Clinical Manifestations.

Background: Alzheimer's disease (AD)-related biomarkers assessed in blood have proved to be useful for detecting dementia and cognitive impairment in the memory clinic. However, less is known about their predictive value in the long-term and in a community-based setting.

Method: We examined six common serum-derived biomarkers of AD (P-tau181, T-tau, Aβ42/Aβ40 ratio, P-tau181/Aβ42 ratio, Nfl, and GFAP) from the baseline assessment of the population-based Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; n = 2071, mean age at baseline = 72 years). At baseline, participants were free from dementia and neurodegenerative disorders and their cognitive level was within normal range (Mini-Mental State Examination score > 23). Global cognition and performance in four specific domains (i.e., episodic and semantic memory, verbal fluency, and perceptual speed) were assessed regularly with a neuropsychological test battery across up to 15 years. Associations of AD-related serum biomarkers with rate of cognitive decline across the follow-up period were examined with linear mixed-effects models.

Result: Effects on rate of change in all examined cognitive domains were observed for all biomarkers, except T-tau. The strongest associations were observed for P-tau181 (global cognition: β = -0.024, 95% CI: -0.029 to -0.020) and for individuals with relatively high biomarker concentrations (3 or 4 quartile). Interactions were explored for age, sex, and APOE ԑ4-carrier-status.

Conclusion: To summarize, this study shows that higher concentrations of blood-based biomarkers for neurodegeneration are associated with faster rates of cognitive decline in the general elderly population.