Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Biomarkers of Cognitive Decline in People Living with HIV

Abstract

Background This study examined the relationship between neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) and cognition in people living with HIV (PLWH) at baseline and over time. Methods Plasma and clinical data were available from PLWH aged ≥45 years with HIV RNA <200 copies/mL enrolled in the AIDS Clinical Trials Group HAILO cohort study. We measured plasma NfL and GFAP using a single molecule array platform. Four neuropsychological assessments, standardized to z-scores and averaged (NPZ-4), were used as a marker of cognitive function. Date of plasma collection marked study baseline; longitudinal changes in NPZ-4 were summarized by slope. Linear regressions between biomarkers and baseline NPZ-4 were adjusted for demographic factors. Regressions of longitudinal data were adjusted for baseline NPZ-4 and weighted by number of visits. Results The study included 503 participants with a median [IQR] age of 52 [48, 57] years, observation of 6 [5, 7] years, and 26% had baseline cognitive impairment defined by HAILO. Cross-sectionally, higher NfL (β=-0.76, p<0.01) and GFAP (β=-0.44, p=0.02) were associated with worse baseline NPZ-4. Longitudinally, the median [IQR] NPZ-4 slope was 0.003 [-0.06, 0.06] units/year with 48% demonstrating cognitive decline (slope<0). Higher NfL (β=-0.08, p<0.01), but not GFAP (β=-0.03, p=0.08), was associated with cognitive decline. Conclusions NfL and GFAP were associated with worse cognition cross-sectionally; only NfL was associated with longitudinal cognitive decline. However, the clinical utility of NfL and GFAP is uncertain given small effect sizes and should be studied in populations with more rapid decline (e.g., aged ≥60).