The associations between nutrition, physical activity, brain structure and function in people with and without type 2 diabetes

Background: Dementia is a major public health concern which has a devastating impact on people's quality of life. People with type 2 diabetes (T2D) are at a higher risk of developing dementia as they have a faster rate of cognitive decline and brain atrophy compared to people without T2D. Diet and physical activity are major modifiable risk factors for both dementia and T2D and may be important targets for prevention. However, it is unclear if specific diets and objectively measured physical activity are associated with markers of dementia in people with T2D. Aims: To examine associations between dietary intake (data-driven dietary patterns, an inflammatory diet, adherence to the Australian Dietary Guidelines), and objectively measured physical activity (steps per day and intensity) with brain structure and cognition. To examine whether any associations with dietary intake differ based on T2D status and if apolipoprotein E-˜í¬µ4 (APOE-˜í¬µ4) and insulin therapy modify any associations with physical activity. Methods: Data was from the Cognition and Diabetes in Older Tasmanians study, a cross-sectional study of 689 people with (n = 343) and without T2D (n = 346) aged 55‚Äö-90 years; and the Cognition and Diabetes in Older Tasmanians-Blood Pressure study, which recruited only participants with T2D (n = 220) aged 55-86 years. In all studies, the 80-item Cancer Council of Victoria food frequency questionnaire was used to assess dietary intake. Dietary intake was examined using three methods: dietary patterns calculated using principal component analysis, an inflammatory diet using the dietary inflammatory index (DII), and the Australian Dietary Guidelines Index (maximum score 90, with a higher score indicating greater compliance with the dietary guidelines). An accelerometer was used to obtain measures of step count and time spent on moderate-to-vigorous physical activity averaged over 7 days. In all studies, neuropsychological tests were used to assess six cognitive domains (verbal memory, visual memory, visuospatial function, executive function, verbal fluency, and attention processing speed) and global cognition. Brain magnetic resonance imaging (MRI) was performed to obtain grey matter, white matter, and hippocampal volumes and markers of small vessel disease (microbleeds, infarcts, and white matter hyperintensities). Results: There were two dietary patterns (prudent and traditional) for people with T2D and three dietary patterns (prudent, traditional, and Western) for those without T2D. For those without T2D, higher adherence to the Western dietary pattern was associated with lower grey matter volume. However, the association was no longer significant after adjusting for a cardiovascular risk score, mood, and physical activity. The other dietary patterns were not associated with brain structure or cognitive function. There were no associations between the DII and any of the brain structure variables in fully adjusted models. T2D modified the association between DII and grey matter volume, which was stronger in people without T2D. No associations were observed between the Australian dietary guideline index and brain MRI or cognitive variables. T2D did not modify any associations between diet and brain MRI or cognitive function. Higher daily step count was associated with better attention-processing-speed and greater total hippocampal volume. APOE-˜í¬µ4 modified the association between moderate-vigorous physical activity and verbal fluency. However, this association was only significant among APOE-˜í¬µ4 carriers. Insulin-therapy modified the association between moderate-vigorous physical activity and attention-processing speed which was stronger in those taking insulin-therapy. Conclusion: In this cross-sectional study, there was little evidence of associations between diet and brain health in people with or without T2D. Future prospective studies need to apply a lifespan approach to clarify the effects of early- and mid-life diet on later life brain heath. Higher step count and greater time spent in moderate-vigorous physical activity may be beneficial for different aspects of brain health in people with T2D. Moderate-vigorous physical activity appeared to particularly benefit cognition for APOE-˜í¬µ4 carriers and those receiving insulin therapy. These factors should be considered in future clinical trials to improve cognitive function in people with T2D.