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Objective: To study to what extent differences in cognitive performance between individuals with different glucose metabolism status are potentially attributable to hyperglycemia, insulin resistance, and blood pressure-related variables.Research Design and Methods: We used cross-sectional data from 2,531 participants from the Maastricht Study (mean age ± SD, 60 ± 8 years; 52% men; n = 666 with type 2 diabetes), all of whom completed a neuropsychological test battery. Hyperglycemia was assessed by a composite index of fasting glucose, postload glucose, glycated hemoglobin (HbA1c), and tissue advanced glycation end products; insulin resistance by the HOMA of insulin resistance index; and blood pressure-related variables included 24-h ambulatory pressures, their weighted SDs, and the use of antihypertensive medication. Linear regression analyses were used to estimate mediating effects.Results: After adjustment for age, sex, and education, individuals with type 2 diabetes, compared with those with normal glucose metabolism, performed worse in all cognitive domains (mean differences in composite z scores for memory -0.087, processing speed -0.196, executive function and attention -0.182; P values <0.032), whereas individuals with prediabetes did not. Diabetes-associated differences in processing speed and executive function and attention were largely explained by hyperglycemia (mediating effect 79.6% [bootstrapped 95% CI 36.6; 123.4] and 50.3% [0.6; 101.2], respectively) and, for processing speed, to a lesser extent by blood pressure-related variables (17.7% [5.6; 30.1]), but not by insulin resistance. None of the factors explained the differences in memory function.Conclusions: Our cross-sectional data suggest that early glycemic and blood pressure control, perhaps even in the prediabetic stage, may be promising therapeutic targets for the prevention of diabetes-associated decrements in cognitive performance. [ABSTRACT FROM AUTHOR]

OBJECTIVE Hypertension and diabetes are both risk factors for cognitive decline, and individuals with both might have an especially high risk. We therefore examined linear and nonlinear (quadratic) associations of 24-h blood pressure (BP) with cognitive performance in participants with and without type 2 diabetes. We also tested the association of nocturnal dipping status with cognitive performance. RESEARCH DESIGN AND METHODS This study was performed as part of the Maastricht Study, an ongoing population- based cohort study. Cross-sectional associations of 24-h BP (n = 713, of whom 201 had type 2 diabetes) and nocturnal dipping status (n = 686, of whom 196 had type 2 diabetes) with performance on tests for global cognitive functioning, information processing speed, verbal memory (immediate and delayed word recall), and response inhibition were tested using linear regression analysis and adjusted for demographics, vascular risk factors, cardiovascular disease, depression, and lipid-modifying and antihypertensive medication use. RESULTS After full adjustment, we found quadratic (inverted U-shaped) associations of 24-h diastolic blood pressure (DBP) with information processing speed (b for quadratic term = -20.0267, P < 0.01) and memory (immediate word recall: b = -0.0180, P < 0.05; delayed word recall: b = -0.0076, P < 0.01) in participants with diabetes, but not in those without. No clear pattern was found for dipping status. CONCLUSIONS This study shows that both low and high 24-h DBP are associated with poorer performance on tests of information processing speed and memory in individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of baseline and incident diabetes on change in cognitive function over 12 years.Research Design and Methods: A sample of 1,290 individuals aged ≥ 40 years at baseline, participating in the Maastricht Aging Study, were cognitively tested at baseline, after 6 years, and after 12 years. Of these, 68 participants had type 2 diabetes at baseline, and 54 and 57 had incident diabetes at the 6- and 12-year follow-up, respectively. Changes in performance on tests of information-processing speed, executive function, and verbal memory from baseline to 6- and 12-year follow-up were compared between groups using linear mixed models. Effects of diabetes on cognitive decline were adjusted for demographic variables, history of smoking, alcohol intake, and comorbid conditions, including hypertension, cardiovascular disease, BMI, and depression.Results: Participants with baseline diabetes showed larger decline in information-processing speed (estimate -7.64; P < 0.01), executive function (21.82; P < 0.01), and delayed word recall (-1.35; P < 0.05) over the 12-year follow-up compared with control subjects. No significant difference in decline was observed for immediate word recall. Compared with control subjects, participants with incident diabetes showed subtle early decline in information-processing speed only. Interestingly, they did not show larger decline in any other cognitive domain.Conclusions: Individuals with baseline type 2 diabetes show accelerated cognitive decline, particularly in information-processing speed and executive function, compared with individuals without diabetes. In incident diabetes, decline in speed becomes detectable first, and cognitive decline seems to increase with increasing exposure time. [ABSTRACT FROM AUTHOR]

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., (© 2021 by the American Diabetes Association.)