From the Rush Alzheimer's Disease Center (A.K., L.Y., P.A.B., L.L.B., D.A.B., J.A.S.), Department of Pathology (A.K., J.A.S.), Department of Neurological Sciences (L.Y., L.L.B., D.A.B., J.A.S.), and Department of Behavioral Sciences (P.A.B., L.L.B.), Rush University Medical Center, Chicago, IL.
Neurology. 2020 Oct 6;95(14):e1951-e1962. doi: 10.1212/WNL.0000000000010454. Epub 2020 Aug 4.
To examine the impact of 3 pathologic groups, pure limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy (LATE) neuropathologic changes (NC), pure Alzheimer disease neuropathologic change (ADNC), and mixed ADNC with LATE-NC, on late-life cognitive decline.
Data came from 1,356 community-based older persons who completed detailed annual cognitive testing and systematic neuropathologic examination at autopsy to identify LATE-NC, ADNC, and other age-related pathologies. Persons were categorized into (0) a group without a pathologic diagnosis of LATE or ADNC (n = 378), (1) LATE-NC without ADNC (n = 91), (2) ADNC without LATE-NC (n = 535), and (3) mixed ADNC with LATE-NC (n = 352). We used mixed-effect models to examine the group associations with rate of decline in global cognition and 5 cognitive domains and then examined whether age modified associations.
Compared to those without LATE-NC or ADNC, those with pure LATE-NC had a faster decline in global cognition ( = 0.025) and episodic memory ( = 0.002); however, compared to persons with pure ADNC, those with pure LATE-NC showed a slower decline. Those with mixed ADNC with LATE-NC showed the fastest decline compared to those with either pathology alone. Persons ≥90 years of age with mixed ADNC with LATE-NC had slower cognitive decline compared to those ≤89 years of age.
Persons with pure LATE-NC follow a slower trajectory compared to those with pure ADNC. Those with mixed LATE/ADNC have a steeper decline than individuals with either pathology alone. In addition, age may modify the effect of pathology on cognitive decline. These findings have important implications for the development of biomarkers and prognosis for late-life cognitive decline.
This study provides Class I evidence that LATE-NC and Alzheimer disease pathologic changes are associated with different trajectories of late-life cognitive decline.
研究 3 种病理组，即单纯边缘为主的年龄相关性跨反应 DNA 结合蛋白 43 脑病（LATE）神经病理改变（NC）、单纯阿尔茨海默病神经病理改变（ADNC）和 LATE-NC 与 ADNC 混合，对晚年认知衰退的影响。
数据来自 1356 名社区老年人，他们在尸检时完成了详细的年度认知测试和系统神经病理学检查，以确定 LATE-NC、ADNC 和其他与年龄相关的病理学。将这些人分为（0）一组没有 LATE 或 ADNC 的病理诊断（n=378）、（1）无 ADNC 的 LATE-NC（n=91）、（2）无 LATE-NC 的 ADNC（n=535）和（3）LATE-NC 与 ADNC 混合（n=352）。我们使用混合效应模型来检验各组与全球认知和 5 个认知领域的下降率之间的关联，然后检验年龄是否会改变关联。
与没有 LATE-NC 或 ADNC 的人相比，单纯 LATE-NC 的人在全球认知（=0.025）和情景记忆（=0.002）方面的下降速度更快；然而，与单纯 ADNC 的人相比，单纯 LATE-NC 的人下降速度较慢。与单独具有任何一种病理学的人相比，具有 LATE/ADNC 混合的人表现出最快的下降。与≤89 岁的人相比，≥90 岁的具有 LATE/ADNC 混合的人认知衰退较慢。
与单纯 ADNC 的人相比，单纯 LATE-NC 的人表现出较慢的轨迹。与单独具有任何一种病理学的人相比，具有 LATE/ADNC 混合的人下降得更陡峭。此外，年龄可能会改变病理学对认知衰退的影响。这些发现对开发与晚年认知衰退相关的生物标志物和预后具有重要意义。
本研究提供了 I 级证据，表明 LATE-NC 和阿尔茨海默病病理变化与晚年认知衰退的不同轨迹有关。
