Plasma-based neurobiological protein biomarkers as predictors of dementia progression: Insights from longitudinal aging study in India - Diagnostic assessment of dementia

BACKGROUND: Major neurocognitive disorder (MNCD) represents a critical public health crisis. From the two waves of the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia, we investigated the predictive power of longitudinal alterations in plasma proteins to predict the progression from mild cognitive impairment (MCI) to MNCD in India. METHODS: This prospective cohort followed 4635 participants over 55 months. Plasma levels of amyloid beta (Aβ) 42/Aβ40 ratio, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau phosphorylated at threonine 181 (pTau181), and total tau (t-tau) were measured via single molecule array technology. Comprehensive geriatric assessments were conducted, and Clinical Dementia Rating (CDR) scores were measured. RESULTS: As participants progressed from MCI to MNCD, significant declines in cognitive and functional parameters coincided with elevated plasma protein levels. Biomarkers (GFAP, NfL t-tau, and pTau181) demonstrated strong predictive accuracy, with area under the curve values of 81%, 71%, 74%, and 67%, respectively. DISCUSSION: Plasma biomarkers effectively estimate dementia progression rates. These findings support using blood-based markers to monitor and track disease trajectory in the Indian population, offering significant clinical utility for early intervention.