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Delineating Resilience Using Fractal Regulation: Cross-Sectional and Longitudinal Evidence from the Rush Memory and Aging Project
17 Pages Posted: 31 Oct 2023
More...Abstract
Background: Many physiological outputs such as motor activity exhibit fractal patterns, i.e., self-similar fluctuations across multiple timescales. Degradation of fractal regulation occurs with aging, accelerates during the progression of Alzheimer’s disease (AD), and predicts future risk of dementia and other adverse outcomes. We examined the associations of fractal regulation with dementia-related neuropathologies and tested whether better maintained fractal regulation buffers cognitive function against neuropathologies.
Methods: Data from 533 autopsied participants in the Rush Memory and Aging Project were analyzed. Neuropathologies were quantified. Cognitive function and actigraphy were examined annually prior to death. Actigraphy data were analyzed to assess fractal regulation in two regions of timescales using two separate metrics (i.e., α1 at < 90 minutes and α2 for 2-10 hours). Linear regressions or logistic regressions were used to examine the associations of α1 and α2 proximate to death with neuropathologies. Linear mixed-effects models were used to examine whether they contributed to cognitive decline independent of 10 dementia-related neuropathologies and demographics such as age at death, sex, and education years.
Findings: Larger α1 was associated with lower burdens of Lewy body disease or cerebrovascular disease pathologies. Specifically, a one standard deviation (SD) increase in α1 corresponded to 19%-23% decreases in the odds of having these four pathologies. α2 was not associated with any of the 10 neuropathologies statistically. Both α1 and α2 were associated with longitudinal cognitive decline, with an effect for each 1-SD change corresponding to that of 0·5-2 unit change in AD pathology. Besides, they explained an additional 2%-3% of the variance in the rate of cognitive decline on top of demographics and all 10 neuropathologies.
Interpretation: Better maintained fractal regulation in late life is associated with resilience and can offset loss of cognition due to brain neuropathologies.
Funding: National Institutes of Health, and the BrightFocus Foundation.
Declaration of Interest: None to declare.
Ethical Approval: The MAP was approved by an Institutional Review Board (IRB) of Rush University Medical Center. Written informed and repository consents, and an Anatomical Gift Act for brain donation were obtained from all participants.
Keywords: Actigraphy, Alzheimer's disease, Reserve, Resilience, Wearable
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