Sin Mo-Kyung, Cheng Yan, Roseman Jeffrey M, Latimer Caitlin, Ahmed Ali, Zamrini Edward
College of Nursing, Seattle University, Seattle, WA 98122-1090, USA.
The School of Medicine & Health Sciences, George Washington University, Washington, DC 20037, USA.
J Clin Med. 2023 Mar 23;12(7):2463. doi: 10.3390/jcm12072463.
Alzheimer's disease (AD) is characterized by cognitive impairment in the presence of cerebral amyloid plaques and neurofibrillary tangles. Less is known about the characteristics and predictors of resilience to cognitive impairment in the presence of neuropathological evidence of AD, the focus of this study. Of 3170 adults age ≥65 years in the National Alzheimer's Coordinating Center (NACC) brain autopsy cohort, 1373 had evidence of CERAD level moderate to frequent neuritic plaque density and Braak stage V-VI neurofibrillary tangles. Resilience was defined by CDR-SOB and CDR-Global scores of 0-2.5 and 0-0.5, respectively, and non-resilience, CDR-SOB and CDR-Global scores >2.5 and >0.5, respectively. Multivariable logistic regression models were used to examine the independent associations of patient characteristics with resilience. There were 62 participants (4.8%) with resilience. Those with resilience were older (mean age, 88.3 vs. 82.4 years), more likely to be women (61.3% vs. 47.3%) and had a lower prevalence of the APOE-e4 carrier (41.9% vs. 56.2%). They also had a higher prevalence of hypertension, heart failure, atrial fibrillation, diuretic use, beta-blocker use, and APOE-e2 carrier status. Greater age at death, diuretic use, and APOE-e2 were the only characteristics independently associated with higher odds of the AD resilience phenotype (adjusted OR, 1.09; 95% CI, 1.05-1.13; < 0.01; 2.00 (1.04-3.87), = 0.04, 2.71 (1.31-5.64), < 0.01, respectively). The phenotype of resilience to cognitive impairment is uncommon in older adults who have neuropathological evidence of AD.
阿尔茨海默病（AD）的特征是在存在脑淀粉样斑块和神经原纤维缠结的情况下出现认知障碍。对于在存在AD神经病理学证据的情况下对认知障碍具有恢复力的特征和预测因素知之甚少，本研究聚焦于此。在国家阿尔茨海默病协调中心（NACC）脑尸检队列的3170名年龄≥65岁的成年人中，1373人有CERAD水平为中度至频繁神经炎性斑块密度和Braak分期V-VI神经原纤维缠结的证据。恢复力分别由CDR-SOB和CDR-Global评分为0-2.5和0-0.5定义，而非恢复力则分别由CDR-SOB和CDR-Global评分>2.5和>0.5定义。使用多变量逻辑回归模型来检验患者特征与恢复力的独立关联。有62名参与者（4.8%）具有恢复力。具有恢复力的人年龄更大（平均年龄，88.3岁对82.4岁），更可能是女性（61.3%对47.3%），且APOE-e4携带者的患病率较低（41.9%对56.2%）。他们还具有更高的高血压、心力衰竭、心房颤动、使用利尿剂、使用β受体阻滞剂和APOE-e2携带者状态的患病率。更高的死亡年龄、使用利尿剂和APOE-e2是与AD恢复力表型较高几率独立相关的仅有的特征（调整后的OR，1.09；95%CI，1.05-1.13；P<0.01；2.00（1.04-3.87），P=0.04，2.71（1.31-5.64），P<0.01，分别）。在有AD神经病理学证据的老年人中，对认知障碍具有恢复力的表型并不常见。
