Cystatin C as an index of cerebral small vessel disease: results of a cross‐sectional study in community‐based Japanese elderly

Wada, Manabu; Nagasawa, Hikaru; Kawanami, Toru; Kurita, Keiji; Daimon, Makoto; Kubota, Isao; Kayama, Takamasa; Kato, Takeshi

doi:10.1111/j.1468-1331.2009.02809.x

Cited by 51 publications

(55 citation statements)

References 32 publications

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“…Although the results of the present study seem to be inconsistent with previous reports [19], studies on atherosclerotic diseases have suggested that rather than circulating protein levels, imbalance between proteases and inhibitors in the local environment, such as the arterial wall, determines their net effects on the cardiovascular system [8,20,21]. In fact, a high plasma CST3 level indicates a high risk for cardiovascular events [22,23,24,25], whereas reduced expression of CST3 in the arterial wall of rodents and humans has an important role in the formation of aneurysms and atheromatous plaques [8,20,21].…”

Section: Discussioncontrasting

confidence: 57%

“…In general, high serum CST3 levels are believed to be associated with small-vessel cerebral diseases [19]. Although the results of the present study seem to be inconsistent with previous reports [19], studies on atherosclerotic diseases have suggested that rather than circulating protein levels, imbalance between proteases and inhibitors in the local environment, such as the arterial wall, determines their net effects on the cardiovascular system [8,20,21].…”

Section: Discussioncontrasting

confidence: 56%

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Contribution of Cystatin C Gene Polymorphisms to Cerebral White Matter Lesions

Mitaki

Nagai²,

Sheikh³

et al. 2011

Cerebrovasc Dis

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Background: Vascular remodeling plays an important role in the development of arteriosclerosis and any of the resulting white matter lesions in the brain. An imbalance between cysteine proteases and the cysteine protease inhibitor cystatin C (CST3) may exacerbate vascular remodeling through degradation of extracellular matrix proteins. Therefore, we evaluated the association between functional polymorphisms in the CST3 gene and the development of cerebral white matter lesions. Methods: In a total of 2,676 participants, 3 CST3 genepolymorphisms were genotyped in 92 cases with severe deep white matter hyperintensity (DWMH), and 184 subjects were randomly selected age- and sex-matched controls without any signs of DWMH. The genetic effects of these polymorphisms on DWMH and plasma CST3 levels were examined. CST3 expression vectors were transfected into an astrocytoma cell line and the expression level of CST3 mRNA was analyzed by quantitative RT-PCR. Intracellular and secreted levels of CST3 in the cell culture were quantified by Western blot and ELISA, respectively. Results: A significant association was found between one CST3 gene haplotype and DWMH (p = 0.002). This haplotype was also associated with lower plasma CST3 levels (p = 0.01). An in vitro transfection study revealed that the +148A allele, which is included in the risk haplotype, significantly reduced the secretion and increased the intracellular accumulation of CST3; however, it had no effect on the mRNA expression. Conclusions: Our study shows that polymorphisms in the CST3 gene are significantly associated with the likelihood of DWMH. Substitution of A for G at +148 of the CST3 gene decreased the extracellular availability of CST3 in vitro, which might result in the activation of protease activity.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussioncontrasting

confidence: 56%

Contribution of Cystatin C Gene Polymorphisms to Cerebral White Matter Lesions

Mitaki

Nagai²,

Sheikh³

et al. 2011

Cerebrovasc Dis

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“…Details of the present study design have been reported previously (12,13). The subjects, all Japanese, were from two different communities in Yamagata Prefecture, i.e., Takahata town and Sagae city.…”

Section: Study Populationmentioning

confidence: 99%

“…All participants underwent ultrasonography of the carotid arteries to obtain maximal intima-media thickness (IMT) measurements as described previously (12,13,16). The difference between the non-infarct group and the total infarct group was tested using a t test or Mann-Whitney U test.…”

Section: Evaluation Of Carotid Atherosclerosismentioning

confidence: 99%

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

et al. 2011

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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.

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“…Previous studies have suggested that diabetes mellitus (DM) is related to dementia (2-6) or cognitive impairment (7). Cerebral ischemic lesions of small vessel origin [small vessel disease (SVD)-related lesions], such as cerebral white matter lesions (WMLs) and lacunar infarcts (LI), which are frequently observed in the elderly brain on magnetic resonance imaging (MRI), are also associated with cognitive dysfunction (8,9). Therefore, SVD-related lesions should be considered in any investigation of the relationship between DM and cognitive dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Impaired Glucose Metabolism Slows Executive Function Independent of Cerebral Ischemic Lesions in Japanese Elderly: The Takahata Study

et al. 2011

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Objective Age is known to influence the risk of both cerebral ischemic lesions and impaired cognitive function. Diabetes mellitus (DM) can also be associated with cognitive impairment. However, there has been no study of neuropsychological performance in association with glucose metabolism status and cerebral ischemic lesions in same-aged, community-dwelling elderly persons. The present study was performed to clarify which cognitive domains are associated with impaired glucose metabolism/DM and whether the association is independent of cerebral ischemic lesions. Subjects and Methods A total of 172 residents in Takahata, Japan, all of whom were 78 years old, were evaluated in multiple domains through neuropsychological tests and brain MR images, as well as a medical check-up including tests for glucose metabolism status and conventional vascular risk factors. Glucose metabolism status was determined by analysis of HbA1c level. Results In multiple regression analyses, performance on a verbal fluency (VF) test and the Trail Making Test-Part B, both of which represent executive function, was associated with HbA1c level, even after adjustment for sex, education, cerebral ischemic lesions, and conventional vascular risk factors. The subjects with DM also showed lower VF scores than did those without DM. ConclusionThe results of the present study demonstrate that impaired glucose metabolism, independent of the conventional vascular risk factors and cerebral ischemic lesions, may be associated with a decline in executive function in community-dwelling elderly.

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Cystatin C as an index of cerebral small vessel disease: results of a cross‐sectional study in community‐based Japanese elderly

Abstract: The present study suggests that there is a close relationship between cystatin C and subclinical cerebral SVD, independently of conventional risk factors, in community-based elderly.

Cited by 51 publications

References 32 publications

Contribution of Cystatin C Gene Polymorphisms to Cerebral White Matter Lesions

Contribution of Cystatin C Gene Polymorphisms to Cerebral White Matter Lesions

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

Impaired Glucose Metabolism Slows Executive Function Independent of Cerebral Ischemic Lesions in Japanese Elderly: The Takahata Study

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