Department of Medicine, University of Washington, Seattle, WA, USA.
VA Puget Sound Health Care System, Geriatric Research Education and Clinical Center, Seattle, WA, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Alzheimers Dement. 2017 Dec;13(12):1307-1316. doi: 10.1016/j.jalz.2017.04.011. Epub 2017 Jun 15.
There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia.
We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments.
During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with ≥ APOE ε4 allele, more extensive Alzheimer's-related neuropathology, and higher proportions with other Alzheimer's dementia genetic risk variants.
A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer's dementia.
在典型的晚发性阿尔茨海默病中,可能存在生物学上相关的异质性。
我们分析了来自前瞻性队列研究的患有偶发性晚发性阿尔茨海默病的人的认知数据。我们确定了记忆、视空间功能、语言和执行功能的个体平均值。我们确定了与平均值相比存在大量损害的领域。我们比较了按相对损害程度定义的组的人口统计学、神经病理学和遗传发现。
在 32286 人年的随访期间,869 人患上了阿尔茨海默病。有 393 人(48%)没有一个领域存在大量相对损害。一些参与者在记忆(148 人,18%)、视空间功能(117 人,14%)、语言(71 人,9%)和执行功能(66 人,8%)方面存在孤立的相对损害。孤立性相对记忆损害组中,具有 APOE ε4 等位基因的比例较高,与阿尔茨海默病相关的神经病理学更广泛,具有其他阿尔茨海默病遗传风险变异的比例也较高。
认知亚组化策略可能会识别出具有生物学上不同的阿尔茨海默病人群亚组。