Blood biomarkers of Alzheimer's disease and 15-year decline in cognitive and motor functions in older adults

Background: Individuals showing concurrent and rapid declines in cognitive and motor performance (i.e., dual decliners) are at increased risk of faster progression to dementia. Still, the role of Alzheimer's disease (AD) pathology in motor/cognitive joint trajectories remains poorly understood. Objectives: To test the association between blood AD biomarkers and different patterns of decline of cognitive and motor functions in an aging, community-dwelling population. Methods: We included 1660 dementia-free participants from the Swedish National Study on Aging and Care in Kungsholmen. Cognitive and motor functions were assessed over 15 years using the Mini-Mental State Examination and gait speed. Based on individual decline rates derived from linear mixed models, participants were classified as slow/non-decliners, fast motor decliners, fast cognitive decliners, or dual decliners. Baseline plasma concentrations of AD biomarkers (amyloid-β [Aβ] 42/40 ratio, phosphorylated tau 217 [p-tau217], phosphorylated tau 181 [p-tau181], total tau, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) were quantified using single-molecule array assays. Associations between standardized biomarker levels and decline patterns were tested using multinomial logistic regression. Results: Higher plasma levels of p-tau217 (odds ratio [OR] 2.69, 95% confidence interval [CI] 2.34–3.09), p-tau181 (OR 1.78, 95% CI 1.60–1.98), and NfL (OR 1.47, 95% CI 1.34–1.61) were most strongly associated with dual decline, compared with slow/no decline. Although a lower Aβ42/40 ratio and higher GFAP levels were mainly linked to isolated cognitive, p-tau217 alone was associated with future isolated motor decline. Conclusions: In this population-based study, distinct AD blood biomarkers were associated with different patterns of cognitive and motor decline. Whether these represent separate pathways or a clinical continuum, further research is needed to clarify underlying mechanisms and inform clinical applications.