Klinger Hannah M, Healy Brian C, Hanseeuw Bernard J, Jones Rich N, Boyle Rory, Townsend Diana L, Properzi Michael J, Coughlan Gillian T, Seto Mabel, Birkenbihl Colin, Farrell Michelle E, Papp Kathryn V, Chhatwal Jasmeer P, Yang Hyun-Sik, Schultz Aaron P, Amariglio Rebecca E, Jacobs Heidi I L, Price Julie C, Johnson Keith A, Rentz Dorene M, Sperling Reisa A, Buckley Rachel F
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Alzheimers Dement. 2024 Dec;20(12):8728-8738. doi: 10.1002/alz.14326. Epub 2024 Oct 29.
While the influence of cross-sectional β-amyloid (Aβ) on longitudinal changes in cognition is well established, longitudinal change-on-change between Aβ and cognition is less explored.
A series of bivariate latent change score models (LCSM) examined the relationship between changes in C-Pittsburgh Compound-B (PiB) positron emission tomography (PET) and the Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) while adjusting for covariates, including cross-sectional medial temporal lobe (MTL) tau-PET burden. We selected 352 clinically normal older participants with up to 9 years of PiB-PET and PACC-5 data from the Harvard Aging Brain Study (HABS).
Aβ accumulation was associated with subsequent cognitive decline beyond the effects of cross-sectional Aβ burden. Within this model including covariates such as age, sex, and apolipoprotein ε4 (APOEε4) status, we found no evidence supporting previously published associations between cross-sectional tau-PET and cognitive intercept/slope.
Short-term Aβ changes are significantly associated with cognitive decline in clinically normal older adults and may eclipse the effect of cross-sectional Aβ and MTL tau.
Aβ accumulation is associated with subsequent cognitive decline. High Aβ burden is not the sole metric signaling impending cognitive decline. Contrary to prior work, MTL tau-PET and cognition were not associated in our models. Models of bivariate latent Aβ and cognitive change may eclipse the effects of MTL tau.
虽然横断面β淀粉样蛋白（Aβ）对认知纵向变化的影响已得到充分证实，但Aβ与认知之间的纵向变化关系却较少被探讨。
一系列双变量潜在变化分数模型（LCSM）检验了C-匹兹堡化合物B（PiB）正电子发射断层扫描（PET）变化与临床前阿尔茨海默病认知综合评分-5（PACC-5）之间的关系，同时对包括横断面内侧颞叶（MTL）tau-PET负荷在内的协变量进行了调整。我们从哈佛衰老大脑研究（HABS）中选取了352名临床正常的老年参与者，他们拥有长达9年的PiB-PET和PACC-5数据。
除了横断面Aβ负荷的影响外，Aβ积累还与随后的认知衰退相关。在这个包括年龄、性别和载脂蛋白ε4（APOEε4）状态等协变量的模型中，我们没有发现证据支持先前发表的横断面tau-PET与认知截距/斜率之间的关联。
短期Aβ变化与临床正常老年人的认知衰退显著相关，可能会掩盖横断面Aβ和MTL tau的影响。
Aβ积累与随后的认知衰退相关。高Aβ负荷并非预示即将发生认知衰退的唯一指标。与先前的研究相反，在我们的模型中MTL tau-PET与认知无关。双变量潜在Aβ和认知变化模型可能会掩盖MTL tau的影响。
