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. 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 (amyloid-β 42/40, total-tau, phosphorylated Tau181, glial fibrillary acidic protein, neurofilament light chain) 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 neurofilament light chain. 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.