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Vascular Cellular Adhesion Molecule-1 (VCAM-1) and Memory Impairment in African-Americans after Small Vessel-Type Stroke

      Abstract

      Background: African-Americans (AA) are 3 times more likely to have small-vessel-type ischemic strokes (SVS) than Whites. Small vessel strokes are associated with cognitive impairment, a relationship incompletely explained by white matter hyperintensity (WMH) burden. We examined whether inflammatory/endothelial dysfunction biomarkers are associated with cognition after SVS in AAs. Methods: Biomarkers were obtained in 24 subjects (median age 56.5 years, 54% women, median 12 years education). Cognition was assessed more than 6 weeks poststroke using the memory composite score (MCS), which was generated using recall from the Hopkins Verbal Learning Test-II and Brief Visuospatial Memory Test-Revised. A semi-automated, volumetric protocol was used to quantify WMH volume (WMHv) on clinical MRI scans. Potential biomarkers including vascular cell adhesion molecule-1 (VCAM-1), interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, interferon gamma, and thrombin-antithrombin (TAT) were log-transformed and correlated with MCS with adjustment for potential confounders. Results: Among serum biomarkers, only VCAM-1-correlated with poorer memory based on the MCS (r = −.659; P = .0006). VCAM-1 (r = .554; P = .005) and age (r = .479; P = .018) correlated with WMHv; VCAM-1 was independently associated with MCS after adjustment for WMHv, age, and education (P = .023). Conclusions: The findings of this exploratory analysis suggest that endothelial dysfunction and inflammation as reflected by VCAM-1 levels may play a role in poststroke cognitive impairment. Additional studies are needed to validate this observation and to evaluate this relationship in non-AAs and with other stroke types and compare this finding to cognitive impairment in nonstroke populations.

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      References

        • Sun J.H.
        • Tan L.
        • Yu J.T.
        Post-stroke cognitive impairment: epidemiology, mechanisms and management.
        Anna Transl Med. 2014; 2: 80
        • Madureira S.
        • Guerreiro M.
        • Ferro J.M.
        Dementia and cognitive impairment three months after stroke.
        Eur J Neurol. 2001; 8: 621-627
        • Makin S.D.
        • Turpin S.
        • Dennis M.S.
        • et al.
        Cognitive impairment after lacunar stroke: systematic review and meta-analysis of incidence, prevalence and comparison with other stroke subtypes.
        J Neurol Neurosurg Psychiatry. 2013; 84: 893-900
        • Hofgren C.
        • Bjorkdahl A.
        • Esbjornsson E.
        • et al.
        Recovery after stroke: cognition, ADL function and return to work.
        Acta Neurologica Scandinavica. 2007; 115: 73-80
        • Hommel M.
        • Miguel S.T.
        • Naegele B.
        • et al.
        Cognitive determinants of social functioning after a first ever mild to moderate stroke at vocational age.
        J Neurol Neurosurg Psychiatry. 2009; 80: 876-880
        • Ohira T.
        • Shahar E.
        • Chambless L.E.
        • et al.
        Risk factors for ischemic stroke subtypes: the atherosclerosis risk in communities study.
        Stroke. 2006; 37: 2493-2498
        • Levine D.A.
        • Kabeto M.
        • Langa K.M.
        • et al.
        Does stroke contribute to racial differences in cognitive decline?.
        Stroke. 2015; 46: 1897-1902
        • Rowan E.
        • Morris C.M.
        • Stephens S.
        • et al.
        Impact of hypertension and apolipoprotein E4 on poststroke cognition in subjects >75 years of age.
        Stroke. 2005; 36: 1864-1868
        • del Ser T.
        • Barba R.
        • Morin M.M.
        • et al.
        Evolution of cognitive impairment after stroke and risk factors for delayed progression.
        Stroke. 2005; 36: 2670-2675
        • Kliper E.
        • Bashat D.B.
        • Bornstein N.M.
        • et al.
        Cognitive decline after stroke: relation to inflammatory biomarkers and hippocampal volume.
        Stroke. 2013; 44: 1433-1435
        • Rafnsson S.B.
        • Deary I.J.
        • Smith F.B.
        • et al.
        Cognitive decline and markers of inflammation and hemostasis: the Edinburgh Artery Study.
        J Am Geriatr Soc. 2007; 55: 700-707
        • Hachinski V.
        • Iadecola C.
        • Petersen R.C.
        • et al.
        National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards.
        Stroke. 2006; 37: 2220-2241
        • O'Sullivan M.
        • Morris R.G.
        • Markus H.S.
        Brief cognitive assessment for patients with cerebral small vessel disease.
        J Neurol Neurosurg Psychiatry. 2005; 76: 1140-1145
        • Wechsler D.
        Adult intelligence scale-revised.
        Psychological Corporation, New York1981
        • Wechsler D.
        WAIS-IIII WMS-III technical manual.
        Psychological Corporation, San Antonio, TX1997
        • Wechsler D.
        Wechsler adult intelligence scal—Third edition administration and scoring manual.
        Psychological Corporation, San Antonio, TX1997
        • Golden CJ.
        The stroop color and word test: a manual for clinical and experimental uses.
        Stoelting, Chicago, IL1978
        • Army Individual Test Battery
        Manual of directions and scoring.
        War Department, Adjutant General's Office, Washington, DC1944
        • Brandt J.B.R.
        Hopkins verbal learning test-revised.
        Psychological Assessment Resources, Inc, Lutz, FL2001
        • Benedict R.H.B.
        Brief visuospatial memory test-revised.
        Psychological Assessment Resources, Inc, Professional manual. Lutz, FL1997
        • Nandigam R.N.
        • Chen Y.W.
        • Gurol M.E.
        • et al.
        Validation of intracranial area as a surrogate measure of intracranial volume when using clinical MRI.
        J Neuroimaging. 2007; 17: 74-77
        • Gurol M.E.
        • Irizarry M.C.
        • Smith E.E.
        • et al.
        Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy.
        Neurology. 2006; 66: 23-29
        • Brown C.M.
        • Bushnell C.D.
        • Samsa G.P.
        • et al.
        Chronic systemic immune dysfunction in African-Americans with small vessel-type ischemic stroke.
        Transl Stroke Res. 2015; 6: 430-436
        • Gottesman R.F.
        • Fornage M.
        • Knopman D.S.
        • et al.
        Brain aging in African-Americans: the atherosclerosis risk in communities (ARIC) experience.
        Curr Alzheimer Res. 2015; 12: 607-613
        • Idelman G.
        • Taylor J.G.
        • Tongbai R.
        • et al.
        Functional profiling of uncommon VCAM1 promoter polymorphisms prevalent in African American populations.
        Hum Mutat. 2007; 28: 824-829
        • Poggesi A.
        • Pasi M.
        • Pescini F.
        • et al.
        Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: a review.
        J Cereb Blood Flow Metabolism. 2016; 36: 72-94
        • Hajjar I.
        • Quach L.
        • Yang F.
        • et al.
        Hypertension, white matter hyperintensities, and concurrent impairments in mobility, cognition, and mood: the Cardiovascular Health Study.
        Circulation. 2011; 123: 858-865
        • Maeda H.
        • Matsumoto M.
        • Handa N.
        • et al.
        Reactivity of cerebral blood flow to carbon dioxide in hypertensive patients: evaluation by the transcranial Doppler method.
        J Hypertens. 1994; 12: 191-197
        • Mulvihill N.T.
        • Foley J.B.
        • Crean P.
        • et al.
        Prediction of cardiovascular risk using soluble cell adhesion molecules.
        Eur Heart J. 2002; 23: 1569-1574
        • Tchalla A.E.
        • Wellenius G.A.
        • Sorond F.A.
        • et al.
        Elevated soluble vascular cell adhesion molecule-1 is associated with cerebrovascular resistance and cognitive function.
        J Gerontol A Biol Sci Med Sci. 2017; 72: 560-566
        • Rouhl R.P.
        • Damoiseaux J.G.
        • Lodder J.
        • et al.
        Vascular inflammation in cerebral small vessel disease.
        Neurobiol Aging. 2012; 33: 1800-1806
        • Kelleher R.J.
        • Soiza RL.
        Evidence of endothelial dysfunction in the development of Alzheimer's disease: is Alzheimer's a vascular disorder?.
        A J Cardiovasc Dis. 2013; 3: 197-226
        • Zuliani G.
        • Cavalieri M.
        • Galvani M.
        • et al.
        Markers of endothelial dysfunction in older subjects with late onset Alzheimer's disease or vascular dementia.
        J Neurol Sci. 2008; 272: 164-170
        • Huang C.W.
        • Tsai M.H.
        • Chen N.C.
        • et al.
        Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia.
        Thromb Haemost. 2015; 114: 1230-1240
        • Sobhani A.
        • Ebrahimi H.
        • Ebrahimi A.
        • et al.
        VCAM-1 as an endothelial factor for diagnosis of dementia in Parkinson's disease.
        J Neurol Neurosci. 2018; 9: 238-243
        • Rothenburg L.S.
        • Herrmann N.
        • Swardfager W.
        • et al.
        The relationship between inflammatory markers and post stroke cognitive impairment.
        J Geriatr Psychiatry Neurol. 2010; 23: 199-205
        • Narasimhalu K.
        • Lee J.
        • Leong Y.L.
        • et al.
        Inflammatory markers and their association with post stroke cognitive decline.
        Int J Stroke. 2015; 10: 513-518