Hassenstab Jason, Monsell Sarah E, Mock Charles, Roe Catherine M, Cairns Nigel J, Morris John C, Kukull Walter
From the Knight Alzheimer's Disease Research Center, Department of Neurology (JH, CMR, NJC, JCM), Washington University School of Medicine, St. Louis, Missouri; and National Alzheimer's Coordinating Center (SEM, CM, WK), University of Washington, Seattle, Washington.
J Neuropathol Exp Neurol. 2015 Nov;74(11):1086-92. doi: 10.1097/NEN.0000000000000254.
To evaluate cognitive performance among persons who did and did not develop clinical Alzheimer disease (AD) but had AD neuropathology at autopsy, we examined neuropsychological performance in cognitively healthy (Clinical Dementia Rating [CDR] = 0) participants who returned for at least 1 follow-up and died within 2 years of their last assessment. Nonprogressors remained at CDR = 0 until death; progressors developed symptomatic AD during life (CDR > 0). Cognitive performance at baseline was compared between progressors and nonprogressors on a global cognitive composite and 4 domain-specific composites (episodic memory, language, attention/working memory, and executive function). Models adjusted for age, education, sex, and non-AD neuropathology. Progressors (n = 173) had worse performance than nonprogressors (n = 141) in nearly all cognitive domains. Progressors scored lower on composites of global cognition (P < 0.001), executive function (P = 0.0006), language (P < 0.0001), and episodic memory (P = 0.0006) but not on attention/working memory (P = 0.91). These data indicate that individuals with underlying AD neuropathology who are clinically healthy but who later develop symptomatic AD have worse performance in a wide range of domains versus individuals with underlying AD neuropathology who are clinically healthy but do not become symptomatic during life. Therefore, subtle cognitive decline at baseline may indicate an increased risk of progression to symptomatic AD.
为了评估那些生前未患临床阿尔茨海默病（AD）但尸检时有AD神经病理学改变的人群以及已患临床AD人群的认知表现，我们对认知健康（临床痴呆评定量表[CDR]=0）且至少返回接受1次随访并在末次评估后2年内死亡的参与者进行了神经心理学表现检查。非进展者直至死亡时CDR仍为0；进展者在生前发展为有症状的AD（CDR>0）。比较了进展者和非进展者在基线时的整体认知综合指标以及4个特定领域综合指标（情景记忆、语言、注意力/工作记忆和执行功能）方面的认知表现。模型对年龄、教育程度、性别和非AD神经病理学进行了校正。进展者（n=173）在几乎所有认知领域的表现均比非进展者（n=141）差。进展者在整体认知（P<0.001）、执行功能（P=0.0006）、语言（P<0.0001）和情景记忆（P=0.0006）综合指标上得分较低，但在注意力/工作记忆方面得分无差异（P=0.91）。这些数据表明，具有潜在AD神经病理学改变但临床健康、后来发展为有症状AD的个体，与具有潜在AD神经病理学改变但临床健康且生前未出现症状的个体相比，在广泛的领域中表现更差。因此，基线时的细微认知衰退可能表明进展为有症状AD的风险增加。
