Circulating Biomarkers of Neurodegeneration and Risk of Cognitive Impairment

作者：Russell P. Sawyer, Aleena Bennett, Jessica Blair, Suzanne E. Judd, Nels C. Olson, Virginia J. Howard, Nicole D. Armstrong, D. Leann Long, Hyacinth I. Hyacinth, Jennifer J. Manly, Mary Cushman · 发表于：Neurology · 年份：2025 · DOI：10.1212/wnl.0000000000213935 · 被引用次数：4 · 研究领域：Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments、Neuroinflammation and Neurodegeneration Mechanisms

BACKGROUND AND OBJECTIVES: Blood-based biomarkers offer a widely available, scalable, and minimally invasive alternative to study neurodegeneration. However, the association between blood-based biomarkers of neurodegeneration and long-term risk of cognitive impairment in a racially diverse cohort remains understudied. The objective was to determine whether baseline biomarkers of neurodegeneration are associated with the development of incident cognitive impairment in a biracial cohort. METHODS: The Reasons for Geographic and Racial Differences in Stroke cohort study enrolled 30,239 Black and White participants from 2003 to 2007 across the continental United States with ongoing follow-up. In a random sample of participants with no baseline cognitive impairment, plasma neurofilament light chain (NfL), total tau, glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) were measured. Incident cognitive impairment was defined using the Six-Item Screener (SIS) and a 4-test battery consisting of Word List Learning, Delayed Recall, Animal Fluency, and Letter "F" Fluency. Models were adjusted for demographics, medical history, prebaseline and incident stroke, lifestyle habits, and depressive symptoms. RESULTS: A total of 724 participants had baseline plasma markers of neurodegeneration measured; the mean baseline age was 66.1 years (SD 11.7), 51.7% were female, and 43.6% self-identified as Black. With a mean follow-up of 12.2 (SD 4.8) years, 8.9% (...