Deconstructing Apathy in Parkinson's Disease: Challenges in Isolating Core Components of Apathy From Depression, Anxiety, and Fatigue
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ABSTRACT:
SUBMITTER: Ineichen C
PROVIDER: S-EPMC8427284 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Depression, anxiety and apathy are common mood disturbances in Parkinson's disease (PD) but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural substrates linked to these disturbances. A systematic review is provided of neuroimaging findings in depression, anxiety and apathy in PD. A PubMed, MEDLINE and EMBASE search of peer-reviewed original research articles on these mood disturbances in PD identified 38 studies on depression, eight on anxiety and 14 on apathy in PD. Most of the imaging studies used either position emission tomography or single-photon emission computed tomography techniques. These studies generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal-limbic networks in depressed patients. Functional imaging studies revealed an inverse correlation between dopaminergic density in the caudate and putamen with the severity of anxiety in PD. There was no consistent correlation between dopaminergic density of thalamus and anxiety. Studies demonstrated both positive and inverse correlations between apathy and metabolism or activity in the striatum, amygdalar, prefrontal, temporal and parietal regions. The clinical variability of study subjects and differences in image pre-processing and analytical strategies may contribute to discrepant findings in these studies. Both nigrostriatal and extra-nigrostriatal pathways (in particular the frontal region and its connecting areas) are affected in mood disorders in PD. Identifying the relative contributions of these neural pathways in PD patients with overlapping motor and mood symptoms could provide new pathophysiological clues for the development of better therapeutic targets for affected patients.
| S-EPMC5084819 | biostudies-other
Project description:Depression, anxiety and apathy are distinct neuropsychiatric symptoms that highly overlap in Parkinson's disease (PD). It remains unknown whether each symptom is uniquely associated with a functional network dysfunction. Here, we examined whether individual differences in each neuropsychiatric symptom predict functional connectivity patterns in PD patients while controlling for all other symptoms and motor function. Resting-state functional connectivity MRI were acquired from 27 PD patients and 29 healthy controls. Widespread reduced functional connectivity was identified in PD patients and explained by either the neuropsychiatric or motor symptoms. Depression in PD predicted increased functional connectivity between the orbitofrontal, hippocampal complex, cingulate, caudate and thalamus. Apathy in PD predicted decreased caudate-thalamus and orbitofrontal-parahippocampal connectivity. Anxiety in PD predicted three distinct types of functional connectivity not described before: (i) increased limbic-orbitofrontal cortex; (ii) decreased limbic-dorsolateral prefrontal cortex and orbitofrontal-dorsolateral prefrontal cortices and (iii) decreased sensorimotor-orbitofrontal cortices. The first two types of functional connectivity suggest less voluntary and more automatic emotion regulation. The last type is argued to be specific to PD and reflect an impaired ability of the orbitofrontal cortex to guide goal-directed motor actions in anxious PD patients.
| S-EPMC5610322 | biostudies-literature
Project description:BackgroundThe relationship between apathy, depression and cognitive impairment in Parkinson's disease (PD) is still controversial. The objective of this study is to investigate whether apathy and depression are associated with inefficient cognitive strategies in PD.MethodsIn this prospective clinical cohort study conducted in a university-based clinical and research movement disorders center we studied 48 PD patients. Based on clinical evaluation, they were classified in two groups: PD with apathy (PD-A group, n = 23) and PD without apathy (PD-NA group, n = 25). Patients received clinical and neuropsychological evaluations. The clinical evaluation included: Apathy Evaluation Scale-patient version, Hamilton Depression Rating Scale-17 items, the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr staging system; the neuropsychological evaluation explored speed information processing, attention, working memory, executive function, learning abilities and memory, which included several measures of recall (immediate free, short delay free, long delay free and cued, and total recall).FindingsPD-A and PD-NA groups did not differ in age, disease duration, treatment, and motor condition, but differed in recall (p<0.001) and executive tasks (p<0.001). Immediate free recall had the highest predictive value for apathy (F = 10.94; p = 0.002). Depression and apathy had a weak correlation (Pearson index= 0.3; p<0.07), with three items of the depression scale correlating with apathy (Pearson index between .3 and.4; p<0.04). The depressed and non-depressed PD patients within the non-apathetic group did not differ.ConclusionApathy, but not depression, is associated with deficit in implementing efficient cognitive strategies. As the implementation of efficient strategies relies on the fronto-striatal circuit, we conclude that apathy, unlike depression, is an early expression of executive impairment in PD.
| S-EPMC3060914 | biostudies-literature
Project description:BackgroundNeuropsychiatric and affective symptoms are prevalent in prodromal and clinical Parkinson's disease (PD). Some evidence suggests that they may also signify risk for motor complications (motor fluctuations and dyskinesias) of dopamine replacement therapy (DRT).ObjectiveTo determine whether neuropsychiatric symptoms present in de novo PD (ie, before DRT initiation) predict the severity of eventual motor complications of DRT.MethodsWe used clinical, demographic, neurobehavioral, and neuroimaging data from the Parkinson's Progression Markers Initiative (PPMI), a multicenter observational PD study. Participants were unmedicated at enrollment and 361 initiated DRT during PPMI follow-up. We used Cox proportional hazard and multivariate ordinal mixed-effects regression models to evaluate the relationship between baseline neuropsychiatric symptoms and motor complications as measured by the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS).ResultsThe cumulative incidences of dyskinesias and motor fluctuations during follow-up (6.0 ± 1.5 years) were 34.3% and 59.9%, respectively. Both apathy and high trait-anxiety (top quartile) conveyed over two-fold increases in hazard for dyskinesia onset and for adverse impact on activities of daily living caused by both dyskinesias and motor fluctuations. The longitudinal severity of motor fluctuations and dyskinesias was significantly predicted by baseline trait-anxiety and apathy, but not depression. Models were adjusted for dimensionally related symptoms (eg autonomic dysfunction) and potential confounding variables (eg DRT dose).ConclusionsApathy and anxiety levels in de novo PD may be neuropsychiatric biomarkers of vulnerability to earlier and more disabling motor complications of DRT.
| S-EPMC7780944 | biostudies-literature
Project description:OBJECTIVES:Both depression and apathy, alone and in combination, have been shown to negatively affect cognition in patients with Parkinson's disease (PD). However, the influence of specific symptom dimensions of depression and apathy on cognition is not well understood. The current study investigated the relationship between symptom dimensions of depression and apathy, based on factors identified in Kirsch-Darrow et al. (2011), and memory and executive function in PD. METHODS:A sample of 138 non-demented individuals with PD (mean age=64.51±7.43 years) underwent neuropsychological testing and completed the Beck Depression Inventory, 2nd Edition, and Apathy Scale. Separate hierarchical regression models examined the relationship between symptom dimensions of depression and apathy ("pure" depressive symptoms, "pure" apathy, loss of interest/pleasure [anhedonia], and somatic symptoms) and three cognitive domain composites: immediate verbal memory, delayed verbal memory, and executive function. RESULTS:After adjusting for general cognitive status and the influence of the other symptom dimensions, "pure" depressive symptoms were negatively associated with the delayed verbal memory composite (p<.034) and somatic symptoms were positively associated with the executive function composite (p<.026). No symptom dimensions were significantly related to the immediate verbal memory composite. CONCLUSIONS:Findings suggest that specific mood symptoms are associated with delayed verbal memory and executive function performance in non-demented patients with PD. Further research is needed to better understand possible mechanisms through which specific symptom dimensions of depression and apathy are associated with cognition in PD. (JINS, 2018, 24, 269-282).
| S-EPMC5820218 | biostudies-literature
Project description:Objective: Anxiety and depression are prominent non-motor symptoms of Parkinson's disease (PD), but their pathophysiology remains unclear. We sought to understand their neurophysiological correlates from chronic invasive recordings of the prefrontal cortex (PFC). Methods: We studied four patients undergoing deep brain stimulation (DBS) for their motor signs, who had comorbid mild to moderate anxiety and/or depressive symptoms. In addition to their basal ganglia leads, we placed a permanent prefrontal subdural 4-contact lead. These electrodes were attached to an investigational pulse generator with the capability to sense and store field potential signals, as well as deliver therapeutic neurostimulation. At regular intervals over 3-5 months, participants paired brief invasive neural recordings with self-ratings of symptoms related to depression and anxiety. Results: Mean age was 61 ± 7 years, mean disease duration was 11 ± 8 years and a mean Unified Parkinson's Disease Rating Scale, with part III (UPDRS-III) off medication score of 37 ± 13. Mean Beck Depression Inventory (BDI) score was 14 ± 5 and Beck Anxiety Index was 16.5 ± 5. Prefrontal cortex spectral power in the beta band correlated with patient self-ratings of symptoms of depression and anxiety, with r-values between 0.31 and 0.48. Mood scores showed negative correlation with beta spectral power in lateral locations, and positive correlation with beta spectral power in a mesial recording location, consistent with the dichotomous organization of reward networks in PFC. Interpretation: These findings suggest a physiological basis for anxiety and depression in PD, which may be useful in the development of neurostimulation paradigms for these non-motor disease features.
| S-EPMC8568318 | biostudies-literature
Project description:Apathy and fatigue have a high prevalence in many pathological populations, but they are also present in healthy adults. The relationship between apathy and fatigue, which are both multidimensional, is still poorly understood. This study aims to describe the associations between the subdimensions of both apathy and fatigue and to investigate their overlaps and dissociations in healthy people. 729 participants (mean age = 30.8 ± 10.7 years) completed online self-assessment questionnaires. The Apathy Motivation Index and Dimensional Apathy Scale were used to assess apathy. The Multidimensional Fatigue Inventory was used to assess fatigue. The executive dimension of apathy showed the strongest correlations with mental fatigue and the two appeared to be underpinned by the same latent factor, according to exploratory factor analysis (EFA). The factor structure of EFA showed overlaps between behavioral apathy and both reduced motivation and activity in fatigue. Emotional and social dimensions of apathy were separately underpinned by a latent factor that comprised no items of fatigue. Apathy and fatigue have reduced activity and mental difficulties in common, whereas emotional and social disorders distinguish apathy from fatigue. This has important implications for assessing apathy and fatigue in the general population, and may be relevant for clinical practice.
| S-EPMC9072543 | biostudies-literature
Project description:Deficits in executive functions occur in up to 93% of patients with Parkinson's disease (PD). Apathy, a reduction of motivation and goal-directed behavior is an important part of the syndrome; affecting both the patients as well as their social environment. Executive functions can be subdivided into three different processes: initiation, shifting and inhibition. We examined the hypotheses, (1) that apathy in patients with Parkinson's disease is only related to initiation and not to shifting and inhibition, and (2) that depression and severity of motor signs correlate with apathy. Fifty-one non-demented patients (19 = female) with PD were evaluated for apathy, depression and executive functions. Executive function variables were summarized with an index variable according to the defined executive processes. Linear regression with stepwise elimination procedure was used to select significant predictors. The significant model (R (2) = 0.41; p < 0.01) revealed influences of initiation (b = -0.79; p < 0.01), gender (b = -7.75; p < 0.01), age (b = -0.07; p < 0.05) and an age by gender interaction (b = 0.12; p < 0.01) on apathy in Parkinson's disease. Motor signs, depression and level of education did not influence the relation. These results support an association of apathy and deficits of executive function in PD. Initiation strongly correlates with apathy, whereas depression does not. We conclude, that initiation dysfunction in a patient with Parkinson's disease heralds apathy. Apathy and depression can be dissociated. Additionally, apathy is influenced by age and gender: older age correlates with apathy in men, whereas in women it seems to protect against it.
| S-EPMC4295432 | biostudies-literature
Project description:Objectives: Impaired awareness of cognitive and functional deficits is a common feature of Alzheimer's disease (AD). Although a lack of awareness has been suggested to be a protective factor against experiencing affective symptoms, such as depression, anxiety, and apathy which are common in AD, there is conflicting evidence about the links between them. This systematic review examines the evidence for an association between impaired awareness and depressive, anxiety, and apathy symptoms in mild to moderate AD. Method: We searched four databases (OvidMedline, Embase, PsycInfo, and PsycArticles) using terms encompassing awareness, apathy, depression, anxiety, and mild-moderate AD. We included studies that assessed the relationship between awareness and depressive symptoms, anxiety symptoms, or apathy. We assessed included papers for quality and report results using a narrative approach, prioritizing high quality studies. Results: We identified 1,544 articles, and twenty-seven studies fulfilled inclusion criteria (high-quality = 15; moderate-quality = 12). Most high-quality studies reported that impaired awareness in early-stage AD is cross-sectionally linked with fewer depressive symptoms and anxiety symptoms (correlation ranged from -0.3 to -0.7), but with more apathy. Conclusions: High-quality studies suggested that in people with early AD, impaired awareness is related to fewer depressive and anxiety symptoms and to more apathy. Future research should focus on elucidating causality among impaired awareness and these symptoms in AD.
| S-EPMC7889585 | biostudies-literature
Project description:Apathy, often-unrecognized in Parkinson's Disease (PD), adversely impacts quality-of-life (QOL) and may increase with disease severity. Identifying apathy early can aid treatment and enhance prognoses. Whether feelings related to apathy (e.g., loss of pleasure) are present in mild PD and how apathy and related feelings increase with disease severity is unknown. 120 individuals (M age: 69.0 ± 8.2 y) with mild (stages 1-2, n = 71) and moderate (stages 2.5-4; n = 49) PD were assessed for apathy and apathy-related constructs including loss of pleasure, energy, interest in people or activities, and sex. Correlations were used to determine the association of apathy with apathy-related constructs. Regression models, adjusted for age, cognitive status, and transportation, compared groups for prevalence of apathy and apathy-related feelings. Apathy-related constructs and apathy were significantly correlated. Apathy was present in one in five participants with mild PD and doubled in participants with moderate PD. Except for loss of energy, apathy-related constructs were observed in mild PD at a prevalence of 41% or greater. Strong associations were noted between all apathy-related constructs and greater disease severity. After adjustment for transportation status serving as a proxy for independence, stage of disease remained significant only for loss of pleasure and loss of energy. People with mild PD showed signs of apathy and apathy-related feelings. Loss of pleasure and energy are apathy-related feelings impacted by disease severity. Clinicians should consider evaluating for feelings related to apathy to enhance early diagnosis in individuals who might otherwise not exhibit psychopathology.
| S-EPMC8775593 | biostudies-literature