Subarachnoid hemorrhage (SAH) accounts for nearly one-third of potential years of life lost among stroke patients before age 65, with an economic burden estimated at over five billion dollars per year. Prognostic indicators have been unreliable in predicting long-term disability from functional and cognitive impairment. Using genetic predictors like the apolipoprotein E (APOE) genotype will help us with risk stratification and identification of therapeutic targets. We hypothesize that the APOE e4 allele is an independent risk factor for long-term disability after SAH. We will perform a prospective observational study in a cohort of all patients with aneurysmal SAH to examine the relationship between APOE e4 allele and outcome measured by the modified Rankin scale, Barthel Index, and a battery of neuropsychological tests at 3, 6, and 12 months after rupture. Blood collection for genotyping will be obtained after informed consent from routine blood draws during hospitalization. Clinical risk factors will be analyzed using univariate and multivariate statistics. We will create a DNA bank in this rigorously characterized cohort for future genetic studies. The proposed project will take advantage of one of the busiest referral centers for intracranial aneurysms with expertise in genetic and cognitive testing. This research will provide useful information about clinical risk factors for long-term disability and the role of APOE in genetic susceptibility after SAH. Identification of genetic susceptibility from APOE in SAH will provide a clinical model to study other candidate genes that may provide the basis for future treatment strategies. A program of didactic courses and mentoring in this project will build upon the candidate's clinical training, and allow her to develop into an independent clinical investigator in neurovascular neurology.
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