Department of Epidemiology and Biostatistics, Temple University, Philadelphia, Pennsylvania.
Department of Neurology, State University of New York Downstate Health Sciences University, Brooklyn.
JAMA Netw Open. 2023 Nov 1;6(11):e2344194. doi: 10.1001/jamanetworkopen.2023.44194.
Blood-based biomarkers associated with increased risk of Alzheimer disease (AD) are understudied in people living with and without HIV, particularly women.
To determine whether baseline or 1-year changes in plasma amyloid-β40 (Aβ40), Aβ42, ratio of Aβ42 to Aβ40, total tau (t-tau), phosphorylated tau 231 (p-tau231), glial fibrillary acidic protein (GFAP), and/or neurofilament light chain (NFL) are associated with neuropsychological performance (NP) among women living with HIV (WLWH) and women living without HIV (WLWOH).
DESIGN, SETTING, AND PARTICIPANTS: This longitudinal, prospective, cohort study with 1-year repeated clinical measures (NP only measured once) and biospecimen collection occurred between 2017 and 2019. Participants were women aged 40 years or older from 10 clinical research sites in cities across the US that were part of the Women's Interagency HIV Study. Data analysis was conducted from April to December 2022.
Laboratory-confirmed HIV status and AD biomarkers.
Sociodemographically adjusted NP T-scores (attention and working memory, executive function, processing speed, memory, learning, verbal fluency, motor function, and global performance) were the primary outcomes. Baseline and 1-year fasting plasma Aβ40, Aβ42, t-tau, p-tau231, GFAP, and NFL levels were measured and analyzed using multivariable linear regression.
The study consisted of 307 participants (294 aged ≥50 years [96%]; 164 African American or Black women [53%]; 214 women with a high school education or higher [70%]; 238 women who were current or former smokers [78%]; and 236 women [77%] who were overweight or obese [body mass index >25]) including 209 WLWH and 98 WLWOH. Compared with WLWOH at baseline, WLWH performed worse on learning (mean [SD] T-score 47.8 [11.3] vs 51.4 [10.5]), memory (mean [SD] T-score 48.3 [11.6] vs 52.4 [10.2]), verbal fluency (mean [SD] T-score 48.3 [9.8] vs 50.7 [8.5]), and global (mean [SD] T-score 49.2 [6.8] vs 51.1 [5.9]) NP assessments. Baseline median Aβ40, GFAP, and NFL levels were higher among WLWH vs WLWOH. There were no differences in 1-year biomarker change by HIV serostatus. Lower learning, memory, and motor NP were associated with 1-year Aβ40 increase; lower learning and motor with Aβ42 increase; lower motor with p-tau231 increase; and lower processing speed, verbal fluency and motor with NFL increase in the entire sample. Among WLWH, a 1-year increase in Aβ40 from baseline to follow-up was associated with worse learning, memory, and global NP; a 1-year increase in t-tau with worse executive function; and a 1-year increase in NFL with worse processing speed. Among WLWOH, a 1-year increase in Aβ40 and Aβ42 were associated with poorer memory performance and NFL was associated with poorer motor performance.
These findings suggest that increases in certain plasma AD biomarkers are associated with NP in WLWH and WLWOH and may be associated with later onset of AD, and measuring these biomarkers could be a pivotal advancement in monitoring aging brain health and development of AD among women with and without HIV.
在患有和不患有 HIV 的人群中，与阿尔茨海默病（AD）风险增加相关的血液生物标志物研究较少，尤其是女性。
确定基线或 1 年血浆淀粉样蛋白-β40（Aβ40）、Aβ42、Aβ42 与 Aβ40 的比值、总 tau（t-tau）、磷酸化 tau231（p-tau231）、神经胶质纤维酸性蛋白（GFAP）和/或神经丝轻链（NFL）的变化是否与 HIV 阳性女性（WLWH）和无 HIV 女性（WLWOH）的神经心理学表现（NP）相关。
设计、地点和参与者：这是一项纵向、前瞻性队列研究，在 2017 年至 2019 年间进行了 1 年的重复临床测量（仅一次测量 NP）和生物样本采集。参与者为来自美国各地 10 个临床研究地点的年龄在 40 岁或以上的女性，这些研究地点是妇女艾滋病研究机构（Women's Interagency HIV Study）的一部分。数据分析于 2022 年 4 月至 12 月进行。
实验室确认的 HIV 状况和 AD 生物标志物。
调整了社会人口统计学的 NP T 评分（注意力和工作记忆、执行功能、处理速度、记忆、学习、语言流畅性、运动功能和整体表现）是主要结果。测量并使用多变量线性回归分析了基线和 1 年的空腹血浆 Aβ40、Aβ42、t-tau、p-tau231、GFAP 和 NFL 水平。
该研究包括 307 名参与者（294 名年龄≥50 岁[96%]；164 名非裔美国或黑人女性[53%]；214 名具有高中或以上学历的女性[70%]；238 名当前或曾经吸烟的女性[78%]；236 名超重或肥胖的女性[体重指数>25]），包括 209 名 WLWH 和 98 名 WLWOH。与 WLWOH 相比，WLWH 在学习（平均[标准差]T 评分 47.8[11.3]vs 51.4[10.5]）、记忆（平均[标准差]T 评分 48.3[11.6]vs 52.4[10.2]）、语言流畅性（平均[标准差]T 评分 48.3[9.8]vs 50.7[8.5]）和整体（平均[标准差]T 评分 49.2[6.8]vs 51.1[5.9]）NP 评估方面表现更差。与 WLWOH 相比，WLWH 的基线中位数 Aβ40、GFAP 和 NFL 水平更高。HIV 血清状态对 1 年生物标志物变化没有影响。整个样本中，1 年 Aβ40 增加与学习、记忆和运动 NP 下降有关；1 年 Aβ42 增加与学习和运动下降有关；1 年 p-tau231 增加与运动下降有关；1 年 NFL 增加与处理速度、语言流畅性和运动下降有关。在 WLWH 中，从基线到随访时 Aβ40 增加 1 年与学习、记忆和整体 NP 下降有关；t-tau 增加 1 年与执行功能下降有关；NFL 增加 1 年与处理速度下降有关。在 WLWOH 中，Aβ40 和 Aβ42 增加 1 年与记忆功能下降有关，NFL 与运动功能下降有关。
这些发现表明，某些血浆 AD 生物标志物的增加与 WLWH 和 WLWOH 的 NP 相关，可能与 AD 的发病较晚有关，测量这些生物标志物可能是监测 HIV 阳性和阴性女性大脑衰老健康和 AD 发展的重要进展。
