APOE4 Carriers Also Reap Cognitive Benefits of Healthy Lifestyle Changes

Megan Brooks

January 23, 2018

Older adults who are genetically susceptible to dementia can still reap the benefits of healthy lifestyle changes, new research shows.

In subgroup analyses of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) study, the cognitive benefits of the multipronged intervention targeting diet, exercise, cognitive training, and vascular risk factors did not significantly differ between apolipoprotein E (APOE) ε4 carriers and noncarriers and might actually be more pronounced in APOE ε4 carriers.

"This is good news for people who worry that genetic risk factors for dementia may somehow hinder potential benefits from healthy lifestyle changes," Alina Solomon, MD, PhD, from the Institute of Clinical Medicine/Neurology, University of Eastern Finland in Kuopio, told Medscape Medical News.

Dr Alina Solomon

"We were very happy to see that this was not the case in our clinical trial. Carriers of the APOE ɛ4 allele clearly benefited from this 2-year multidomain lifestyle intervention that was started early, before the occurrence of substantial cognitive impairment," Dr Solomon added.

The study was published online January 22 in JAMA Neurology.

Significant Benefit

"We knew from previous observational studies that people with genetic susceptibility for dementia [based on the APOE genotype] are also more susceptible to the detrimental effects of various lifestyle-related risk factors," said Dr Solomon. "But we did not know the impact of this genetic susceptibility in an actual intervention that targeted several of these risk factors simultaneously to prevent cognitive decline."

The FINGER study, published in 2015 and reported by Medscape Medical News, was the first large randomized controlled trial to find beneficial effects on cognition for a 2-year multicomponent lifestyle intervention. The study included 1260 older at-risk individuals from the general population.

The subgroup analyses by APOE genotype involved 1109 of the 1260 participants in the FINGER trial (mean age, 69 years; 46% women), including 362 APOE ε4 allele carriers (173 intervention and 189 control) and 747 noncarriers (380 intervention and 367 control).

The effects of the lifestyle intervention did not differ significantly between APOE ε4 carriers and noncarriers for any cognitive domain (test of interaction).  

However, within-group findings (intervention vs control) by APOE ε4 carrier status showed a significant benefit of the intervention in ε4 carriers for annual change in the neuropsychological test battery (NTB) total score (estimate, 0.037; P = .045) and abbreviated memory (estimate, 0.070; P = .03), but not in noncarriers (estimate, 0.014; P = .28 for NTB total score and 0.022; P = .34 for abbreviated memory).

Given the nonsignificant tests of interaction, "the promising within-group findings cannot be considered as definitive evidence that the FINGER intervention was significantly more effective among APOE ε4 carriers," the authors note.  They add that further studies are needed to clarify whether APOE ε4 carriers may benefit more from lifestyle interventions. 

"The extended 7-year FINGER follow-up will provide additional data for investigating whether the multidomain lifestyle intervention is effective for preventing dementia, whether this effect is modified by APOE genotype, and whether the cognitive change pattern observed among ε4 carriers persists for a longer period," they write.

 "The FINGER intervention model for preventing cognitive decline is currently being adapted and tested outside Finland (e.g. in Europe, the USA, Singapore, China) as part of the World Wide FINGERS initiative. These clinical trials will provide further opportunities to investigate the interplay between genetic and environmental factors in very diverse populations," said Dr Solomon.

Delayed Decline?

Reached for comment, Ronald Petersen, MD, PhD, neurologist and director of the Mayo Clinic Alzheimer's Disease Research Center and the Mayo Clinic Study of Aging, Rochester, Minnesota, noted that APOE ε4 carriers are at an increased risk for Alzheimer's disease. "So a concern could be that the lifestyle intervention in the FINGER study might only be applicable to noncarriers and that the genetic effect of being an ε4 carrier might overemphasize the disease process such that the intervention is not going to be useful. But it appears that the intervention was useful for both carriers and noncarriers," he said.

"If you are an ε4 carrier, it doesn't mean you are going to get the disease but you are at an increased risk," Dr Petersen added. "If you are an APOE ε4 heterozygote (1 allele), your risk is maybe three to four times over the general population. If you are a homozygote and have two ε4 copies, your risk is 10 times or more over the general population.  So this [study] is encouraging in that if you under take this intervention or something like it, you may be able to forestall a decline," Dr Petersen said.

The study had no commercial funding. The authors and Dr Petersen have disclosed no relevant financial relationships.

JAMA Neurol. Published online January 22, 2018. Abstract

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