Longitudinal Associations Between Neurodegenerative Biomarkers and Cognitive Decline in Older Adults: Insights From the LASI-DAD Study.

BACKGROUND: The Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) is a nationally representative study of cognitive aging and dementia in older adults. This study aims to investigate the longitudinal relationship between neurodegenerative biomarkers such as amyloid-beta (Aβ) 42/40 ratio, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (pTau), and total tau, and cognitive decline among older adults in India. METHODS: Data from 1181 participants (aged ≥ 60 years) who completed both Wave 1 (2017-2019) and Wave 2 (2022-2024) of LASI-DAD with biomarker data were analyzed. General cognitive factor score was used as a comprehensive measure of cognitive performance, and biomarkers including NFL, Aβ42/Aβ40 ratio, GFAP, pTau, and total Tau were measured using Simoa technology. Generalized Estimating Equations (GEE) were used to analyze the association between change in cognition and biomarkers, adjusting for demographic covariates and comorbidities. RESULTS: The median age at Wave 1 was 66 years (IQR: 63-71), with 51.9% female participants and 64.4% from rural areas. In Model 3, adjusted for age, sex, education, habitat, and comorbidities, higher GFAP levels (β = -1.68 × 10-3, p = 0.005) and higher NfL (β = -1.94 × 10-3, p = 0.002) were associated with greater cognitive decline over time. Domain-specific analysis showed GFAP and NfL were linked to language and memory decline; Aβ42/Aβ40 ratio was associated with language decline. CONCLUSIONS: Our findings suggest that biomarkers, including GFAP and NfL, are associated with cognitive decline over time in older adults in India. These biomarkers may serve as important indicators for monitoring cognitive aging and dementia risk in this population.