Associations between blood-based neurodegenerative biomarkers and cognitive functioning and decline in India

Background: Mounting evidence supports the use of blood-based neurodegenerative biomarkers as a low-cost, minimally invasive tool for studying Alzheimer's disease and other dementias, but existing data largely come from clinical samples or high-income settings. Despite emphasis in the literature on the importance of understanding the utility of neurodegenerative biomarkers in diverse populations, published analyses are limited. Objective: To assess the utility of neurodegenerative biomarkers in India by quantifying associations between biomarkers and cognitive outcomes in a nationally representative cohort study. Methods: We quantified associations between five neurodegenerative blood biomarkers (amyloid-β 42/40 (Aβ_42/40), total tau, phosphorylated Tau181 (pTau-181), glial fibrillary acidic protein (GFAP), neurofilament light (NfL)) and cross-sectional and longitudinal cognitive outcomes using nationally-representative data from the Longitudinal Aging Study in India–Diagnostic Assessment of Dementia (N = 4096). Results: We observed associations between biomarkers and cross-sectional cognitive functioning (Aβ_42/40, GFAP, and NfL) and longitudinal cognitive change (pTau-181 and NfL). NfL had the strongest associations; each SD increase in log NfL was associated with 0.007 (95% CI 0.000 to 0.014) SD unit/year worse cognitive decline, equivalent to about 35% of the mean longitudinal decline in the sample. We saw little evidence of effect modification by demographic variables or APOE ε4 status. Conclusions: Neurodegenerative biomarkers were associated with cross-sectional and longitudinal outcomes as well as mortality, though there was variation in outcome-specific findings across biomarkers. Findings generally support the use of neurodegenerative biomarkers in India. Future research in India should leverage these biomarkers to address a range of research topics, including heterogeneity in dementia phenotypes.