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Association of Type 2 Diabetes, According to the Number of Risk Factors Within Target Range, With Structural Brain Abnormalities, Cognitive Performance, and Risk of Dementia

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posted on 27.07.2021, 22:14 by April C.E. van Gennip, Coen D.A. Stehouwer, 2 Martin P.J. van Boxtel, Frans R.J. Verhey, Annemarie Koster, Abraham A. Kroon, Sebastian Köhler, Marleen M.J. van Greevenbroek, Anke Wesselius, Simone J.P.M. Eussen, Walter H. Backes, Jacobus F. Jansen, Miranda T. Schram, Ronald M.A. Henry, Archana Singh-Manoux, Thomas T. van Sloten
Objective Type 2 diabetes is associated with increased risks of cognitive dysfunction and brain abnormalities. The extent to which risk factor modification can mitigate these risks is unclear. We investigated the associations between incident dementia, cognitive performance and brain abnormalities among individuals with type 2 diabetes, according to the number of risk factors on target, compared to controls without diabetes.

Research Design and Methods Prospective data from UK Biobank of 87,856 individuals (n=10,663 diabetes/n=77,193 controls; baseline 2006-2010; dementia follow-up until February, 2018). Individuals with diabetes were categorized according to the number of seven selected risk factors within guideline-recommended target range (nonsmoking; guideline-recommended levels of HbA1c, blood pressure, BMI, albuminuria, physical activity, diet). Outcomes were incident dementia, domain-specific cognitive performance, white matter hyperintensities and total brain volume.

Results After a mean follow-up of 9.0 years, 147(1.4%) individuals with diabetes and 412(0.5%) controls had incident dementia. Among individuals with diabetes, excess dementia risk decreased stepwise for a higher number of risk factors on target. Compared to controls (incidence rate per 1,000 person-years 0.62(95%CI:0.56;0.68)), individuals with diabetes who had 5-7 risk factors on target had no significant excess dementia risk (absolute rate difference per 1,000 person-years 0.20(-0.11;0.52); HR:1.32(0.89;1.95)). Similarly, differences in processing speed, executive function, and brain volumes were progressively smaller for a higher number of risk factors on target; these results were replicated in the Maastricht Study.

Conclusions Among individuals with diabetes, excess dementia risk, lower cognitive performance and brain abnormalities decreased stepwise for a higher number of risk factors on target.

Funding

The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid (grant 31O.041), Stichting De Weijerhorst, the Pearl String Initiative Diabetes, CVC Maastricht, CARIM Maastricht, Perimed, CAPHRI Maastricht, NUTRIM Maastricht, Stichting Annadal, Health Foundation Limburg, Janssen-Cilag B.V., Novo Nordisk Farma B.V., Sanofi-Aventis Netherlands B.V., The Netherlands Organization for Health Research and Development (ZonMW), Netherlands Consortium of Dementia Cohorts, and the Memorabel programme.TVS is supported by a VENI research grant (916.19.074) from the Netherlands Organization for Scientific Research and the Netherlands Organization for Health Research and Development, and a Dutch Heart Foundation research grant (2018T025).

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