Mukerji Shibani S, Bachanová Petra, Park Hemi, Rosen Linzy V, Kashlan Rommi, Kivisäkk Pia, Anderson Albert M, Chow Felicia C, Wu Kunling, Dastgheyb Raha M, Rubin Leah H, Tassiopoulos Katherine, Parker Robert A, Hyle Emily P
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
J Infect Dis. 2025 Apr 15;231(4):946-956. doi: 10.1093/infdis/jiae623.
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.
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.
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.
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.
我们在基线期及纵向研究中，考察了人类免疫缺陷病毒（HIV）感染者神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）与认知功能之间的关系。
在艾滋病临床试验组HAILO研究中，收集了年龄≥45岁、病毒得到抑制的HIV感染者（PWH）的血浆和临床数据。四项标准化并平均后的神经心理学评估（NPZ-4）代表认知功能。血浆采集日期标记为基线期；斜率总结了NPZ-4的纵向变化。线性回归分析考察了生物标志物与基线期NPZ-4及纵向变化之间的关联。
该研究纳入了503名参与者，中位年龄为52岁（四分位间距[IQR，48 - 57]），观察期为6年（IQR，5 - 7），26%的参与者根据HAILO标准存在基线期认知障碍。横断面分析显示，较高的NfL（β = -0.76，P < 0.01）和GFAP（β = -0.44，P = 0.02）与较差的NPZ-4相关。纵向分析显示，NPZ-4的中位斜率为0.003（IQR，-0.06至0.06）单位/年，48%的参与者表现出认知功能下降。较高的NfL（β = -0.08，P < 0.01）与认知功能下降相关，而GFAP（β = -0.03，P = 0.08）则无此关联。
NfL和GFAP在横断面分析中与较差的认知功能相关；仅NfL与认知功能下降相关。鉴于效应量较小，它们的临床应用价值仍不确定，应在认知功能下降更快的人群中进行研究。
