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Thromb Haemost 2015; 114(06): 1230-1240
DOI: 10.1160/TH14-11-0938
Endothelium and Angiogenesis
Schattauer GmbH

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

Chi-Wei Huang
1   Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
,
Meng-Han Tsai
1   Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
,
Nai-Ching Chen
1   Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
,
Wei-Hsi Chen
1   Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
,
Yan-Ting Lu
1   Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
,
Chun-Chung Lui
2   Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
,
Ya-Ting Chang
1   Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
,
Wen-Neng Chang
1   Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
,
Alice Y. W. Chang
3   Department of Physiology, National Cheng Kung University, Tainan, Taiwan
4   Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan
,
Chiung-Chih Chang
1   Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
› Author Affiliations Financial support: This work was supported in part by grants CMRPG 8B1492 and CMRPG8C0572 from the Chang Gung Memorial Hospital and NSC 102–2314-B-182A-059 from the National Science Council to C. C.C and CMRPG8B1491 to C. W.H and CMRPG8C0571 to C. C. L.
Further Information

Publication History

Received: 16 November 2014

Accepted after major revision: 03 July 2015

Publication Date:
30 November 2017 (online)

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Summary

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.

Keywords

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

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