Women With AD Risk Allele Lose Weight Faster in Late Life

Megan Brooks

October 09, 2015

Women with APOE ε4 allele associated with Alzheimer’s disease (AD) have a steeper decline in body mass index (BMI) after age 70 years than their peers without this gene variant, regardless of whether they go on to develop dementia, researchers have found.

The finding adds to a body of evidence suggesting that body weight change may aid in the diagnosis and management of AD, they say.

The study was published online September 16 in the Journal of Alzheimer's Disease.

Some studies have shown that being overweight or obese in midlife may increase risk for dementia, while being overweight in later life might be protective. Studies have also shown that after age 70 years, adults who develop dementia may lose weight more rapidly relative to those who do not develop dementia. Yet little is known about the modifying effect of the APOE genotype, the major susceptibility gene for AD, on the BMI-dementia adult life course trajectory, the researchers write.

To investigate, they analyzed data on 1462 Swedish women followed for more than 3 decades as part of the Prospective Population Study of Women. At baseline, the women were 38 to 60 years old.

"We tracked their BMI in relation to dementia onset, and considered the potential role of the APOE ε4 allele, a known risk factor for late-onset dementia," lead author Deborah Gustafson, PhD, MS, professor of neurology at SUNY Downstate Medical Center, Brooklyn, New York, and affiliate researcher, University of Gothenburg, Sahlgrenska Academy, Neuropsychiatric Epidemiology Research Unit, in Sweden, said in a statement.

In 2000, 559 surviving women (age 70 to 92 years) consented to genetic analysis of blood samples. Within this genetic subsample, 97 developed dementia during 37 years of follow-up.

The researchers found that the trajectories of BMI over 37 years differed by APOE ε4 allele status.

"While women gained BMI similarly from mid-life to age 70 years, women with at least 1 APOE ε4 allele experienced BMI decline more quickly after age 70 years compared to women without an APOE ε4 allele," they report.

In analyses stratified by dementia occurrence, "we show that those with the APOE ε4 allele experience greater or steeper decline in BMI after age 70 years, whether they develop dementia or not," Dr Gustafson said.

These findings "bring to light the interaction of a modifiable risk factor, BMI, and an innate risk factor, the APOE ε4genotype," the authors note in their article.

Dr Gustafson added, "Body weight change and BMI are easily measured, noninvasive potential prognostic indicators for dementia. Better understanding of a relatively common risk allele such as APOE ε4 and how it modifies risk may aid in our understanding of how we can better intervene among those at highest risk for dementia."

The study was funded by the EU seventh framework LipiDiDiet project, the Swedish Research Council for Health, Working Life and Welfare, the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the State University of New York Research Foundation, and other noncommercial entities. The authors have disclosed no relevant financial relationships.

J Alzheimers Dis. Published online September 16, 2015. Abstract

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