Sharp Weight Loss For Older Women With Alzheimer’s Related Gene

Finding may aid in the treatment of dementia.

Researchers led by Deborah Gustafson, PhD, MS, professor of neurology at SUNY Downstate Medical Center, have shown that women with a gene variant (APOEe4 allele) associated with Alzheimer’s disease experience a steeper decline in body mass index (BMI) after age 70 than those women without the version of the gene, whether they go on to develop dementia or not. The finding adds to a body of evidence suggesting that body weight change may aid in the diagnosis and management of Alzheimer’s disease.

The results of the study are published online in the Journal of Alzheimer’s Disease. The article is entitled, “37 Years of Body Mass Index and Dementia: Effect Modification by the APOE Genotype: Observations from the Prospective Population Study of Women in Gothenburg, Sweden.” Dr. Gustafson is also docent and affiliate researcher, University of Gothenburg, Sahlgrenska Academy, Neuropsychiatric Epidemiology Research Unit, in Sweden.

Photo of an old lady.

From middle age to approximately 70 years of age, adults gain weight on average. After age 70, weight tends to decrease on average. This weight change over the life course may be due to aging, changes in body composition, energy metabolism, sensory changes, and changes in the brain related to regulation of basic body processes. Image is for illustrative purposes only.

Dr. Gustafson notes that women tend to evidence a U-shaped relationship between age and body weight or body mass index (BMI), a common marker of overweight and obesity. From middle age to approximately 70 years of age, adults gain weight on average. After age 70, weight tends to decrease on average. This weight change over the life course may be due to aging, changes in body composition, energy metabolism, sensory changes, and changes in the brain related to regulation of basic body processes.

Among adults who develop dementia, however, the life course of BMI differs. Studies have shown that being more overweight or obese in mid-life may increase risk for dementia. Studies have also shown that after age 70 years, adults who develop dementia may lose weight more rapidly compared to those who do not develop dementia and that if one is a bit more overweight in later life, it is protective for both dementia and death.

Dr. Gustafson explains, “In this study, we followed Swedish women for almost 40 years from mid-life ages of 38-60 years. We tracked their BMI in relation to dementia onset, and considered the potential role of the APOEe4 allele, a known risk factor for late-onset dementia.” She adds, “In a previous publication, we showed that development of dementia is associated with specific pattern of BMI change over the life course. Women who developed dementia after age 65 tended to gain BMI at a slower rate during middle age.”

Dr. Gustafson concludes, “Now, we show that those with the APOEe4 allele experience greater or steeper decline in BMI after age 70 years, whether they develop dementia or not. Body weight change and BMI are easily measured, noninvasive potential prognostic indicators for dementia. Better understanding of a relatively common risk allele such as APOEe4 and how it modifies risk may aid in our understanding of how we can better intervene among those at highest risk for dementia.”

About this Alzheimer’s disease research

Funding: The research leading to the results published in the Journal of Alzheimer’s Disease has received funding from the EU 7th framework LipiDiDiet project (FP7/2007-2015) under grant agreement no211696; Swedish Research Council for Health, Working Life and Welfare (AGECAP 2013-2300; 2013-2496); National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases(NIAID) U01 318345; Swedish Research Council (523-2005-8460; 2013-8717; 11267; 825-2012-5041) and the State University of New York Research Foundation. Other funders include the National Institutes of Health/National Institutes on Aging; Swedish Council for Working Life and Social Research, The Alzheimer’s Association Stephanie B. Overstreet Scholars (IIRG-00-2159), Sahlgrenska University Hospital (ALF),Swedish Alzheimer Association, Stiftelsen Söderström-Königska Sjukhemmet, Stiftelsen för Gamla Tjänarinnor, Hjalmar Svenssons Foundation, The Swedish Society of Medicine, The Gothenburg Medical Society, the Lions Foundation, the Dr. Felix Neubergh Foundation, the Wilhelm and Martina Lundgren Foundation, the Elsa and Eivind Kison Sylvan Foundation, the Alzheimer’s Association Zenith Award, and State University of New York Research Foundation. All researchers are independent of funders.

Source: Ron Najman – Suny Downstate Medical Center
Image Credit: The image is in the public domain
Original Research: Abstract for “37 Years of Body Mass Index and Dementia: Effect Modification by the APOE Genotype: Observations from the Prospective Population Study of Women in Gothenburg, Sweden” by Bäckman, EJ; Waern, M; Östling, S; Guo,X; Blennow, K; Skoog, I; and Gustafson, DR in Journal of Alzheimer’s Disease. Published online October 5 2015 doi:10.3233/JAD-150326


Abstract

37 Years of Body Mass Index and Dementia: Effect Modification by the APOE Genotype: Observations from the Prospective Population Study of Women in Gothenburg, Sweden

Background: Overweight and obesity in mid- and late-life may increase risk for dementia, whereas a decline in body weight or body mass index (BMI) and underweight in years preceding a clinical dementia diagnosis are also associated with dementia. Little is known about the modifying effect of the APOE genotype, a major susceptibility gene for Alzheimer’s disease (AD), on the BMI-dementia adult life course trajectory.

Objective: We evaluated the exposure, BMI, in relationship to the outcome, clinical dementia, over 37 years, considering the effect modification of the APOE ɛ4 allele.

Methods: The Prospective Population Study of Women (PPSW) in Sweden is a systematic sample of 1462 women born 1908, 1914, 1918, 1922, and 1930 and aged 38–60 years at baseline. Examinations occurred in 1968, 1974, 1980, 1992, 2000, and 2005; 559 women had information on dementia, BMI, and APOE ɛ4 allele status, in addition to covariates. Statistical analyses were conducted using mixed effects regression models.

Results: Trajectories of BMI over 37 years differed by APOE ɛ4 allele status. While women gained BMI similarly from mid-life to age 70 years, women with at least one APOE ɛ4 allele experienced BMI decline more quickly after age 70 years compared to women without an APOE ɛ4 allele. However, upon stratifying the sample by dementia occurrence, it appeared that dementia drove the overall BMI-trajectory. There was a main effect of age, interactions of age by APOE ɛ4 allele status, and age by presence versus absence of dementia.

Conclusions: Women with similar average BMI at mid-life exhibited different BMI trajectories in relation to dementia occurrence. In addition, the pattern of BMI decline in late-life differed on the basis of APOE ɛ4 allele possession. Thus, these data suggest roles for both dementia- and APOE-associated changes in BMI during the adult life course.

“37 Years of Body Mass Index and Dementia: Effect Modification by the APOE Genotype: Observations from the Prospective Population Study of Women in Gothenburg, Sweden” by Bäckman, EJ; Waern, M; Östling, S; Guo,X; Blennow, K; Skoog, I; and Gustafson, DR in Journal of Alzheimer’s Disease. Published online October 5 2015 doi:10.3233/JAD-150326

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