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

BackgroundMounting 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.ObjectiveTo assess the utility of neurodegenerative biomarkers in India by quantifying associations between biomarkers and cognitive outcomes in a nationally representative cohort study.MethodsWe 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).ResultsWe 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.ConclusionsNeurodegenerative 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.