Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain Lifestyle Intervention: A Subgroup Analysis of a Randomized Clinical Trial
Open accessAbstract
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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The two-year FINGER trial combined diet, exercise, cognitive training, and management of metabolic and vascular risks; it reported cognitive benefits even in apoE4 carriers.
“Positive effects on cognition were reported108,110 even in subjects with the apoE4 allele110.”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [108]
The FINGER multidomain lifestyle intervention trial found that interventions in nutrition, exercise, cognitive training, and management of metabolic and vascular risk factors benefitted an at-risk population, even in APOEε4 carriers.
“The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial found that interventions in nutrition, exercise, cognitive training, and management of metabolic and vascular risk factors benefitted an at-risk population [181], even in APOEε4 carriers [182]”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [182]
In the FINGER trial, the improvement was observed regardless of demographic and socioeconomic factors and was also seen in people with APOE*4 genetic susceptibility to Alzheimer's disease.
“The improvement was observed regardless of demographic and socioeconomic factors, and was also seen in people with genetic susceptibility (APOE*4 positive) to Alzheimer's disease 105 .”
From Mental health care for older adults: recent advances and new directions in clinical practice and research (2022) · cites this paper as [105]
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- Authors
- Solomon, A., Turunen, H., Ngandu, T., Peltonen, M., Levälahti, E., Helisalmi, S., Antikainen, R., Bäckman, L., Hänninen, T., Jula, A., Laatikainen, T., Lehtisalo, J., Lindström, J., Paajanen, T., Pajala, S., Stigsdotter-Neely, A., Strandberg, T., Tuomilehto, J., Soininen, H., & Kivipelto, M.
- Affiliations
- Stockholm University (SE)
- University of Eastern Finland (FI)
- Karolinska Institutet (SE)
- Finnish Institute for Health and Welfare (FI)
- Institute of Health Sciences/Geriatrics, University of Oulu and Oulu University Hospital, Oulu, Finland
- Kuopio University Hospital (FI)
- University of Helsinki (FI)
- Finnish Institute of Occupational Health (FI)
- Department of Social and Psychological Studies, Karlstad University, Karlstad, Sweden
- Universität für Weiterbildung Krems (AT)
- Corresponding author
- Solomon, Alina
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2018-04-01
- Volume
- 75
- Issue
- 4
- Pages
- 462
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC5885273
- OpenAlex
- W2790972967
- Cited by
- 213
- References
- 41
- Citations by year
- 2026: 15 · 2025: 32 · 2024: 28 · 2023: 23 · 2022: 25 · 2021: 31 · 2020: 27 · 2019: 18 · 2018: 13 · 2017: 1
- FWCI
- 17.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Helsingin Yliopisto
- Imperial College London
- King Abdulaziz University
- Dasman Diabetes Institute
- School of Public Health, Imperial College London
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- apolipoprotein E, APOE ε4, multidomain lifestyle intervention, cognitive decline, dementia prevention, FINGER trial, older adults, cognitive training, physical activity, diet, vascular risk management, neuropsychological test battery, cognitive impairment prevention, serum cholesterol, cardiovascular risk factors, subgroup analysis, intention-to-treat analysis
- MeSH terms
- Healthy Lifestyle, Aged, Cognition Disorders, Diet, Female, Finland, Persons with Disabilities, Humans, Male, Middle Aged, Neuropsychological Tests, Retrospective Studies, Exercise, Cognitive Behavioral Therapy, Apolipoprotein E4
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