Physical activity attenuates age-related biomarker alterations in preclinical AD

Abstract

Objective: To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults.

Methods: Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent (11)C-Pittsburgh compound B-PET (n = 186) and (18)F-fluorodeoxyglucose-PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity.

Results: There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group.

Conclusions: In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life.

Figure. Exercise engagement favorably alters age-associated biomarker alterations

Blue bars = younger participants (i.e., <60 years); red bars = older participants (i.e., ≥60 years). (A) Percentage of participants whose PiB scans were rated as being unambiguously positive for Aβ in an AD-like pattern. (B–E) adjusted means and standard error for (B) FDG posterior cingulate glucose metabolism, (C) hippocampal volume, (D) Immediate Memory, and (E) Visuospatial Ability. Sample sizes for the analyses were 317 for hippocampal volume and cognition, 186 for PiB, and 152 for FDG. Cell counts are as follows: for hippocampal volume and cognition, inactive and younger n = 45, inactive and older n = 34, active and younger n = 95, and active and older n = 143; for PiB, inactive and younger n = 29, inactive and older n = 23, active and younger n = 47, and active and older n = 87; and for FDG, inactive and younger n = 23, inactive and older n = 18, active and younger n = 43, and active and older n = 68. Aβ = β-amyloid; AD = Alzheimer disease; FDG = ¹⁸F-fluorodeoxyglucose; PiB = ¹¹C-Pittsburgh compound B.