Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain Lifestyle Intervention: A Subgroup Analysis of a Randomized Clinical Trial.
Level 2 - randomized trial
Prespecified subgroup analysis of an individual randomized controlled trial
PubMed 29356827 · doi:10.1001/jamaneurol.2017.4365
What was done
This was a prespecified subgroup analysis of the FINGER randomized clinical trial across 6 centers in Finland. The study evaluated 1,109 at-risk older adults (aged 60–77 years, CAIDE risk score ≥6, cognition at or slightly below expected for age) with available APOE genotype data and at least 1 postbaseline assessment. Participants were randomized 1:1 to a 2-year multidomain intervention (diet, exercise, cognitive training, and vascular risk management; n=553) or a control group receiving general health advice (n=556). Primary outcome was the annual change in a comprehensive neuropsychological test battery (NTB) total score evaluated using a modified intention-to-treat analysis.
What was found
Among 362 APOE ε4 carriers (173 intervention, 189 control), the difference between intervention and control in annual NTB total score change was 0.037 (95% CI, 0.001 to 0.073). Among 747 noncarriers (380 intervention, 367 control), the difference was 0.014 (95% CI, -0.011 to 0.039). The intervention effect was not significantly different between carriers and noncarriers (interaction difference 0.023; 95% CI, -0.021 to 0.067).
Why it matters
These findings suggest that genetic susceptibility via the APOE ε4 allele does not prevent at-risk older adults from benefiting cognitively from multidomain lifestyle changes. Early multi-target lifestyle interventions remain applicable regardless of APOE status.
Limits
The trial population was restricted to older Finnish individuals, limiting generalizability to other racial or ethnic groups. From 1,260 enrolled participants, 151 were omitted due to missing APOE data (n=85) or lack of postbaseline assessments. The abstract does not report long-term conversion to dementia beyond the 2-year trial duration.
Cited by
- supports The FINGER study demonstrated cognitive improvement in participants experiencing cognitive decline, including those carrying the APOE4 allele.