J. Vincent Filoteo

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.

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.

To provide a select review of our applications of quantitative modeling to highlight the utility of such approaches to better understand the neuropsychological deficits associated with various neurologic and psychiatric diseases. We review our work examining category learning in various patient populations, including individuals with basal ganglia disorders (Huntington's Disease and Parkinson's disease), amnesia and Eating Disorders. Our review suggests that the use of quantitative models has enabled a better understanding of the learning deficits often observed in these conditions and has allowed us to form novel hypotheses about the neurobiological bases of their deficits. We feel that the use of neurobiologically inspired quantitative modeling holds great promise in neuropsychological assessment and that future clinical measures should incorporate the use of such models as part of their standard scoring. Appropriate studies need to be completed, however, to determine whether such modeling techniques adhere to the rigorous psychometric properties necessary for a valid and reliable application in a clinical setting. (PsycINFO Database Record

To examine set shifting in a group of women previously diagnosed with anorexia nervosa who are now weight-restored (AN-WR) and then apply a biologically based computational model (Competition between Verbal and Implicit Systems [COVIS]) to simulate the pattern of category learning and set shifting performances observed. Nineteen AN-WR women and 35 control women (CW) were administered an explicit category learning task that required rule acquisition and then a set shift following a rule change. COVIS was first fit to the behavioral results of the controls and then parameters of the model theoretically relevant to AN were altered to mimic the behavioral results. Relative to CW, the AN-WR group displayed steeper learning curves (i.e., hyper learning) before the rule shift, but greater difficulty in learning the new categories after the rule shift (i.e., a deficit in set shifting). Hyper learning and set shifting deficits in the AN-WR group were not associated and differentially correlated with clinical measures. Hyper learning in the AN-WR group was simulated by increasing the model parameter that represents sensitivity to negative feedback (δ parameter), whereas the deficit in set shifting was simulated by altering the parameters that represent changes in rule selection and flexibility (λ and γ parameters, respectively). These simulations suggest that multiple factors can impact category learning and set shifting in AN-WR individuals (e.g., alterations in sensitivity to negative feedback, rule selection deficits, and inflexibility) and provide an important starting point to further investigate this pervasive deficit in adult AN.

Previously we found that Parkinson's disease (PD) patients are impaired in procedural-based category learning when category membership is defined by a nonlinear relationship between stimulus dimensions, but these same patients are normal when the rule is defined by a linear relationship (Filoteo et al., 2005; Maddox & Filoteo, 2001). We suggested that PD patients' impairment was due to a deficit in recruiting ‘striatal units' to represent complex nonlinear rules. In the present study, we further examined the nature of PD patients' procedural-based deficit in two experiments designed to examine the impact of (1) the number of categories, and (2) category discontinuity on learning. Results indicated that PD patients were impaired only under discontinuous category conditions but were normal when the number of categories was increased from two to four. The lack of impairment in the four-category condition suggests normal integrity of striatal medium spiny cells involved in procedural-based category learning. In contrast, and consistent with our previous observation of a nonlinear deficit, the finding that PD patients were impaired in the discontinuous condition suggests that these patients are impaired when they have to associate perceptually distinct exemplars with the same category. Theoretically, this deficit might be related to dysfunctional communication among medium spiny neurons within the striatum, particularly given that these are cholinergic neurons and a cholinergic deficiency could underlie some of PD patients’ cognitive impairment.

The present study examined the impact of engaging frontal-mediated working memory processes on implicit and explicit category learning. Two stimulus dimensions were relevant to categorization, but in some conditions, a third, irrelevant dimension was also presented. Results indicated that in both implicit and explicit conditions, the inclusion of the irrelevant dimension impaired performance by increasing the reliance on suboptimal unidimensional strategies. With three-dimensional stimuli, a striking dissociation was observed between implicit and explicit category learning when participants performed a sequential working memory task. With explicit category learning, performance was impaired further, and there was an increased use of suboptimal unidimensional strategies. However, with implicit category learning, the performance impairment decreased, and there was an increased use of optimal strategies. These findings demonstrate the paradoxical situation in which learning can be improved under sequential-task conditions and have important implications for training, decision making, and understanding interactive memory systems.

Recent studies have shown that self-perceived health status (HS) in Parkinson's disease (PD) is associated with motor, cognitive, or mood symptoms, with the greatest association typically occurring with mood. The purpose of this study was to determine if these associations are present in nondepressed and nondemented individuals with PD by using sensitive neuropsychological measures and statistically derived factors from mood and motor scales. The best predictors of poor HS in PD participants (N = 32) without dementia or depression were mood symptoms, specific to self-reported cognitive impairment and anxiety. Bivariate correlations between HS and number of correct categories on the Wisconsin Card Sorting Test and the gait–balance factor from the Unified Parkinson's Disease Rating Scale Part III were also significant or approached significance. These findings suggest that specific mood and cognitive symptoms continue to be important factors in HS in those individuals who lack clinical levels of depression or dementia.