Healthy Lifestyle May Protect Against Dementia in Older Adult Carriers of APOE ε4

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The APOE ε4 allele is currently the strongest genetic predictor for the development of Alzheimer disease.
The APOE ε4 allele is currently the strongest genetic predictor for the development of Alzheimer disease.

Healthy lifestyle changes may provide protection against cognitive dysfunction among older patients who carry the apolipoprotein E (APOE) ε4 allele and are at risk for dementia, according to research published in JAMA Neurology.

Adult patients aged 60 to 77 years who were considered at risk for dementia were included in this randomized trial (N=1109). The investigators compared individuals who carried the APOE ε4 allele (n=362) with those who did not carry the allele (n=747). Participants were randomly assigned to a lifestyle modification arm that consisted of dietary changes, exercise, cognitive training, and vascular risk management (n=553) or a control group that consisted of general health advice (n=556). The investigators used a comprehensive neuropsychological test battery to assess change in cognition following the interventions.

At baseline, there was no difference between the participants who carried the APOE ε4 allele and noncarriers. Participants in the intervention group who were APOE ε4 carriers had significantly lower baseline memory performance (−0.07 vs 0.08; P =.04) and higher baseline diastolic blood pressure (81.08 vs 79.01 mm Hg; P =.048) compared with carriers in the control group.

Differences between intervention and control arms in the annual neuropsychological test battery total score change were 0.037 (95% CI: 0.001-0.073; P =.045) and 0.014 (95% CI: -0.011 to 0.039; P =.28) among carriers and noncarriers, respectively. There was no significant difference regarding the effect of the lifestyle intervention between allele carriers and noncarriers (0.023; 95% CI: -0.021 to 0.067; P =.30). Significant differences were observed between APOE ε4 carriers who were randomly assigned to intervention or control for abbreviated memory (estimate, 0.070; 95% CI: 0.006-0.135; P =.03).

The investigators were unable to determine the mechanisms that fueled the within-group effects for carriers of the APOE ε4 allele. Additionally, since individuals with high levels of cognitive impairment were excluded from this trial, the findings from this study may not be applicable to a wider patient population with existing cognitive dysfunction.

Overall, the results from this study indicate “the importance of early prevention strategies that target multiple modifiable risk factors simultaneously” for protecting at-risk patients against dementia.

Reference

Solomon A, Turunen H, Ngandu T, et al. Effect of the apolipoprotein E genotype on cognitive change during a multidomain lifestyle intervention: a subgroup analysis of a randomized clinical trial [published online January 22, 2018]. JAMA Neurol. doi:10.1001/jamaneurol.2017.4365

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