Cross-sectional associations between lifecourse dementia risk factors, plasma neurodegenerative biomarkers, and cognition in older adults in India

BACKGROUND Plasma neurodegenerative biomarkers are a potential low-cost tool for studying Alzheimer’s disease and dementia in population-based research, especially in low- and middle-income countries (LMIC). However, their associations with modifiable risk factors and utility as an outcome in epidemiologic studies remain unclear. OBJECTIVE Our objective was to estimate the cross-sectional association between modifiable lifecourse risk factors for dementia and plasma-based neurodegenerative biomarkers, and to compare those with the associations between lifecourse risk factors and cognition in a population-representative Indian sample. METHODS Using nationally representative data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (N=1625, average age 68.2 years), we estimated linear regressions to compare cross-sectional associations between lifecourse risk factors and both neurodegenerative biomarkers (β-amyloid 42/40, total-tau, phosphorylated Tau181, GFAP, NfL) and cognitive outcomes (general cognition, memory). RESULTS Despite significant associations between seven of thirteen risk factors and cognitive outcomes, associations between risk factors and neurodegenerative biomarkers were largely null with some exceptions; for example, hypertension (β=0.17SD; 95% CI:0.08,0.26) and diabetes (β=0.21SD; 95% CI:0.09, 0.32) were associated with higher NfL. CONCLUSIONS While we found expected associations between lifecourse risk factors for dementia and cognition, there was not strong evidence of cross-sectional associations between risk factors for dementia and plasma-based biomarkers.