Blood Pressure Parameters and Risk of Cognitive Decline and Dementia in Type 2 Diabetes: Results From the ADVANCE Trial
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(Published version)
Date
2026
Authors
Shajahan, S.
Woodward, M.
Anderson, C.S.
Carcel, C.
Wang, N.
Tully, P.J.
Peters, R.
Harrap, S.
Poulter, N.
Mancia, G.
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Journal article
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Journal of the American Heart Association, 2026; 15(7):e044061-1-e044061-11
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Sultana Shajahan, Mark Woodward, Craig S. Anderson, Cheryl Carcel, Nelson Wang, Phillip J. Tully, Ruth Peters, Stephen Harrap, Neil Poulter, Giuseppe Mancia, Stephen MacMahon, John Chalmers, Katie Harris
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Abstract
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:// clinical trials. gov; Unique Identifier: NCT00145925.
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© 2026 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial- NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.