Cognitive Function and Neurodegenerative Blood Biomarkers in an Aging Indian Population: Insights From LASI-DAD Wave...

Cognitive aging and dementia are major public health challenges in India's aging population. This study examines associations between cognition and neurodegenerative biomarkers among community-dwelling older adults using data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) Wave 2.

LASI-DAD Wave 2 included 4635 participants aged ≥ 60 years. Cognitive assessments covered memory, executive function, language, and visuospatial abilities. Age-, sex-, and education-adjusted cut-offs identified low cognitive performance. Blood biomarkers, including total tau, phosphorylated tau-181 (pTau-181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and β-amyloid (Aβ42/Aβ40 ratio) were collected and log-transformed. Generalized linear model (GLM) adjusted for demographic and clinical variables were used to examine the associations between biomarker levels and poor cognitive performance.

Median participant age was 70 years (IQR: 66-76); 54.6% were female. Poor cognitive performance was present in 828 (27.6%) participants. Higher NfL (Median 27.2 vs. 21.8 pg/mL, p < 0.001), GFAP (Median 120.4 vs. 102.9 pg/mL, p < 0.001) and p-Tau 181 (Median 37.5 vs. 35.4, p = 0.003) were associated with poor cognition. In GLM, NfL (RR: 1.411, 95% CI 1.162-1.714, p = 0.001), GFAP (RR: 1.425, 95% CI 1.147-1.769, p = 0.003) were associated with poor cognition, while Aβ42/Aβ40 ratio total tau and p-Tau 181 were not (adjusted for age, sex, body mass index, serum creatinine, hypertension, diabetes, heart disease and stroke). Additionally, higher NfL and GFAP were associated with poor performance in most cognitive domains, except recognition memory. Higher Aβ42/Aβ40 ratio with poor recognition memory, higher p-Tau 181 with lower orientation scores, and lower total tau with lower recognition memory and visuospatial score.

Among older Indian adults, elevated NfL and GFAP levels were strongly associated with poor cognitive performance. These biomarkers could aid future dementia screening and prognostication efforts. Longitudinal studies are needed to validate their role in large-scale screening programs.