Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Biomarkers of Cognitive Decline in People With Human Immunodeficiency Virus

Abstract

Background: We examined the relationship between neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) and cognition in people with human immunodeficiency virus (HIV) at baseline and longitudinally.

Methods: Plasma and clinical data were available from virally suppressed people with HIV (PWH) aged ≥45 years in the AIDS Clinical Trials Group HAILO study. Four neuropsychological assessments standardized and averaged (NPZ-4) represented cognition. Plasma collection date marked baseline; slope summarized longitudinal NPZ-4 changes. Linear regressions examined biomarkers associations with baseline NPZ-4 and longitudinal change.

Results: The study included 503 participants with a median age of 52 (interquartile range [IQR, 48-57]) years and observation of 6 (IQR, 5-7) years, and 26% had baseline cognitive impairment defined by HAILO. Cross-sectionally, higher NfL (β = -.76, P < .01) and GFAP (β = -.44, P = .02) were associated with worse NPZ-4. Longitudinally, the median NPZ-4 slope was 0.003 (IQR, -0.06 to 0.06) units/year with 48% demonstrating cognitive decline. Higher NfL (β = -.08, P < .01), but not GFAP (β = -.03, P = .08), was associated with cognitive decline.

Conclusions: NfL and GFAP were associated with worse cognition cross-sectionally; only NfL was associated with cognitive decline. Their clinical utility remains uncertain given small effect sizes and should be studied in populations with more rapid decline.

Keywords: NPZ-4 score; aging; cognition; cognitive decline; plasma biomarkers.