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

Shibani S Mukerji; Petra Bachanová; Hemi Park; Linzy V Rosen; Rommi Kashlan; Pia Kivisäkk; Albert M Anderson; Felicia C Chow; Kunling Wu; Raha M Dastgheyb; Leah H Rubin; Katherine Tassiopoulos; Robert A Parker; Emily P Hyle

doi:10.1093/infdis/jiae623

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

J Infect Dis. 2024 Dec 26:jiae623. doi: 10.1093/infdis/jiae623. Online ahead of print.

Authors

Shibani S Mukerji^{1

2

3

4}, Petra Bachanová⁴, Hemi Park^{1

4}, Linzy V Rosen⁵, Rommi Kashlan^{1

4}, Pia Kivisäkk¹, Albert M Anderson⁶, Felicia C Chow⁷, Kunling Wu⁸, Raha M Dastgheyb⁹, Leah H Rubin¹⁰, Katherine Tassiopoulos¹¹, Robert A Parker^{3

12

13}, Emily P Hyle^{2

3

5

13}

Affiliations

¹ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
² Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
³ Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
⁴ Vaccine and Immunotherapy Center, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA.
⁵ Medical Practice Evaluation Center, Massachusetts General Hospital, 100 Cambridge Street, Boston, MA 02114, USA.
⁶ Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA.
⁷ Departments of Neurology and Medicine (Infectious Diseases) and Weill Institute for Neurosciences, University of California, 1651 4th Street, San Francisco, CA 94158, USA.
⁸ Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, 651 Huntington Avenue, Boston, MA 02115, USA.
⁹ Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
¹⁰ Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21205, USA.
¹¹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
¹² Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, 125 Nashua Street, Boston, MA 02114, USA.
¹³ Center for AIDS Research, Harvard University, 42 Church Street, Cambridge, MA 02138, USA.

PMID: 39723835
DOI: 10.1093/infdis/jiae623

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).

Keywords: Aging; Cognition; Cognitive decline; NPZ-4 score; Plasma biomarkers.

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