Glasgow study reveals 'significant role' of genetics in Alzheimer's disease
The research, led by the University of Glasgow, published in the journal npj Dementia, found that while better memory, reasoning, and reaction times were linked to a lower risk of Alzheimer's disease up to 15 years later, this protective effect was significantly reduced in people with a higher genetic risk.
Researchers focused on the APOE e4 genotype, which is present in roughly one in four people and is the strongest known genetic predictor of late-onset Alzheimer's.
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A single copy of the APOE e4 gene increases Alzheimer's risk threefold, while two copies raise the risk by twelvefold.
Dr Donald Lyall, senior lecturer in population brain health at the University of Glasgow's School of Health and Wellbeing, said: "Our study adds to the knowledge gap that exists on the relationship between genetic factors, cognitive health generally, and subsequent risk of dementia in later life.
"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."
In the study, people with above-average reasoning ability were found to have a 36% lower risk of developing Alzheimer's within 15 years.
However, for those who also carried the APOE e4 gene, the risk reduction dropped to just 21%.
More strikingly, individuals with high reasoning skills but who carried the APOE e4 genotype were more likely to develop Alzheimer's than those with below-average reasoning but no genetic risk factor.
The researchers analysed data from over 252,000 UK Biobank participants aged 55 and older, with the average age at the start of the study being just over 62.
To ensure long-term accuracy, individuals diagnosed with Alzheimer's within two years of testing were excluded.
Researchers excluded individuals diagnosed with Alzheimer's within two years of cognitive testing.
The study reinforces the challenges in identifying effective therapies for Alzheimer's, particularly given the influence of genetic factors.
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Dr Lyall said: "Our study has important implications regarding dementia; namely that genetics clearly plays a significant role in influencing someone's overall risk of Alzheimer's disease as they age."
The findings underscore the complex interplay between cognitive health and genetics and the challenges in developing therapies that can effectively prevent or treat Alzheimer's.
While cognitive resilience still matters, the research highlights the urgent need to understand genetic risk factors in the fight against one of the world's most devastating neurodegenerative conditions.
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