Kaiser Permanente, Washington Health Research Institute, Seattle, Washington, USA.
Department of Pathology, University of Washington, Seattle, Washington, USA.
Alzheimers Dement. 2021 Dec;17(12):1879-1891. doi: 10.1002/alz.12348. Epub 2021 Apr 26.
The AT(N) research framework categorizes eight biomarker profiles using amyloid (A), tauopathy (T), and neurodegeneration (N), regardless of dementia status. We evaluated associations with dementia risk in a community-based cohort by approximating AT(N) profiles using autopsy-based neuropathology correlates, and considered cost implications for clinical trials for secondary prevention of dementia based on AT(N) profiles. We used Consortium to Establish a Registry for Alzheimer's Disease (moderate/frequent) to approximate A+, Braak stage (IV-VI) for T+, and temporal pole lateral ventricular dilation for (N)+. Outcomes included dementia prevalence at death and incidence in the last 5 years of life. A+T+(N)+ was the most common profile (31%). Dementia prevalence ranged from 14% (A-T-[N]-) to 79% (A+T+[N]+). Between 8% (A+T-[N]-) and 68% (A+T+[N]-) of decedents developed incident dementia in the last 5 years of life. Clinical trials would incur substantial expense to characterize AT(N). Many people with biomarker-defined preclinical Alzheimer's disease will never develop clinical dementia during life, highlighting resilience to clinical expression of AD neuropathologic changes and the need for improved tools for prediction beyond current AT(N) biomarkers.
AT(N) 研究框架使用淀粉样蛋白 (A)、tau 病 (T) 和神经退行性变 (N) 对八种生物标志物特征进行分类，无论痴呆状态如何。我们通过使用基于尸检的神经病理学相关性来近似 AT(N) 特征，评估了其与社区队列中痴呆风险的关联，并根据 AT(N) 特征考虑了临床试验用于痴呆二级预防的成本影响。我们使用阿尔茨海默病协会注册研究 (中度/频繁) 来近似 A+，Braak 阶段 (IV-VI) 用于 T+，以及颞极侧脑室扩张用于 (N)+。结果包括死亡时的痴呆患病率和生命最后 5 年的发病率。A+T+(N)+是最常见的特征 (31%)。痴呆患病率从 14%(A-T-[N]-)到 79%(A+T+[N]+)不等。在生命的最后 5 年中，有 8%(A+T-[N]-)到 68%(A+T+[N]-)的死者发生了新发痴呆。为了描述 AT(N)，临床试验将产生大量费用。许多有生物标志物定义的临床前阿尔茨海默病的人在一生中永远不会发展为临床痴呆症，这突显了对 AD 神经病理学变化临床表达的弹性，以及对当前 AT(N)生物标志物之外的预测工具的改进需求。
