Primary age-related tauopathy is increasingly recognized as a separate neuropathological entity different from Alzheimer's disease. Both share the neuropathological features of tau aggregates and neuronal loss in the temporal lobe, but primary age-related tauopathy lacks the requisite amyloid plaques central to Alzheimer's disease. While both have similar clinical presentations, individuals with symptomatic primary age-related tauopathy are commonly of more advanced ages with milder cognitive dysfunction. Direct comparison of the neuropsychological trajectories of primary age-related tauopathy and Alzheimer's disease has not been thoroughly evaluated and thus, our objective was to determine how cognitive decline differs longitudinally between these two conditions after the onset of clinical symptoms. Data were obtained from the National Alzheimer's Coordinating Center on participants with mild cognitive impairment at baseline and either no neuritic plaques (i.e. primary age-related tauopathy) or moderate to frequent neuritic plaques (i.e. Alzheimer neuropathological change) at subsequent autopsy. For patients with Alzheimer's disease and primary age-related tauopathy, we compared rates of decline in the sum of boxes score from the CDR® Dementia Staging Instrument and in five cognitive domains (episodic memory, attention/working memory, executive function, language/semantic memory, and global composite) using z-scores for neuropsychological tests that were calculated based on scores for participants with normal cognition. The differences in rates of change were tested using linear mixed-effects models accounting for clinical centre clustering and repeated measures by individual. Models were adjusted for sex, age, education, baseline test score, Braak stage, apolipoprotein ε4 (APOE ε4) carrier status, family history of cognitive impairment, and history of stroke, hypertension, or diabetes. We identified 578 participants with a global CDR of 0.5 (i.e. mild cognitive impairment) at baseline, 126 with primary age-related tauopathy and 452 with Alzheimer's disease. Examining the difference in rates of change in CDR sum of boxes and in all domain scores, participants with Alzheimer's disease had a significantly steeper decline after becoming clinically symptomatic than those with primary age-related tauopathy. This remained true after adjusting for covariates. The results of this analysis corroborate previous studies showing that primary age-related tauopathy has slower cognitive decline than Alzheimer's disease across multiple neuropsychological domains, thus adding to the understanding of the neuropsychological burden in primary age-related tauopathy. The study provides further evidence to support the hypothesis that primary age-related tauopathy has distinct neuropathological and clinical features compared to Alzheimer's disease.

中文翻译：

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原发性年龄相关 tau 蛋白病引起的轻度认知障碍的认知轨迹。


原发性年龄相关性 tau 蛋白病越来越被认为是一种不同于阿尔茨海默病的独立神经病理学实体。两者都具有 tau 蛋白聚集和颞叶神经元丢失的神经病理学特征，但原发性年龄相关 tau 蛋白病缺乏阿尔茨海默氏病所必需的淀粉样斑块。虽然两者具有相似的临床表现，但患有症状性原发性年龄相关 tau 蛋白病的个体通常年龄较大，认知功能障碍较轻。原发性年龄相关 tau 蛋白病和阿尔茨海默氏病的神经心理学轨迹的直接比较尚未得到彻底评估，因此，我们的目标是确定临床症状出现后这两种疾病之间认知能力下降的纵向差异。数据来自国家阿尔茨海默病协调中心，参与者在基线时患有轻度认知障碍，并且在随后的尸检中要么没有神经炎斑块（即原发性年龄相关性tau蛋白病），要么中度至频繁的神经炎斑块（即阿尔茨海默神经病理学改变）。对于患有阿尔茨海默病和原发性年龄相关 tau 蛋白病的患者，我们比较了 CDR® 痴呆分期仪的方框评分总和以及五个认知领域（情景记忆、注意力/工作记忆、执行功能、语言/语义）的下降率。记忆和整体综合），使用 z 分数进行神经心理学测试，该测试是根据具有正常认知的参与者的分数计算得出的。使用考虑临床中心聚类和个体重复测量的线性混合效应模型来测试变化率的差异。 模型根据性别、年龄、教育程度、基线测试分数、Braak 分期、载脂蛋白 ε4 (APOE ε4) 携带状况、认知障碍家族史以及中风、高血压或糖尿病史进行调整。我们确定了 578 名基线时总体 CDR 为 0.5（即轻度认知障碍）的参与者，其中 126 名参与者患有原发性年龄相关 tau 病，452 名参与者患有阿尔茨海默病。通过检查 CDR 框总和和所有领域评分的变化率差异，患有阿尔茨海默氏病的参与者在出现临床症状后比患有原发性年龄相关 tau 病的参与者出现了更急剧的下降。调整协变量后，情况仍然如此。这项分析的结果证实了之前的研究表明，在多个神经心理学领域，原发性年龄相关 tau 病的认知能力下降速度比阿尔茨海默氏病更慢，从而增加了对原发性年龄相关 tau 病神经心理负担的理解。该研究提供了进一步的证据来支持以下假设：与阿尔茨海默氏病相比，原发性年龄相关 tau 蛋白病具有独特的神经病理学和临床特征。