Plasma neurofilament light (NfL) is a marker for neurodegenerative diseases. Few studies have examined the association of NfL with middle-aged changes in cognitive performance, and no studies have examined differential NfL effects by race. Using data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 625, Agev1: 30–66 y, 41.6% male, 56.3% African American, 27.8% below poverty), we investigated the associations of initial NfL levels and annualized change with cognitive performance over time in global mental status, verbal and visual memory, fluency, attention, and executive function. We used ordinary least squares and mixed-effects regressions stratified by race, while exploring differential associations by age group, sex, and poverty status. Over a mean follow-up of 4.3 years, we found initial NfL level was associated with a faster decline on normalized mental status scores in Whites only and in those >50 years old. Annualized increase in NfL was associated with a greater decline in verbal fluency in men. In other exploratory analyses, annualized increase in NfL was associated with a slower decline in verbal memory among individuals living above poverty; in the older group (>50 years), first-visit NfL was linked with better performance at baseline in global mental status and verbal memory. In summary, first-visit NfL was primarily associated with the global mental status decline among Whites, while exhibiting inconsistent relationships in some exploratory analyses. Plasma NfL levels can be detected and quantified in non-demented middle-aged adults and changes can be analyzed over time. More longitudinal studies are needed to address the clinical utility of this biomarker for early cognitive defects.

等离子神经丝光 (NfL) 是神经退行性疾病的标志物。很少有研究检查 NfL 与中年认知能力变化的关联，也没有研究检查不同种族的 NfL 影响。使用来自全生命周期多样性社区健康老龄化 (HANDLS) 研究的数据 ( n = 625，Agev1：30-66 岁，41.6% 男性，56.3% 非裔美国人，低于贫困水平 27.8%），我们调查了初始 NfL 水平和年化变化与全球精神状态、语言和视觉记忆随时间推移的认知表现之间的关联、流畅性、注意力和执行功能。我们使用了按种族分层的普通最小二乘法和混合效应回归，同时探索了按年龄组、性别和贫困状况的差异关联。在平均 4.3 年的随访中，我们发现初始 NfL 水平仅与白人和 50 岁以上的白人正常化精神状态评分下降更快有关。NfL 的年增长率与男性语言流畅度的下降幅度更大有关。在其他探索性分析中，NfL 的年增长率与生活在贫困以上的个人的语言记忆下降速度较慢有关；在老年组（> 50 岁）中，首次就诊 NfL 与整体精神状态和语言记忆的基线表现更好有关。总之，首次访问 NfL 主要与白人的整体精神状态下降有关，同时在一些探索性分析中表现出不一致的关系。可以检测和量化非痴呆中年人的血浆 NfL 水平，并且可以分析随时间的变化。需要更多的纵向研究来解决这种生物标志物对早期认知缺陷的临床效用。首次访问 NfL 主要与白人的整体精神状态下降有关，同时在一些探索性分析中表现出不一致的关系。可以检测和量化非痴呆中年人的血浆 NfL 水平，并且可以分析随时间的变化。需要更多的纵向研究来解决这种生物标志物对早期认知缺陷的临床效用。首次访问 NfL 主要与白人的整体精神状态下降有关，同时在一些探索性分析中表现出不一致的关系。可以检测和量化非痴呆中年人的血浆 NfL 水平，并且可以分析随时间的变化。需要更多的纵向研究来解决这种生物标志物对早期认知缺陷的临床效用。