Relationship between body weight change and incident dementia in older people with type 2 diabetes

Abstract

INTRODUCTION AND LITERATURE REVIEW: Type 2 diabetes mellitus (T2DM) is a chronic illness associated with many late life morbidities, including dementia. Obesity is a common comorbidity of T2DM, with complex mechanisms influencing one another, both causing various adverse health outcomes. Intentional weight loss is often recommended in obese patients. However, despite some evidence pointing out the beneficial effects of losing weight on cognition, there are many observational studies showing that major change in body weight might be related to poorer cognitive outcomes, particularly in older individuals. A systemic review on the relationship between weight change and dementia in the T2DM population was conducted, suggesting that weight loss is associated with increased risk of dementia in older T2DM subjects. However, due to limited existing literature, the topic requires further investigation.

METHODS: The Edinburgh Type 2 Diabetes Study (ET2DS) is a longitudinal study of 1066 people with type 2 diabetes, aged 60-75 at baseline, which was followed from 2006 to 2018. The study database consists of obesity related factors at baseline and year 4 follow up, including body mass index (BMI), waist circumference (WC) and waist hip ratio (WHR), as well as a wide range of demographic and biological measurements. Incident dementia during the follow-up period was extracted from health records. Cognitive tests at baseline and year 4 follow-up were used for post-hoc analysis. The first part of analysis in this study was focused on the relationship between baseline obesity related factors and outcome of incident dementia. In the second part, the individual changes in obesity related factors from baseline to year four were used to predict outcome of incident dementia. Demographic, biological and genetic factors were used as covariables in regression models, and competing risks were considered in survival models.

RESULTS: In the ET2DS population, baseline BMI was negatively associated with incident dementia outcome (HR=0.82 (per 5 kg/m2 increase), p=0.091). Hazard ratios of incident dementia were significantly lower in overweight or obese BMI groups compared to normal BMI group, with or without competing risks considered (HR=0.55, p=0.037 in overweight group; HR=0.46, p=0.010 in class I obesity; HR=0.40, p=0.012 in class II and III obesity). A negative association was also present between WC and incident dementia, but this did not reach statistical significance (HR=0.92 (per 5 cm increase), p=0.056). The trend in WHR was inconclusive.

The cox proportional hazard function survival models in the second part of analysis demonstrated that stable or major increase in body weight (defined as over 5% increase in body weight), compared to major decrease, was associated with lower incidence of dementia (HR=0.46, p=0.003 in the stable group; HR=0.29, p=0.002 in the major increase group). The trend was also present after taking competing risks and other covariables into consideration but this did not reach statistical significance (HR=0.94, p=0.870 in the stable group; HR=0.42, p=0.140 in the major increase group). There was no obvious association between the waist circumference change and outcome of dementia in the survival models.

In the post-hoc analysis on cognitive test results, the population with incident dementia had significantly poorer cognitive performance in all cognitive domains at baseline and significant decline in domains such as memory and executive function. Both body weight increase and waist circumference increase were associated with better general cognitive factor ‘g’ at baseline (Association with baseline ‘g’, beta= 0.061, p=0.016 in percentage body weight change, beta=0.081, p=0.003 in waist circumference change). In terms of the individual cognitive domains, both weight change and waist circumference change were positively associated with executive function at baseline (association with baseline trial making test B, beta= 0.078, p=0.002 in percentage body weight change, beta=0.093, p<0.001 in waist circumference change).

CONCLUSIONS: The findings of this study support body weight loss being an early sign of dementia in elder people with T2DM. Although the association between lower body weight and increased risk of dementia did not reach statistical significance in the competing risks survival model, leading to the possibility of the associations being found by chance, the findings were in line with those from previous studies in both T2DM and older general populations. It has been hypothesized that a steep decrease in body weight may be an early sign of dementia and the finding of poorer baseline general cognitive ability associated with body weight decrease supported this hypothesis. There was some limited evidence that differences in executive function may be a possible mediator in the relationship between cognitive decline and body weight loss, with poor nutritional intake and poor glycaemic control in turn leading to poor protein synthesis and sarcopenia in subjects with T2DM. Further investigation is required to identify precise underlying mechanisms.