Effect of intensive blood pressure control on cognitive outcomes and brain structures in adults with type 2 diabetes: prespecified analysis of secondary outcomes of BPROAD randomised controlled trial

Objective To evaluate the effect of intensive compared with standard treatment of systolic blood pressure (SBP) on cognitive outcomes and brain structures in adults with type 2 diabetes. Design Multicentre, open label, outcome assessor masked, randomised controlled trial. Setting 145 clinical centres across seven geographical regions in China. Participants 12 821 adults aged ≥50 years with type 2 diabetes, raised SBP, and increased cardiovascular risk, of whom 12 434 without probable dementia at baseline were included in this cognitive ancillary study. Further assessments were performed annually and at the end of study. Interventions Participants were randomly assigned to receive intensive treatment targeting SBP <120 mm Hg or standard treatment targeting SBP <140 mm Hg for up to five years. Main outcome measures The primary cognitive outcome was a composite of all cause dementia or mild cognitive impairment. Secondary cognitive outcomes included all cause dementia, mild cognitive impairment, changes in cognitive functions, and changes in brain magnetic resonance imaging (MRI) characteristics. A subset of participants underwent brain MRI at baseline (n=862) and at the end of study (n=605) to assess changes in white matter lesion volume and total brain volume. Results 6219 participants were assigned to receive intensive treatment and 6215 to receive standard treatment. Baseline mean age was 63.7 years, and 5567 (44.8%) participants were women. After one year, mean SBP was 121.6 mm Hg in the intensive treatment group and 133.2 mm Hg in the standard treatment group. During a median follow-up of 3.8 years, the primary cognitive outcome of all cause dementia or mild cognitive impairment occurred in 747 participants (3.69 events per 100 person years) in the intensive treatment group and 783 participants (3.89 events per 100 person years) in the standard treatment group (hazard ratio 0.96, 95% confidence interval (CI) 0.86 to 1.06; P=0.38). In the MRI substudy (428 intensive treatment v 434 standard treatment), the intensive treatment group had a smaller increase in white matter lesion volume compared with the standard treatment group (between group difference −0.09 inverse hyperbolic sine (asinh) transformed cm 3 , 95% CI −0.15 to −0.02; P=0.01). Conclusions Over a median of about four years, no statistically significant difference in incidence of a composite of all cause dementia or mild cognitive impairment was observed among adults with type 2 diabetes receiving standard treatment of SBP (target <140 mm Hg) and intensive treatment (target <120 mm Hg). Intensive treatment was, however, associated with a reduction in the accrual of cerebral white matter lesion volume. Trial registration ClinicalTrials.gov NCT03808311 .