Blood Biomarkers of Alzheimer's Disease and Gait Speed Trajectories in Community‐Dwelling Older Adults: A Cohort Study

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ABSTRACT Background Gait speed (GS) has been suggested as a predictor of incident dementia in old age. However, the mechanisms underlying this body–mind connection remain unclear, and it is still unknown whether trajectories of GS decline differ according to levels of blood biomarkers related to Alzheimer's disease ( AD ). This study aims to investigate the association between levels of seven blood biomarkers related to AD and long‐term GS changes in dementia‐free older adults living in the community. Methods The present study included 1665 community‐dwelling adults ≥ 60 years, followed for 15 years, drawn from the Swedish National study on Aging and Care in Kungsholmen (SNAC‐K). GS (m·s −1 ) was assessed at baseline and at five subsequent follow‐up time points. Blood biomarkers, including serum amyloid‐ β 42 to amyloid‐ β 40 ratio (A β 42/40), phosphorylated Tau181 ( p ‐Tau181) and Tau217 ( p ‐Tau217), total Tau ( t ‐Tau), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), were collected from peripheral venous blood samples at baseline. Linear mixed‐effects models were implemented to investigate the association between blood biomarkers and GS changes over time. Results After adjusting for potential confounders, participants in the highest quartile of p ‐Tau181 (Model I; 4th quartile β : −0.008, 95% CI: −0.013; −0.003), p ‐Tau217 (Model I; 4th quartile β : −0.010, 95% CI: −0.015; −0.005), NfL (Model I; 4th quartile β : −0.013, 95% CI: −0.019; −0.006) and GFAP (Model I; 4th quartile β : −0.007, 95% CI: −0.013; −0.002) exhibited a steeper decline in GS over time, as compared with those in the lowest quartile. Notably, participants in these highest quartiles developed mobility limitations (GS < 0.8 m·s −1 ), on average, 2.3 to 6.0 years earlier. Of note, only the association between NfL and GS changes over time persisted after further adjusting for time‐varying global cognition. Conclusions Higher blood biomarker levels of AD are associated with accelerated trajectories of GS decline and earlier onset of mobility limitations. Consequently, a faster decline in GS may reflect underlying neurodegeneration and indicate changes in brain health.

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