BACKGROUND AND OBJECTIVES Cerebral amyloid angiopathy (CAA) is common in older adults and is associated with dementia. Less is known whether this association is mediated by Alzheimer disease (AD) neuropathologic changes, the examination of which was the objective of this study. METHODS This was a retrospective cross-sectional examination of the Kaiser Permanente Washington database of the Adult Changes in Thought (ACT) autopsy cohort with information on CAA, dementia, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) (amyloid neuritic plaques), and Braak (tau neurofibrillary tangles). CAA was diagnosed by immunohistochemistry and dementia by ACT Consensus Diagnostic Conference. AD neuropathology was categorized by CERAD scores and Braak stages. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% CIs of the associations of CAA with dementia, adjusting for age at death and sex, and with additional adjustments separately for CERAD scores (moderate-severe vs mild-absent), Braak stages (V-VI vs 0-IV), APOE ε4, and stroke. Formal mediation analyses were conducted to estimate age-sex-adjusted OR (95% CI) for natural indirect effects (NIEs) of CERAD scores and Braak stages. RESULTS The 848 participants had a mean age of 86.7 ± 4.6 years at death, and 57.6% were female. CAA was present in 322 participants (38.0%), of whom 152, 145, and 25 had mild, moderate, and severe CAA, respectively. Dementia was present in 384 participants (45.3%), of whom 317 had AD. Dementia was more common in those with CAA than without (53.7% vs 40.1%; age-sex-adjusted OR 1.57, 95% CI 1.18-2.10). This association remained significant after separate adjustment for other covariates but lost significance when adjusted for CERAD scores (OR 1.27, 95% CI 0.93-1.71) and Braak stages (OR 0.96, 95% CI 0.69-1.33). Findings from our formal mediation analyses show that ORs (95% CIs) for NIE of CERAD scores and Braak stages were 1.25 (1.13-1.37) and 1.63 (1.38-1.88), respectively, and CERAD scores and Braak stages mediated 53% and 111% of the total association, respectively. DISCUSSION We observed a significant association between CAA and dementia that disappeared when adjusted for CERAD or Braak stages. Findings from our mediation analyses suggest that the CAA-dementia association may be potentially mediated by AD neuropathologic changes. This hypothesis needs to be tested in future mechanistic studies in AD accounting for unmeasured confounders.

中文翻译：

---

脑淀粉样血管病、痴呆和阿尔茨海默病神经病理学变化：ACT 尸检队列的结果。


背景和目标 脑淀粉样血管病 （CAA） 在老年人中很常见，与痴呆有关。目前尚不清楚这种关联是否由阿尔茨海默病 （AD） 神经病理学变化介导，本研究的目的是对其进行检查。方法 这是对成人思想变化 （ACT） 尸检队列的 Kaiser Permanente Washington 数据库的回顾性横断面检查，其中包含有关 CAA、痴呆、建立阿尔茨海默病登记处联盟 （CERAD） （淀粉样神经炎斑块） 和 Braak （tau 神经原纤维缠结）的信息。CAA 通过免疫组化诊断，痴呆由 ACT 共识诊断会议诊断。AD 神经病理学按 CERAD 评分和 Braak 分期分类。多变量 logistic 回归模型用于估计 CAA 与痴呆关联的比值比 （ORs） 和 95% CIs，调整死亡年龄和性别，并分别对 CERAD 评分 （中重度 vs 轻度 - 不存在）、Braak 分期 （V-VI vs 0-IV） 、APOE ε4 和中风进行额外调整。进行正式中介分析以估计 CERAD 评分和 Braak 分期的自然间接效应 （NIE） 的年龄-性别调整 OR （95% CI）。结果 848 名参与者死亡时的平均年龄为 86.7 岁± 4.6 岁，其中 57.6% 为女性。322 名参与者 （38.0%） 存在 CAA，其中 152 名、145 名和 25 名分别患有轻度、中度和重度 CAA。384 名参与者 （45.3%） 患有痴呆症，其中 317 名患有 AD。痴呆症在 CAA 患者中比无 CAA 患者更常见 （53.7% vs 40.1%;年龄-性别校正 OR 1.57,95% CI 1.18-2.10）。这种关联在单独调整其他协变量后仍然显著，但在调整 CERAD 评分 （OR 1.27,95% CI 0.93-1.71） 和 Braak 分期 （OR 0.96,95% CI 0.69-1.33）。我们正式中介分析的结果显示，CERAD 评分和 Braak 分期的 NIE 的 ORs （95% CIs） 分别为 1.25 （1.13-1.37） 和 1.63 （1.38-1.88），CERAD 评分和 Braak 分期分别介导了总相关性的 53% 和 111%。我们观察到CAA与痴呆之间存在显著关联，当调整为CERAD或Braak阶段时，这种关联消失了。我们的中介分析结果表明，CAA 与痴呆的关联可能是由 AD 神经病理学变化介导的。这一假设需要在 AD 的未来机制研究中进行测试，以解释未测量的混杂因素。