Good cognitive health lowers risk of Alzheimer’s disease later in life – but genetics can weaken that protection
Published: 18 June 2025
People with better cognitive health are at lower risk of later Alzheimer’s disease, but genetics can interfere with this, according to a new study
People with better cognitive health are at lower risk of later Alzheimer’s disease, but genetics can interfere with this, according to a new study.
The study – led by the University of Glasgow and published in the journal npj Dementia – describes how genetics may play a significant role in interpreting someone’s fundamental risk of Alzheimer’s disease as they age.
The findings suggest that APOE e4 genotype is an important predictor of developing Alzheimer’s disease, and having this genotype weakens the protective role of earlier life cognitive health on later dementia risk.
The research found that, overall, people with better memory, reasoning and reaction times had a significantly lower overall risk of Alzheimer’s disease, up to 15 years later. Furthermore, people with better-than-average scores tended to be diagnosed at older ages, too – around six months later.
However, the findings also suggest that participants who also had a higher genetic risk for dementia – people with APOE e4 genotype, found in around one-quarter of the general population – had much less protection from developing the condition.
For example, the study found that while people with ‘good’ (i.e. above average) reasoning scores had a 36% lower risk of Alzheimer’s disease within 15 years, people with good reasoning scores who also carried a risk e4 genotype had only 21% protection.
The findings suggest that APOE e4 genotype is an important predictor of developing Alzheimer’s disease, and it weakens the protective benefits of better earlier cognitive health. Indeed, participants with ‘good’ reasoning scores who possess APOE e4 genotype are at higher average risk of developing the disease than participants with below average reasoning scores with no such genetic risk factor.
To date, strategies to identify effective therapies for Alzheimer’s disease have been problematic, with the largest single risk factor for common, late-onset Alzheimer’s disease (i.e. 65 years and above) after increased age being the possession of APOE e4 genotype. Where one copy of the risk genotype increases the risk of developing the disease around three-fold, two copies of e4 increases risk around twelve-fold (versus the neutral and most common e3e3 genotype), with each often associated with earlier age at onset of the disease.
In addition, poorer lifetime cognitive health is generally a consistent predictor of worse outcomes into older age, including earlier mortality and Alzheimer’s disease risk.
For the study, researchers looked at 252,340 participants from UK Biobank, aged ≥55 years at time of cognitive testing, of whom 117,869 were male (46.7%), with an average baseline age of 62.13. The authors excluded any participants who were diagnosed with Alzheimer’s disease within two years of cognitive testing. The average age of diagnosis was 76 years old.
Dr Donald Lyall, Senior Lecturer in Population Brain Health at the University’s School of Health and Wellbeing, 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.
“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.”
The study, ‘Associations and interactions between premorbid cognitive health, apolipoprotein e4 genotype, and incident Alzheimer’s disease in UK Biobank’ is published in npj Dementia.
Enquiries: ali.howard@glasgow.ac.uk or elizabeth.mcmeekin@glasgow.ac.uk
First published: 18 June 2025