Summary: Among adults aged 80 and older, maintaining a healthy lifestyle—regular physical activity, a balanced diet, moderate or no alcohol use, not smoking, and healthy body weight—was linked to substantially lower odds of cognitive impairment, even for people who carry the genetic risk variant APOE ε4.
Source: PLOS
New analysis of data from the oldest-old shows that lifestyle matters for cognition regardless of APOE ε4 status.
Researchers led by Xurui Jin from Duke Kunshan University examined how lifestyle and the APOE ε4 genotype relate to cognitive function in adults aged 80 years and older. Their results, published in PLOS Medicine, indicate that healthier lifestyle patterns are associated with significantly lower odds of cognitive impairment in this age group and that this benefit is observed whether or not a person carries the APOE ε4 allele—the gene variant most strongly linked to Alzheimer’s disease risk.
The study used cross-sectional data from 6,160 participants in the genetic substudy of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a nationwide cohort that began in 1998 with repeated follow-ups. Cognitive status was measured with the Mini-Mental State Examination (MMSE), and cognitive impairment was defined as an MMSE score below 18. Lifestyle was assessed through a composite profile that included smoking, alcohol consumption, dietary pattern, physical activity, and body weight, and was categorized as unhealthy, intermediate, or healthy. Participants were also genotyped to determine APOE ε4 carrier status.
After adjusting for age, sex, education, marital status, residence (urban/rural), disability, and number of chronic conditions, the authors found that participants with an intermediate lifestyle profile had 28 percent lower adjusted odds of cognitive impairment compared with those with an unhealthy lifestyle. Those with a healthy lifestyle profile had 55 percent lower adjusted odds. Independently, carrying the APOE ε4 allele was associated with a modestly higher odds of cognitive impairment (about 17% higher in adjusted models).
Importantly, the protective association between lifestyle and cognitive function did not differ significantly between APOE ε4 carriers and noncarriers. In other words, people aged 80 and older appeared to benefit from healthier habits regardless of genetic dementia risk. The study’s findings support the idea that modifiable lifestyle factors remain relevant for cognitive health even in very advanced age.
The authors acknowledge several study limitations. Lifestyle measures were self-reported and lacked fine-grained detail, making precise exposure measurement difficult. The cross-sectional design cannot establish causality or the direction of associations, and the sample—older adults in China—may not be fully representative of populations in other countries, particularly given differences such as average body weight. Despite these caveats, the large sample of the oldest-old and inclusion of genetic data strengthen the evidence that lifestyle relates to cognition late in life.
This analysis builds on prior work linking favorable lifestyles to lower dementia risk in younger older adults, extending that observation to those aged 80 and above. Previous studies suggested that lifestyle benefits might be attenuated among people at high genetic risk; this new study, however, did not find a significant interaction between APOE ε4 status and lifestyle, suggesting that adopting healthy behaviors could contribute to better cognitive outcomes across genetic risk groups in the oldest-old.
Future research planned by the team will use a polygenic risk score for Alzheimer’s disease (AD-PRS) and longitudinal CLHLS data to investigate how genetic risk and lifestyle interact over time and to better clarify temporal relationships. Longitudinal analyses will help determine whether lifestyle changes can predict slower cognitive decline or lower incident dementia in later life.
About this aging and cognition research news
Source: PLOS
Contact: Lijing Yan – PLOS
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Original Research: Open access. “Association of APOE ε4 genotype and lifestyle with cognitive function among Chinese adults aged 80 years and older: A cross-sectional study” by Xurui Jin et al., PLOS Medicine.
Abstract
Association of APOE ε4 genotype and lifestyle with cognitive function among Chinese adults aged 80 years and older: A cross-sectional study
Background
Apolipoprotein E (APOE) ε4 is the strongest single-gene risk factor known for cognitive impairment and Alzheimer’s disease. Lifestyle behaviors—including smoking, alcohol use, diet, physical activity, and body weight—also influence cognitive health. The study investigated whether the relationship between lifestyle and cognition differs by APOE genotype in the oldest-old population.
Methods and findings
This cross-sectional analysis included 6,160 participants aged 80–113 years (mean age 90.1, standard deviation 7.2) from the genetic substudy of the CLHLS. Women made up 57.6% of the sample; 17.5% were APOE ε4 carriers. The mean MMSE score was 21.4 (SD 9.2), and 25% of participants met the study definition for cognitive impairment (MMSE < 18).
Lifestyle profiles were constructed from smoking status, alcohol use, dietary pattern, physical activity, and body weight and categorized as unhealthy, intermediate, or healthy. Multivariable logistic regression models adjusted for demographic and health covariates showed that compared with an unhealthy lifestyle, intermediate and healthy lifestyle profiles were associated with 28% and 55% lower adjusted odds of cognitive impairment, respectively. Carrying APOE ε4 corresponded to 17% higher adjusted odds of cognitive impairment. The association between lifestyle and cognition did not significantly differ by APOE ε4 status (interaction P = 0.30).
Study limitations include self-reported and nonspecific lifestyle measures, cross-sectional design, and potential limited generalizability beyond the Chinese oldest-old population, which differs from high-income country cohorts in characteristics such as body weight distribution.
Conclusions
In this large cross-sectional sample of adults aged 80 and older, healthier lifestyle profiles were associated with better cognitive function regardless of APOE genotype. These findings suggest that modifiable lifestyle factors may help preserve cognitive health in the oldest-old, even among those with elevated genetic risk.