Predicting resistance to amyloid-beta deposition and cognitive resilience in the oldest-old

Objective To explore long-term predictors of avoiding beta-amyloid (A beta) deposition and maintaining unimpaired cognition as outcomes in the oldest old. Methods In a longitudinal observational cohort study, 100 former participants of the Ginkgo Evaluation of Memory Study (GEMS; 2000-2008) completed biannual Pittsburgh compound B-PET imaging and annual clinical-cognitive evaluations beginning in 2010. Most recent A beta status and cognitive status were selected for each participant. Longitudinal outcomes included change in serial A beta and cognitive tests. Baseline predictors from GEMS included neuropsychological tests, daily functioning, APOE genotype, lifestyle variables, occupational measures, health history, sleep, subjective memory, physical and cognitive activities, depressive symptoms, and physical performance and health indices, among others. Results Mean age at the last cognitive evaluation was 92.0 (range 86-100) years. Mean follow-up time from baseline to last measured A beta status was 12.3 (SD 1.9) years and to last cognitive evaluation was 14.1 (SD 1.9) years. The APOE*2 allele predicted last A beta status (n = 34 A beta negative vs n = 66 A beta positive). Baseline cognition predicted cognitive status (n = 30 unimpaired vs n = 70 impaired). Predictors of cognitive status among A beta-positive participants only (n = 14 normal cognition vs n = 52 impaired) were baseline cognitive test scores and smoking history. Baseline pulse pressure predicted longitudinal A beta increase; paid work engagement and life satisfaction predicted less cognitive decline. Conclusions The APOE*2 allele and lower pulse pressure predict resistance to A beta deposition in advanced aging. Cognitive test scores 14 years prior, likely reflecting premorbid abilities, predict cognitive status and maintenance of unimpaired cognition in the presence of A beta. Several lifestyle factors appear protective.