Characteristics and Predictors of Alzheimer's Disease Resilience Phenotype

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; p < 0.01; 2.00 (1.04-3.87), p = 0.04, 2.71 (1.31-5.64), p < 0.01, respectively). The phenotype of resilience to cognitive impairment is uncommon in older adults who have neuropathological evidence of AD.