Modifiable risk factors for cognitive decline in people with type 2 diabetes

Introduction: Type 2 diabetes is a known risk factor for cognitive decline and dementia and continues to be one of the most common non-communicable diseases in the world. Obesity, a hallmark of type 2 diabetes is often associated with general inactivity and chronic increased levels of systemic inflammation. The literature suggests that obesity, along with systemic inflammation and inactivity levels are associated with cognitive decline and dementia in the general population. There is uncertainty as to what effect (if any) obesity, systemic inflammation and activity levels have on people with diabetes. Aims: To determine whether systemic inflammation, obesity and physical (in) activity levels are associated with cognitive decline and/or dementia in older people with type 2 diabetes. Methods: The Edinburgh Type 2 Diabetes Study (ET2DS) is a representative prospective cohort of 1066 men and women living in Scotland, aged 60-75 years at baseline. Cognitive data was gathered by means of a comprehensive cognitive test battery, at baseline and at year 10 followup. Other data on medical history, vascular events, circulating biomarkers, physiological examination and activity levels was also gathered at each phase of data collection. Criteria were developed to determine probable cases of dementia at year 10 follow-up. Principal component analysis (PCA) was used to derive a latent general cognition variable ‘g’ using imputed data to provide a summary score of the different cognitive tests. Multivariable regression analysis was used to assess the association of risk factor variables with general cognition, cognitive decline and dementia. Statistical models adopted the correction method, where baseline cognitive ability was used to correct for follow-up cognitive ability, in order to provide an indication of the association of a risk factor on cognitive decline. Logistic multivariable regression models were used to explore the effect of risk factors on incident dementia. Adjustment variables included a wide range of demographic, vascular-related and diabetes-related risk factors. Results: In the ET2DS, associations were found between waist to hip ratio (WHR) and cognitive decline (standardised beta= -0.076; p=0.020), in fully adjusted models but not with body mass index (BMI). Waist circumference (WC) was found to be associated with cognitive decline (standardised beta= 0.059; p= 0.032), however in fully adjusted models this association was no longer statistically significant. Findings supported a possible association of higher plasma fibrinogen (standardised beta= -0.059; p=0.032) and IL-6 (standardised beta= -0.064; p=0.018) with cognitive decline, however in fully adjusted models this association was no longer statistically significant. Physical activity and sedentary behaviour were shown to be associated with a decline in cognitive ability (standardised beta= 0.171; p<0.001, standardised beta= -0.135; p<0.001, respectively), in fully adjusted models. Obesity-related variables associated with incident dementia included BMI (OR 0.95; 95% CI 0.90- 0.99; p<0.05), WC (OR 0.97; 95% CI 0.95-0.99; p<0.05) and percentage body fat (OR 0.94; 95% CI 0.90-0.98; p<0.01). Baseline inflammation marker IL-6 was identified as a possible risk factor for incident dementia (OR 1.56; 95% CI 1.08- 2.27; p < 0.05). Physical activity and sedentary behaviour were also associated with dementia prevalence at year 10 (OR 0.53; 95% CI 0.36 - 0.78; p<0.001, OR 2.01; 95% CI 1.31 – 3.08; p