A provocative new study is suggesting a gene variant strongly associated with increased Alzheimer's risk in later life could affect cognitive health in childhood. The research reveals those carrying the gene score slightly lower on IQ tests in childhood, implying cognitive decline is apparent at a younger age than ever previously realized.

The most well-known gene variant associated with increased late-onset Alzheimer's disease risk is called APOE4. Thought to be present in around 15 percent of the population, those who carry one copy of APOE4 are three times more likely to develop Alzheimer's compared to those without the gene.

Exactly why APOE4 confers an increased risk of Alzheimer's is the source of much current research, and the prevailing view is that the gene codes for a protein that somehow heightens the ability for other toxic proteins to accumulate in the brain. It is this progressive mechanism that ultimately results in the neurodegeneration associated with Alzheimer's.

However, some researchers hypothesize the APOE4 gene variant may be associated with structural brain differences that can be detected in early infancy. The implication is that this specific genetic variant could be linked to lowered cognitive performance in childhood, ultimately lowering a person's cognitive reserve, which is something known to mitigate the impact of Alzheimer's pathology in one's senior years.

To investigate this association a collaborative team of scientists from UC Riverside and the University of Colorado, Boulder, compared IQ test scores from children with different APOE genotypes. Data was analyzed from over 1,300 subjects between the ages of six and 18.

IQ scores were found to be, on average, two points lower for every copy of the APOE4 gene a person carried. This effect was much more prominent in females than males, with women averaging three IQ points less for each copy of APOE4 carried. Although it is unclear why the effect seems to be more prominent in females than males, the observation interestingly builds on the growing interest in understanding why women suffer from Alzheimer's at higher rates than men.

Chandra Reynolds, corresponding author on the new study, admits the ultimate effect on IQ may be small but it is undeniably statistically significant. A recent study investigating the association between education and dementia suggests the larger the cognitive reserve a person has, the longer they can stay cognitively functional in later life.

What this new research intriguingly implies is that the effects of the APOE4 gene variant on cognition may come into play at a much earlier age than initially thought. Instead of just playing a role in the progression of cognitive decline in adulthood, the gene may have an influence on fundamental brain structure and general intelligence, which ultimately adds to a person's susceptibility to cognitive decline later in life.

"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 and her team conclude in the newly published study.

The next step for the researchers will be to expand the scope of the study, looking at IQ and cognitive ability data from subjects spanning 28 to 46 years of age. This data will help further elucidate any connection between the APOE4 gene and cognition in younger years. The ultimate goal of the work will be to understand whether cognitive development in younger years can be enhanced to grow a person's cognitive reserve and help protect from more dramatic declines in old age.

The new study was published in the journal Neurobiology of Aging.

Source: UC Riverside