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Thromb Haemost. 2015 Nov 25;114(6):1230-40. doi: 10.1160/TH14-11-0938. Epub 2015 Aug 20.

Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia.

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Alice Y. W. Chang PhD, Department of Biological Science, National Sun Yat-sen University, Kaohsiung, Taiwan, Tel.: +886 06 235 3535 ext. 5445, Fax: +886 06 236 2780, E-mail:
Chiung-Chih Chang, MD, PhD, Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niaosung, Kaohsiung 833, Taiwan, Tel.: +886 7 731 7123 ext. 3389, Fax: +886 7 735 1334, E-mail:


Endothelial dysfunction leads to worse cognitive performance in Alzheimer's dementia (AD). While both cerebrovascular risk factors and endothelial dysfunction lead to activation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, it is not known whether these biomarkers extend the diagnostic repertoire in reflecting intracerebral structural damage or cognitive performance. A total of 110 AD patients and 50 age-matched controls were enrolled. Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured and correlated with the cognitive performance, white matter macro-structural changes, and major tract-specific fractional anisotropy quantification. The AD patients were further stratified by clinical dementia rating score (mild dementia, n=60; moderate-to-severe dementia, n=50). Compared with the controls, plasma levels of VCAM-1 (p< 0.001), ICAM-1 (p=0.028) and E-selectin (p=0.016) were significantly higher in the patients, but only VCAM-1 levels significantly reflected the severity of dementia (p< 0.001). In addition, only VCAM-1 levels showed an association with macro- and micro- white matter changes especially in the superior longitudinal fasciculus (p< 0.001), posterior thalamic radiation (p=0.002), stria terminalis (p=0.002) and corpus callosum (p=0.009), and were independent of, age and cortical volume. These tracts show significant association with MMSE, short term memory and visuospatial function. Meanwhile, while VCAM-1 level correlated significantly with short-term memory (p=0.026) and drawing (p=0.025) scores in the AD patients after adjusting for age and education, the significance disappeared after adjusting for global FA. Endothelial activation, especially VCAM-1, was of clinical significance in AD that reflects macro- and micro-structural changes and poor short term memory and visuospatial function.


Alzheimer’s dementia; cell adhesion molecule-1; magnetic resonance imaging; white matter disease

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