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

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. 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. 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. 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.