OBJECTIVES Exploration of medical histories and medications associated with Alzheimer disease neuropathologic change (ADNC) absence and potential resistance may identify protective factors against ADNC. This was a retrospective examination of data from participants age ≥90 years who enrolled in The 90+ Study, a longitudinal study based in California. Participants underwent neuropathologic analysis for the presence of neuritic amyloid plaques (NPs) (any), beta amyloid plaques (Thal phase > 0), and neurofibrillary tangles (>2). Odds ratios (ORs) for the presence of pathologic changes to APOE genotype, self-reported medical histories, and medication use were estimated by logistic regression and (a)djusted for sex, age at death (continuous), and education. RESULTS We examined 267 participants; 75% were female, with a mean age at death of 98 (± 3.5) years. Variables associated with ADNC absence/presence were for NPs: heart disease (adjusted OR [aOR] = 0.46), APOE-ε4 (aOR = 3.48), angiotensin-converting enzyme (ACE) inhibitors (aOR = 0.46), cataracts (aOR = 0.26), and beta-blockers (aOR = 0.51); for Aβ: heart disease (aOR = 0.33) and APOE-ε4 (aOR = 8.10); and for neurofibrillary tangles: ACE inhibitors (aOR = 0.46), glaucoma (aOR = 0.29), HTN (aOR = 0.44), seizures (aOR = 0.16), APOE-ε2 presence (aOR = 0.39), and vasodilators (aOR = 0.36). These observations would not survive multiple comparison corrections. DISCUSSION Cataract formation, APOE status, ACE inhibitors, and beta-blockers may be associated with ADNC absence because of differential lipid trafficking. Survival bias and type 1 errors warrant consideration.

中文翻译：

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与最年长老年人不存在阿尔茨海默病神经病理学变化相关的病史：90+ 研究。


目的 探索与阿尔茨海默病神经病理学变化 （ADNC） 缺失和潜在耐药相关的病史和药物可能会确定对 ADNC 的保护因素。这是对参加 90+ 研究的 ≥90+ 参与者的数据的回顾性检查，这是一项位于加利福尼亚州的纵向研究。参与者接受了神经病理学分析，以确定神经炎淀粉样蛋白斑块 （NPs） （任何）、β 淀粉样蛋白斑块 （Thal 期 > 0） 和神经原纤维缠结 （>2） 的存在。通过 logistic 回归估计 APOE 基因型病理变化、自我报告的病史和药物使用存在的优势比 （ORs），并 （a） 根据性别、死亡年龄（连续）和教育程度进行调整。结果： 我们检查了 267 名参与者;75% 为女性，平均死亡年龄为 98 （± 3.5） 岁。与 ADNC 缺失/存在相关的变量是 NP：心脏病 （校正 OR [aOR] = 0.46）、APOE-ε4 （aOR = 3.48）、血管紧张素转换酶 （ACE） 抑制剂 （aOR = 0.46）、白内障 （aOR = 0.26） 和 β 受体阻滞剂 （aOR = 0.51）;对于 Aβ：心脏病 （aOR = 0.33） 和 APOE-ε4 （aOR = 8.10）;对于神经原纤维缠结：ACE 抑制剂 （aOR = 0.46）、青光眼 （aOR = 0.29）、HTN （aOR = 0.44）、癫痫发作 （aOR = 0.16）、APOE-ε2 存在 （aOR = 0.39） 和血管扩张剂 （aOR = 0.36）。这些观察结果无法在多次比较校正后幸存下来。讨论 白内障形成、APOE 状态、ACE 抑制剂和 β 受体阻滞剂可能与 ADNC 缺失有关，因为脂质运输差异。值得考虑生存偏倚和 1 型错误。