Body mass index and risk of dementia

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Given the rapidly growing burden of Alzheimer's disease and other dementias and the absence of sufficient treatment options [1], strategies to prevent or delay the disease onset are urgently warranted. Among potentially modifiable determinants of dementia, body mass index (BMI) has been extensively investigated. Late-life obesity has been linked to lower risk of dementia; a phenomenon attributed to reverse causality. Unintended weight loss in the preclinical stage, up to a decade before dementia onset, is thought to be a consequence of underlying pathophysiological processes rather than a risk factor for dementia [2]. Thus, studies that address only late-life BMI are likely to observe higher risk of dementia in the lower BMI groups. As dementia develops over decades, it is critical to pay attention to risk factors in midlife [3]. One meta-analysis of 15 prospective studies showed that in comparison to being normal-weight, being underweight as well as being overweight or obese in midlife conferred an elevated risk of Alzheimer's disease and other dementias [4]. This was recently corroborated in two detailed long-term observational studies that elegantly showed how the association of BMI and dementia is modified by age of BMI measurement – suggesting that low BMI in old age is a marker of weight loss and that midlife obesity is associated with higher risk of dementia compared with normal weight [5▪▪,6▪▪]. Accordingly, guidelines including the recent Lancet ‘Commission on Dementia Prevention, Intervention, and Care’ highlight obesity during midlife (45–65 years) as a potentially modifiable risk factor for dementia [7▪▪].

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