- APOE genotype modulates associations between IGF-1, global cognition, and life-course factors, revealing genotype-specific patterns of metabolic ageing and cognitive performance.
- IGF-1 and MMSE related to age and sex in ε2 and ε3 carriers; IGF-1 additionally linked to early-life conditions, occupation, and education.
- Only ε4 carriers showed modest partial reciprocity between IGF-1 and global cognition, indicating bidirectional but limited longitudinal associations.
Exp Gerontol. 2026 Sep 10:113315. doi: 10.1016/j.exger.2026.113315. Online ahead of print.
ABSTRACT
Insulin-like growth factor-1 (IGF-1) plays a crucial role in brain health and cognitive function, with levels varying across APOE genotypes, a major risk factor for Alzheimer’s disease. Here, cross-lagged path modeling was used to examine longitudinal associations between IGF-1 levels, cognitive performance, and sociodemographic factors across APOE genotypes in 1247 older adults from the Rancho Bernardo Study of Healthy Aging. Distinct association patterns emerged across genotypes. Both IGF-1 and Mini-Mental State Examination (MMSE) were associated with age and sex in ε2 and ε3 carriers. IGF-1 was differently related to early-life conditions, occupation, and education across genotypes, while MMSE was related to early-life conditions, occupation, and physical activity. Evidence of partial reciprocity was observed between IGF-1 and global cognition only among ε4 carriers, although associations were modest. These findings suggest genotype-specific patterns linking metabolic aging, cognitive performance, and life trajectories, and provide support for associations between early-life experiences and cognitive reserve proxies.
PMID:42722213 | DOI:10.1016/j.exger.2026.113315
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