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Association of diabetes, homocysteine, and HDL with cognition and disability after stroke

From the Department of Neurology (G.C.N.), Albert Einstein Medical Center, Philadelphia, PA; Public Health (H.B.), Weill Medical College of Cornell University, New York, NY; Department of Neurology (S.I.H.), University of Wisconsin, Madison; and Department of Neurology (J.F.T.), Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC.

Address correspondence and reprint requests to Dr. George C. Newman, Chair, Department of Neurosensory Sciences, Albert Einstein Medical Center, 5401 Old York Road, Suite 300, Philadelphia, PA 19141 newmang{at}einstein.edu

Objective: To delineate factors associated with cognitive function following stroke and test the hypothesis that vascular risk factors associated with oxidative stress impair recovery.

Method: We performed a post hoc analysis of the extensive longitudinal database from the 3,680 subjects (over 35 years old) entered between 1996 and 2003 into the Vitamin Intervention for Stroke Prevention trial using a linear mixed effects model. The primary outcome variables were scores on the Mini-Mental State Examination (MMSE) and modified Rankin Scale (mRS).

Results: MMSE and mRS gradually improved during the 2-year follow-up period. Increased age and nonwhite race, recurrent stroke, diabetes mellitus, left hemisphere cortical lesions, and values of high-density lipoprotein and homocysteine were independent predictors of less successful cognitive recovery. A strong interaction between homocysteine and age indicated a threshold effect beginning in the late 50s. No vitamin treatment effects were identified. Similar factors were identified for recovery of disability as assessed by the mRS, although there were qualitative and quantitative differences.

Conclusions: The finding that diabetes, high-density lipoprotein, and homocysteine predict poorer cognitive function and greater disability after stroke is consistent with the hypothesis that metabolic stress plays a significant role in the poststroke period.

Abbreviations: ACE = angiotensin converting enzyme inhibitor; CABG = coronary artery bypass graft surgery; CEA = carotid endarterectomy; CHF = congestive heart failure; DM = diabetes mellitus; GEE = generalized estimating equation; HDL = high-density lipoprotein; LDL = low-density lipoprotein; LMM = linear mixed effects model; MI = myocardial infarction; MMSE = Mini-Mental State Examination; mRS = modified Rankin Scale; VCI = vascular cognitive impairment; VISP = Vitamin Intervention in Stroke Prevention.

The VISP trial was supported by the NIH/National Institute of Neurological Disorders and Stroke.

Disclosure: Drs. Newman, Bang, and Toole received research support to conduct the original VISP trial. There are no other potential conflicts of interest.

Received October 25, 2006. Accepted in final form June 4, 2007.