Blood Pressure Parameters and Risk of Cognitive Decline and Dementia in Type 2 Diabetes: Results From the ADVANCE Trial

Background Blood pressure (BP) variability and cumulative BP load are significantly associated with cardiovascular disease risk beyond mean systolic BP, but less is known regarding their associations with cognitive decline/dementia and whether these associations differ by cognitive function at baseline or by sex. The aims of this study were to determine associations of different BP parameters with cognitive decline/dementia in patients with type 2 diabetes and explore differences by mild cognitive impairment at baseline and sex. Methods Using data from the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) study, BP parameters were calculated from an 18‐month exposure window comprising measurements at 3, 4, 6, 12, and 18 months, after randomization. Logistic regression was used to estimate the odds ratio (OR) per SD higher and 95% CI for the associations of BP parameters with the composite outcome of cognitive decline (≥3 points from baseline on the Mini‐Mental State Examination) or clinical diagnosis of dementia. Results Of the 11 140 ADVANCE participants, 9586 patients had 5 complete BP measurements within the 18‐month exposure window. After a mean follow‐up of 3.5 years, 1674 (17.5%) participants were diagnosed with cognitive decline and/or dementia. Overall, variability and baseline pulse pressure (PP), but not BP load, were associated with higher odds of cognitive decline/dementia (OR: variability in systolic BP, 1.11 95% CI, 1.05–1.17; diastolic BP, 1.11 95% CI, 1.05–1.17; PP, 1.05 95% CI, 1.00–1.11; mean arterial pressure, 1.13 95% CI, 1.07–1.19; and baseline PP, 1.19 95% CI, 1.13–1.25). There were no differences by mild cognitive impairment at baseline or sex. Conclusions Higher BP variability and baseline PP, but not mean BP or BP load, were associated with higher odds of cognitive decline/dementia in patients with type 2 diabetes. BP variability and PP may be important therapeutic markers for the preservation of brain health. Registration URL: https://clinicaltrials.gov ; Unique Identifier: NCT00145925.