Dementia Risk Following Ischemic Stroke: A Systematic Review and Meta-Analysis of Factors Collected at Time of Stroke Diagnosis

ObjectiveTo assess incidence rates and predictors of dementia after ischemic stroke. MethodsA search was conducted on Embase and Medline for reports published up to November 2019. Studies were included if they: 1) assessed dementia incidence among patients with ischemic stroke diagnosis and 2) excluded patients with prevalent dementia at baseline. The main analysis included: 1) absolute risk; 2) incidence rates (per 100 person-years) and 3) patient-level predictors (demographics, CVD history and major cardiac events, previous stroke and TIA, stroke location, disability post-stroke, chronic brain change and stroke mechanism). Additional predictors assessed included study setting (clinic or registry), method of dementia diagnosis (Diagnostic and Statistical Manual of Mental Disorders (DSM), National Institute of Neurological Disorders and Stroke (NINDS) or both) and inclusion of patients with recurrent or first-ever stroke. A random effects meta-analysis was undertaken. Risk of bias in included studies was assessed in terms of selection, comparability and outcome. Results4,325 studies were screened in the title and abstract phase after removing duplicates and 280 eligible studies were screened for full text. A total of 21 studies met the inclusion criteria and were included in the meta-analysis, representing 55,183 patients with ischemic stroke, with average age of 70 years (range 65-80 years) and average follow-up of 29 months. The majority of included studies were conducted in a hospital setting (n=17/21). The overall rate of dementia after ischemic stroke was 13.0 per 1000 person-years (95% CI 6.0, 36.0). Incidence rates were eight times higher in hospital-based studies (17.0, 95% CI 8.0, 36.0) compared to registry-based studies (1.8, 95% CI 0.8, 4.0). Absolute dementia risk after stroke was 20% at 5 year, 30% at 15 years and 48% at 25 years of follow-up. Incidence rates were 1.5 times higher in studies that included patients with recurrent ischemic stroke compared to estimates from studies that included first-time ever stroke patients only. There was 33% difference in dementia incidence in the later study periods (2007 - 2009) compared to (1996 - 2006). Statistically significant predictors of dementia after ischemic stroke included female gender (OR=1.2, 95% CI 1.1, 1.4), hypertension (1.4, 95% 1.1, 2.0), diabetes mellitus (1.6, 95% 1.3, 2.1), atrial fibrillation (1.9, 95% 1.2, 3.0), previous stroke (2.0, 95% CI 1.6, 2.6), presence of stroke lesion in dominant hemisphere (2.4, 95% 1.3, 4.5), brain stem/cerebellum (0.5, 95% CI 0.3, 0.9) or frontal lobe (3.7, 95% CI 1.2, 12.0), presence of aphasia (7.9, 95% CI 2.4, 26.0), dysphasia (5.8, 95% CI 3.0, 11.3), gait impairment (1.7, 95% CI 1.1, 2.7), presence of white matter hyperintensities (3.2, 95% CI 2.0, 5.3), medial temporal lobe atrophy (3.9, 95% CI 1.9, 8.3) and transient ischemic attack (TIA) as the predisposing aetiology for ischemic stroke (0.44, 95% CI 0.22, 0.88). ConclusionFactors routinely collected at time of admission guide informed monitoring of patients at highest risk of progression to dementia after acute ischemic stroke. Predictors of dementia after acute ischemic stroke should be assessed as distinct features from those established for general dementia. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the likelihood of progression to dementia after ischemic stroke? And what are the individual predictors? FindingsThe overall rate of dementia after ischemic stroke was 13.0 per 1000 person-years (95% CI 6.0, 36.0). Incidence rates were eight times higher in hospital-based studies (17.0, 95% CI 8.0, 36.0) compared to registry-based studies (1.8, 95% CI 0.8, 4.0). Absolute dementia risk after stroke was 20% at 5 years, 30% at 15 years and 48% at 25 years of follow-up. Incidence rates were 1.5 times higher in studies that included patients with recurrent ischemic stroke compared to estimates from studies that included first-time ever stroke patients only. There was 33% difference in dementia incidence in the later study periods (2007 - 2009) compared to (1996 - 2006). Statistically significant predictors of dementia after ischemic stroke included female gender, hypertension, diabetes mellitus, atrial fibrillation, previous stroke, presence of stroke lesion in dominant hemisphere, brain stem/cerebellum or frontal lobe, presence of aphasia, dysphasia, gait impairment, presence of white matter hyperintensities, medial temporal lobe atrophy and transient ischemic attack (TIA) as the predisposing aetiology for ischemic stroke. MeaningFactors routinely collected at time of admission guide informed monitoring of patients at highest risk of progression to dementia after acute ischemic stroke. Predictors of dementia after acute ischemic stroke should be assessed as distinct features from those established for general dementia.