14.8 (3.0) 15.1(2.1) Ns
DOPA meds 98.8% --
Anti-depress 51% 20% p <.01
Yrs. Symptoms 6.4 (5.7) 8.0 (7.8) Ns
Hoehn-Yahr stage 2.4 (.67)
motor score(UPDRS) 29.5(10.8)
A comparison of PD patient and DYS patient demographic variables is presented
in Table 1-1. As shown, the PD and DYS groups did not significantly differ with respect
to the number of years they have experienced disease symptoms, t(96) = -1.04, p = .30.
However, they did significantly differ with respect to age, gender, and the percentage of
patients prescribed anti-depressant medications. PD patients were significantly older
(t(98) = 3.22,p < .01), more likely to be male (t(98) = -3.32,p < .01), and more likely to
be taking anti-depressant medications (t(96) = 2.47, p < .01).
Procedures and Assessment Instruments
Prior to participation in the present study, informed consent had been obtained from
each participant according to University and Federal guidelines. All testing was
conducted at the Medical Plaza at the University of Florida during routine neurological
appointments. During the present study, participants completed a variety of mood
questionnaires including the following in order of completion: Beck Depression
Inventory (BDI [Beck, 1978]), modified Apathy Evaluation Scale (AES [Marin, 1991]
modified by Starkstein et al., 1992), Center for Epidemiological Studies-Depression scale
(CES-D [Radloff, 1977]), and the Beck Hopelessness Scale (BHS [Beck, Weissman,
Lester, & Trexler, 1974]). Completion of questionnaires took approximately 30 minutes.
Depression Assessment Instruments
Beck Depression Inventory (BDI). The BDI is a 21 item scale widely used for
both research and clinical purposes. Each item addresses an aspect of the experience and
symptoms of depression (i.e., mood, guilt, indecisiveness, appetite and sleep changes).
Items include statements rated on a 0-3 Likert scale based on severity of feelings of
depression over the last week. For example, "O-I do not feel sad," "1-I feel sad," 2-I
am sad all the time and I can't snap out of it," "3-I am so sad or unhappy that I can't
stand it." The score is the sum of all items, with higher scores indicating more severe
depression. Classification of depression severity has been defined in multiple ways.
Lezak (2004) refers to the following classification of depression: minimal < 13, mild =
14-19, moderate = 20-28, severe > 29. This classification is used in the present study.
The BDI can be divided into items that focus on depressive cognitions and ideations (i.e.,
ideationall symptoms,' items 1 through 13), and items that focus on bodily concomitants
of depression (i.e., 'somatic symptoms,' items 14-21). These domains are particularly
useful to examine in the present study because elderly and medically disabled patients
may endorse somatic items that may not be related to depression (e.g., fatigue caused by
medical disorder vs. depression). The BDI has been shown to have substantial support
for its reliability and validity. Beck, Steer, & Garbin (1988) reviewed the psychometric
properties of the BDI in a meta-analysis. They found that the internal consistency
reliability as measured by Cronbach's coefficient alpha ranged from .73 to .95 and that
the concurrent validity with scales such as the Hamilton Psychiatric Rating Scale, the
Zung Self-Reported Depression Scale, and the MMPI depression scale ranged from .60
to.76 (Beck, Steer, & Garbin, 1988). The BDI is thought to have excellent reliability and
validity in use with Parkinson's patients (Levin, Llabre, & Weiner, 1988). In addition,
previous studies that have examined apathy and depression together have used the BDI
(Pluck & Brown, 2002).
Center for Epidemiologic Studies-Depression Scale (CES-D). The CES-D is a
20 item scale that measures depressive symptoms. Example items include the following:
"I felt that I could not shake off the blues even with help from my family or friends," "I
though my life had been a failure." Each item is rated on a 0-3 Likert scale based on the
frequency with which the symptom occurred in the last week ("0= Less than 1 day," "1-
1-2 days," "2-3-4 days," "3-5-7 days). A score of > 16 has typically been used to
classify significant depressive symptoms in the general population. However, this has
been criticized as producing a high false-positive rate and poor specificity in medical
outpatients and inpatients (Schein & Koenig, 1997; Schulberg et al., 1985). Therefore,
Schein and Koenig's (1997) recommended cut-score of 20 was used for the present study.
The CES-D has shown good internal consistency reliability for older adults (between .86
and .89) (Davidson et al., 1994; Williamson and Schulz, 1992). It has been widely used
in assessing medical patients in epidemiological studies (e.g., Bodurka-Bevers et al.,
2000; Chwastiak et al., 2002; Lyketsos et al., 1993).
Beck Hopelessness Scale (BHS). The BHS is a 20 item scale of true-false
statements that assess hopelessness/negative beliefs about the future. It is useful for the
present study because of its focus on cognitive symptoms (e.g., hopelessness, pessimistic
thoughts). It does not contain somatic items. Example items are: "I might as well give
up because there is nothing I can do about making things better for myself," "All I can
see ahead of me is unpleasantness rather than pleasantness." A total score is calculated
by summing up the pessimistic responses for each of the 20 items. Beck and Steer (1988)
reported high internal consistency reliability across diverse clinical populations (ex.
Major Depressive Disorders, Dysthymic Disorders, etc), with Kuder-Richardson
reliabilities ranging from .87 to .93. One week test-retest reliability was adequate (.69).
Patients with high scores on the BHS and/or BDI and CES-D were followed up, and
when needed, provided with appropriate referrals.
Apathy Evaluation Scale-modified (AES). The AES-modified is a 14 item scale
measuring cognitive, emotional, and behavioral symptoms of apathy. Some examples of
items are: "Are you interested in learning new things?" "Are you indifferent to things?"
"Does someone have to tell you what to do each day?" Each item is rated on a 0 to 3
Likert scale, with 0=not at all, slightly, 2= some, 3= a lot.
The scale is an abridged version of the original 18 item version developed by
Robert Marin (1991). He validated the original scale on approximately 90 subjects aged
55-85 years with a diagnosis of either stroke, Alzheimer's disease, or Major depressive
disorder. He compared these diagnostic groups with normal elderly controls. Internal
consistency reliability average was .86, test-retest reliability (X=25.4 day interval) was
.76. Convergent and divergent validity with other scales (e.g., anxiety and depression
scales) was clearly established with the multitrait-multimatrix method (Marin,
Biedrzycki, & Firinciogullari, 1991). Interestingly, predictive validity and external
validity were investigated by observing participants in various scenarios (e.g., playing
video games, examining novelty gadgets in a waiting area). Self-reported apathy scores
negatively correlated with total score on the videogames and difficulty level at which
participants chose to play. Thus, it appeared that there was a behavioral correlate with
The original scale was shortened by 4 items, and modified in wording to be simpler
by Starkstein et al. in 1992. This modified AES was reported to have excellent
psychometric properties in PD (Internal consistency reliability/Cronback's alpha =.76,
test-retest reliability of 1 week r = .90). The modified version was used in the present
To test the first prediction (PD patients will exhibit a significantly higher
prevalence of apathy as defined by > 14 on the apathy scale than DYS patients), a 2-way
Chi square test for independence was used with categories of group type and apathy
presence/absence. To test the second prediction (PD patients will exhibit a significantly
greater level of apathy than DYS patients), an Independent samples t-test was used with
apathy score as the dependent variable. Next, both of types of analyses (e.g., both
prevalence and level) were repeated with depression score from the Beck Depression
Inventory and the Centers for Epidemiological Studies-Depression Scale (prevalence cut
scores of > 14 BDI, > 20 CES-D). To control for uneven distribution of anti-depressant
usage between groups, anti-depressant usage was used as a covariate in the depression
analyses. As a further check, post-hoc groups of all patients not prescribed anti-
depressants were created and were analyzed in the same manner as the complete set.
To investigate whether a larger proportion of PD patients exhibited apathy in the
absence of depression then DYS patients, patients were analyzed with respect to those
who exhibited apathy only (> 14 on the Apathy Evaluation Scale without > 14 on the
Beck Depression Scale), depression only (> 14 on the Beck Depression Scale without >
14 on the Apathy Evaluation Scale), and both apathy and depression (> 14 on the both
scales). Two-way Chi squared tests for independence were utilized to examine
prevalence for each of the categories listed above.
A final set of analyses examined the relationship between apathy and depression
symptoms and severity of PD (prediction being that apathy would be significantly greater
in more severe stages disease and depression would be significantly greater in earlier
stages of disease). Parkinson's patients were divided into mild, moderate, and severe
stages of illness based on the Hoehn-Yahr Staging Scale. A one-way ANOVA was
conducted with apathy score as the dependent variable and Severity Stage as the
independent variable. A one-way ANOVA was then conducted with depression score as
the dependent variable and Severity Stage as the independent variable. Correlational
analyses were performed between apathy symptoms and the disease and demographic
variables of age, motor UPDRS score, and duration of illness.
Apathy Prevalence and Severity
The initial analysis examined whether Parkinson's patients exhibited a
significantly higher prevalence of apathy (defined by > 14 on the Apathy Evaluation
Scale) than Dystonia patients. A 2 x 2 Chi squared test for independence was conducted
with Group (PD, DYS) and Apathy (presence, absence) as categories. Results indicated
that Parkinson's patients (freq.= 51%, 41/80) had a significantly higher prevalence of
apathy than Dystonia patients (freq.= 20%, 4/20), X2 (1, N= 100) = 6.31, p = .012, 4
correlation coefficient=.25]. See Figure 4-1 below.
Figure 4-1. Prevalence of apathy in Parkinson's disease and Dystonia controls.
Next, the severity of apathy was examined between groups. It was predicted that
Parkinson's patients would show significantly greater apathy scores than Dystonia
patients. An independent samples t-test was conducted with Group as the independent
variable and apathy score as the dependent variable. The apathy scores of the
Parkinson's patients (M= 13.06, SD = 7.28) were significantly higher than those of the
Dystonia patients (M= 9.4, SD = 7.25), t(98) = 2.01,p = .041, d= .5. Thus, Parkinson's
patients had more severe apathy than Dystonia patients, and the effect size was moderate.
Depression Prevalence and Severity
The prevalence of depression was examined between the two groups using the
Beck Depression Inventory and the Centers for Epidemiologic Studies-Depression Scale
(defined by scores of > 14 BDI, > 20 CES-D). A 2 x 2 Chi squared test for independence
was conducted with Group (PD, DYS) and depression (presence, absence) as categories.
Results from the BDI indicated that the prevalence of depression in Parkinson's patients
(freq.= 26.3%, 21/80) was not significantly different from the prevalence in Dystonia
patients (freq.= 30%, 6/20), X2(1, N= 100) = .114, p =.74, 4 correlation coefficient =
.034. This result is depicted in Figure 4-2. Similar findings occurred with the CES-D.
The CES-D depression scores were not significantly different between groups (PD freq.=
31.2%, 24/771, DYS freq= 30.0%, 6/20, 2= 0.01,p = .92, 4 correlation coefficient =
1 Note: CES-D data were missing from 3 participants.
50% ns 30%
Figure 4-2. Prevalence of BDI depression in Parkinson's disease and Dystonia controls.
Severity of depression was investigated between the two groups via Independent
samples t-tests. Neither BDI score nor CES-D score were significantly different between
groups. Statistics for the BDI and CES-D scores were, respectively, t(97) = 1.15, p=.25,
d= .29 and t(95) = .588,p=.34, d= .15. See Table 4-1 for means and standard
The BDI contains items that detect cognitive/ideational depression symptoms, and
items that detect bodily/somatic depression symptoms. Both the ideational and somatic
scores from the BDI were analyzed using separate independent samples t-tests. The
results of these analyses indicated that there were no differences between the PD and
Dystonic patients in terms of their ideational scores (t(97) = .397, p = .69, d= .1) or their
somatic scores (t(97) = 1.7, p = .09, d= .43). These scores are shown in Table 4-1.
Additionally, hopelessness cognitions as measured by the Beck Hopelessness Scale were
not significantly different between the PD and Dystonia groups, t(94) = .89, p = .38, d=
.22). See Table 4-1.
Table 4-1. Means and Standard Deviations for Depression Scales.
Scale PD patients DYS patients
(n 80) (n 20) p value
BDI total 10.2 (6.8) 8.3 (5.5) .25
BDI-Ideational 3.9 (3.8) 3.5 (3.4) .69
BDI-Somatic 6.4 (3.7) 4.8 (3.3) .09
CES-D total 12.8 (10.2) 11.3 (11.2) .56
BHS total 4.7(4.6) 3.7(4.2) .38
Of potential importance, the Parkinson and Dystonia groups differed according to
the percentage of patients who were prescribed anti-depressant medications. Fifty-one
percent of Parkinson's patients had been prescribed anti-depressant medication versus
only 20% of the Dystonia patients. It is thus possible that the depression scores of the
Parkinson's patients may have been "artificially lowered" due to their higher use of
antidepressants. Two post-hoc analytic approaches were undertaken to examine this
possibility. In the first, the use of anti-depressants was used as a covariate in the
examination of depression scores. In the second approach, the subset of Parkinson
patients who were NOT taking anti-depressant medications were compared to the
Dystonia patients who were not taking anti-depressants.
The results of the first approach indicated that controlling for anti-depressants did
not change the earlier finding of no significant difference on BDI score between PD (M=
10.0, SD = 6.6) and Dystonia groups (M= 8.1, SD = 6.4), t(94) =.76,p = .56, d= .29. In
the second approach, subgroups of patients who had not been prescribed anti-depressants
were created and included 38 PD patients and 14 Dystonia patients. Group comparisons
using independent t-tests revealed that the PD patients tended to have higher total BDI
scores than the Dystonia patients, t(50) = 1.93, p = .059, d= .6. See Table 4-2 for means
and standard deviations. When the BDI scores were further examined, ideational scores
did not differ between groups, while somatic symptoms were significantly higher in
Parkinson's (M= 6.6, SD= 3.8) than in Dystonia (M= 3.4, SD = 2.4), t(50) = 2.88, p
=.006, d= .898. Further, CES-D score and BHS scores were not significantly different
between groups, respectively, t(50) = .720, p = .475, d= .059 and t(50) = 1.03, p = .31, d
Table 4-2. Means and Standard Deviations for Patients Not Using Anti-Depressants
Scale PD patients DYS patients
(n 38) (n 14) p value
BDI total 10.7 (7.6) 6.4 (5.0) .059+
BDI-Ideational 4.1 (4.2) 3.0 (3.2) .403
BDI-Somatic 6.6 (3.8) 3.4 (2.4) .006*
CES-D total 12.5 (11.0) 10.0 (11.6) .475
BHS total 4.9 (5.3) 3.3 (3.4) .306
Denotes that the values are significantly different.
+ Denotes that the values are significantly different at the level of a trend.
Relationship between Apathy and Depression Prevalence
Another set of analyses investigated the relationship between apathy and
depression symptoms in the two groups in order to test the prediction that a larger
proportion of PD patients exhibited apathy in the absence of depression than did the DYS
patients. Patients were analyzed with respect to those who exhibited apathy only (> 14
on the Apathy Evaluation Scale without > 14 on the Beck Depression Scale), those who
exhibited depression only (> 14 on the Beck Depression Scale without > 14 on the
Apathy Evaluation Scale), and those who exhibited both apathy and depression (> 14 on
the both scales). Two-way Chi squared tests for independence were used to examine
prevalence for each of the categories listed above. The prevalence of patients exhibiting
apathy alone (e.g., in the absence of depression) was significantly higher in the
Parkinson's group (freq.= 28.8%, 23/80) than in the Dystonia group (freq.= 0%, 0/20),
Fisher's exact significance (used to correct for less than 5 per cell) =.006. The
prevalence of depression alone (in the absence of apathy) was not significantly different
between Parkinson's (freq= 4%, 3/80) and Dystonia (freq.= 10%, 2/20), Fisher's exact
significance =.261. Additionally, the prevalence of patients exhibiting apathy and
depression together was not significantly different between Parkinson's (freq.= 22.5%,
18/80) and Dystonia (freq.=20.0%, 4/20), Fisher's exact significance= 1.0. See Figure 4-
3. Thus, approximately thirty percent of the Parkinson's sample exhibited apathy without
depression while none of the Dystonia sample exhibited apathy without depression.
There was no significant difference between groups in terms of those exhibiting
depression alone or combined apathy and depression.
50% O Parkinson's
S40%- 29% Dystonia
Apathy and Apathy only Depression only
Figure 4-3. Overlap between apathy and depression, apathy alone, and depression alone
Relationship with Severity of Parkinson's Disease
A final set of analyses was conducted to investigate the relationship between
apathy and depression symptoms and severity of Parkinson's disease. It was predicted
that apathy would be significantly greater in more severe stages and depression would be
significantly greater in earlier stages. As noted earlier, the Hoehn-Yahr is a Staging
system of severity of Parkinson's disease and ranges from 0 (no disease) to 5 (bedridden).
Three severity groups were created according to Stages ofPD: (a) Mild (Stages 1-2,
unilateral disease to bilateral disease without impairment of balance, n = 40), (b)
Moderate (Stages 2.5-3, mild bilateral with recovery on the pull test and mild to moderate
bilateral disease with some postural instability, n = 22), and (c) Severe (Stage 4, severe
disability, unable to walk or stand unassisted, n = 5). A oneway ANOVA was conducted
with Severity Group as the independent variable and apathy score as the dependent
variable. Results suggested that apathy was significantly different between groups, F(2,
64) = 7.68, p =.001. However, Levene's test found that the assumption of homogeneity
of variance could not be supported, F(2, 64) = 4.57, p = .014). Therefore, the more
conservative Brown-Forsyth F-statistic is reported. Results indicate that apathy is higher
at more severe stages of illness at the level of a trend, F(2, 6.65) = 4.4, p = .061. Means
and standard deviations are as follows: Mild (M= 10.6, SD = 6.8), Moderate (M= 15.8,
SD= 4.9), Severe (M= 20.4, SD = 11.3).
Apathy score was also examined in relation to patient age, duration of disease,
and motor score on the United Parkinson Disease Rating scale (obtained while "on"
dopaminergic medications). Bivariate correlations were used to examine these
relationships (See Table 4-3). Duration of illness (e.g., years of symptoms) was not
significantly related to apathy score (p = .82), while UPDRS motor score severity was
significantly positively related to apathy (r = .25, p = .003) and age was significantly
positively related to apathy (r = .24, p = .03).
To examine the effects of severity on BDI depression scores, a one-way ANOVA
was performed with Severity Group as the independent variable and depression score as
the dependent variable. Levene's test found that the assumption of homogeneity of
variance was supported. There was a significant difference between Severity Group and
depression score, F(2, 64) = 10.3, p < .001. Bonferroni corrected post hoc followup tests
were utilized to locate the significant effects. Moderate and Severe Groups were
significantly higher in depression than the Mild group, t(64) = 3.89, p = .001 and t(64) =
3.23, p = .008, respectively. Means and standard deviations are as follows: Mild (M=
7.78, SD = 5.55), Moderate (M= 14.0, SD = 5.66), and Severe (M= 16.8, SD = 11.17).
Depression score was also examined in relationship to duration of illness, age, and motor
UPDRS score (See Table 4-3). Results indicated that depression (BDI) scores were not
significantly related to duration of illness (p = .98) or age (p = .95), but were significantly
positively related to motor score severity (r = .314, p = .003).
Table 4-3. Intercorrelations Between PD Apathy Scores, Depression Scores, and Disease
AES BDI CESD DUR. AGE H&Y UPDRS-M
1. AES -- .671* .640* -.026 .241+ .411* .250+
2. BDI -- .817* .033 .012 .462* .348*
3. CES-D -- .033 -.007 .449* .314*
4. Duration -- .022 .353* .348*
(Years of Symptoms)
5. Age .395* .221
6. Hoehn-Yahr -- .708*
7. UPDRS motor
Significant atp < .01.
+ Significant atp < .05.
The present study investigated three hypotheses. The first hypothesis was that
Parkinson's disease patients would display higher levels of apathy than a clinical control
group of Dystonia patients. Specifically, we predicted that: a) PD patients would show a
significantly higher prevalence of apathy than Dystonia patients, and b) PD patients
would show significantly more severe apathy than Dystonia patients. This was based on
the idea that certain frontal-subcortical systems putatively involved in apathy (e.g.,
anterior cingulate/mesial frontal cortex) are more disrupted in Parkinson's disease than in
Dystonia. The second hypothesis was that apathy is a core feature of Parkinson's disease
and not simply a symptom of depression. Therefore, it was predicted that a larger
proportion of Parkinson's disease patients would exhibit apathy in the absence of
depression than Dystonia patients. The third hypothesis involved the relationship
between apathy and depression and stage of illness of Parkinson's disease. It was
hypothesized that greater apathy would occur at more severe stages of disease, and that
greater depression would occur at the early stages of disease. This was based on the idea
that while both types of mood symptoms may worsen as a direct result of progressing
pathology of the illness, apathy may be more linked to this progression whereas
depression may also be seen as a reaction to being diagnosed with a progressive
Summary and Interpretation of the Findings
The first hypothesis was supported by the data. The prevalence of apathy was
significantly higher in Parkinson's disease than in Dystonia. Approximately half of the
Parkinson's patients showed apathy, whereas only one fifth of Dystonia patients showed
apathy. Parkinson's patients had significantly more severe apathy scores than Dystonia
patients. Both the effect of prevalence and the effect of severity were moderately large.
This suggests that the differences between the groups may be large enough to be
clinically meaningful in addition to being statistically significant. Further, when
depression was examined between groups there was no significant difference found for
prevalence using either the Beck Depression Inventory (BDI) or the Centers for
Epidemiologic Studies-Depression (CES-D) scale. There was also no significant
difference between severity of depression between groups using either scale. Further,
groups did not differ on endorsement of hopelessness cognitions-- as measured by the
Beck Hopelessness Scale (BHS). Because the Parkinson's patients were significantly
more likely to be taking anti-depressant medications than the Dystonia patients (and
perhaps scores were "artificially" lowered due to this), post-hoc groups were created of
38 PD patients and 14 Dystonia patients who were not taking anti-depressants. Analyses
revealed that although the CES-D and BHS continued to show no difference between
groups, the BDI scores revealed that Parkinson patients more severe at the level of a trend
(p=.059). Interestingly, when further examined, it appeared that somatic symptoms were
driving this difference-with ideational scores not differing significantly. Therefore, it
seems plausible that this difference between groups may been due to Parkinson's patients
experiencing more somatic complaints than Dystonia and not depression per se.
Although it cannot be completely ruled out that these symptoms represent depression, the
above interpretation seems likely when taken in light of findings from the other two
The second hypothesis was also supported by the data. Parkinson's patients had
significantly greater prevalence of apathy in the absence of depression than Dystonia
patients. Twenty-nine percent of Parkinson's patients showed apathy in the absence of
depression, whereas no Dystonia patients showed this result. This was the most dramatic
and potentially important finding of the study. It suggests that apathy, in Parkinson's but
not Dystonia manifests at a significant level independent of depression level. Further,
prevalences of both apathy and depression together and depression alone were not
significantly different between groups. Apathy in the absence of depression was a unique
finding for Parkinson patients and suggests the importance of this mood symptom
specifically in this disorder. It is proposed that some of the differences in apathy
expression between the two groups may be due to pathological differences between
Dystonia and Parkinson's disease. Both disorders are thought to affect the basal ganglia;
however, they are believed to have differential connections to cortex. PD has been
proposed to disrupt mesial frontal/anterior cingulated cortex connections. This area of
the frontal cortex is reportedly involved in apathy in other neurologic conditions
(Cummings, 1993). It is also the area of the frontal cortex thought to be involved in the
extreme syndrome of apathy-akinetic mutism (Tranel, 1992). Dystonia, in contrast to
PD, has been proposed to disrupt caudal supplemental motor areas, prefrontal cortex, and
the caudate nucleus (Hallett, 1998). However, the neuropathology of apathy in PD has
not been systematically addressed in the literature. It was not the intent of the present
study to do so. Carefully controlled neuroimaging studies should be undertaken to
further the hypotheses about proposed brain area involvement.
The third hypothesis was partially supported. Apathy was associated with greater
disease severity as measured by the Hoehn-Yahr Staging scale. Thus, greater severity of
illness was related to higher apathy. In addition to severity, apathy was also correlated
with age and motor score, but not with duration of illness (e.g., how many years patients
had experienced symptoms). It was hypothesized that depression would be greater in the
earlier stages. Contrary to the hypothesis, depression was significantly greater in the
more severe stages of disease. However, this result is not counter to findings in the
Parkinson's disease literature. Findings suggest a relationship between subcortical
neuron degeneration (as the disease becomes more severe) and an increase in depressive
symptoms (McDonald, Richard, & DeLong, 2003). In regards to the high depression in
earlier stages, this often occurs around the time of diagnosis. Patients in this sample had
a wide range of year since diagnosis, and the majority were not recently diagnosed.
Thus, all of the above factors may have played into the finding that depression was
related to later rather than earlier stages of illness. In addition, depression was related to
motor severity, but not with duration of illness or age.
The fact that neither apathy nor depression were significantly related to duration
of illness, but were related to severity of illness may at first seem counterintuitive.
However, it is reasonable given the variability of progression of the disease across
patients. Some patients can stay relatively healthy with PD for 10-15 plus years, whereas
others may decline more rapidly (Nutt, Hammerstad, & Gancher, 1992; Peretz &
Cummings, 1988). Therefore, whereas the occurrence of apathy and depression
symptoms appear to increase with increasing severity of illness, the duration of the illness
per se is not associated with increased psychiatric symptoms.
Comparing Prevalence and Severity Across Current Literature
The finding of a high prevalence of apathy in Parkinson's disease is consistent with
the current literature. Three studies (Pluck & Brown, 2002; Starkstein et al., 1992; Isella
et al., 2002) have examined self-reported apathy in PD and, respectively, each has
reported the prevalence of apathy as 38%, 42%, and 43%. These rates are similar to that
found in the current study (51%). In addition, two of these studies broke down their
prevalence figures into apathy alone, depression alone, and apathy and depression
together. Starkstein et al. (1992) reported 12% apathy alone (6 of 50 PD subjects), 21.6%
depression alone (13 of 50 PD subjects), and 30% apathy and depression together (15 of
50 PD subjects). The percentage of apathy and depression together is similar to that
found in the present study; however, the percentage of apathy alone was lower than the
present study (12% vs. 29%). Isella et al. (2002) reported 23.3% apathy alone (7 of 30
PD subjects), 13% depression alone (4 of 30 PD subjects), and 46.6% apathy and
depression together (14 of 30 subjects). These prevalence values are similar to those
found in the present study. However, these values should be taken with caution because
they were based on an Italian translation of the original scale. Turning to the severity of
apathy in these two studies, findings indicate that PD showed significantly more severe
apathy than normal elderly controls and significantly more severe apathy than
Although problems surrounding the use of caregiver ratings of apathy were
presented earlier, it remains of theoretical interest to examine the results from the
remaining three apathy studies that relied on the caregiver rated Neuropsychiatric
Inventory (NPI). Overall, these studies found lower rates of overall apathy than the
present study. Aarsland (1999) used a comprehensive epidemiological sample of 139 PD
patients, and found a prevalence rate for apathy of 16.5% (23 of 139 PD subjects), with
4.3% of the total PD subjects showing apathy in the absence of depression (6 of 139 PD
subjects). Aarsland (2001) used a subset of the same data and not surprisingly,
reproduced his original result for apathy in PD (e.g., 16.5%, 17 of 103 patients). Finally,
Levy (1998) found that 5% of patients showed apathy alone (2 of 40 PD subjects), and
28% of patients showed a combination of apathy and depression (11 of 40 PD subjects).
These values on the whole are much lower those that from self-report scales (ex. 38-51%
total apathy in self-reported versions vs. 16.5%-33% in caregiver rated versions). There
may be several explanations for this. First of all, Levy's data (1998) were based on a
selected sample-that of surgery candidates. Participants are often screened for
significant psychiatric symptoms before being deemed surgery candidates; therefore they
may have a lowered rate of overall psychiatric symptoms. Secondly, the NPI caregiver
scale assesses fewer symptoms of apathy (and depression) than rating scales such as the
AES or BDI. For example, there is only one item assessing behavioral presentation of
apathy on the NPI versus five on the AES. There are approximately 8 questions for each
mood category on the NPI (e.g., apathy, depression, anxiety, etc), and they often do not
cover the full diagnostic criteria. Not covering as many symptoms as the other versions
of the scales could artificially lower the apathy scores for many Parkinson's patients.
Despite the above criticisms, it is important to mention that all studies reviewed
found some proportion of their sample to present with apathy in the absence of
depression. As such, it appears that apathy and depression may indeed be separable in
Parkinson's disease, and that apathy may have a key place in the mood profile of the
disorder. It may be important, therefore, for clinicians to screen for both apathy and
depression. In this way, patients can be triaged into appropriate treatment groups. There
are currently effective pharmacological and psychotherapeutic treatments for depression
in Parkinson's disease. However, some treatments are not necessarily helpful for apathy
and may have harmful side effects without benefits. For example, Lexapro
(escitalopram) is frequently prescribed for depression in Parkinson's patients.
Escitalopram is not necessarily proven to improve apathy symptoms, but has a possible
side-effect profile of agitation/restlessness, blurred vision, diarrhea, difficulty sleeping,
drowsiness, dry mouth, fever, indigestion, and nausea. Thus, prescription of this
medication for an apathetic patient might cause the above side-effects without relief of
apathy symptoms. Additionally, it is helpful for caregivers and spouses to understand
that apathy is a characteristic of this disorder, and likely a direct result of disease
pathology. This allows caregivers to understand that apathetic behavior is not under the
PD patient's voluntary control, and thus is not laziness or oppositional behavior but a
symptom of the disease.
More theoretic in nature, it is of interest to understand whether separate neural
systems underlie depression and apathy. It may be that orbitofrontal-subcortical
connections underlie depression in PD, whereas mesial frontal/anterior cingulate
subcortical connections underlie apathy. It may additionally be important to study
subgroups of patients that show high levels of apathy. For example, the recent literature
proposes a relationship between PD apathy and certain cognitive deficits. High apathy
PD groups showed decreased performance compared to low apathy PD groups in terms
of verbal fluency (based on the Category test and Controlled Oral Word Fluency),
changing mental categories or "set shifting" (based on the Wisconsin Card Sort
categories sorted and errors) speeded task performance (based color naming and word
naming on the Stroop and Trails B) and inhibition (Stroop color-word naming) (Isella et
al., 2002; Pluck & Brown, 2002). The continued examination of the relationship between
cognitive abilities and apathy is an important area of future research.
Limitations of the Present Study
Several limitations of the current study must be addressed. First, although every
attempt was made to obtain patients that matched the Parkinson's group in terms of
demographics, this was not possible on all variables. The Dystonia group tended to be
younger (DystoniaM= 60.9, SD = 11.9 vs. Parkinson's M= 68.9, SD = 9.5) and
composed of more women (Dystonia 70% vs. Parkinson's 31%). They also were less
likely to be on anti-depressant medications (Dystonia 20% vs. Parkinson's 51%). The
possibility that the findings were driven by these demographic differences cannot be
completely ruled out. However, reassuringly, it appears that at least some of the findings
from the present study are not those that would be expected if demographic variables
were driving the results. For example, by virtue of the increased general population
incidence of depression for women over men, the Dystonia group should have shown
more depression than the Parkinson's group. However, findings were that groups did not
differ in terms of depression. Additionally, post hoc analyses were utilized to explore
possible biases due to the Parkinson's disease group having more anti-depressant usage.
Results of these analyses revealed no differences between BHS and CES-D scores, but a
trend for Parkinson's disease to be more severe on the somatic symptoms of the BDI. It
cannot be completely ruled out that this is due to depression differences given the
ambiguity of interpretation of somatic symptoms with medical illnesses.
Turning to a methodological critique of the study, one limitation is the use of
depression symptom checklists rather than using psychiatric interviews and DSM-IV
diagnoses. This would have allowed for distinctions between depression symptoms, and
produced concrete diagnoses of Major Depressive Disorder, Dysthymia, and other
depressive mood disorders. Individual interviews with each patient would also have
allowed us to examine previous psychiatric history. Inability to compare current results
to past psychiatric histories is a limitation of this study.
A further limitation to using symptom checklists is that apathy and depression
have overlapping symptoms, and as such, the scales overlap in content. For example, the
BDI includes item content that overlaps with apathy (e.g., Item 4: "I don't enjoy things
the way I used to," Item 12: "I am less interested in other people than I used to be").
Thus, it is possible that a particular symptom endorsement on the BDI might better
represent apathy, but is actually being counted in the depression total score. Clearly, this
is a disadvantage to using total scores for BDI and AES instead of examining individual
Directions for Future Research
One way to address the limitation of apathy and depression total scores is to use a
different methodological approach. This would be to use item factor analysis to
investigate whether apathy and depression factors can be identified. Items that are
thought to relate more to depression or more to apathy would be delineated a priori, and
data would be examined whether responses fall into proposed groups. Based on the
requirements of factor analysis, this approach will require several hundred subjects.
Efforts are currently underway to continue subject recruitment in order to meet this goal.
Further, it should be noted that the present study was based on an outpatient
population presenting to a Movement Disorders Specialty clinic. It is of interest for
future studies to examine the prevalence based on this sample to those of epidemiological
samples using self-report apathy and depression scales. In this way, differences between
types of samples and levels of apathy/depression can be examined.
Another potentially important future line of research is to examine whether there
is a relationship between reduced physiological reactions to emotion in PD (e.g., palm
sweating and startle eyeblink response) and level of apathy. Recent research from our
laboratory has shown that Parkinson's patients have a blunted physiological reaction to
emotional pictures. It is of interest to examine whether the more apathetic patients are
the ones that also show the most physiological blunting. Related, it may be of interest
examine how apathy changes in response to dopaminergic therapy. It is unknown how
"on" "off" fluctuations relate to the experience of apathy.
To conclude, findings from the present study provide support for the hypothesis
that apathy and depression may be similar, but separable experiences of mood states.
Further, apathy in the absence of depression appears to play a key role in the profile of
patients presenting with Parkinson's disease. This suggests that clinicians would be well
advised to screen for both apathy and depression during clinical care. As the presentation
of apathy is delved into further, differential pathology, clinical correlates, and effective
treatments may be discovered.
LIST OF REFERENCES
Aarsland, D., Larsen, J.P., Lim, N.G., Janvin, C., Karlsen, K., Tandberg, E., et al. (1999).
Range of neuropsychiatric disturbances in patients with Parkinson's disease.
Journal ofNeurology, Neurosurgery, and Psychiatry, 67, 492-496.
Aarsland, D., Litvan, I., & Larsen, J.P. (2001). Neuropsychiatric symptoms of patients
with Progressive Supranuclear Palsy and Parkinson's disease. Journal of
Neuropsychiatry and Clinical Neuroscience, 13(1), 42-49.
Beck, A.T. (1978). Beck Depression Inventory. San Antonio, TX: The Psychological
Beck, A.T., & Steer, R.A. (1988). Beck Hopelessness Scale manual. San Antonio, TX:
The Psychological Corporation.
Beck, A.T., Steer, R.A., & Garbin, M.G. (1988). Psychometric properties of the Beck
Depression Inventory: Twenty-five years of evaluation. Clinical Psychology
Review, 8, 77-100.
Beck, A.T., Weissman, A., Lester, D., & Trexler, L. (1974). The measurement of
pesimism: The Hopelessness Scale. Journal of Consulting and Clinical Psychology,
Bodurka-Bevers, D., Basen-Engquist, K., Carmack, C.L., Fitzgerald, M.A., Wolf, J.K.,
Moor C. et al. (2000). Depression, anxiety, and quality of life in patients with
epithelial overian cancer. Gynecological oncology, 78(3), 302-308.
Brown, R. G. & Pluck, G. (2000). Negative symptoms: the 'pathology' of motivation and
goal directed behaviour. Trends in Neuroscience, 23(9), 412-417.
Cebellos-Baumann, A.O., Passingham, R.E., Warner, T., Playford, E.D., Marsden, C.D.,
& Brooks, D.J. (1995). Overactive prefrontal and underactive motor cortical areas
in idiopathic dystonia. Annals ofNeurology, 37, 363-372.
Chwastiak, L., Ehde, D.M., Gibbons, L.E., Sullivan, M., Bowen, J.D. & Kraft, G.H.
(2002). Depressive symptoms and severity of illness in multiple sclerosis:
epidemiological study of a large community sample. American Journal of
Psychiatry, 159(11), 1862-1868.
Cohen, L.G., & Hallett, M. (1988). Hand cramps: clinical features and electromyographic
patterns in focal dystonia. Neurology, 38, 1005-1012.
Comella, C.L., Leurgans, S., Wuu, J., Stebbins, G.T., Chmura, T. & Dystonia Study
Group. (2002). Rating scales for Dystonia: A multicenter assessment. Movement
Disorders, 18(3), 303-312.
Cummings, J.L. (1993). Frontal-subcortical circuits and human behavior. Arch Neurol,
Damasio, A.R., & Van Hoesen, G.W. (1983). Emotional disturbances associated with
focal lesions of the limbic frontal lobe. In K.M. Heilman & P. Satz (Eds.),
Neuropsychology ofHuman Emotion (pp. 85-110). New York: Guilford.
Davidson, H., Feldman, P.H., & Crawford, S. (1994). Measuring depressive symptoms in
the frail elderly. J. Gerontol. Psychol. Sci. 49, P159-P164.
Fahn, S., Elton R. L., & Members of the UPDRS Development Committee (1987).
Unified Parkinson's Disease Rating Scale. In S. Fahn, C.D. Marsden, D.B. Calne,
& A. Lieberman (Eds.), Recent Developments in Parkinsons Disease: Vol. 2.
(pp.153-163). New Jersey: Macmillan Health Care Information.
Fahn, S., Bressman, S.B., & Marsden, C.D. (1998). Classification of Dystonia. In S.Fahn,
C.D. Marsden, & M. DeLong (Eds.), Dystonia 3: Advances in Neurology: Vol. 78.
(pp.1-10). Philadelphia, PA: Lippincott-Raven Publishers.
Farmer, S.F., Sheean, G.L., & Mayston, M.J. (1998). Abnormal motor unit
synchronization of antagonist muscles underlies pathological co-contraction in
upper limb dystonia. Brain, 121, 801-814.
Fearnley, J.M., & Lees, A.K. (1991). Ageing and Parkinson's disease: substantial nigra
regional selectivity. Brain, 114, 283-301.
Hallett, M. (1998). Physiology of Dystonia. In S. Fahn, C.D. Marsden, & M. R. DeLong
(Eds.), Dystonia 3: Advances in Neurology: Vol. 78 (pp. 11-18). Philadelphia, PA:
Halliday, G.M., McRitchie, D.A., Cartwright, H., Pamphlett, R., Hely, M.A., & Morris,
J.G. (1996). Midbrain neuropathology in idiopathic Parkinson's disease and diffuse
Lewy body disease. Journal of Clinical Neuroscience, 3, 52-60.
Hoehn, M., & Yahr, M. (1967). Parkinsonism: Onset, progression, and mortality.
Neurology, 42, 1142-1146.
Hughlings-Jackson, J. (1931). Selected Writings. Philadelphia, PA: Hodder & Stoughton.
Isella, V., Melzi, P., Grimaldi, M., Iurlaro, S., Piolti, R., Ferrarese, C. et al. (2002).
Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's
disease. Movement Disorders, 17(2), 366-371.
Jankovic, J. (1992). Pathophysiology and clinical assessment of motor symptoms in
Parkinson's disease. In Koller (Ed.), Handbook ofParkinson 's Disease, 2nd edition
(pp. 129-151). New York: Marcel Dekker.
Jankovic, J. & Fahn, S. (2002).Dystonic disorders. In J.J. Jankovic, & Tolosa, E. (Eds.),
Parkinson 's disease and Movement disorders, 4 edition (pp.331-357).
Philadelphia, PA: Lippincott Williams & Wilkins.
Levin, B.E., Llabre, M.M., & Weiner, W.J. (1988). Parkinson's disease and depression:
Psychometric properties of the Beck Depression Inventory. Journal ofNeurology,
Neurosurgery, andPsychiatry, 51(11), 1401-1404.
Levy, M.L., Cummings, J.L., Fairbanks, L.A., Masterman, D., Miller, B.L., Craig, A. H.
et al. (1998). Apathy is not depression. Journal ofNeuropsychiatry and Clinical
Neuroscience, 10, 314-319.
Lezak, M.D., Howieson, D.B., & Loring, D.W. (2004). Tests of personal adjustment and
emotional functioning. In Neuropsychological Assessment, 4 edition. (pp 738-
754). New York, New York: Oxford University Press.
Lieberman, A. (1995). Parkinson's disease. In J.P. Mohr & J. C. Gautier (Eds.), Guide to
clinical neurology (pp. 865-870). New York: Churchill Livingstone.
Lyketsos, C.G., Hoover, D.R., Guccione, M., Senterfitt, W., Dew, M.A., Wesch, J., et al.
(1993). Depression symptoms as predictors of medical outcomes in HIV infection.
Multicenter AIDS cohort study. Journal of the Americal Medical Association,
Marin, R.S., Biedrzycki, R.C., & Firinciogullari, S. (1991). Reliability and validity of the
Apathy Evaluation Scale. Psychiatry Research, 38, 143-162.
Marin, R.S. (1991). Apathy: a neuropsychiatric syndrome. Journal ofNeuropsychiatry
and Clinical Neuroscience, 3, 243-254.
Martin, W.E., Loewenson, R.B., Resch, J.A., & Baker, A.B. (1983). Parkinson's disease:
Clinical analysis of 100 patients. Neurology, 23, 783-790.
Masterman, D.L. & Cummings, J.L. (1997). Frontal-subcortical circuits: The anatomic
basis of executive, social, and motivated behaviors. Journal of
Psychopharmacology, 11, 107-114.
Mayeau, R., Marder, K., & Cote, L.J. (1995). The frequency of idiopathic Parkinson's
disease by age, ethnic group, and sex in northern Manhattan, 1988-1993. Am J
Epidemiol, 142, 820-827.
McDonald, W.M., Richard, I.H., & DeLong, M.R. (2003). Prevalence, etiology, and
treatment of depression in Parkinson's disease. Biological Psychiatry, 54, 363-375.
Neary, D., Snowden, J.S., Gustafson, L., Passant, U., Stuss, D., Black, S. et al. (1998).
Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria.
Neurology, 51, 1546-1554.
Nutt, J.G., Hammerstad, J.P., & Gancher, S.T. (1992). Parkinson's disease. 100 maxims.
St. Louis, MO: Mosby Year Book.
Okun, M.S., & Vitek, J.L. (1997). Parkinson's disease: pathophysiology and medical
therapy. In Wilkins, R.H. & Rengachary, S.S. (Eds.), Neurosurgery. (pp. 20-45).
New York: McGraw-Hill.
Peretz & Cummings. (1988).Subcortical dementia. In U. Holden (Ed.), Neuropsychology
and aging. New York: University Press.
Peto, V., Jenkinson, C., Fitzpatrick, R., & Greenhall, R. (1995). The development and
validation of a short measure of functioning and well being for individuals with
Parkinson's disease. Quality ofLife Research, 4(3), 241-248.
Pluck, G.C., & Brown, R. G. (2002). Apathy in Parkinson's disease. Journal of
Neurology, Neurosurgery, and Psychiatry, 73(6), 636-637.
Poewe, W. & Seppi, K. (2001). Treatment options for depression and psychosis in
Parkinson's disease. Journal ofNeurology, 248 (S3), 12-21.
Radloff, L.S. (1977). The CES-D scale: A self-report depression scale for research in the
general population. Applied Psychological Measurement, 1, 385-401.
Schein, R., & Koenig, H. (1997). The Center for Epidemiological Studies-Depression
(CES-D) Scale: assessment of depression in the medically ill elderly. International
Journal of Geriatric Psychology, 12, 436-446.
Schulberg, H.C., Saul, M., McClelland, M., Ganguli, M., Christy, W., & Frank, R.
(1985). Assessing depression in primary medical and psychiatric practices. Arch
Gen. Psychiat,. 42, 1164-1170.
Schwab, R.S.. & England, A.C. (1969). Projection technique for evaluating surgery in
Parkinson's disease. In F.J. Gillingham, & I.M.L. Donaldson (Eds). Third
symposium on surgery in Parkinson's disease (pp. 152-157). Edinburg:
Slaughter, J.R., Slaughter, K.A., Nichols, D., Holmes, S.E., & Martens, M.P. (2001).
Prevalence, clinical manifestations, etiology, and treatment of depression in
Parkinson's disease. Journal ofNeuropsychiatry and Clinical Neurosciences, 13,
Starkstein, S.E., Mayberg, H.S., Preziosi, T.J., Andrezejewski, P., Leiguarda, R., &
Robinson, R. G. (1992). Reliability, validity, and clinical correlates of apathy in
Parkinson's disease. Journal ofNeuropsychiatry, 4 (2), 134-139.
Starkstein, S.E., Petracca, G., Chemerinski, E., & Kremer, J. (2001). Syndromic validity
of apathy in Alzheimer's disease. Americal Journal ofPsychiatry, 158, 872-877.
Tanner, C.M., Goldman, S.M., & Ross, G.W. (2002). Etiology of Parkinson's disease. In
Jankovic, J.J., & Tolosa, E. Parkinson's disease and movement disorders, 4th
edition. (pp. 90-103). Philadelphia, PA: Lippincott Williams & Wilkins.
Tranel, D. (1992). Functional Neuroanatomy: neuropsychological correlates of cortical
and subcortical damage. In S.C. Yudofsky & R. E. Hales (Eds.), The American
Psychiatric Press textbook of neuropsychiatry (pp. 58-88). Washington, D.C.:
American Psychiatric Press.
Tyler, K.L. (1992). A history of Parkinson's disease. In W. Koller (Ed.), Handbook of
Parkinson's disease (pp. 1-34). New York: Marcel Dekker, Inc.
Ware, J.E., & Shelboume, C.D. (1992). The MOS 36 Item Short Form Health Survey
(SF 36). Med Care, 30, 473-483.
Williamson, G.M. & Schultz, R. (1992). Physical illness and symptoms of depression
among elderly outpatients. Psychol. Aging 7, 343-351.
Zgaljardic, D.J., Borod, J.C., Foldi, N.S., & Mattis, P. (2003). A review of the cognitive
and behavioral sequelae of Parkinson's disease: Relationship to frontostriatal
circuitry. Cognitive and Behavioral Neurology, 16(4), 193-210.
Lindsey Kirsch was born in Atlanta, GA, and received her B.S. in neuroscience
from Furman University. She obtained research experience at the Centers for Disease
Control & Prevention, Atlanta, GA. She is currently pursuing her doctorate in clinical
psychology, with a specialty in neuropsychology, at the University of Florida. She
currently co-directs a NIH clinical trial involving Parkinson's disease and deep brain
stimulation's effects of mood, motor, and cognitive symptoms. Current research and
clinical interests include cognition in Parkinson's disease, Alzheimer's disease, and Mild
Cognitive Impairment. Current clinical interests also include treatment of psychogenic