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Alina Solomon, Heidi Turunen, Tiia Ngandu | JAMA Neurology | (2018)
Key Takeaways
Plain English Takeaway
Healthy habits like eating well, exercising, and keeping your mind active can help older people keep their brains sharp, even if they have genes that raise their risk for memory problems.
Study Aim
The study set out to determine if carrying the APOE ε4 allele (a version of a gene linked to higher dementia risk) changes how much older adults benefit from a program that targets several lifestyle factors at once. The researchers wanted to see if people with this genetic risk would gain more, less, or the same cognitive benefits from healthy changes in diet, exercise, brain training, and managing heart health, compared to those without the risk gene.
Simply put: The study wanted to know if people with a higher genetic risk for memory loss get the same brain benefits from healthy living as everyone else.
Study Design
This research was a randomized clinical trial called the FINGER study. It included older adults in Finland, aged 60 to 77, who were at risk for memory problems but did not have dementia. Participants were randomly assigned to either a multidomain lifestyle intervention group (which included diet changes, physical activity, brain exercises, and heart health management) or a control group that received general health advice. The main outcome was change in thinking and memory skills, measured by a set of cognitive tests over two years. APOE genotype data was available for 1175 out of 1260 participants, and the analysis included 1109 people who had at least one follow-up test.
Simply put: The study tested if a healthy lifestyle program helps memory in older adults, comparing those with and without a certain risk gene.
Findings
The study found that both people with and without the APOE ε4 allele (the risk gene for dementia) showed cognitive improvement from the lifestyle intervention, but the difference in benefit between the two groups was not statistically significant. This means that carrying the risk gene did not make the intervention more or less effective overall. The authors suggest that healthy lifestyle changes can help protect thinking skills in older adults, even for those with a genetic risk for dementia. They recommend early prevention strategies that address several risk factors at once, regardless of genetic background.
Simply put: Healthy habits can help keep your brain healthy as you age, no matter your genetic risk for memory problems.
Abstract
Importance: The role of the apolipoprotein E (APOE) ε4 allele as an effect modifier in lifestyle interventions to prevent cognitive impairment is still unclear. Objective: To examine whether the APOE ε4 allele modifies the previously reported significant cognitive benefits of a multidomain lifestyle intervention (prespecified subgroup analysis). Design, Setting, and Participants: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a randomized clinical trial in 6 centers across Finland (screening and randomization performed from September 7, 2009, through November 24, 2011; intervention duration, 2 years). Data analysis was performed from August 1, 2015, to March 31, 2016. The study population was at-risk older individuals from the general population. Inclusion criteria were age of 60 to 77 years; Cardiovascular Risk Factors, Aging, and Dementia risk score of at least 6 points; and cognition at a mean level or slightly lower than expected for age. Individuals with dementia or substantial cognitive impairment and conditions that prevented cooperation or safe engagement in the intervention were excluded. APOE genotype data were available for 1175 of the 1260 participants. Interventions: Participants were randomly assigned in a 1:1 ratio to a multidomain intervention group (diet, exercise, cognitive training, and vascular risk management) or a control group (general health advice). Group allocation was not actively disclosed to participants, and outcome assessors were masked to group allocation. Main Outcomes and Measures: Primary outcome was change in cognition measured through a comprehensive neuropsychological test battery. Analysis was based on modified intention to treat (participants with at least 1 postbaseline assessment). Results: A total of 1109 participants (mean [SD] age, 69.3 [4.7] years; 514 [46.3%] female) were included in the analysis: 362 APOE ε4 allele carriers (173 intervention and 189 control) and 747 noncarriers (380 intervention and 367 control). The APOE ε4 carriers and noncarriers were not significantly different at baseline (except for serum cholesterol level). The difference between the intervention and control groups in annual neuropsychological test battery total score change was 0.037 (95% CI, 0.001 to 0.073) among carriers and 0.014 (95% CI, -0.011 to 0.039) among noncarriers. Intervention effect was not significantly different between carriers and noncarriers (0.023; 95% CI, -0.021 to 0.067). Conclusions and Relevance: Healthy lifestyle changes may be beneficial for cognition in older at-risk individuals even in the presence of APOE-related genetic susceptibility to dementia. Whether such benefits are more pronounced in APOE ε4 carriers compared with noncarriers should be further investigated. The findings also emphasize the importance of early prevention strategies that target multiple modifiable risk factors simultaneously. Trial Registration: ClinicalTrials.gov Identifier: NCT01041989.
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Created: May 18, 2026