Alzheimer's Disease and concomitant pathologies in SuperAgers

Abstract

Background: “SuperAgers” are oldest‐old adults (ages 80+) with memory performance resembling adults in their 50s to mid‐60s. This study assessed presence and levels of Alzheimer's disease (AD) neuropathologic change (ADNC) and concomitant neuropathologies in SuperAgers, AD cases, and oldest‐old controls using three national cohorts. Method: Harmonized, longitudinal memory, executive function, and language scores and cross‐sectional neuropathology data in Non‐Hispanic White participants were gathered from the ADSP Phenotype Harmonization Consortium (ACT, ROSMAPMARS, and NACC). SuperAgers (N = 240) included individuals ages 80+ with a memory score equal to or exceeding individuals ages 50‐64 and language and executive function domain scores within normal limits who remain cognitively normal until death if longitudinal datapoints are available. Analyses also included age‐matched Alzheimer's disease (AD) cases (N = 1,181) and cognitively normal controls (N = 225). We performed binary logistic regression analyses comparing presence and degree of Alzheimer's Disease neuropathologic change (ADNC), neocortical/medial temporal lobe TDP‐43, hippocampal sclerosis, alpha‐synucleinopathy, cerebrovascular disease, and cerebral amyloid angiopathy (CAA) of SuperAgers and their counterparts, adjusting for sex, education, and age at death. We adjusted for multiple comparisons using the Benjamini‐Hochberg procedure. Result: Compared to AD dementia cases, SuperAgers had significantly less ADNC and concomitant neuropathologies. SuperAgers, AD dementia cases, and controls had similar presence of microinfarcts, lacunes, and whole brain vascular disease (p > 0.05). Compared to age‐matched controls, SuperAgers had lower likelihood and level of neuritic plaques, CAA, and neocortical/medial temporal lobe TDP‐43 (Figure 1). Conclusion: Across three national cohorts, SuperAgers with optimal memory performance had fewer neuritic plaques, CAA, and neocortical/medial temporal lobe TDP‐43 compared to AD dementia cases and other oldest‐old adults with typical memory performance. In contrast, despite their optimal memory performance, SuperAgers had similar levels of cerebrovascular pathology to AD cases and controls.