Abstract
Background
Apathy is a prevalent, multidimensional neuropsychiatric condition in Parkinson's disease (PD). Several authors have proposed apathy subtypes in PD, but no study has examined the classification of PD patients into distinct apathy subtypes, nor has any study examined the clinical utility of doing so.
Objectives
The current study used a data‐driven approach to explore the existence and associated clinical characteristics of apathy subtypes in PD.
Method
The Apathy Scale (AS) was administered to 157 non‐demented individuals with PD. Participants were classified into apathy subgroups through cluster analysis. Differences among apathy subtypes on external clinical indicators were explored across apathy subgroups.
Results
Individuals with PD were classified into three subgroups: a Non‐Apathetic group with low levels of apathy symptoms, a Low Interest/Energy group, characterized by elevated symptoms of low interest/energy and minimal low initiation/emotional indifference symptoms, and a Low Initiation group, characterized by an absence of low interest/energy symptoms and elevated levels of low initiation/emotional indifference symptoms. Both Low Interest/Energy and Low Initiation groups exhibited worse depression, fatigue, anxiety, health‐related quality of life, and caregiver burden than the Non‐Apathetic subgroup. The Low Initiation group exhibited worse overall cognition, emotional well‐being, state anxiety, communicative ability, and functional ability than the Low Interest/Energy group. Importantly, disease‐related characteristics did not differ across apathy symptom subgroups.
Conclusions
Non‐demented PD patients can be separated into distinct apathy symptom subgroups, which are differentially associated with important clinical variables. Apathy subgroup membership may reflect disruption to different neural systems independent of disease progression.
Keywords: apathy subgroups; clinical correlates; cluster analysis; Parkinson's disease
Apathy is present in an estimated 40% of Parkinson's disease (PD) patients 1 and is associated with higher levels of anxiety, 2 lower levels of health‐related quality of life, 3 increased risk of subsequent development of dementia, 4 , 5 and greater caregiver of burden. 2 , 6 , 7 , 8 , 9 Marin originally conceptualized apathy as “loss of motivation,” which is clinically expressed in three domains: (a) goal‐directed behavior, (b) goal‐directed cognition, and (c) the emotional concomitants of goal‐directed behavior. 10 A multidimensional conceptualization was retained in subsequent diagnostic criteria for apathy. 11 , 12 More recently, Levy and Dubois 13 described distinct cognitive and neurobiological mechanisms underlying these three dimensions with reduced goal‐directed behavior described as difficulty activating thoughts or motor programs owing to lesions in the basal ganglia; reduced goal‐directed cognition attributed to deficits in the ability to construct action plans resulting from disruption to the dorsolateral prefrontal cortex; and reduced goal‐directed emotion reflecting an inability to associate affective signals with ongoing behavior as a result of orbital‐medial prefrontal cortex disruption. Factor analyses of commonly used measures of apathy in PD have consistently yielded multiple latent factors underlying these measures, providing further empirical support for a multidimensional conceptualization of apathy in PD. 14 , 15 , 16
Although hypothesized, to our knowledge, no study to date has demonstrated whether PD patients themselves present with distinct profiles of apathy symptoms, which would enable them to be classified into separable apathy subtypes. 17 As noted above, past studies have focused only on whether items on apathy scales are best explained by one or more multiple latent variables. Therefore, we sought empirically to evaluate the existence of PD apathy subtypes, the apathy symptoms that characterize them, and their clinical correlates. In previous work, we have shown that apathy symptoms as measured by the Starkstein Apathy Scale (AS) 18 can be explained by cognitive‐behavioral and emotional apathy latent factors using exploratory factor analysis. 16 In the current study, we aim to extend this work by using a data‐driven approach (ie cluster analysis) to demonstrate that PD patients themselves can be reliably classified into apathy subtypes based on their profile of apathy symptoms. Based on our previous work, 16 we hypothesized that PD patients would be classified into three distinct apathy symptom subgroups. Specifically, we predicted that patients would be broadly classified as non‐apathetic or apathetic. Within this latter classification, we predicted the emergence of two apathy subgroups characterized by interest/energy versus initiation/emotional indifference symptoms. An additional aim of this study was to explore clinical signs and symptoms previously demonstrated to correlate with global apathy across apathy subtypes. We predicted that the PD patients classified into one of the two apathy symptom subgroups would be associated with a different profile of clinical signs and symptoms, further supporting the separability of these subgroups.
Methods
Participants
Participants consisted of 170 individuals who met UK Brain Bank criteria 19 for PD and were diagnosed by a board‐certified neurologist. Participants were recruited from ongoing studies of Parkinson's disease at the San Diego VA Health Care System and the University of California, San Diego. Participants were excluded if they had a history of neurologic condition other than PD, major depression prior to PD diagnosis, severe mental illness, substance abuse, or neurosurgery, or if they met criteria for dementia. Dementia was diagnosed in accordance with the Diagnostic and Statistical Manual of Mental Disorders–IV criteria defined by Emre and colleagues 20 and by a cutoff score of ≤123 21 on the Mattis Dementia Rating Scale. 22 Eight cases were excluded based on these criteria. An additional five cases were excluded for not being administered the AS. After exclusion, the final sample size was 157 PD patients. All participants provided verbal and written informed consent and the Veterans Affairs Institutional Review Board approved the study. Table 1 presents demographic, medication, Finger Tapping Test performance, 23 and modified Hoehn and Yahr 24 staging information on the overall sample.
TABLE 1.
Demographic characteristics of the overall sample
| Age | 67.64 (8.27) |
| Education (Years) | 16.54 (2.36) |
| Disease duration (Months) | 66.14 (62.62) |
| Levodopa equivalent dosage | 747.83 (756.76) |
| Finger tapping – dominant | 39.67 (11.19) |
| Finger tapping – non‐dominant | 37.14 (9.27) |
| % Caucasian | 93.0% |
| % On dopamine agonist | 60.7% |
| Hoehn & Yahr stage | |
| 0.0 | 1.3% |
| 1.0 | 24.3% |
| 1.5 | 1.3% |
| 2.0 | 50.7% |
| 2.5 | 7.9% |
| 3.0 | 11.2% |
| 3.5 | 0.7% |
| 4.0 | 1.8% |
| 5.0 | 0.7% |
Measures
The AS was used to evaluate apathy symptom profiles. Following our previous factor analysis of the AS, 16 items 3, 13, and 14 were removed from this scale due to the poor psychometric properties of these items. Demographic and disease‐related characteristics, measures of cognition, mood symptoms, functional disability, health‐related quality of life, and caregiver burden were examined as external indicators among apathy symptom subgroups. Disease‐related characteristics included fine motor assessment (FTT), 23 disease stage (H&Y), 24 disease duration (months), and medication usage (levodopa equivalent dose [LED], 25 use of dopamine agonist). Cognition was assessed with the Mattis Dementia Rating Scale. 22 Mood and fatigue symptoms were measured with the Geriatric Depression Scale, 26 the State–Trait Anxiety Scale, 27 and the Modified Fatigue Impact Scale. 28 Functional disability was measured using a modified version of the Lawton and Brody Activities of Daily Living Scale 29 and health‐related quality of life by the Parkinson's Disease Questionnaire–39. 30 Finally, caregiver burden was evaluated with the Caregiver Burden Scale. 31
Statistical Analyses
Data analysis involved three steps. In the first step, principal component analysis with varimax rotation and Kaiser normalization was conducted on the AS. The number of components extracted was based on consideration of multiple criteria, namely, scree plot visual analysis, Kaiser‐Guttman rule (eigenvalues>1), stability of components (ie sufficient number of indicators per component), and theoretical interpretability of resulting components.
Next, component scores of this principal component analysis were submitted to cluster analysis. Cluster analysis is a statistical method to classify individuals with similar characteristics into distinct groups. In the current study, cluster analysis used Ward's method and squared Euclidean distance to identify apathy symptom subgroups. Multiple cluster solutions were initially evaluated, and several criteria were applied to determine the optimal clustering solution. First, we inspected the dendogram cluster plot to determine the point at which further clustering was trivial. Next, we evaluated agreement between cluster solutions derived from a hierarchical agglomerative method (ie Ward's method) and an iterative partitioning method (K‐means clustering). Agreement between solutions was evaluated using Cohen's Kappa. Finally, to quantitatively confirm the significance of the cluster solution, discriminant function analysis was conducted with component scores entered as the independent variables and the cluster solution as the grouping variable. This analysis enabled us to determine the extent to which cluster groups differed by severity of symptoms across apathy dimensions. We also examined the stability of cluster solutions by evaluating the degree of agreement between discriminant function predicted group membership and observed cluster group membership. Agreement was evaluated within the sample data and in a cross‐validation sample created through a leave‐one‐out procedure. A high level of agreement between predicted and observed cluster group assignment indicated strong cluster stability. Differences in the percentage of cases classified to each cluster group were then evaluated with Chi‐square tests.
In the third step, we explored differences among apathy symptom subgroups on a series of external indicators. External indicators were selected on the basis of previous research demonstrating their association with apathy in PD and consisted of measures of depression, fatigue, anxiety, cognition, motor ability, functional ability, health‐related quality of life, and caregiver burden. We also evaluated differences in demographic characteristics (age, education, gender, race/ethnicity), H&Y Stage, disease duration, and medication (LED, use of dopamine agonist) across groups. One‐way ANOVAs were conducted across apathy symptom subgroups on continuous external indicators and Chi square tests for categorical external indicators. Significant omnibus tests were followed‐up with Least Significant Difference post‐hoc tests.
Results
Dimensions of Apathy Symptoms
Principal components analysis revealed a two‐component structure to the AS. These components reflected the interest/energy and initiation/emotional indifference dimensions of apathy. We named these components Interest/Energy and Initiation, respectively. This principal components analysis is largely consistent with previous principal components analysis and factor analytic studies of this measure in PD. 14 , 16 Together, these components accounted for 46.03% of the variance in the scale (see Supplementary Table S1).
Apathy Symptom Subgroups
Visual inspection of the cluster solution dendogram suggested a two or three cluster solution. Comparisons between hierarchical agglomerative (ie Ward's) and iterative partitioning (ie K‐means clustering) cluster methods revealed that the three cluster solution (κ = .70, P < .001) demonstrated better agreement than the two cluster solution (κ = .42, P < .001). Therefore, the three cluster solution was selected.
Inspection of the Z score means and standard deviations on the AS principal component scores of the three cluster groups revealed that the three clusters reflected a Non‐Apathetic group (low interest/energy/and low initiation symptoms, n = 48), a Low Interest/Energy group (high interest/energy and low initiation symptoms, n = 76), and a Low Initiation group (low interest/energy and high initiation symptoms, n = 33) (see Figure 1 for a plot of Z score mean and standard error AS component scores for all three cluster groups). The percentage of PD patients assigned to each cluster group significantly differed, χ2 (2, N = 157) = 18.20, P < .001. There were more PD patients classified into the Low Interest/Energy group than the Low Initiation group, χ2 (1, N = 109) = 16.96, P < .001, or the Non‐apathetic group, χ2 (1, N = 124) = 6.32, P = .01. However, cluster group size did not differ between the Low Initiation and Non‐apathetic groups, χ2 (1, N = 81) = 2.78, P = .10.
FIGURE 1.
Z score mean and standard error plot of non‐apathetic (n = 48), low interest/energy (n = 76), and low initiation (n = 33) groups
Discriminant function analysis provided further support for the three‐cluster solution. Two discriminant functions were computed, with a combined χ 2 (4, N = 157) of 267.60, P < .001, ηp 2 = .412. This indicates that cluster groups were clearly separated on the AS component scores. After removal of the first discriminant function, cluster groups and component scores were still associated, χ 2 (1, N = 157) = 86.34, P < .001, ηp 2 = .154. Inspection of the centroid plot revealed that the first discriminant function distinguished the Low Interest/Energy group from the Non‐Apathetic and Low Initiation groups, while the second function maximally separated the Non‐Apathetic group from the Low Interest/Energy and Low Initiation groups (See Figure S1). The three‐cluster solution also resulted in a high level of classification accuracy. Specifically, 93.6% of cases were correctly classified in the original sample and 93.0% were correctly classified in a jackknifed cross‐validation sample. Classification accuracy was ≥87% in each subgroup across the original and cross‐validated samples as well. Overall, this indicates good stability of the three‐cluster solution.
External Indicator Differences among Apathy Symptom Subgroups
Differences on demographic variables and external indicators were explored among the three apathy subgroups (See Table 2). A significant difference in age was found across groups, with the Low Initiation group exhibiting an older age than the Low Interest/Energy group. No other demographic factor or disease‐related characteristic (ie disease duration or stage, finger tapping speed, LED) differed across groups. In order to adjust for differences in age across groups, age was entered as a covariate in all subsequent analyses.
TABLE 2.
Demographics and characteristics of non‐apathetic, low interest/energy, and low initiation groups
| Non‐apathetic (n = 48) | Low interest/Energy (n = 76) | Low initiation (n = 33) | Omnibus test | Post‐Hoc | |
|---|---|---|---|---|---|
| Demographics | |||||
| Age | 67.94 (7.31) | 66.07 (7.89) | 70.82 (9.60) | F(2,154) = 4.00* | N = I, IE = N, IE < I |
| Education (Years) | 16.89 (2.26) | 16.51 (2.44) | 16.12 (2.33) | F(2,154) = 1.12 | |
| Disease duration (Months) | 75.34 (70.07) | 59.83 (56.78) | 67.28 (59.34) | F(2,154) = 0.74 | |
| LED (mg) | F(2,151) = 1.83 | ||||
| % on Dopamine agonist | 68.1% | 59.2% | 51.6% | χ 2(2, N = 154) = 2.21 | |
| H & Y stage (%) | χ 2(16,N = 154) = 19.37 | ||||
| 0.0 | 0.00 | 1.3 | 3.1 | ||
| 1.0 | 31.9 | 25.3 | 12.5 | ||
| 1.5 | 2.1 | 1.3 | 0.0 | ||
| 2.0 | 51.1 | 49.3 | 53.1 | ||
| 2.5 | 6.4 | 4.0 | 18.6 | ||
| 3.0 | 6.4 | 13.3 | 12.5 | ||
| 3.5 | 0.0 | 1.3 | 0.0 | ||
| 4.0 | 0.0 | 4.0 | 0.0 | ||
| 5.0 | 2.1 | 0.00 | 0.0 | ||
| % Male | 70.8% | 64.6% | 72.7% | χ 2(2, N = 157) = 0.95 | |
| % Non‐Hispanic white | 93.8% | 92.1% | 93.9% | χ 2(2, N = 157) = 0.18 | |
| Mood symptoms | |||||
| GDS | 4.25 (4.89) | 6.92 (5.07) | 7.70 (5.25) | F(2,154) = 6.68** | N < IE = I |
| STAI ‐ State Anxiety | 31.37 (8.65) | 35.29 (10.03) | 38.44 (10.49) | F(2,154) = 6.46** | N < IE < I |
| STAI ‐ Trait Anxiety | 30.57 (8.62) | 36.04 (9.08) | 37.91 (9.40) | F(2,154) = 9.38** | N < IE = I |
| Fatigue | |||||
| MFIS | 23.74 (15.47) | 35.78 (17.09) | 39.66 (15.26) | F(2,154) = 12.09*** | N < IE = I |
| Cognition | |||||
| MDRS | 138.85 (3.52) | 139.38 (2.98) | 135.91 (4.99) | F(2, 154) = 7.93*** | N = IE > I |
| Motor symptoms | |||||
| FTT‐dominant | 40.83 (13.51) | 39.61 (11.91) | 39.19 (15.50) | F(2, 152) = 0.21 | |
| FTT‐Non‐Dominant | 39.27 (13.40) | 41.09 (13.18) | 39.13 (12.96) | F(2, 151) = 0.25 | |
| Functional Disability | |||||
| IADLs | 14.77 (1.48) | 14.28 (2.12) | 13.17 (2.48) | F(2,134) = 4.50* | N = IE > I |
| Health‐related quality of life (PDQ‐39) | |||||
| Mobility | 9.63 (13.53) | 22.66 (19.51) | 28.03 (19.85) | F(2,153) = 12.19*** | N < IE = I |
| Activities of daily living | 13.03 (13.94) | 18.37 (13.56) | 26.14 (16.97) | F(2,153) = 8.35*** | N < IE < I |
| Emotional well‐being | 12.41 (13.30) | 17.60 (14.27) | 23.36 (14.39) | F(2,153) = 7.86** | N < IE < I |
| Stigma | 12.10 (18.49) | 13.32 (14.30) | 14.96 (18.88) | F(2,153) = 0.88 | |
| Social support | 5.67 (10.58) | 10.96 (14.92) | 13.64 (15.84) | F(2,153) = 3.98* | N < IE = I |
| Cognition | 19.15 (19.04) | 21.55 (14.73) | 28.22 (17.05) | F(2,153) = 3.46* | N = IE < I |
| Communication | 12.41 (18.78) | 20.29 (18.85) | 28.79 (25.09) | F(2,153) = 8.23*** | N < IE < I |
| Bodily discomfort | 20.21 (18.85) | 30.04 (22.98) | 31.57 (23.27) | F(2,153) = 3.71* | N < IE = I |
| Total | 19.55 (18.75) | 30.63 (18.00) | 38.88 (20.31) | F(2,153) = 12.23*** | N < IE < I |
| Caregiver burden | |||||
| Caregiver burden scale | 7.72 (5.48) | 13.84 (11.91) | 15.53 (11.62) | F(2,134) = 6.24** | N < IE = I |
Abbreviations: FTT, Finger Tapping Test; GDS, Geriatric Depression Scale; H&Y, Hoehn & Yahr; I, Low initiation group; IADLs, Lawton and Brody Instrumental Activities of Daily Living Scale; IE, Low interest/energy group; LED, Levodopa Equivalent Dosage; MDRS, Mattis Dementia Rating Scale; MFIS, Modified Fatigue Impact Scale; N, Non‐apathetic group; PDQ–39, Parkinson's Disease Questionnaire–39; STAI, State–Trait Anxiety Inventory.
P < .05.
P < .01.
P < .001.
Exploration of group differences on mood symptoms, cognitive, motor, and functional ability, health‐related quality of life, and caregiver burden revealed a number of differences across apathy symptom groups. Post‐hoc tests revealed that the Low Interest/Energy group differed from the Non‐Apathetic group on the Geriatric Depression Scale, Modified Fatigue Impact Scale, the State and Trait Anxiety Scale, the Caregiver Burden Scale, and the Mobility, Activities of Daily Living, Emotional Well‐Being, Social Support, Communication, and Bodily Discomfort subscales of the Parkinson's Disease Questionnaire–39, as well as the Total score on the Parkinson's Disease Questionnaire–39. Similarly, the Low Initiation group differed from the Non‐Apathetic group on all of these measures, as well as the Mattis Dementia Rating Scale, the Instrumental Activities of Daily Living Scale, and the Activities of Daily Living and Cognition subscales of the Parkinson's Disease Questionnaire–39.
Importantly, comparisons between Low Interest/Energy and Low Initiation subgroups also revealed differences. The Low Initiation group exhibited worse cognitive functioning (Mattis Dementia Rating Scale) and their informants reported worse functional ability on the Instrumental Activities of Daily Living scale. In addition, the Low Initiation group self‐reported worse state anxiety on the State–Trait Anxiety Scale and worse activities of daily living, cognitive functioning, emotional well‐being and communicative ability as well as worse overall health‐related quality of life on the Parkinson's Disease Questionnaire–39 than the Low Interest/Energy group.
Discussion
The current study used a data‐driven approach (ie cluster analysis) to demonstrate that non‐demented PD patients could be separated into more homogeneous subgroups based on their apathy symptom profiles. These groups reflected a Non‐Apathetic group (31% prevalence) with low levels of apathy symptoms, a Low Interest/Energy group (48% prevalence) characterized by high levels of apathy symptoms having to do with interest and energy, and low levels of apathy symptoms having to do with initiation and emotional indifference, and a Low Initiation group (21% prevalence) characterized by high levels of apathy symptoms having to do with initiation and emotional indifference and low levels of apathy symptoms associated with interest and energy. Notably, both apathetic subgroups exhibited high levels of apathy in only a single apathy dimension and we did not find a fourth subgroup defined by elevations in both apathy symptom dimensions. This suggests that apathy subgroups reflected distinct apathy profiles and did not simply differ in overall severity, breadth, or quantity of apathy symptoms.
Both the Low Interest/Energy and Low Initiation groups exhibited more severe clinical profiles than the Non‐apathetic group, with worse scores on measures of depression, fatigue, anxiety, health‐related quality of life, and caregiver burden. Importantly, the Low Initiation and Low Interest/Energy groups also differed on external indicators, with the Low Initiation group exhibiting worse subjective cognitive functioning and reporting worse functional ability, objective cognitive functioning, state anxiety, emotional well‐being and communicative abilities. However, while the Low Initiation group exhibited a worse clinical profile than the Low Interest/Energy group, Low Interest/Energy group membership was more prevalent.
These results are largely consistent with previous research on apathy in PD. Previous studies have also demonstrated that apathy in PD is associated with a worse clinical presentation, especially on measures of cognition, 1 depression, 1 functional ability, 1 caregiver burden, 1 fatigue, 32 , 33 anxiety, 2 and health‐related quality of life. 2 We expanded on these previous findings in several ways. Most importantly, we demonstrated that not only do apathy symptoms covary along multiple underlying dimensions, but more crucially, that PD patients themselves cluster into distinct subgroups defined by these apathy symptom profiles. This suggests that there are homogeneous and separable subtypes of apathy in PD. The distinction between apathy subtypes was further supported by differences in their clinical presentation. While the apathy symptom subgroups did not differ across most demographic (ie education, gender) and disease‐related characteristics (ie disease duration and stage, finger tapping speed, or LED), the Low Initiation group was characterized by worse cognitive functioning, communicative ability, emotional well‐being, state anxiety, and functional ability than the Low Interest/Energy group. Together, these findings suggest that the identified apathy subgroups reflect distinct clinical presentations and are not simply a reflection of greater disease progression. Notably, the Low Interest/Energy subgroup was characterized by both cognitive and behavioral features of apathy and the Low Initiation group by behavioral and emotional features. Among behavioral features, the Low Interest/Energy group tended to exhibit behavioral problems related more to behavioral maintenance whereas the Low Initiation group endorsed difficulties specific to behavioral initiation. These different behavioral features are believed to rely on partially distinct neuroanatomical circuits, with behavioral maintenance dependent on largely right‐hemisphere dominant dorsomedial and ventromedial prefrontal cortices, anterior insula, intraparietal sulcus, temporoparietal junction, cerebellar vermis, thalamus, putamen, and midbrain regions, 34 and behavioral initiation on the anterior cingulate gyrus, rostral medial prefrontal cortex and supplementary motor area. 35 , 36 Further, the cognitive dimension of apathy has been hypothesized to result from loss of dopaminergic projections emanating from the dorsolateral caudate and the emotional dimension of apathy from cell loss in the ventromedial caudate nucleus disrupting circuits connecting the nucleus accumbens to the medial and orbital prefrontal cortex. 37 Although speculative, the apathy symptom subgroups documented in this study may reflect regional differences in neuropathology.
These findings have important clinical implications for understanding apathy in PD. For one, the current approach of summing across all scale items when assessing apathy may not accurately capture the heterogeneity of apathy presentations in PD. Instead, apathy assessment should attempt to determine which apathy symptoms predominate in order to classify individuals into apathy subgroups. For another, the current findings suggest that high levels of emotional indifference symptoms may warrant extra scrutiny, as Low Initiation subgroup membership appears to be associated with a worse clinical presentation. Finally, treatments aimed at reducing apathy in PD may benefit from tailoring of interventions to the specific apathy profile of PD patients.
These findings should be understood in the context of this study's limitations. The current study used only a single measure to explore subgroups of apathy. Evaluation of the generalizability of these subtypes to alternative measures of apathy such as the Lille Apathy Rating Scale 38 will help validate these apathy subtypes. In addition, we did not include measures of underlying cognitive and neurobiological mechanisms contributing to subtypes of apathy. Thus, it remains to be determined whether the subgroups identified in the current study map on to the previously hypothesized neurocognitive mechanisms of cognitive, behavioral, and emotional dimensions of apathy. 13 , 17 Further, 26 participants in this sample exhibited elevated depression symptoms on the Geriatric Depression Scale, which may have confounded results. However, we re‐ran all analyses excluding these participants and results were nearly identical. Finally, the current study was cross‐sectional in nature and thus the longitudinal course of these apathy subgroups is unknown. Future research should explore the stability of these subgroups and the progression of clinical symptoms within subgroups over time.
Author Roles
1. Research project: A. Conception, B. Organization, C. Execution;
2. Statistical analysis: A. Design, B. Execution, C. Review and Critique;
3. Manuscript preparation: A. Writing the first draft, B. Review and Critique.
G.M.L.E.: 1A, 1B, 1C, 2A, 2B, 3A
F.V.L.: 1A, 1B, 1C, 2A, 2B, 3A
D.M.S.: 1C, 3B
E.P.T.: 1C, 3B
I.L.: 1C, 3B
S.L.: 1C, 3B
J.V.F.: 1A, 1B, 1C, 2A, 2C, 3B
Disclosures
Ethical Compliance Statement
We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The VASDHS ethics committee approved this retrospective study, and all participants provided written informed consent (IRB Protocol #: H130079).
Funding Sources and Conflicts of Interest
This project was funded by VA Merit Award grants to Dawn Schiehser (1I01RX001691‐01A1) and J. Vincent Filoteo (5I01CX000813–04). The authors report no conflicts of interest.
Financial Disclosures for Previous 12 Months
Drs. Dawn Schiehser and J. Vincent Filoteo are recipients of VA Merit Grants 1I01RX001691‐01A1 and 5I01CX000813–04, respectively. Francesca V. Lopez is funded by the NINDS T32 Interdisciplinary Training Program in Movement Disorders and Neurorestoration at the University of Florida (T32‐NS082168). The remaining authors report no sources of funding and no conflicts of interest.
Supporting information
Table S1. Principal components analysis with Varimax rotation of Starkstein's Apathy Scale
Figure S1. Mean cluster centroids plotted in discriminant function space
Acknowledgments
We thank members of the NeuroCognition and Movement Laboratory for their help in collecting and scoring data. We would like to thank all the participants for their contributions to this study.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1. Principal components analysis with Varimax rotation of Starkstein's Apathy Scale
Figure S1. Mean cluster centroids plotted in discriminant function space