Sex differences in predictors for cognitive decline and dementia in people with stroke or transient ischemic attack in the PROGRESS trial

Stroke and transient ischemic attack confer greater risk of cognitive decline and dementia.We used data from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a blood pressure-lowering randomized controlled trial in stroke/transient ischemic attack. We evaluated overall and sex-specific differences in treatment effects for cognitive decline/dementia, as well as associations with vascular and stroke-specific predictors,considering death as a competing risk.Multinomial logistic regression was used to estimate overall and sex-specific odds ratios (OR) (95% confidence intervals (CI)) for treatment effects and predictors associated with the risk of cognitive decline/dementia, and the women-to-men ratio of odds ratio (RORs).Over a median four years, 763 cognitive decline/dementia (30.9% women) were recorded in 5888 participants. Women had lower odds of cognitive decline/dementia than men (OR 0.78, 95%CI 0.63-0.95). Active treatment was associated with lower odds of cognitive decline/dementia (0.84, 0.72-0.98), with no evidence of sex difference. Higher education (0.96,0.94-0.98 (per year)) and baseline Mini-Mental State Examination (MMSE)) were associated with lower odds of cognitive decline/dementia (0.84,0.82-0.86 (per point higher)). Higher diastolic blood pressure (1.11,1.02-1.20 (per 10 mmHg)), low estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (1.27,1.03-1.58), and peripheral arterial disease (1.78,1.26-2.52) were associated with higher odds of cognitive decline/dementia. APOE ɛ4 was not associated with cognitive decline/dementia (1.05 (0.85-1.30)). Low eGFR was more strongly associated with cognitive decline/dementia in women than men (RORs, 1.60 (1.03-2.48)). Diabetes was more strongly associated with men than women.Several risk factors were associated with cognitive decline/dementia in people with prior stroke/transient ischemic attack, with notable sex differences. Long-term cognitive sequelae of stroke should be considered to strengthen joint prevention strategies for stroke, cognitive decline, and dementia.Trial Registration: This trial was not registered because enrolment began before 1 July 2005.