Plasma Fibrinogen, Global Cognitive Function, and Cerebral Small Vessel Disease: Results of a Cross-Sectional Study in Community-Dwelling Japanese Elderly

Abstract

Objective Recent studies suggest that hemostatic and endothelial factors play a pivotal role in the development of cerebral small vessel disease (SVD). Although plasma fibrinogen is an essential factor in the coagulation cascade, the relationship among fibrinogen, cognitive function, and SVD has not been clarified in community-based Asian populations. Because fibrinogen levels of Asians have been reported to be lower than these of Caucasians, the impact of fibrinogen on the development of SVD or dementia in Asians may be different from that of Caucasians. Methods We performed a cross-sectional study using MRI to determine the relationships among fibrinogen, cognitive function, and subclinical SVD in community-based Japanese elderly. Results Subjects with raised fibrinogen levels tended to have more lacunes and higher grades of white matter lesions (WMLs). Additionally, an independent association between fibrinogen and WMLs was determined by logistic regression analyses. Subjects with high fibrinogen levels accompanied by high von Willebrand factors or thrombomodulin levels had an increased tendency for the presence of WMLs. The relationship between the mean Mini-Mental State Examination (MMSE) scores and the quartiles of fibrinogen levels was not statistically significant after controlling for age, gender, and WMLs; however, the mean MMSE scores in subjects without WML were related to the tertiles of the fibrinogen levels even after adjusting for conventional risks and high sensitivity C-reactive protein. ConclusionThe present study suggests that there is a close relationship between fibrinogen levels and subclinical WMLs, which are independent of conventional risk factors and inflammation, in community-based Japanese elderly.

Induction of Genes Expressed in Endothelial Cells of the Corpus Callosum in the Chronic Cerebral Hypoperfusion Rat Model

“…Our finding that the upregulation of Vwf was associated with neuropathologic changes in the corpus callosum after day 7 suggests that vWF is associated with the development of WMLs. Recent findings that the severity of WMLs is associated with increased plasma levels, and activity of vWF in elderly people support our hypothesis [33,34]. The role of vWF in the development of WMLs remains unclear, although it has been reported that vWF-deficient mice are protected from brain ischemia/reperfusion injury, indicating that vWF is critically involved in cerebral ischemia [51,52,53].…”

“…Disruption of the BBB is observed in chronic cerebral hypoperfusion animals as well as in patients with WMLs [27,28,29,30,31]. Endothelial activation and an increase in biomarkers of endothelial dysfunction are observed in patients with small vessel disease such as lacunar infarction and leukoaraiosis [32,33,34]. Our findings suggest that endothelial dysfunction has an important role in the development of WMLs in the 2VO rats.…”

Alterations of the Cerebral White Matter in a Middle-Aged Patient with Turner Syndrome: An MRI Study

“…She has had diabetes for years; it is possible that her diabetes may have contributed to the development of diffuse white matter ischemia of the brain. However, this possibility is not supported by the following: (1) the severity of her white matter lesions was classified as grade 3 on the Fazekas rating scale [11], which is too severe for patients without any vascular risk factors except diabetes; (2) her diabetes is mild and well controlled without any medication, and the severity of white matter lesions is not associated with diabetes, as shown in previous studies [12, 13]; (3) she had no blood hypertension or dyslipidemia, and (4) she had no atherosclerotic lesions on carotid ultrasonography or on MRA of the brain, and the results of her ankle brachial index and funduscopic examination did not show any signs of apparent peripheral atherosclerotic changes.…”

Diagnostic Values of Serum Levels of Homocysteine and Uric Acid for Predicting Vascular Mild Cognitive Impairment in Patients with Cerebral Small Vessel Disease

“…Vascular mild cognitive impairment (VMCI) is an abnormal condition caused by vascular diseases, and the patients are often identified with cognitive deficits that are not severe enough to fit the criteria for dementia [8]. In the early stage, most VMCI patients have no obvious clinical symptoms [9]; therefore, it is urgent to find new reliable molecular markers able to predict cognitive impairments in SVD patients.…”