Converging evidence suggests that subjective cognitive concerns (SCC) are associated with biomarker evidence of Alzheimer's disease (AD) prior to objective clinical impairment. However, the sensitivity of SCC reports in early AD may be biased by demographic factors. Here, we sought to investigate whether age, education, and sex influence the relationship between SCC and amyloid (Aβ) burden.

In this cross-sectional study, we examined 252 clinically normal (CN) individuals (57.7% females) enrolled in the Harvard Aging Brain Study, ages 63–90 years (mean 73.7±6) with 6–20 years of education (mean 15.8±3). SCC was assessed as a composite score comprising three questionnaires. Cortical Aβ burden was assessed with Pittsburgh compound B positron emission tomography imaging. A series of linear regression models assessed the potential modifying role of demographic variables with respect to Aβ burden and SCC. A post-hoc mediation model was implemented to further understand the relationship between Aβ burden and SCC via their relationship with education.

Age (β = −0.84, p = 0.36) and sex (β = −0.55, p = 0.22) did not modify the relationship between SCC and Aβ burden. Fewer years of education was correlated with greater SCC (r = −0.12, p = 0.05), but the relationship between Aβ burden and SCC was stronger in those with more education (β = 1.16, p < 0.05). A partial mediation effect was found of Aβ burden on SCC via education (b = −0.12, 95% CI [−0.31, −0.02]).

These findings suggest that the association between SCC and Aβ burden becomes stronger with greater educational attainment. Thus, SCC may be of particular importance in highly educated CN individuals harboring amyloid pathology.