Obesity and Longer Term Risks of Dementia in 65–74 Year Olds

Kirsty Bowman; Madhav Thambisetty; George A. Kuchel; Luigi Ferrucci; David Melzer

Disclosures

Age Ageing. 2019;48(3):367-373. 

In This Article

Abstract and Introduction

Abstract

Background: overweight or obesity at ages <65 years associates with increased dementia incidence, but at ≥65 years estimates are paradoxical. Weight loss before dementia diagnosis, plus smoking and diseases causing weight loss may confound associations.

Objective: to estimate weight loss before dementia diagnosis, plus short and longer-term body mass index associations with incident dementia in 65–74 year olds within primary care populations in England.

Methods: we studied dementia diagnosis free subjects: 257,523 non-smokers without baseline cancer, heart failure or multi-morbidity (group A) plus 161,927 with these confounders (group B), followed ≤14.9 years. Competing hazard models accounted for mortality.

Results: in group A, 9,774 were diagnosed with dementia and in those with repeat weight measures, 54% lost ≥2.5 kg during 10 years pre-diagnosis. During <10 years obesity (≥30.0 kg/m2) or overweight (25.0 to <30.0) were inversely associated with incident dementia (versus 22.5 to <25.0). However, from 10 to 14.9 years, obesity was associated with increased dementia incidence (hazard ratio [HR] 1.17; 95% CI: 1.03–1.32). Overweight protective associations disappeared in longer-term analyses (HR, 1.01; 95% CI: 0.90–1.13). In group B, (n = 6,070 with incident dementia), obesity was associated with lower dementia risks in the short and longer-term.

Conclusions: in 65–74 year olds (free of smoking, cancer, heart failure or multi-morbidity at baseline) obesity associates with higher longer-term incidence of dementia. Paradoxical associations were present short-term and in those with likely confounders. Reports of protective effects of obesity or overweight on dementia risk in older groups may reflect biases, especially weight loss before dementia diagnosis.

Introduction

Dementia is a major health challenge and in the absence of a treatment, there is great interest in modifiable risk factors. For middle aged adults, most studies report increased dementia risk for body mass index (BMI) obese range (≥30.0 kg/m2) subjects versus the normal range (18.5 to <25.0).[1–3] However, an electronic health records analysis (ages ≥40 years) cast doubt on this association, reporting reduced dementia risks in overweight subjects versus BMI 20.0 to <25.0.[4] However, a recent meta-analysis including this above study showed midlife (aged 35–65 years) obesity associates with increased dementia risk.[5] For older aged adults (aged ≥65 years) and especially 65–74 year olds, obesity and dementia associations are particularly unclear.[6–10]

Weight loss precedes a clinical diagnosis of dementia by at least a decade[11–13] and could obscure BMI associations. Greater weight loss in the 6 years preceding dementia diagnosis (versus those without dementia) was reported in Japanese American men.[11] Knopman et al.[12] found increasing weight differences in women (but not men) present for 20 years before dementia diagnosis, with e.g. 8.0 pounds median weight loss 10 years pre-diagnosis versus 2.0 pounds (median) for those without dementia, with a similar finding from LeBlanc et al..[13] Thus pre-diagnosis weight loss would lower BMI, and could potentially produce 'reverse causation biases' in shorter-term (<10 years) estimates. Examining associations with BMI measures >10 years before outcome ascertainment is less likely to be confounded by pre-diagnosis weight loss. Furthermore, smokers have lower weight but high mortality,[14] tending to die of competing causes before dementia diagnosis. Additionally, smokers have been shown to be at a higher dementia risk.[15] We also showed that weight loss is most strongly associated with cancer, heart failure and multi-morbidity in older primary care patients.[16]

Overall, there are consistent BMI dementia associations for ages <65 years, but it remains unclear whether raised BMI at ages 65–74 is a risk or protective factor for dementia. Here we used the Clinical Practice Research Datalink (CPRD) linked primary and secondary care health records for complete older populations in England registered with primary care providers. We considered two groups without dementia at baseline: group A excluding suggested confounders (i.e. smoking, cancer, heart failure or multi-morbidity at baseline) and group B with these confounders. First, we estimated the prevalence of BMI categories in those in group A who developed incident dementia in each year before diagnosis. We then estimated shorter (0 to <10 years from baseline BMI measure) and longer-term (10–14.9 years) associations between BMI and dementia diagnosis in groups A and B. Using this dichotomy allows us to take into account the 10 years pre-diagnosis weight loss, and to examine the prognostic value of BMI in the longer-term.

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