Low body mass index does not cause Alzheimer’s disease – in spite of a statistical link, Danish researchers have reported.
It is most likely that weight loss is a sign of the disease rather than a cause of it, the researchers reported yesterday.
Dr Ruth Frikke-Schmidt of Rigshospitalet in Copenhagen, Denmark, and colleagues tested samples of blood and DNA from 95,578 people taking part in a long-term population study.
The DNA of the 645 individuals who developed Alzheimer’s disease was compared against the rest of the participants. In particular, the presence of five genetic variants strongly linked to body mass index was measured, and from this, participants were split into four groups for risk of low body mass index.
In further tests, genetic variants from 249,796 people in a large DNA study were analysed to find those related to low body mass index.
Having identified participants with variants strongly linked to low body mass index, the researchers found no increased risk of Alzheimer’s disease. This group of participants also had no raised risk of type 2 diabetes.
Dr Frikke-Schmidt said: "Although prior studies found an association between Alzheimer’s disease and low body mass index, the new findings suggest this is not a causal relationship.
"The association can likely be explained by the fact that individuals with Alzheimer’s disease are more likely to have low body mass index due to loss of appetite and weight loss in the early stages of the disease.
"Since genetic variants are not affected by other risk factors or diseases, this is a clean measure that can help to determine causality. The findings highlight that testing causality of a risk factor is pivotal before considering changing public health recommendations based on observational data alone."
Findings appeared yesterday evening (9 May) in The Journal of Clinical Endocrinology & Metabolism.
Frikke-Schmidt, R. et al. Body Mass Index and Risk of Alzheimer Disease: a Mendelian Randomization Study of 399,536 Individuals. The Journal of Clinical Endocrinology & Metabolism 9 May 2017; doi: 10.1210/jc.2017-00195
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