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Background: Poststroke dementia and cognitive impairment are associated with poor long-term outcomes after stroke. The contribution of genetic factors such as the presence of apolipoprotein (ApoE) ɛ4 allele and its association with cognitive impairment poststroke remains inconclusive, particularly in Middle Eastern regions. Objective: The aim of this study is to examine all correlates and potential predictors of cognitive impairment including self-awareness and regulation deficits in stroke patients and compare these functions with healthy older adults from a Middle Eastern population. Methods: A prospective stroke sample of 200 patients (case group) and 100 healthy aging individuals (control group) will be recruited from the largest medical complex in Bahrain. A neuropsychological battery of cognitive assessments (global, executive, and metacognition) will be conducted on all participants. Participants will be categorized into 4 subgroups (nonvascular cognitive impairment, vascular cognitive impairment with no dementia, vascular dementia, and mixed dementia) using standardized cognitive assessment scores and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, dementia criteria. Biomarkers will include ApoE genotype, soluble form of receptor for advanced glycation end products, neprilysin, beta-secretase 1, biochemistry, and hematology measurements. Results: The primary study outcome is to determine early risk factors for cognitive impairment after stroke in a Bahraini cohort. The study has received full ethical approval from the Bahrain Ministry of Health and from the affiliated university. Conclusions: With increasing stroke incidence rates in the Middle East, this research study will provide useful biological and epidemiological data for future development and planning of health policies and guidelines for stroke care within the Gulf region. [JMIR Res Protoc 2016;5(4):e223]