Total daily physical activity, brain pathologies, and parkinsonism in older adults

Abstract

Objective: We examined the association of physical activity, postmortem brain pathologies, and parkinsonism proximate to death in older adults.

Methods: We studied the brains of 447 older decedents participating in a clinical-autopsy cohort study. We deployed a wrist worn activity monitor to record total daily physical activity during everyday living in the community-setting. Parkinsonism was assessed with 26 items of a modified motor portion of Unified Parkinson's Disease Rating Scale (UPDRS). We used linear regression models, controlling for age and sex, to examine the association of physical activity with parkinsonism with and without indices of Alzheimer's disease and related disorders (ADRD) pathologies. In separate models, we added interaction terms to examine if physical activity modified the associations of brain pathologies with parkinsonism.

Results: Mean age at death was 90.9 (SD, 6.2), mean severity of parkinsonism was 14.1 (SD, 9.2, Range 0-59.4), and 350 (77%) had evidence of more than one ADRD pathologies. Higher total daily physical activity was associated with less severe parkinsonism (Estimate, -0.315, S.E., 0.052, p<0.001). The association of more physical activity with less severe parkinsonism persisted after adding terms for ten brain pathologies (Estimate, -0.283, S.E., 0.052, p<0.001). The associations of brain pathologies with more severe parkinsonism did not vary with the level of physical activity.

Conclusion: The association of higher physical activity with less severe parkinsonism may be independent of the presence of ADRD brain pathologies. Further work is needed to identify mechanisms through which physical activity may maintain motor function in older adults.

Fig 1. Scientific framework for Hypothesis Testing.

Our prior work has shown that a higher level of physical activity is related to less severe parkinsonism (A [6]), physical activity and brain pathologies are related (B [9]), and brain pathologies are related to the severity of parkinsonism (C [7,8,10]). Based on these findings, this study tested the hypothesis that brain pathology links (mediates) the association of physical activity with parkinsonism. If the hypothesized sequence of events shown in D is correct, then adding the term for brain pathology to the model would attenuate the association of physical activity with parkinsonism, which would no longer be significant. If brain pathology does not mediate this association, both physical activity and brain pathology would be independently associated with parkinsonism.