Fischer Barbara, Van Hulle Carol Ann, Langhough Rebecca, Norton Derek, Zuelsdorff Megan, Gooding Diane Carol, Wyman Mary F, Johnson Adrienne, Lambrou Nickolas, James Taryn, Bouges Shenikqua, Carter Fabu Phillis, Salazar Hector, Kirmess Kristopher, Holubasch Mary, Meyer Matthew, Venkatesh Venky, West Tim, Verghese Philip, Yarasheski Kevin, Carlsson Cynthia M, Johnson Sterling C, Asthana Sanjay, Gleason Carey E
Madison VA GRECC William S. Middleton Memorial Hospital Madison Wisconsin USA.
Department of Neurology University of Wisconsin-Madison School of Medicine and Public Health Madison Wisconsin USA.
Alzheimers Dement (N Y). 2023 Sep 25;9(3):e12414. doi: 10.1002/trc2.12414. eCollection 2023 Jul-Sep.
It is critical to develop more inclusive Alzheimer's disease (AD) research protocols to ensure that historically excluded groups are included in preclinical research and have access to timely diagnosis and treatment. If validated in racialized groups, plasma AD biomarkers and measures of subtle cognitive dysfunction could provide avenues to expand diversity in preclinical AD research. We sought to evaluate the utility of two easily obtained, low-burden disease markers, plasma amyloid beta (Aβ)42/40, and intra-individual cognitive variability (IICV), to predict concurrent and longitudinal cognitive performance in a sample of Black adults.
Two hundred fifty-seven Black participants enrolled in the African Americans Fighting Alzheimer's in Midlife (AA-FAIM) study underwent at least one cognitive assessment visit; a subset of = 235 had plasma samples. Baseline IICV was calculated as the standard deviation across participants' scores on five cognitive measures: Rey Auditory Verbal Learning Test Delayed Recall, Trail Making Test Parts A and B (Trails A and B), and Boston Naming Test. Using mixed effects regression models, we compared concurrent and longitudinal models to baseline plasma Aβ42/40 or IICV by age interactions. PrecivityAD assays quantified baseline plasma Aβ42/40.
IICV was associated with concurrent/baseline performance on several outcomes but did not modify associations between age and cognitive decline. In contrast, plasma Aβ42/40 was unrelated to baseline cognitive performance, but a pattern emerged in interactions with age in longitudinal models of Trails A and B and Rey Auditory Verbal Learning Test total learning trials. Although not significant after correcting for multiple comparisons, low Aβ42/40 was associated with faster cognitive declines over time.
Our results are promising as they extend existing findings to an Black American sample using low-cost, low-burden methods that can be implemented outside of a research center, thus supporting efforts for inclusive AD biomarker research.
制定更具包容性的阿尔茨海默病(AD)研究方案至关重要,以确保历来被排除在外的群体能够参与临床前研究,并获得及时的诊断和治疗。如果在不同种族群体中得到验证,血浆AD生物标志物和细微认知功能障碍的测量方法可为扩大临床前AD研究的多样性提供途径。我们试图评估两种易于获取、负担较小的疾病标志物,即血浆淀粉样β蛋白(Aβ)42/40和个体内认知变异性(IICV),对预测黑人成年人样本中同时期和纵向认知表现的效用。
257名参与“美国中年黑人抗击阿尔茨海默病”(AA - FAIM)研究的黑人参与者至少接受了一次认知评估访视;其中235人的子集有血浆样本。基线IICV通过参与者在五项认知测量上的分数标准差来计算:雷伊听觉词语学习测验延迟回忆、连线测验A和B部分(连线A和连线B)以及波士顿命名测验。使用混合效应回归模型,我们通过年龄交互作用比较了同时期和纵向模型与基线血浆Aβ42/40或IICV。PrecivityAD检测法对基线血浆Aβ42/40进行了定量。
IICV与多个结果的同时期/基线表现相关,但并未改变年龄与认知衰退之间的关联。相比之下,血浆Aβ42/40与基线认知表现无关,但在连线A和连线B以及雷伊听觉词语学习测验总学习试验的纵向模型中,与年龄的交互作用呈现出一种模式。尽管在进行多重比较校正后不显著,但低Aβ42/40与随时间更快的认知衰退相关。
我们的结果很有前景,因为它们使用了低成本、低负担且可在研究中心外实施的方法,将现有研究结果扩展到了美国黑人样本,从而支持了包容性AD生物标志物研究的努力。