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Mild Motor Signs Matter in Typical Brain Aging: The Value of the UPDRS Score Within a Functionally Intact Cohort of Older Adults.

ABSTRACT: Objectives: To characterize the clinical correlates of subclinical Parkinsonian signs, including longitudinal cognitive and neural (via functional connectivity) outcomes, among functionally normal older adults. Methods: Participants included 737 functionally intact community-dwelling older adults who performed prospective comprehensive evaluations at ~15-months intervals for an average of 4.8 years (standard deviation 3.2 years). As part of these evaluations, participants completed the Unified Parkinson's Disease Rating Scale (UPDRS) longitudinally and measures of processing speed, executive functioning and verbal episodic memory. T1-weighted structural scans and task-free functional MRI scans were acquired on 330 participants. We conducted linear mixed-effects models to determine the relationship between changes in UPDRS with cognitive and neural changes, using age, sex, and education as covariates. Results: Cognitive outcomes were processing speed, executive functioning, and episodic memory. Greater within-person increases in UPDRS were associated with more cognitive slowing over time. Although higher average UPDRS scores were significantly associated with overall poorer executive functions, there was no association between UPDRS and executive functioning longitudinally. UPDRS scores did not significantly relate to longitudinal memory performances. Regarding neural correlates, greater increases in UPDRS scores were associated with reduced intra-subcortical network connectivity over time. There were no relationships with intra-frontoparietal or inter-subcortical-frontoparietal connectivity. Conclusions: Our findings add to the aging literature by indicating that mild motor changes are negatively associated with cognition and network connectivity in functionally intact adults.

SUBMITTER: Zitser J

PROVIDER: S-EPMC7904682 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Although aging is associated with changes in brain structure and cognition it remains unclear which specific structural changes mediate individual cognitive changes. Several studies have reported that white matter (WM) integrity, as assessed by diffusion tensor imaging (DTI), mediates, in part, age-related differences in processing speed (PS). There is less evidence for WM integrity mediating age-related differences in higher order abilities (e.g., memory and executive functions). In 165 typically aging adults (age range 54-89) we show that WM integrity in select cerebral regions is associated with higher cognitive abilities and accounts variance not accounted for by PS or age. Specifically, voxel-wise analyses using tract-based spatial statistics (TBSS) revealed that WM integrity was associated with reasoning, cognitive flexibility and PS, but not memory or word fluency, after accounting for age and gender. While cerebral fractional anisotropy (FA) was only associated with PS; mean (MD), axial (AD) and radial (RD) diffusivity were associated with reasoning and flexibility. Reasoning was selectively associated with left prefrontal AD, while cognitive flexibility was associated with MD, AD and RD throughout the cerebrum. Average WM metrics within select WM regions of interest accounted for 18% and 29% of the variance in reasoning and flexibility, respectively, similar to the amount of variance accounted for by age. WM metrics mediated ~50% of the age-related variance in reasoning and flexibility and different proportions, 11% for reasoning and 44% for flexibility, of the variance accounted for by PS. In sum, (i) WM integrity is significantly, but variably, related to specific higher cognitive abilities and can account for a similar proportion of variance as age, and (ii) while FA is selectively associated with PS; while MD, AD and RD are associated with reasoning, flexibility and PS. This illustrates both the anatomical and cognitive selectivity of structure-cognition relationships in the aging brain.

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Mild Motor Signs Matter in Typical Brain Aging: The Value of the UPDRS Score Within a Functionally Intact Cohort of Older Adults.

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