Published on: Jun 18, 2025
A new study led by the University of Glasgow, published in npj Dementia, reveals that while strong cognitive health — including memory, reasoning, and reaction time — is associated with a lower risk of developing Alzheimer’s disease, genetic factors like the APOE e4 genotype can significantly reduce this protection.
Researchers analyzed data from over 252,000 UK Biobank participants aged 55 and older. They found that individuals with better-than-average cognitive scores had a significantly reduced risk of Alzheimer’s — up to 36% lower over 15 years. These individuals also tended to receive a diagnosis about six months later than others.
However, the protective effect of cognitive health was notably diminished in those carrying the APOE e4 genotype, which is present in around 25% of the population. For instance, individuals with strong reasoning skills and an e4 risk variant only saw a 21% reduction in Alzheimer’s risk. Strikingly, e4 carriers with good cognitive scores still faced higher risk than non-carriers with lower cognitive scores.
The study confirms that APOE e4 is a powerful genetic predictor of late-onset Alzheimer’s. One copy of the e4 allele triples risk, while two copies raise it twelve-fold compared to the neutral e3e3 genotype. These risks often correlate with earlier disease onset.
Lead researcher Dr. Donald Lyall emphasized, Our findings suggest that genetics plays a more significant role than previously thought and may influence the risk or protection conferred by other factors like premorbid cognitive health.
These results highlight the need to consider both cognitive and genetic profiles when assessing Alzheimer’s disease risk and suggest that even individuals with high cognitive functioning are not immune to the influence of their genetic background.
Source: https://www.gla.ac.uk/colleges/mvls/news/headline_1186677_en.html
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