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Methods
For this retrospective cohort study, we used a cohort of 1 958 191 individuals derived from the United Kingdom Clinical Practice Research Datalink (CPRD) which included people aged 40 years or older in whom BMI was recorded between 1992 and 2007. Follow-up was until the practice's final data collection date, patient death or transfer out of practice, or first record of dementia (whichever occurred first). People with a previous record of dementia were excluded. We used Poisson regression to calculate incidence rates of dementia for each BMI category.
Findings
Our cohort of 1 958 191 people from UK general practices had a median age at baseline of 55 years (IQR 45–66) and a median follow-up of 9·1 years (IQR 6·3–12·6). Dementia occurred in 45 507 people, at a rate of 2·4 cases per 1000 person-years. Compared with people of a healthy weight, underweight people (BMI <20 kg/m2) had a 34% higher (95% CI 29–38) risk of dementia. Furthermore, the incidence of dementia continued to fall for every increasing BMI category, with very obese people (BMI >40 kg/m2) having a 29% lower (95% CI 22–36) dementia risk than people of a healthy weight. These patterns persisted throughout two decades of follow-up, after adjustment for potential confounders and allowance for the J-shape association of BMI with mortality.
Interpretation
Being underweight in middle age and old age carries an increased risk of dementia over two decades. Our results contradict the hypothesis that obesity in middle age could increase the risk of dementia in old age. The reasons for and public health consequences of these findings need further investigation.
It's important to realise that this finding doesn't mean that gaining weight will somehow protect you against dementia. Many dietary, environmental and genetic factors are likely to influence both BMI and dementia, so the relationship is complex.
However, we do know that being overweight or obese is bad for your health. The same is true for people who are underweight as they are not getting the nutrients their body needs, which may be one of the reasons why they were found to have an increased risk of dementia in this study.
First is the possibility of selection bias. Around half (48%) of eligible people did not have a BMI record, so were excluded from the study. A further third (31%) with BMI records were excluded for not having at least 12 months of previous health records. The study team were aware of this, saying: «If BMI is more likely to be measured in people with comorbidities than in healthy people, which might in turn be associated with dementia risk, then some bias is possible.»
Residual confounding is also a possibility. The researchers had to use variables collected in the GP records, which didn't cover everything they would have wanted.
Other unavailable potential confounders, such as physical activity level, socioeconomic status and ethnic origin, might also have influenced the recorded association between BMI and dementia. We can't say to what extent.
Maintaining a healthy weight is recommended to reduce the risk of heart disease, diabetes and some cancers. This study suggests the benefits of this may not extend to reducing the risk of dementia, but the relationship is likely to be complex and is not yet fully understood.
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