A new study suggests that middle-aged adults should be tested for the APOE gene, which researchers believe is responsible for over 90% of Alzheimer's cases and is associated with earlier cognitive decline. The findings underscore the critical need for midlife interventions to potentially mitigate the effects of this genetic risk factor.

Professor Wei Chen, the study's lead author, highlighted that while the APOE gene has long been recognized as a major risk factor for Alzheimer's, new research indicates that carriers of the APOE e4 variant show a faster rate of cognitive decline from the age of 70 compared to non-carriers. This accelerated decline supports the consideration of APOE e4 testing and targeted risk communication in midlife, enabling early implementation of promising interventions such as Mediterranean-style diets, structured cognitive training, and regular physical activity to attenuate decline before dementia onset.

Published in the journal JAMA Neurology, the study followed 4,392 Taiwanese participants enrolled in the Health Aging Longitudinal Study. Among these, 723 participants carried one copy of the APOE e4 gene, 33 had two copies, and the remainder were non-carriers. Participants, around 68 years old and dementia-free at the study's start, were tracked for just over six years. Their cognitive function was assessed using the Mini-Mental State Examination (MMSE), a screening test scoring mental abilities out of 30, with scores below 23 indicating mild to severe cognitive impairment.

At the study's inception, participants averaged a good cognitive function score of 27/30. Over the six-year period, scores dropped by approximately 0.2 points annually, totaling a 1.3-point reduction. However, those with the APOE e4 variant exhibited a significantly faster age-related cognitive decline after turning 70, particularly individuals with two copies of the gene, who experienced a drop of around 2 points by the study's conclusion. Other genetic variants, like APOE e2 which previously showed a protective effect, did not have measurable impacts in this study.

The researchers concluded that their results align with prior longitudinal studies demonstrating APOE e4-associated cognitive decline before overt dementia. They noted that approximately 17% of their participants were e4 carriers who could benefit from early counseling and preventive strategies. Future research aims to evaluate the cost-effectiveness and optimal timing of these interventions.

The study, however, acknowledged several limitations. Cognitive function was assessed using only one screening test at two intervals, which might underestimate cognitive ability. Furthermore, the findings may not be generalizable to the broader population due to the small cohort consisting solely of a Chinese population. The researchers also stressed that carrying a high-risk gene does not guarantee dementia, as lifestyle and environmental factors—such as smoking, poor cardiovascular health, and social isolation—significantly influence risk.

This research builds upon landmark findings published earlier this year, which indicated the APOE gene could be responsible for over 90% of Alzheimer's cases, suggesting that neutralizing its harmful influence might prevent three-quarters or more of these cases. Dementia is the UK's biggest killer, claiming around 76,000 lives annually, with Alzheimer's affecting approximately 982,000 people. Experts believe about 45% of dementia cases could be preventable or delayed through lifestyle interventions and improved screening.

Michelle Dyson, chief executive of Alzheimer's Society, welcomed the findings, stating that genes influence dementia risk, but rarely cause it alone. She emphasized the importance of this study as the first of its kind in a Chinese population, adding to the understanding of how APOE4 affects diverse ethnic groups, as most previous work focused on white populations. Dyson cautioned that the study's limitations, including reliance on a single cognitive test and lack of data on subsequent dementia diagnoses, mean more evidence is needed before recommending APOE4 screening and tailored interventions. She reiterated that having a higher risk gene is not a diagnosis and the best way to reduce risk remains simple: stay active, eat well, avoid smoking, drink within guidelines, and maintain social and mental engagement.