. Body Mass Index and Risk of Alzheimer's Disease: A Mendelian Randomization Study of 399,536 Individuals. J Clin Endocrinol Metab. 2017 Jul 1;102(7):2310-2320. PubMed.


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  1. We were also puzzled about the apparent increased dementia risk for those with low BMI, and have written about this in a correspondence letter in Lancet Diabetes & Endocrinology in 2015 (see Strand et al., 2015). 

    We followed this up in a full paper, recently published in the Journals of Gerontology, where we found that BMI loss in midlife was predictive for dementia-related mortality, while maintaining a low (or high) BMI was not related to any increased risk (Strand et al., 2017). 

    The findings of no causal relationship between stable low BMI and Alzheimer´s disease in this paper by Frikke-Schmidt et al., wherein they apply Mendelian randomization to avoid confounding and reverse causality, is intriguing, and fits with our findings described above. Thus, the increased AD risk for those with low BMI in several observational studies might be due to reverse causality. Their results fit with ours; those with stable low BMI through midlife (35-62 years) were not at increased risk of dementia-related mortality, while only those with decreased BMI in midlife were at increased risk, up to four decades later. Gaining weight reduced the risk in our analyses.  Why weight loss is related to dementia is poorly understood, and there is an ongoing discussion on this issue. Reverse causality has been suggested, especially in studies where BMI is measured in old age. Our study members were measured at baseline when they were 35-49 years and then followed up five-13 years later for a second BMI measurement at ages 40-62 years. We argued our results were less prone to reverse causality due to young age and very long follow-up time (as long as 35 years follow-up time after the second BMI measure), but we cannot rule it out even in this fairly young population. This new paper, using Mendelian randomization, strongly supports reverse causality as the main driver linking low weight with AD.


    . Does midlife obesity really lower dementia risk?. Lancet Diabetes Endocrinol. 2015 Jul;3(7):498-9. PubMed.

    . Weight Change in Midlife and Risk of Mortality From Dementia up to 35 Years Later. J Gerontol A Biol Sci Med Sci. 2016 Aug 10; PubMed.

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  1. No, Being Thin Does Not Lead to Alzheimer’s Disease