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People who are underweight at middle age are one-third more likely to develop dementia than those with a healthy BMI, according to a study published in The Lancet Diabetes & Endocrinology.
Further, in contrast to previous findings, the researchers also found that people with obesity, defined as BMI greater than 30, at middle age are nearly 30% less likely to develop dementia than those with a healthy BMI.
“Our results suggest that doctors, public health scientists and policymakers need to rethink how to best identify who is at high risk of dementia. We also need to pay attention to the causes and public health consequences of the link between underweight and increased dementia risk, which our research has established,” study author Stuart Pocock, PhD, of the London School of Hygiene & Tropical Medicine, said in a press release.
“However, our results also open up an intriguing new avenue in the search for protective factors for dementia — if we can understand why people with a high BMI have a reduced risk of dementia, it’s possible that further down the line, researchers might be able to use these insights to develop new treatments for dementia.”
For the study, Pocock and colleagues from the London School of Hygiene & Tropical Medicine and OXON Epidemiology examined data from 1,958,191 individuals derived from the United Kingdom Clinical Practice Research Datalink, which is a large database of patient information recorded during routine general practice for nearly 20 years in the United Kingdom.
Median age at baseline was 55 years and median BMI was 26.5.
During a median follow-up of 9.1 years, 45,507 people were diagnosed with dementia at a rate of 2.4 cases per 1,000 person-years, according to the data.
People who were underweight, defined as a BMI less than 20, were 34% (95% CI, 29-38) more likely to be diagnosed with dementia than those of a healthy weight, defined as a BMI of 20 to 24.9.
Risk for dementia, however, declined with increasing BMI, the researchers noted, with people with BMIs greater than 40 being 29% (95% CI, 22-36) less likely to develop dementia than those in the normal-weight range. An increase in BMI was linked to a substantial, steadily decreasing risk for dementia for a BMI of up to 25, with risk for dementia decreasing more gradually with BMI above 25. This trend continued up to a BMI of 35 or greater.
These patterns persisted after adjustment for potential confounders, through 2 decades of follow-up and after allowance for the J-shape association of BMI with mortality, according to the study results.
“The reasons why a high BMI might be associated with a reduced risk of dementia aren’t clear, and further work is needed to understand why this might be the case,” lead study author Nawab Qizilbash, MD, of OXON Epidemiology in London and Madrid, Spain, said in the release.
“If increased weight in mid-life is protective against dementia, the reasons for this inverse association are unclear at present. Many different issues related to diet, exercise, frailty, genetic factors and weight change play a part.”
In a linked comment, Debora Gustafson, PhD, of SUNY Downstate Medical Center in New York, noted the conflicting research and complex issues surrounding this topic.
“The published literature about BMI and dementia is equivocal. Some studies report a positive association between high mid-life BMI and dementia, whereas others do not,” Gustafson wrote.
“Many considerations are needed in the assessment of the epidemiology of the association between BMI and late-onset dementia, as is the case for many recorded associations involving late-life disorders. To understand the association between BMI and late-onset dementia should sober us to the complexity of identifying risk and protective factors for dementia. The report by Qizilbash and colleagues is not the final word on this controversial topic,” Gustafson concluded.
