The Effects of Cardiorespiratory and Motor Skill Fitness on Intrinsic Functional Connectivity of Neural Networks in Individuals with Parkinson's Disease.

BACKGROUND: Studies in aging older adults have shown the positive association between cognition and exercise related fitness, particularly cardiorespiratory fitness. These reports have also demonstrated the association of high cardiorespiratory fitness, as well as other types of fitness, on the reversal of age-related decline in neural network connectivity, highlighting the potential role of fitness on age- and disease-related brain changes. While the clinical benefits of exercise are well-documented in Parkinson's disease (PD), the extent to which cardiorespiratory fitness (assessed by estimated VO2max testing) or motor skill fitness (assessed by the Physical Performance Test (PPT)) affects neural network connectivity in PD remains to be investigated. The purpose of this study was to explore the hypothesis that higher fitness level is associated with an increase in the intrinsic network connectivity of cognitive networks commonly affected in PD. METHODS: In this cross-sectional resting state fMRI, we used a multivariate statistical approach based on high-dimensional independent component analysis (ICA) to investigate the association between two independent fitness metrics (estimated VO2max and PPT) and resting state network connectivity. RESULTS: We found that increased estimated VO2max was associated with increased within network connectivity in cognitive networks known to be impaired in PD, including those sub-serving memory and executive function. There was a similar trend for high levels of PPT to be associated with increased within network connectivity in distinct resting state networks. The between functional network connectivity analysis revealed that cardiorespiratory fitness was associated with increased functional connectivity between somatosensory motor network and several cognitive networks sub-serving memory, attention, and executive function. CONCLUSION: This study provides important empirical data supporting the potential association between two forms of fitness and multiple resting state networks impacting PD cognition. Linking fitness to circuit specific modulation of resting state network connectivity will help establish a neural basis for the positive effects of fitness and specific exercise modalities and provide a foundation to identify underlying mechanisms to promote repair.

Thalamic volume mediates associations between cardiorespiratory fitness (VO2max) and cognition in Parkinson's disease.

INTRODUCTION: Cognitive deficits occur in Parkinson's disease (PD). Cardiorespiratory fitness (CRF) is associated with better cognitive performance in aging especially in executive function (EF) and memory. The association between CRF and cognitive performance is understudied in people with PD. Brain structures underlying associations also remains unknown. This cross-sectional study examined the associations between CRF and cognitive performance in PD. We also examined associations between CRF and brain structures impacted in PD. Mediation analysis were conducted to examine whether brain structures impacted in PD mediate putative associations between CRF and cognitive performance. METHODS: Individuals with PD (N = 33) underwent magnetic resonance imaging (MRI), CRF evaluation (estimated VO2max), and neuropsychological assessment. Composite cognitive scores of episodic memory, EF, attention, language, and visuospatial functioning were generated. Structural equation models were constructed to examine whether MRI volume estimates (thalamus and pallidum) mediated associations between CRF and cognitive performance (adjusting for age, education, PD disease duration, sex, MDS-UPDRS motor score, and total intracranial volume). RESULTS: Higher CRF was associated with better episodic memory (Standardized ß = 0.391; p = 0.008), EF (Standardized ß = 0.324; p = 0.025), and visuospatial performance (Standardized ß = 0.570; p = 0.005). Higher CRF was associated with larger thalamic (Standardized ß = 0.722; p = 0.004) and pallidum (Standardized ß = 0.635; p = 0.004) volumes. Thalamic volume mediated the association between higher CRF and better EF (Indirect effect = 0.309) and episodic memory (Indirect effect = 0.209) performance (p < 0.05). The pallidum did not significantly mediate associations between CRF and cognitive outcomes. CONCLUSION: The thalamus plays an important role in the association between CRF and both EF and episodic memory in PD.

Mild cognitive impairment, psychiatric symptoms, and executive functioning in patients with Parkinson's disease.

OBJECTIVE: Mild cognitive impairment (MCI) and psychiatric symptoms (anxiety, depression, and apathy) are common in Parkinson's disease (PD). While studies have supported the association between psychiatric symptoms and cognitive performance in PD, it is unclear if the magnitude of link between psychiatric symptoms and cognitive health is stronger by MCI status. The purpose of this study was to examine the association between cognitive performance and psychiatric symptoms in PD and whether MCI status moderates this association. METHODS/DESIGN: Participants (N = 187) completed a comprehensive neuropsychological assessment that included measures of attention, language, executive function (EF), visuospatial ability, episodic memory, and psychiatric symptoms. Participants were classified as PD-MCI (N = 73) or PD-normal cognition (NC; N = 114). Linear regression analyses were conducted to examine the association between psychiatric symptoms and cognitive performance and the moderating effect of PD-MCI status. RESULTS: There were no differences in mean psychiatric symptoms between PD-MCI and PD-NC. Psychiatric symptoms were predominantly associated with worse EF. The magnitude of the association between anxiety and worse EF was larger in participants with PD-MCI compared with PD-NC. A multivariable regression analysis examining the independent contributions of each symptom demonstrated the most robust association between EF and anxiety. CONCLUSIONS: Symptoms of anxiety, depression, and apathy are associated with worse executive functioning in individuals with PD. PD-MCI may be important in moderating the association between cognitive performance, specifically anxiety, and EF. Factors that promote cognitive resilience may serve as key therapeutic modalities in managing neuropsychiatric symptoms in PD.

Worse cognitive performance predicts increased anxiety and depressive symptoms in patients with Parkinson's disease: A bidirectional analysis.

OBJECTIVE: Symptoms of anxiety, depression commonly co-occur with cognitive decline in patients with Parkinson's disease (PD). The directionality of this association is unclear, however, in that poor cognitive performance may lead to increased symptoms of anxiety and depression or higher anxiety and depressive symptoms may lead to cognitive decline. The purpose of this study was to elucidate the directionality of the association between symptoms of anxiety and depression with cognitive performance in newly diagnosed patients with PD. METHOD: Longitudinal data from 362 nondemented participants from the Parkinson's Progression Markers Initiative (PPMI) were examined. Participants completed as many as five assessments of anxiety symptoms, depressive symptoms, and cognitive performance over a 4-year period. Bivariate dual change score models were fit to examine the dynamic association between level and change of anxiety and depressive symptoms with level and change in cognitive performance. RESULTS: Across all cognitive domains, worse performance was associated with subsequently higher state anxiety, trait anxiety, and depressive symptoms. The reverse direction was not significant as higher state anxiety, trait anxiety, and depressive symptoms were not associated with subsequent declines in cognitive performance. CONCLUSIONS: Poorer cognitive performance, across all cognitive domains, was a risk factor for increased symptoms of anxiety and depression a year later. No support was present for the alternative hypothesis that anxiety and depression are associated with subsequent cognitive decline. Clinical implications include the importance of psychoeducation, as well as assessing and monitoring anxiety and depression in patients with PD with poor cognitive performance. (PsycINFO Database Record (c) 2019 APA, all rights reserved).