Summary: Children with the APOE E4 gene perform lower on verbal and general IQ tests than their peers without the genetic risk factor. APOE E4 is a genetic risk factor for Alzheimer’s disease. The study suggests the effects of the gene manifests before adulthood and could be the earliest biomarker for later vulnerability to Alzheimer’s disease.
A gene linked to Alzheimer’s Disease may impact cognitive health much sooner than previously realized.
The APOE gene creates a protein, apolipoprotein E, which packages cholesterol and other fats to transport them through the bloodstream. There are three versions, or alleles, of APOE. One of those is the APOE4 allele, present in about 15 percent of the population. APOE4 carriers are up to three times more likely to develop late-onset Alzheimer’s disease, which occurs in people 65 and older.
It’s been demonstrated the gene is linked to changes in cognitive ability that are noticeable as early as one reaches his or her 50s. But new research from UCR professor Chandra Reynolds and her colleagues holds that APOE4 starts manifesting much earlier–before adulthood.
In the journal Neurobiology of Aging, Reynolds asserts that those carrying the APOE4 gene score lower on IQ tests during childhood and adolescence. And the effect was stronger in girls than in boys.
The study involved an analysis of three to four-decades-old studies, the Colorado Adoption Project and the Longitudinal Twin Study, that included genotyping data from 1,321 participants when they were 6 ½ to 18 years old. Gender among participants was split almost evenly, and 92 percent of the participants were white, with 8 percent from other races. The findings are based on three IQ assessments between childhood and adolescence.
Overall, Full-scale IQ scores were lower by 1.91 points for each APOE4 allele individuals may carry. Boys scored .33 points lower on IQ tests, and women scored almost 3 points lower for each APOE4 allele. The traits most affected related to reasoning. The effect of E4 on IQ performance multiplies with each E4 allele present: a person can have up to two APOE4 alleles.
The IQ difference seems small. But long-term, Reynolds said the findings can mean fewer cognitive reserves as the APOE4 carrier ages, with the disadvantage becoming progressively magnified. Cognitive reserve is the brain’s ability to navigate problems and improvise. Cognitive Reserve Theory holds that people with fewer reserves have more trouble withstanding disease as they age.
Research has also shown an association between lower childhood IQ and increased biological aging–cell and tissue damage–and cardiovascular disease before age 65.
“Our results suggest that cognitive differences associated with APOE may emerge early and become magnified later in the life course, and if so, childhood represents a key period of intervention to invest in and boost reserves,” Reynolds wrote in the paper, titled “APOE effects on cognition from childhood to adolescence.”
Funding: The research was funded by the National Institutes of Health.
In addition to Reynolds, authors include Elizabeth Munoz of UCR, and Andrew Smolen, Robin Corley, Naomi Friedman, Soo Hyun Rhee, Michael Stallings, John DeFries, and Sally Wadsworth, all of the Institute for Behavioral Genetics at the University of Colorado, Boulder.
About this neuroscience research article
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APOE effects on cognition from childhood to adolescence
The ε4 allele of APOE is a well-established genetic risk factor for cognitive aging and dementia, but its influence on early life cognition is unknown. Consequently, we assessed associations of APOE genotypes with cognitive performance during 7, 12, and 16 year-assessments in our ongoing Colorado Adoption/Twin Study of Lifespan behavioral development (CATSLife). In general, APOE ε4 was associated with lower Verbal, Performance, and Full Scale IQ scores during childhood and adolescence (e.g., Full Scale IQ was lower by 1.91 points per ε4 allele, d = −0.13), with larger effects in females (e.g., average Full Scale IQ scores were 3.41 points lower in females per each ε4 allele vs. 0.33 points lower in males). Thus, these results suggest that deleterious effects of the APOE ε4 allele are manifested before adulthood, especially in females, and support both early origin theories and differential life-course vulnerabilities for later cognitive impairment.