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

Abstract

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 with control subjects without diabetes.

Research design and methods: Prospective data were from UK Biobank of 87,856 individuals (n = 10,663 diabetes, n = 77,193 control subjects; baseline 2006-2010), with dementia follow-up until February 2018. Individuals with diabetes were categorized according to the number of seven selected risk factors within the guideline-recommended target range (nonsmoking; guideline-recommended levels of glycated hemoglobin, blood pressure, BMI, albuminuria, physical activity, and 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 individuals (1.4%) with diabetes and 412 control subjects (0.5%) had incident dementia. Among individuals with diabetes, excess dementia risk decreased stepwise for a higher number of risk factors on target. Compared with control subjects (incidence rate per 1,000 person-years 0.62 [95% CI 0.56; 0.68]), individuals with diabetes who had five to seven risk factors on target had no significant excess dementia risk (absolute rate difference per 1,000 person-years 0.20 [-0.11; 0.52]; hazard ratio 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.

Figure 1

UK Biobank: adjusted HRs for incident dementia according to the number of risk factors within target range among individuals with type 2 diabetes compared with control subjects. The following seven risk factors were considered with cutoff values based on recommendations in current clinical guidelines: glycated hemoglobin level (cutoff value, <53 mmol/mol [<7%]), systolic and diastolic blood pressure (cutoff value, <130 mmHg for systolic blood pressure and <80 mmHg for diastolic blood pressure), BMI (cutoff value, ≥20 and <25 kg/m²), smoking (being a nonsmoker), albuminuria (absence of micro- or macroalbuminuria), physical activity (cutoff value, ≥150 min/week moderate-to-vigorous physical activity), and dietary habits (optimal as defined by the five-item healthy diet score of the American Heart Association [13]). All analyses adjusted for age, sex, and education. *Control subjects were defined as individuals without diabetes or prediabetes.

Figure 2

UK Biobank: adjusted regression coefficients for domain-specific cognitive performance (A) and structural brain abnormalities (B) according to the number of risk factors within target range among individuals with type 2 diabetes compared with control subjects. The following seven risk factors were considered with cutoff values based on recommendations in current clinical guidelines: glycated hemoglobin level (cutoff value, <53 mmol/mol [<7%]), systolic and diastolic blood pressure (cutoff value, <130 mmHg for systolic blood pressure and <80 mmHg for diastolic blood pressure), BMI (cutoff value, ≥20 and <25 kg/m²), smoking (being a nonsmoker), albuminuria (absence of micro- or macroalbuminuria), physical activity (cutoff value, ≥150 min/week moderate-to-vigorous physical activity), and dietary habits (optimal as defined by the five-item healthy diet score of the American Heart Association [13]). All analyses adjusted for age, sex, and education. Analyses with structural brain abnormalities as the outcome were additionally adjusted for time between baseline examination and MRI examination and intracranial volume. *Control subjects were defined as individuals without diabetes or prediabetes.

Figure 3

The Maastricht Study: adjusted effect estimates for domain-specific cognitive performance (A) and structural brain abnormalities (B) according to the number of risk factors within target range among individuals with type 2 diabetes compared with control subjects. The following seven risk factors were considered with cutoff values based on recommendations in current clinical guidelines: glycated hemoglobin level (cutoff value, <53 mmol/mol (<7%)), systolic and diastolic blood pressure (cutoff value, <130 mmHg for systolic blood pressure and <80 mmHg for diastolic blood pressure), body mass index (cutoff value, ≥20 and <25 kg/m²), smoking (being a nonsmoker), albuminuria (absence of micro- or macroalbuminuria), physical activity (cutoff value, ≥150 min/week moderate-to-vigorous physical activity), and dietary habits (optimal as defined by the five-item healthy diet score of the American Heart Association [13]). All analyses adjusted for age, sex, and education. Analyses with structural brain abnormalities as the outcome were additionally adjusted for time between baseline examination and MRI examination, and analyses with brain volumes as the outcome were additionally adjusted for intracranial volume. *Control subjects were defined as individuals without diabetes or prediabetes.