Parental History of Memory Impairment and β-Amyloid in Cognitively Unimpaired Older Adults

ImportanceStudies have suggested that maternal history of late-onset Alzheimer disease, but not paternal, predisposes individuals to higher brain beta-amyloid (A beta) burden, reduced brain metabolism, and lower gray matter volumes. ObjectiveTo characterize maternal vs paternal history of memory impairment in terms of brain A beta-positron emission tomography (A beta-PET) and baseline cognition among a large sample of cognitively unimpaired older adults. Design, Setting, and ParticipantsThis cross-sectional study leveraged data from 4413 individuals who were screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer (A4) study, a randomized clinical trial conducted across 67 sites in the US, Australia, Canada, and Japan aimed at Alzheimer disease prevention. Data were collected between April 2014 and December 2017 and analyzed from December 2022 to June 2023. Participants were cognitively unimpaired adults (Clinical Dementia Rating = 0 and/or Mini-Mental State Examination score >= 25) between the ages of 65 and 85 years who underwent PET imaging to assess cortical A beta levels for trial eligibility. A total of 4492 participants were screened, and 79 missing data were excluded. Main Outcomes and MeasuresDemographic characteristics (eg, age, sex, education), apolipoprotein E genotyping, participant-reported parental history of memory impairment and parental age at symptom onset were collected as variables. Parental history was assessed in terms of continuous neocortical 18F-florbetapir A beta-PET and the Preclinical Alzheimer Cognitive Composite. ResultsOf 4413 individuals (mean [SD] age, 71.27 [4.66] years, 2617 women [59.3%]), mean A beta-PET was elevated in individuals with history of memory impairment in both parents (n = 455; mean [SD] standardized uptake value ratio [SUVR] = 1.12 [0.19]; Wilcoxon P = 1.1 x 10-5) and in those with only maternal history (n = 1772; mean [SD] SUVR = 1.10 [0.19]; Wilcoxon P = 2.70 x 10-5) compared with those with only paternal history (n = 632; mean [SD] SUVR = 1.08 [0.18]; Wilcoxon P = 1.1 x 10-5) or no family history (n = 1554; mean [SD] SUVR = 1.08 [0.19]; Wilcoxon P = 1.1 x 10-5). Paternal history of early-onset memory impairment (age <65 years) but not late-onset (age >= 65 years) was associated with elevated participant A beta-PET (mean [SD] SUVR = 1.19 [0.21]; P = 3.00 x 10-6) in comparison with no paternal history (mean [SD] SUVR = 1.09 [0.19]) whereas maternal history was associated with elevated A beta in both early-onset and late-onset groups. There was no association with cognition. Conclusions and RelevanceIn this study, maternal history (at any age) and paternal history of early-onset memory impairment were associated with A beta burden among asymptomatic older individuals. Sex-specific parental history may help inform clinicians on likelihood of A beta burden in offspring and help identify high-risk individuals at the earliest stages of disease for prevention.