Brain Behav. 2012 May;2(3):221-30. doi: 10.1002/brb3.47.
Asymptomatic Alzheimer disease (ASYMAD) is characterized by normal cognition despite substantial AD pathology. To identify factors contributing to cognitive resilience, we compared early changes in regional cerebral blood flow (rCBF) in individuals subsequently diagnosed as ASYMAD with changes in cognitively impaired (CI) and normal older participants from the Baltimore Longitudinal Study of Aging. Participants underwent annual positron emission tomography (PET) rCBF measurements beginning 10.0 (SD 3.6) years before death and while cognitively intact. Based on clinical and autopsy information, subjects were grouped as cognitively normal (CN = 7), ASYMAD (n= 6), and CI (=6). Autopsy material was analyzed using CERAD and Braak scores and quantitative stereologic measures of tau and amyloid. ASYMAD and CI groups had similar CERAD and Braak scores, similar amounts of β-amyloid and tau in middle frontal (MFG), middle temporal (MTG), and inferior parietal (IP) regions, and more β-amyloid than CN in precuneus, MFG, and IP areas. Voxel-based PET analysis identified similarities and differences in longitudinal rCBF change among groups across a 7.2-year interval. Both ASYMAD and CI groups showed similar longitudinal rCBF declines in precuneus, lingual, and MTG regions relative to CN. The CI also showed greater rCBF decreases in anterior and posterior cingulate, cuneus, and brainstem regions relative to ASYMAD and CN, whereas ASYMAD showed greater relative rCBF increases over time in medial temporal and thalamic regions relative to CI and CN. Our findings provide evidence of early functional alterations that may contribute to cognitive resilience in those who accumulate AD pathology but maintain normal cognition.
无症状阿尔茨海默病（ASYMAD）的特征是认知正常，尽管存在大量 AD 病理学。为了确定导致认知弹性的因素，我们比较了随后被诊断为 ASYMAD 的个体与认知障碍（CI）和正常老年参与者在认知完整时的早期区域脑血流（rCBF）变化。参与者接受了每年一次的正电子发射断层扫描（PET）rCBF 测量，测量开始于死亡前 10.0 年（标准差为 3.6 年），并且认知完整。根据临床和尸检信息，将受试者分为认知正常（CN=7）、ASYMAD（n=6）和 CI（n=6）。使用 CERAD 和 Braak 评分以及 tau 和淀粉样蛋白的定量立体测量分析尸检材料。ASYMAD 和 CI 组的 CERAD 和 Braak 评分相似，中额（MFG）、中颞（MTG）和下顶（IP）区域的β-淀粉样蛋白和 tau 含量相似，并且在楔前叶、MFG 和 IP 区域的β-淀粉样蛋白含量高于 CN。基于体素的 PET 分析确定了 7.2 年间隔内各组纵向 rCBF 变化的相似性和差异。ASYMAD 和 CI 组相对于 CN 组在楔前叶、舌回和 MTG 区域均表现出相似的纵向 rCBF 下降。CI 相对于 ASYMAD 和 CN 组在前后扣带回、楔叶和脑干区域也表现出更大的 rCBF 下降，而 ASYMAD 组相对于 CI 和 CN 组在颞叶和丘脑区域的 rCBF 增加更为明显。我们的研究结果提供了早期功能改变的证据，这些改变可能有助于在积累 AD 病理学但保持认知正常的个体中产生认知弹性。
