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.
Key Words
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References
- Post-stroke cognitive impairment: epidemiology, mechanisms and management.Anna Transl Med. 2014; 2: 80
- Dementia and cognitive impairment three months after stroke.Eur J Neurol. 2001; 8: 621-627
- 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
- Recovery after stroke: cognition, ADL function and return to work.Acta Neurologica Scandinavica. 2007; 115: 73-80
- Cognitive determinants of social functioning after a first ever mild to moderate stroke at vocational age.J Neurol Neurosurg Psychiatry. 2009; 80: 876-880
- Risk factors for ischemic stroke subtypes: the atherosclerosis risk in communities study.Stroke. 2006; 37: 2493-2498
- Does stroke contribute to racial differences in cognitive decline?.Stroke. 2015; 46: 1897-1902
- Impact of hypertension and apolipoprotein E4 on poststroke cognition in subjects >75 years of age.Stroke. 2005; 36: 1864-1868
- Evolution of cognitive impairment after stroke and risk factors for delayed progression.Stroke. 2005; 36: 2670-2675
- Cognitive decline after stroke: relation to inflammatory biomarkers and hippocampal volume.Stroke. 2013; 44: 1433-1435
- Cognitive decline and markers of inflammation and hemostasis: the Edinburgh Artery Study.J Am Geriatr Soc. 2007; 55: 700-707
- National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards.Stroke. 2006; 37: 2220-2241
- Brief cognitive assessment for patients with cerebral small vessel disease.J Neurol Neurosurg Psychiatry. 2005; 76: 1140-1145
- Adult intelligence scale-revised.Psychological Corporation, New York1981
- WAIS-IIII WMS-III technical manual.Psychological Corporation, San Antonio, TX1997
- Wechsler adult intelligence scal—Third edition administration and scoring manual.Psychological Corporation, San Antonio, TX1997
- The stroop color and word test: a manual for clinical and experimental uses.Stoelting, Chicago, IL1978
- Manual of directions and scoring.War Department, Adjutant General's Office, Washington, DC1944
- Hopkins verbal learning test-revised.Psychological Assessment Resources, Inc, Lutz, FL2001
- Brief visuospatial memory test-revised.Psychological Assessment Resources, Inc, Professional manual. Lutz, FL1997
- Validation of intracranial area as a surrogate measure of intracranial volume when using clinical MRI.J Neuroimaging. 2007; 17: 74-77
- Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy.Neurology. 2006; 66: 23-29
- Chronic systemic immune dysfunction in African-Americans with small vessel-type ischemic stroke.Transl Stroke Res. 2015; 6: 430-436
- Brain aging in African-Americans: the atherosclerosis risk in communities (ARIC) experience.Curr Alzheimer Res. 2015; 12: 607-613
- Functional profiling of uncommon VCAM1 promoter polymorphisms prevalent in African American populations.Hum Mutat. 2007; 28: 824-829
- Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: a review.J Cereb Blood Flow Metabolism. 2016; 36: 72-94
- Hypertension, white matter hyperintensities, and concurrent impairments in mobility, cognition, and mood: the Cardiovascular Health Study.Circulation. 2011; 123: 858-865
- Reactivity of cerebral blood flow to carbon dioxide in hypertensive patients: evaluation by the transcranial Doppler method.J Hypertens. 1994; 12: 191-197
- Prediction of cardiovascular risk using soluble cell adhesion molecules.Eur Heart J. 2002; 23: 1569-1574
- 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
- Vascular inflammation in cerebral small vessel disease.Neurobiol Aging. 2012; 33: 1800-1806
- 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
- Markers of endothelial dysfunction in older subjects with late onset Alzheimer's disease or vascular dementia.J Neurol Sci. 2008; 272: 164-170
- Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia.Thromb Haemost. 2015; 114: 1230-1240
- VCAM-1 as an endothelial factor for diagnosis of dementia in Parkinson's disease.J Neurol Neurosci. 2018; 9: 238-243
- The relationship between inflammatory markers and post stroke cognitive impairment.J Geriatr Psychiatry Neurol. 2010; 23: 199-205
- Inflammatory markers and their association with post stroke cognitive decline.Int J Stroke. 2015; 10: 513-518
Article info
Publication history
Published online: February 14, 2020
Accepted:
December 28,
2019
Received in revised form:
December 13,
2019
Received:
April 25,
2019
Footnotes
Funding: This study was funded by the American Heart Association/Bugher Foundation (grant number 00775001).
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104646
Copyright
© 2020 Elsevier Inc. All rights reserved.
