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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., Competing Interests: 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., (© 2020 International Parkinson and Movement Disorder Society.)

Objective: Although medication management is a necessary daily activity for individuals with Huntington's disease (HD), medication management abilities and their relation to cognitive functioning have not been evaluated., Method: Twenty individuals with HD and 20 healthy adults (HA) completed the Medication Management Abilities Assessment (MMAA). Individuals with HD also completed a self-report medication management measure and neuropsychological tests assessing executive function, retrospective memory, and prospective memory., Results: Individuals with HD performed significantly poorer and made more undertaking errors on the MMAA as compared to HA. No group differences were found in overtaking errors. In the HD group, significant associations were found between undertaking errors and perceived medication management ability as well as between MMAA task performance and measures assessing prospective memory and executive functions., Conclusions: Medication management capacity was negatively affected in individuals with HD and may be associated with difficulty remembering to take medications in the future., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Apathy Scale (AS), a popular measure of apathy in Parkinson's disease (PD), has been somewhat limited for failing to characterize dimensions of apathy, such as those involving cognitive, behavioral, and emotional apathy symptoms. This study sought to determine whether factors consistent with these apathy dimensions in PD could be identified on the AS, examine the associations between these factors and disease-related characteristics, and compare PD patients and healthy control (HCs) on identified factors., Methods: Confirmatory (CFA) and exploratory factor analysis (EFA) were conducted on AS scores of 157 nondemented PD patients to identify AS factors. These factors were then correlated with important disease-related characteristics, and PD and HC participants were compared across these factors., Results: Previously proposed AS models failed to achieve an adequate fit in CFA. A subsequent EFA revealed two factors on the AS reflecting joint cognitive-behavioral aspects of apathy (Motivation-Interest-Energy) and emotional apathy symptoms (Indifference). Both factors were associated with anxiety, depression, health-related quality of life, and independent activities of daily living, with Indifference associated more with the latter. In addition, only the Indifference factor was associated with cognitive functioning. PD patients reported higher levels of symptoms than HCs on both factors, with the group difference slightly larger on the Motivation-Interest-Energy factor., Conclusion: The AS can be decomposed into two factors reflecting Motivation-Interest-Energy and Indifference symptoms. These factors are differentially associated with clinical variables, including cognition and independent activities of daily living, indicating the importance of evaluating apathy from a multidimensional perspective.

Background: Parkinson's disease (PD) and Huntington's disease (HD) are two neurodegenerative diseases affecting frontal-striatal function and memory ability. Studies using the original California Verbal Learning Test (CVLT) to examine recall and recognition abilities between these groups have produced mixed findings. Some found that individuals with HD demonstrate worse recall and recognition than those with PD, whereas others reported comparable performance., Objective: We utilized multiple indices of recall and recognition discriminability, provided by the second and third editions of the CVLT (CVLT-II and CVLT-3, respectively), that allow for a more thorough assessment of more nuanced aspects of verbal memory function., Methods: We examined differences between individuals with PD (n = 72) and those with HD (n = 77) on CVLT-II indices of recall discriminability (immediate, short delay free and cued, long delay free and cued) and recognition discriminability (total, source, semantic, and novel) using standardized scores while controlling for education and Dementia Rating Scale-2 scores., Results: The HD group performed significantly worse than the PD group on all measures of recall and recognition discriminability (ps < 0.05), and group differences were associated with large Cohen's d effect sizes., Conclusions: Our findings suggest that individuals with HD are more impaired than individuals with PD in more nuanced aspects of recall and recognition memory function. These CVLT indices yield more thorough assessments of recall and recognition memory function and have the potential to improve efforts to characterize and distinguish profiles of memory loss in different neurodegenerative populations, including PD and HD.

The Geriatric Depression Scale (GDS) is recommended for screening depression in individuals with Parkinson's disease (PD). Empirical evidence, however, is limited regarding its validity and factor structure in PD. Thus, the current study sought to evaluate the convergent and divergent validity of the GDS, as well as the structure and validity of the derived factors., Method: Nondemented individuals with PD (n = 158) completed the GDS-30, and items were subjected to a principle component analysis. Geriatric Depression Scale total and factor scores were correlated with depression items from the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRSd) and Hamilton Rating Scale for Depression (HAMDd), as well as with the Apathy Scale (AS), State-Trait Anxiety Inventory (STAI), Modified Fatigue Impact Scale (MFIS), Parkinson's disease Sleep Scale, and a Subjective Cognitive Function composite score., Results: The GDS total score was strongly correlated with divergent neuropsychiatric measures (AS, r = 0.57; STAI, r = 0.66; MFIS, r = 0.60), while only moderately correlated with convergent measures (MDS-UPDRSd, r = 0.36; HAMDd, r = 0.32; Ps < 0.05). Linear regression analyses revealed standardized measures of anxiety, apathy, and fatigue independently predicted the GDS total score, while depression items (MDS-UPDRSd and HAMDd) failed to reach significance. Three independent factors were identified: Anxiety, Apathy, and Fatigue. These factors were significantly predicted by their respective convergent measures., Conclusions: Taken together, our findings suggest that the GDS and its subscales appear to primarily measure anxiety, apathy, and fatigue in PD, or alternatively, these symptom dimensions may be predominant in PD-depression. Future research with clinically diagnosed samples is needed to confirm these initial findings., (© 2018 John Wiley & Sons, Ltd.)

Evidence from small-scale studies indicates that impairments in postural stability are an early and disabling feature of Huntington's disease (HD) and may be a useful clinical endpoint for disease modifying trials. Larger studies are needed to confirm these preliminary findings and the suitability of postural stability outcomes as clinical endpoints. Static and dynamic postural stability were evaluated in 54 premanifest HD, 36 manifest HD and 45 healthy individuals using the Sensory Organization Test (SOT) and Limits of Stability (LOS) test. Manifest HD displayed significantly lower scores on all SOT conditions and on the SOT composite score and had more falls than healthy and premanifest HD (p < 0.05). Premanifest and manifest HD demonstrated significantly lower endpoint excursion (p < 0.001), maximum excursion (p ≤ 0.001), and directional control (p ≤ 0.004) values than healthy individuals on the LOS test. Deficits in LOS were found to manifest on the left side of premanifest HD. Significant but low associations were observed between UHDRS-TMS, disease burden score, diagnostic confidence level, SOT conditions and SOT composite score. We confirm here that individuals with premanifest and manifest HD display significant impairments in static and dynamic postural stability. Dynamic posturography assessments should be considered as clinical endpoints for future disease modifying trials.

Background: Visual Hallucinations (VH) are a common symptom experienced by individuals with Parkinson's disease (PD); however, a validated measure of VH has yet to be established for this population. The North-East Visual Hallucinations Interview (NEVHI), a promising VH measure, has not been well validated in PD. The aim of this study was to evaluate the convergent and discriminant validity of the NEVHI as well as the proportional identification and characteristics of VH in PD., Methods: One hundred seventeen individuals with PD completed the NEVHI as well as evaluations of psychological, cognitive, motor, and visual functioning as measures of convergent and divergent validity. The hallucination items from the Neuropsychiatric Inventory (NPI) and the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Scale (MDS-UPDRS) were used to assess convergent validity., Results: The NEVHI identified 20.5% of PD patients with VH, which consisted of all individuals detected by the MDS-UPDRS and NPI and nine additional individuals not detected by the other measures. The NEVHI was strongly correlated with the MDS-UPDRS hallucinations item, and weakly correlated with the NPI VH item. Weak to non-significant correlations were found between the NEVHI and measures of psychological, cognitive, motor, visual, and demographic characteristics., Discussion: The NEVHI identified a greater number of individuals with VH than either the MDS-UPDRS or NPI. Results demonstrated good convergent validity between the NEVHI and a clinician-administered-to-patient-report measure of VH and excellent divergent validity, supporting the NEVHI as a valid and preferable measure for assessing the presence of VH in PD., Competing Interests: Disclosures The authors report no conflicts of interest.

Objectives: To examine the relationship between anxiety, depression, apathy, and cognitive decline in Parkinson disease (PD)., Design: Longitudinal study design to assess whether specific neuropsychiatric, demographic, and clinical features predict future cognitive decline., Setting: Veterans Affairs San Diego Medical Center and the University of California, San Diego., Participants: PD patients (N = 68) and healthy controls (N = 30)., Measurements: Participants were administered self-report measures of depression (Geriatric Depression Scale), anxiety (State Trait Anxiety Scale), and apathy (Apathy Scale), and a comprehensive neuropsychological battery assessing attention, language, visuospatial function, verbal and visual learning and memory, and executive function. Participants were tested at baseline and after an approximate 2-year period., Results: Anxiety and depression at baseline were the strongest predictors of longitudinal decline on measures of verbal and visual learning, over and above other clinical and demographic characteristics. However, baseline neuropsychiatric symptoms did not significantly correlate with decline in other cognitive domains. No significant correlations were detected between neuropsychiatric symptoms and cognition in the healthy control group., Conclusions: These results suggest that anxiety and depression in PD may be risk factors for subsequent declines in learning. Emerging evidence suggests nonmotor symptoms are critical determinants of PD prognosis, and the results of this study highlight the importance of assessment of depression and anxiety early in PD., (Published by Elsevier Inc.)

One important limitation of prior studies examining functional decline in Huntington's disease (HD) has been the reliance on self-reported measures of ability. Since report-based methods can be biased by lack of insight, depression, and cognitive impairment, contrasting self-reported ability with measures that assess capacity may lead to a more comprehensive estimation of real-world functioning. The present study examined self-reported ability to perform instrumental activities of daily living (iADLs) and performance-based financial management capacity in 20 patients diagnosed with mild-moderate Huntington's disease (HD) and 20 demographically similar healthy adults. HD patients reported significantly greater declines in their ability to manage finances. On the capacity measure of financial management, HD patients performed significantly below healthy adults. Additionally, in the HD group there were no significant correlations between self-reported ability and capacity measures of financial management. HD patients endorsed declines in global iADL ability and exhibited deficits in functional capacity when performing a financial management task. Capacity measures may aid in assessing the extent to which HD patients accurately estimate real-world iADL performance, and the present findings suggest that such measures of capacity may be related to the cognitive, but not motor or affective, symptoms of HD.

Objective: To examine longitudinal changes in cognition in individuals with Parkinson's disease (PD) with and without a history of traumatic brain injury (TBI)., Methods: Twenty-five PD participants with a history of mild-moderate post-acute (>9 months) TBI and 25 demographically-matched PD controls without a history of TBI were administered measures of cognition (Mattis Dementia Rating Scale), mood, and motor functioning at baseline and at a two-year follow-up evaluation., Results: Individuals with PD and a history of TBI evidenced significantly greater decrements in overall cognition over the two year follow-up period compared to those without a history of TBI. Secondary subscale analyses suggest cognitive decrements may be mainly in the area of executive function, while a trend for group differences on the memory subscale was also observed. Groups did not differ on demographic, motor function, disease severity, cognitive, and mood profiles at baseline and evidenced comparable changes in mood and motor symptoms from baseline to follow-up., Conclusion: Findings suggest that a history of mild-moderate TBI is a risk factor for cognitive decline in individuals with PD., (Published by Elsevier Ltd.)

Memory for the temporal order of items or events in a sequence has been shown to be impaired in older adults and individuals with Parkinson's disease (PD). The present study examined the effects of high and low interference on temporal order memory in individuals diagnosed with PD (n=20) and demographically similar healthy older adults (n=20) utilizing a computerized task used in previously published studies. During the sample phase of each trial, a series of eight circles were randomly presented one at a time in eight different spatial locations. Participants were instructed to remember the sequence in which the circles appeared in the locations. During the choice phase, participants were presented with two circles in two different locations and were asked to indicate which circle appeared earliest in the sample phase sequence. The two circles were separated by one of four possible temporal separation lags (0, 2, 4, and 6), defined as the number of circles occurring in the sample phase sequence between the two choice phase circles. Shorter temporal lags (e.g., 0 and 2 lags) were hypothesized to result in higher interference compared to longer temporal lags (e.g., 4 and 6 lags). The results demonstrated that on trials involving high interference, no differences were found between the two groups. However, healthy older adults significantly outperformed individuals with PD (p<0.05) on trials involving low interference. Although differences were found between the PD and healthy older adult groups, both groups significantly improved on low interference trials compared to high interference trials (p<0.001). The findings indicate that temporal order memory improves in healthy older adults and individuals with PD when interference is reduced. However, individuals with PD demonstrated poorer temporal order memory even with less interference. Therefore, temporal order memory is differentially affected by interference in healthy older adults and individuals with PD. Given that both groups did improve with lessened interference, behavioral interventions that minimize temporal interference potentially could improve memory function in older adults and to a lesser extent in individuals with PD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Changes in episodic memory are common early in Parkinson's disease (PD) and may be a risk factor for future cognitive decline. Although medial temporal lobe (MTL) memory and frontostriatal (FS) executive systems are thought to play different roles in distinct components of episodic memory impairment in PD, no study has investigated whether different aspects of memory functioning are differentially associated with MTL and FS volumes in nondemented patients without mild cognitive impairment (PD-woMCI)., Objectives: The present study investigated MRI markers of different facets of memory functioning in 48 PD-woMCI patients and 42 controls., Methods: Regional volumes were measured in structures comprising the MTL and FS systems and then correlated with key indices of memory from the California Verbal Learning Test., Results: In PD-woMCI patients, memory was impaired only for verbal learning, which was not associated with executive, attention/working memory, or visuospatial functioning. Despite an absence of cortical atrophy, smaller right MTL volumes in patients were associated with poorer verbal learning, long delayed free recall, long delayed cued recall, and recognition memory hits and false positives. Smaller right pars triangularis (inferior frontal) volumes were also associated with poorer long delayed cued recall and recognition memory hits. These relationships were not found in controls., Conclusions: The findings indicate that MTL volumes are sensitive to subtle changes in almost all facets of memory in PD-woMCI, whereas FS volumes are sensitive only to memory performances in cued-testing formats.