Maternal history of memory impairment at any age and paternal history of early-onset memory impairment were associated with higher brain β-amyloid levels in cognitively unimpaired older adults.
Published in JAMA Neurology, researchers investigated the association between parental history of memory impairment and brain β-amyloid (Aβ) levels in 4,413 cognitively unimpaired adults with a mean age of 71 years; 2,617 were women. Participants were screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer (A4) study across 67 sites in the U.S., Australia, Canada, and Japan between 2014 and 2017.
The authors collected demographic data, apolipoprotein E (APOE) genotype, participant-reported parental history of memory impairment, and parental age at symptom onset. Neocortical 18F-florbetapir Aβ-PET and the Preclinical Alzheimer Cognitive Composite were used to assess Aβ burden and cognition.
Mean Aβ-PET was elevated in 455 individuals with a history of memory impairment in both parents and in 1,772 with only maternal parent compared with 632 with only paternal history or 1,554 with no parental history.
Paternal history of early-onset memory impairment over age 65 was associated with elevated participant Aβ-PET compared with no paternal history, whereas maternal history was associated with elevated Aβ in both early-onset and late-onset groups.
The association between maternal history and Aβ burden remained significant after adjusting for APOE ε2 and ε4 allele counts. Sensitivity analyses using stricter parental Alzheimer disease diagnosis criteria (clinically diagnosed or autopsy-confirmed) yielded similar results. There was no interaction between offspring sex and parental history on Aβ levels.
Study authors suggested a preferential maternal transmission of AD risk starting in the preclinical stage. Maternal history and paternal history of early-onset memory impairment may help identify asymptomatic individuals at higher risk for Aβ accumulation. Further longitudinal studies are needed to clarify parental history's influence on AD trajectory.
Full disclosures can be found in the published research.