Incidence and prognostic indicators of dementia in patients with TIA and stroke: the population- based Rotterdam Study

Abstract

Introduction: Cognitive impairment is common after transient ischemic attack (TIA) and stroke, but population-based estimates of dementia risk by stroke severity are scarce. We aimed to determine risk and prognostic indicators of dementia after TIA and stroke. Methods: We included all individuals from the population-based Rotterdam Study with first-ever TIA or stroke between 2002-2018, who were dementia-free at time of event, and matched those 1:3 to reference participants on age and sex, using incidence density sampling. We determined risk of dementia by event severity (TIA vs. minor stroke [NIHSS≤3] vs. major stroke [NIHSS>3]) using the subdistribution hazard cumulative incidence function, and investigated prognostic indicators of dementia risk. Results: Of 1302 patients with first-ever TIA or stroke (mean age: 78.2±8.9 years, 57% women), 551 had TIA, 357 minor stroke, and 394 major stroke. During 10-year follow-up, dementia occurred in 202/1302 (15.5%) patients without pre-event dementia. Absolute risks by stroke severity are shown in the figure. Compared to reference participants, dementia risk was higher after minor stroke (hazard ratio [95%CI]: 1.36 [1.03-1.79]), but not after TIA (HR: 1.00 [0.78-1.27]). Patients with major stroke were at higher risk of dementia in the first 3 years after stroke, but not thereafter (overall HR: 1.14 [0.85-1.52]), due in part to high competing risk of death. In multivariable models, dementia risk was associated with age (per year: 1.04 [1.02-1.05]), right hemispheric (1.47 [1.06-2.03]) or vertebrobasilar territory stroke (1.54 [1.00-2.39]), premorbid MMSE (per 1-point: 0.93 [0.86-1.01]), and APOE-ε4 genotype (1.77 [1.31-2.40]). Among 482 patients with available brain MRI, dementia risk was higher in those with a higher burden of white matter hyperintensities (per 1% increase in proportion of total brain volume: 1.20 [1.02-1.41]) or cerebral microbleeds (≥2 microbleeds: HR: 1.99 [1.05-3.79]), but not significantly dependent on hippocampal volume or total brain volume. Discussion: Dementia risk after stroke is highest in the first years after major stroke, whereas patients with minor stroke are at persistently increased long-term risk. A combination of clinical characteristics and imaging markers of cerebral small vessel disease may aid in dementia risk stratification.