There is conflicting evidence on whether high adiposity (shown physically as being overweight or obese) causes Alzheimer’s disease (AD). In a new debate published in Alzheimer’s Research & Therapy today, Deborah Gustafson (State University of New York, USA) and José Luchsinger (Columbia University, USA) review the evidence for and against this controversial association.

Some of the most convincing evidence for an association is from studies of mid-life risk factors. Some epidemiologic studies show that a high BMI, or central obesity, in mid-life is a risk factor for dementia, with an association measured at least a decade prior to a clinical dementia diagnosis. Biological evidence also supports high adiposity as an independent risk factor for dementia. For example, type 2 diabetes, cardiovascular diseases and hypertension are known to increase dementia risk, and high adiposity is associated with these conditions.

On the other hand, some epidemiologic studies of mid-life adiposity have not found an association with dementia. This includes a cohort study of Japanese-American men and a cohort of Swedish women. Other studies demonstrate lower risk or non-linear associations and there are also reports of an inverse association between high adiposity levels and dementia. In their debate article, Gustafson and Luchsinger stress that it seems unlikely that high levels of adiposity are beneficial to cognition and explain that leptin (which is elevated with high adiposity) is known to be neuroprotective and may account for this. Another suggestion is that because high adiposity is a risk factor for increased mortality, people may not reach the age at which they would develop AD in some cohorts.

In mid-life it is possible that high adiposity could be considered a risk factor for dementia/AD, but this relationship seems much more complicated in late-life. For example reverse causality could be plausible given that dementia is linked to weight loss in old age, and fewer studies show an association between high adiposity and dementia in late-life (over 65 years).

There are therefore many possible reasons for the conflicting evidence. As the population continues to live longer and the obesity epidemic increases, further research is needed to determine whether a balance between negative and beneficial factors associated with adiposity has an effect on cognition.

Read the full debate here.

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