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. 2025 Jun 10;80(7):glaf110.
doi: 10.1093/gerona/glaf110.

Relationship of Alzheimer's Disease and Related Dementias Plasma Biomarkers With Mobility in Cognitively Unimpaired Older Adults

Atalie C Thompson  1   2 , Xiaoyan Leng  3 , Michael E Miller  4 , Thomas C Register  5 , Paul J Laurienti  6 , Michelle M Mielke  2   7 , Suzanne Craft  2 , Stephen B Kritchevsky  2
Affiliations

Relationship of Alzheimer's Disease and Related Dementias Plasma Biomarkers With Mobility in Cognitively Unimpaired Older Adults

Atalie C Thompson et al. J Gerontol A Biol Sci Med Sci. .

Abstract

Background: Temporal relationships between physical and cognitive decline with aging are poorly understood, and little is known about the underlying mechanisms linking these conditions. We hypothesized that plasma biomarkers of Alzheimer's disease and related dementias may be associated with mobility performance in older adults who are cognitively unimpaired.

Methods: We constructed separate linear mixed models to examine the cross-sectional associations of 5 plasma Alzheimer's disease and related dementias and aging-related biomarkers with 4 measures of mobility in a cohort of 192 cognitively unimpaired older adults. We secondarily described the association of the same biomarkers with 4 cognitive domain scores.

Results: Higher phorphorylated-tau181 was associated with worse performance on the expanded short physical performance battery, slower 4 m gait speed, and shorter balance time. Higher neurofilament light was associated with worse expanded short physical performance battery, slower 4 m gait speed, and slower 400 m gait speed in adjusted models. However, there was no association of Aβ42/Aβ40, p-tau217, or glial fibrillary acidic protein with mobility. Only p-tau217 was associated with global and processing speed cognitive domain scores in multivariable models, but not after adjusting for multiple comparisons.

Conclusions: These data suggest that p-tau181 and neurofilament light are potential markers of mobility performance in cognitively normal older adults, even when they are not associated with cognitive performance. Future studies should examine how such markers predict change over time in mobility and cognitive function and whether they may indicate pathways that could be targeted for preventive management.

Keywords: Alzheimer’s disease; Functional performance; Gait.

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Conflict of interest statement

Dr. Mielke has served on scientific advisory boards and/or has consulted for Acadia, Biogen, Eisai, Lilly, Merck, Novo Nordisk, and Roche. The other authors have no relevant conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Correlations of plasma biomarkers and physical performance measures. Heatmap of Spearman’s correlation between plasma biomarkers and physical performance measures. The correlation coefficient magnitude is shown in the calibration bar, and all values are adjusted for plate. Unadjusted correlations (p < .05) are bolded. Adjusted p values < .05 (Benajmini–Hochberg FDR < 0.05) are labeled by *.
Figure 2.
Figure 2.
Heatmap of standardized beta coefficients of the association of plasma biomarkers with physical performance measures. Heatmap of standardized beta coefficients from unadjusted Model 1 and fully adjusted Model 2 for plasma biomarkers with measures of physical performance. All models are adjusted for plate. The shades of the heat map represent the p values as shown in the calibration bar. Significant unadjusted correlations (p < .05) are bolded. Adjusted p values < .05 (Benjamini–Hochberg FDR < 0.05) are labeled by *.
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