Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia.
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.
Chi-Wei
CW
Huang
Meng-Han
MH
Tsai
Nai-Ching
NC
Chen
Wei-Hsi
WH
Chen
Yan-Ting
YT
Lu
Chun-Chung
CC
Lui
Ya-Ting
YT
Chang
Wen-Neng
WN
Chang
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: aywchang@mail.ncku.edu.tw.
Alice Y W
AY
Chang
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: neur099@adm.cgmh.org.tw.
Chiung-Chih
CC
Chang
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000453:epidemiology; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D056324:Diffusion Tensor Imaging; D050171:Dyslipidemias / Q000453:epidemiology; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000453:epidemiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D066127:White Matter / Q000473:pathology*
D053327:Apolipoprotein E4; D019040:E-Selectin; C546936:SELE protein, human; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
Alzheimer’s dementia; cell adhesion molecule-1; magnetic resonance imaging; white matter disease