Low Body Mass Index and Alzheimer Disease: Is There a Link?

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Researchers conducted the analysis by creating 2 genetic instruments using 5 variants most associated with BMI.
Researchers conducted the analysis by creating 2 genetic instruments using 5 variants most associated with BMI.

Individuals with a low body mass index (BMI) are not at increased risk for Alzheimer disease, according to recent research published in the Journal of Clinical Endocrinology & Metabolism.

Ruth Frikke-Schmidt, MD, DMSc, PhD, from the Department of Clinical Biochemistry at Rigshospitalet, Copenhagen University Hospital, Denmark, and fellow researchers analyzed the risk for Alzheimer disease in 95,578 men and women from the Copenhagen General Population Study (CGPS), using a Mendelian randomization approach, and also analyzed data on 303,958 individuals from the Genetic Investigation of Anthropometric Traits (GIANT) and the International Genomics of Alzheimer's Project (IGAP).

 

Patients were a minimum of 20 years old and had follow-up data available for up to 36 years. Of the CGPS individuals, 645 developed Alzheimer disease and 3281 people developed type 2 diabetes.

Genetic analyses of BMI were conducted by creating 2 genetic instruments from the 5 genetic variants that have the strongest association with BMI. First, the researchers created a weighted allele score that consisted of alleles associated with decreasing BMI in 4 groups that corresponded "to the sum of the individual β-coefficients for the BMI decreasing alleles in each individual adjusted for age and sex." The second instrument was a simple allele score determined by counting BMI decreasing alleles in each of the patients, who were then also categorized into 4 groups.

The researchers found a 0.98 causal odds ratio (95% CI, 0.77-1.23) for a genetically determined 1 kg/m2 decrease in BMI when determining the weighted allele score for the CGPS database. Participants in the CGPS database also had a hazard ratio of 1.07 (95% CI, 1.05-1.09) for a 1 kg/m2 decrease in BMI and a hazard ratio of 1.32 (95% CI, 1.20-1.46) for a decrease in BMI of 1 standard deviation.

Using consortia data from GIANT and IGAP, the researchers found a decrease in BMI of 1 standard deviation had a causal odds ratio of 1.02 (95% CI, 0.86-1.22).

"Previous studies and a recent meta-analysis concluded that midlife obesity increases dementia risk whereas obesity at older ages is associated with lower risk of Alzheimer disease," the researchers wrote. "Recently, large-scale population evidence from the UK [Clinical Practice Research Datalink] study reported that low BMI in all age groups was associated with high risk of Alzheimer disease. These conflicting results reflect well-known problems in observational epidemiology where associations are prone to confounding and reverse causation -- the latter of special concern when estimating effects of BMI and Alzheimer disease."


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