Articles
BMI and risk of dementia in two million people over two decades: a retrospective cohort study

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Summary

Background

Dementia and obesity are increasingly important public health issues. Obesity in middle age has been proposed to lead to dementia in old age. We investigated the association between BMI and risk of dementia.

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.

Funding

None.

Introduction

Obesity in middle age might increase the risk of dementia at older ages,1, 2, 3 whereas obesity in old age could reduce the dementia risk.4 An understanding of the association of BMI (measured in kg/m2) with dementia is a public health priority because the number of people affected by dementia worldwide is expected to rise from 30 million in 2010, to 106 million in 2050,5 and the prevalence of obesity is also increasing worldwide.6 In England, the prevalence of obesity has almost doubled between 1993 and 2010,7 and the global burden of obesity in 2008 was estimated to be 1·46 billion overweight adults (BMI ≥25 kg/m2) and 502 million obese adults (BMI ≥30 kg/m2).8

However, the association between BMI and risk of dementia is far from clear. Several studies report that being overweight (BMI ≥25 kg/m2) in mid-life is associated with an increased risk of cognitive impairment and dementia in later life2, 9 whereas being overweight in later life might be associated with reduced dementia risk.10 This situation has been cited as another example of the so-called obesity paradox.10 Furthermore, low BMI (<20 kg/m2) is associated with an increased risk of dementia in short-term studies of elderly people10 and weight loss reportedly occurs before a diagnosis of dementia.4 Inconsistencies might arise because previous studies have been quite small with short durations of follow-up. We report our findings of the largest study so far of the association between BMI and risk of dementia.

Section snippets

Methods

We did a retrospective cohort study using routine UK primary care data from the Clinical Practice Research Datalink (CPRD). The CPRD contains patient information recorded during routine general practice, such as diagnoses, prescriptions, physiological measurements, diagnostic tests, lifestyle information, and referrals to secondary care. Data in the CPRD represent around 9% of the UK population. Data collection began in 1987 and we used data up to July, 2013, in our study.

We calculated BMI from

Results

Figure 1 shows the creation of the analysis dataset. Of 6 098 128 people in CPRD aged 40 years or older between 1992 and 2007, 2 944 587 had BMI data available. We excluded people who did not have at least 12 months of historical data, those judged to be outliers, and those with a previous history of dementia, leaving a total of 1 958 191 people (representing 18 786 640 person-years of follow-up) to include in our analysis. The median BMI was 26·4 kg/m2 (IQR 23·5–30·0), the median age at

Discussion

This cohort study in which nearly 2 million people were followed retrospectively for two decades showed an inverse monotonic association between BMI and the incidence of dementia. The association was not explained by age, sex, duration of follow-up, or available baseline covariates.

One of our key findings is that underweight people have a notably raised risk of developing dementia, and that this risk persists even 15 years after underweight is recorded. This finding might seem surprising, since

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