Genetic low BMI not associated with increased risk for Alzheimer’s disease

In a study published in the Journal of Clinical Endocrinology and Metabolism, researchers from Denmark reported lifelong low BMI was not linked with an increased risk for Alzheimer’s disease.

“Understanding the association between BMI and dementia is becoming a public health priority due to increasing prevalence of dementia and obesity worldwide,” Liv Tybjaerg Nordestgaard, of the department of clinical biochemistry at Copenhagen University Hospital, and colleagues wrote. “Despite the recent strong observational evidence between low BMI and increased risk of dementia, such data cannot overcome the problems of reverse causation and confounding, and therefore do not have the ability to establish causality.”

The researchers performed a Mendelian randomization study of 95,578 patients in the Copenhagen General Population Study, as well as consortia data from 303,958 patients in the Genetic Investigation of Anthropometric Traits and the International Genomics of Alzheimer’s Project. The primary outcome was risk for Alzheimer’s disease. The researchers reported 645 Alzheimer’s disease events and 3,956 deaths over the course of 36 years of follow-up. Of those deaths, 159 patients died with Alzheimer’s disease. Median age for those without Alzheimer’s disease was 58 years, while median age for those with Alzheimer’s disease was 76 years.

Patients with a 1 kg/m² lower genetic BMI had a causal OR of 0.98 (95% CI, 0.77-1.23) in the Copenhagen General Population Study, the researchers wrote. When Nordestgaard and colleagues used 32 BMI decreasing variants from the Genetic Investigation of Anthropometric Traits and International Genomic of Alzheimer’s Project, the causal OR for a 1-standard deviation genetically lower BMI was 1.02 (95% CI, 0.86-1.22). In the Copenhagen General Population Study, a 1 kg/m² genetically lower BMI was associated with a 1.07 observational HR for Alzheimer’s disease (95% CI, 1.05-1.09), while a 1-standard deviation lower BMI was associated with a 1.32 observational HR (95% CI, 1.2-1.46).

“In conclusion, combining common genetic variation in five key BMI genes into strong genetic instruments and supplementing these analyses with data on Alzheimer’s disease risk of 32 BMI variants from international consortia, we found that genetic and hence lifelong low BMI is not associated with high risk of Alzheimer’s disease in the general population,” Nordestgaard and colleagues wrote. “These data suggest that low BMI is not a causal risk factor for Alzheimer’s disease, and that the corresponding observational association most likely is explained by reverse causation or confounding.” – by Andy Polhamus

Disclosure: The researchers report no relevant financial disclosures.