Parental history of memory impairment predicts β‐amyloid burden and positivity in a preclinical population

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is highly heritable, and previous studies suggest that a maternal family history of AD confers a greater risk for AD than paternal history. Whether the maternal and paternal history of AD dementia impacts AD endophenotypes among cognitively unimpaired individuals is not fully described. We examine the effects of parental history of dementia on brain amyloid levels and both subjective and objective measures of cognition.MethodMeasures of objective and subjective cognition (Preclinical Alzheimer’s Cognitive Composite; Cognitive Function Index), APOE‐e4 genotype, ß‐amyloid (Aß) PET, and self‐reported parental history of memory impairment and AD dementia were obtained from 4,429 cognitively unimpaired individuals screening for the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study (mean(SD); age = 71.2(4.7), %male = 40.7, %Non‐Hispanic White = 87.9). Aß was measured with 18F‐florbetapir‐PET using a mean neocortical composite referenced to whole cerebellum (Aß+threshold:1.11 SUVr). Linear regression models assessed the association between maternal or paternal history with cross‐sectional cortical Aß levels and cognition covarying for the participant’s age, sex, and years of education where relevant.ResultAs previously reported, parental history of memory impairment (one or both parents) was significantly associated with elevated neocortical Aß (p<0.001). The association between Aß and history in both parents remained significant when covarying for APOE‐e4 allele count (p = 0.002). In interaction models, parental history in either one or both parents did not modulate the association between APOE‐e4 and Aß. Mean amyloid levels were elevated in individuals with history in both parents (n = 456, p<0.001) and in those with only maternal family history (n = 1776, p<0.001), compared to those with only paternal history (n = 634) or no family history (n = 1563, Figure 1B). Regression models confirmed this finding: ß = 0.03, p<0.001 in individuals with maternal history, ß = 0.01, p = 0.1 in individuals with paternal history. The results remained consistent for participants whose parents received a clinical diagnosis of AD dementia (ßmaternal = 0.02, pmaternal = 0.01; ßpaternal = 0.02, ppaternal = 0.2). No associations with subjective or objective cognition were observed.ConclusionWe confirm that self‐reported family history of dementia is associated with elevated brain amyloid independently of APOE‐e4 status in the A4 Study, with evidence that maternal family history has a stronger impact on Aß burden among asymptomatic older individuals.