Younes Kyan, Johns Emily, Young Christina B, Kennedy Gabriel, Mukherjee Shubhabrata, Vossler Hillary A, Winer Joseph, Cody Karly, Henderson Victor W, Poston Kathleen L, Betthauser Tobey J, Bevis Bill, Brooks William M, Burns Jeffrey M, Coombes Stephen A, DeCarli Charles, DiFilippo Frank P, Duara Ranjan, Fan Audrey P, Gibbons Laura E, Golde Todd, Johnson Sterling C, Lepping Rebecca J, Leverenz James, McDougall Sean, Rogalski Emily, Sanders Elizabeth, Pasaye Joshua, Sridhar Jaiashre, Saykin Andrew J, Sridharan Anjali, Swerdlow Russell, Trittschuh Emily H, Vaillancourt David, Vidoni Eric, Wang Wei-En, Mez Jesse, Hohman Timothy J, Tosun Duygu, Biber Sarah, Kukull Walter A, Crane Paul K, Mormino Elizabeth C
Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, California, USA.
Department of Medicine, The University of Washington, Seattle, Washington, USA.
Alzheimers Dement. 2025 Mar;21(3):e70075. doi: 10.1002/alz.70075.
Amyloid positron emission tomography (PET) is increasingly available for diagnosis of Alzheimer`s disease (AD); however, its practical implications in heterogenous cohorts are debated.
Amyloid PET from 890 National Alzheimer`s Coordinating Center participants with up to 10 years post-PET follow up was analyzed. Cox proportional hazards and linear mixed models were used to investigate amyloid burden prediction of etiology and prospective functional status and cognitive decline.
Amyloid positivity was associated with progression from unimpaired to mild cognitive impairment and dementia. Amyloid burden in the unimpaired group was associated with lower initial memory levels and faster decline in memory, language, and global cognition. In the Impaired group, amyloid was associated with lower initial levels and faster decline for memory, language, executive function, and global cognition.
Amyloid burden is an important prognostic marker in a clinically heterogeneous cohort. Future work is needed to establish the proportion of decline driven by AD versus non-AD processes in the context of mixed pathology.
Our findings highlight the importance of amyloid positron emission tomography (PET) in heterogenous cohorts, including diverse demographics, clinical syndromes, and underlying etiologies. The results also provide evidence that higher amyloid levels were linked to functional progression from unimpaired cognition to mild cognitive impairment (MCI) and from MCI to dementia. In cognitively unimpaired individuals, higher amyloid burden was associated with poorer memory at baseline and subsequent declines in memory, language, and global cognition. Among individuals with cognitive impairment, amyloid burden was associated with worse initial memory, language, executive function, and global cognition, and faster declines over time.
淀粉样蛋白正电子发射断层扫描（PET）在阿尔茨海默病（AD）诊断中的应用日益广泛；然而，其在异质性队列中的实际意义仍存在争议。
分析了来自国家阿尔茨海默病协调中心的890名参与者的淀粉样蛋白PET数据，这些参与者在PET检查后长达10年进行了随访。采用Cox比例风险模型和线性混合模型来研究淀粉样蛋白负荷对病因、前瞻性功能状态和认知衰退的预测作用。
淀粉样蛋白阳性与从认知正常进展为轻度认知障碍和痴呆相关。认知正常组的淀粉样蛋白负荷与较低的初始记忆水平以及记忆、语言和整体认知功能的更快衰退相关。在认知障碍组中，淀粉样蛋白与记忆、语言、执行功能和整体认知的较低初始水平以及更快衰退相关。
淀粉样蛋白负荷是临床异质性队列中的一个重要预后标志物。在混合病理情况下，需要进一步开展研究以确定AD与非AD过程导致的衰退比例。
我们的研究结果强调了淀粉样蛋白正电子发射断层扫描（PET）在异质性队列中的重要性，这些队列包括不同的人口统计学特征、临床综合征和潜在病因。结果还提供了证据表明，较高的淀粉样蛋白水平与从认知正常到轻度认知障碍（MCI）以及从MCI到痴呆的功能进展相关。在认知正常的个体中，较高的淀粉样蛋白负荷与基线时较差的记忆力以及随后记忆、语言和整体认知功能的衰退相关。在认知障碍个体中，淀粉样蛋白负荷与较差的初始记忆、语言、执行功能和整体认知功能相关，并且随着时间的推移衰退更快。
