Summary: Children and adolescents who carry the APOE ε4 (APOE4) allele score lower on verbal and overall IQ measures than their peers without this genetic variant. APOE4 is a known genetic risk factor for late‑onset Alzheimer’s disease. New analysis indicates that subtle cognitive differences associated with APOE4 can be detected well before adulthood and may represent an early marker of later vulnerability to cognitive decline.
Source: UCR
A gene tied to Alzheimer’s disease appears to influence cognitive performance decades earlier than previously believed.
The APOE gene encodes apolipoprotein E, a protein that transports cholesterol and other lipids through the bloodstream. APOE exists in three common forms (alleles); one of them, APOE ε4 (commonly called APOE4), is carried by roughly 15 percent of people and is associated with an increased risk—up to threefold—of developing late‑onset Alzheimer’s disease (typically after age 65).
While prior research has linked APOE4 to cognitive decline that becomes apparent in midlife and beyond, a recent study led by University of California, Riverside professor Chandra Reynolds examined whether the allele’s influence begins much earlier. Published in Neurobiology of Aging, the paper reports that APOE4 is associated with lower IQ scores during childhood and adolescence, with a notably stronger effect in females.
The analysis pooled genotyping and cognitive data from long‑running longitudinal samples: the Colorado Adoption Project and the Longitudinal Twin Study. Together, these data sets included 1,321 participants who were assessed when they were between 6½ and 18 years old. The cohort was almost evenly split by gender and was predominantly white (approximately 92 percent). Cognitive performance was measured at three time points across childhood and adolescence, enabling the researchers to examine consistent patterns over time.
Overall, each APOE4 allele was associated with a decrement of 1.91 points in Full‑Scale IQ. When analyzed by sex, the effect differed markedly: males showed an average reduction of about 0.33 IQ points per APOE4 allele, while females averaged nearly a 3‑point reduction per allele. The cognitive domains most affected were those related to reasoning and problem solving. Because individuals can carry zero, one, or two ε4 alleles, the impact on measured IQ increases with each additional allele present.
Although the numeric differences in IQ scores may seem modest at the individual level, the authors emphasize the potential long‑term consequences. Reynolds and colleagues note that smaller differences in cognitive performance early in life could translate into reduced cognitive reserve as people age. Cognitive reserve refers to the brain’s capacity to cope with injury or disease by using alternative strategies or compensatory networks. According to Cognitive Reserve Theory, individuals with fewer reserves are less able to tolerate pathological changes associated with aging and neurodegenerative disease, making early disadvantages potentially consequential decades later.
Additional research has linked lower IQ scores in childhood to accelerated biological aging—manifested as greater cellular and tissue damage—and to a higher risk of cardiovascular disease before age 65. These associations underscore how early life cognitive differences can relate to broader trajectories of health across the lifespan.
“Our results suggest that cognitive differences associated with APOE may emerge early and become magnified later in the life course,” Reynolds and coauthors write. “If so, childhood may be a critical window for interventions aimed at strengthening cognitive reserves.” The paper, titled “APOE effects on cognition from childhood to adolescence,” argues that recognizing and investing in early interventions could help reduce later life vulnerabilities linked to genetic risk.
Funding: This research was supported by the National Institutes of Health.
The research team included Chandra A. Reynolds (University of California, Riverside) with collaborators Elizabeth Munoz (UCR) and Andrew Smolen, Robin Corley, Naomi Friedman, Soo Hyun Rhee, Michael Stallings, John DeFries, and Sally Wadsworth, all affiliated with the Institute for Behavioral Genetics at the University of Colorado, Boulder.
Source:
UCR
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John Warren – UCR
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The image is in the public domain.
Original Research: Open access. Article: “APOE effects on cognition from childhood to adolescence” by Chandra A. Reynolds et al. Published in Neurobiology of Aging. DOI: 10.1016/j.neurobiolaging.2019.04.011
Abstract (summary):
The ε4 allele of APOE is a well‑established genetic risk factor for cognitive aging and dementia, but its influence on early‑life cognition has been unclear. In this study, APOE ε4 was associated with lower Verbal, Performance, and Full‑Scale IQ scores at ages 7, 12, and 16 in the Colorado Adoption/Twin Study of Lifespan behavioral development (CATSLife). Full‑Scale IQ was lower by about 1.91 points per ε4 allele (effect size d = −0.13), with larger effects observed in females (approximately 3.41 points lower per allele in females vs. 0.33 points lower per allele in males). These findings suggest that harmful effects of APOE ε4 may appear before adulthood—especially in females—and support theories that early life differences and sex‑specific life‑course vulnerabilities contribute to later cognitive impairment.