Hyperhomocysteinemia is associated with volumetric white matter change in patients with small vessel disease

Wong, Adrian; Mok, Vincent; Fan, Yu; Lam, Wynnie W M; Liang, Kae‐Woei; Wong, Ka Sing

doi:10.1007/s00415-005-0022-x

Cited by 51 publications

(41 citation statements)

References 22 publications

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“…Studies have suggested that high homocysteine levels are associated with an increased risk of brain damage such as silent brain infarcts or white matter hyperintensities that are themselves associated with an increased risk of dementia [37][38][39][40][41][42] , although we could not confirm this hypothesis in a previous study [3] .…”

Section: Discussioncontrasting

confidence: 56%

Homocysteine, Folate and Cognition in a Large Community-Based Sample of Elderly People – The 3C Dijon Study

et al. 2008

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Background: Hyperhomocysteinemia is associated with an increased risk of cognitive impairment in the elderly. Recent studies suggest that folate level may also influence the course of cognitive decline. Objective: We performed the cross-sectional analysis of the relationship between homocysteine and folate levels and cognitive performances in a population-based study including 3,914 subjects aged 65 years and older. Method: Subjects had an evaluation of their cognitive level using five neuropsychological tests. A Cognitive Summary Score was computed as the sum of each of the 5 cognitive tests score standardized. Relations of folate and homocysteine levels with cognition were first studied separately in a covariance analysis. Stratified analyses were also performed because of interaction between folate and homocysteine in relation to cognition. Results: Subjects in the higher quartile of homocysteine (high homocysteine group) and subjects in the lower quartile of folate (low folate group) had consistently lower cognitive performances in all tests. When stratified on folate level, high homocysteinemia was associated with lower cognitive performances only in subjects with a low folate level. Conclusion: In this large population-based sample of elderly people, the association between high homocysteinemia and decreased cognition was only seen in participants with low folate levels.

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Section: Discussioncontrasting

confidence: 56%

Homocysteine, Folate and Cognition in a Large Community-Based Sample of Elderly People – The 3C Dijon Study

et al. 2008

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“…In univariate analysis, the WMH score was the highest in the top Hcy tertile (median 16, interquartile range 12-21), followed by the middle tertile (13, 8.5-19) and the bottom tertile (12,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20); p =0.001). Prevalence of sv-WMH was significantly different among the Hcy tertiles: 45.3% for the top tertile, 29.1% for the middle tertile, and 28.8% for the bottom tertile (p = 0.01 for the trend).…”

Section: Resultsmentioning

confidence: 96%

“…For exploring the role of hyperhomocysteinemia in the development of cerebral SVD, several studies investigating the association between blood Hcy level and white matter lesions have been performed in the western populations [11][12][13][14][15][16]. However, there have been few studies on this issue among Asians [17,18] although it has been recognized that Asians have a higher risk for cerebral SVD than Caucasians [19,20]. The purpose of this study was to examine the relationship between plasma Hcy level and WMH in a cohort of Taiwanese stroke patients.…”

Section: Introductionmentioning

confidence: 97%

Association of plasma homocysteine concentration with cerebral white matter hyperintensity on magnetic resonance images in stroke patients

Tseng

Chang

Liu

et al. 2009

Journal of the Neurological Sciences

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“…Hyperhomocysteinemia has emerged as an independent risk factor for cerebral small vessel disease, which may lead to lacunar infarction and accounts for about 25% of ischemic strokes (19,(39)(40)(41)(42). In older individuals, several large cross-sectional studies have linked hyperhomocysteinemia with depression and with small vessel disease-related dementias, including Alzheimer disease (43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Homocysteine inhibits neoangiogenesis in mice through blockade of annexin A2–dependent fibrinolysis

Jacovina¹,

Deora²,

Qi³

et al. 2009

J. Clin. Invest.

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When plasma levels of homocysteine (HC), a thiol amino acid formed upon methionine demethylation, exceed 12 μM, individuals are at increased risk of developing large vessel atherothrombosis and small vessel dysfunction. The annexin A2 complex (termed "A2") is the cell surface coreceptor for plasminogen and TPA and accelerates the catalytic activation of plasmin, the major fibrinolytic agent in mammals. We previously showed that HC prevents A2-mediated, TPA-dependent activation of plasminogen in vitro by disulfide derivatization of the "tail" domain of A2. We also demonstrated that fibrinolysis and angiogenesis are severely impaired in A2-deficient mice. We now report here that, although hyperhomocysteinemic mice had a normal coagulation profile and normal platelet function, fibrin accumulated in their tissues due to reduced perivascular fibrinolytic activity and angiogenesis was impaired. A2 isolated from hyperhomocysteinemic mice failed to fully support TPAdependent plasmin activation. However, infusion of hyperhomocysteinemic mice with fresh recombinant A2, which localized to neoangiogenic endothelial cells, resulted in normalization of angiogenesis and disappearance of peri-and intravascular fibrin. We therefore conclude that hyperhomocysteinemia impairs postnatal angiogenesis by derivatizing A2, preventing perivascular fibrinolysis, and inhibiting directed endothelial cell migration. These findings provide a mechanistic explanation for microvascular dysfunction and macrovascular occlusion in individuals with hyperhomocysteinemia.

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Hyperhomocysteinemia is associated with volumetric white matter change in patients with small vessel disease

Cited by 51 publications

References 22 publications

Homocysteine, Folate and Cognition in a Large Community-Based Sample of Elderly People – The 3C Dijon Study

Homocysteine, Folate and Cognition in a Large Community-Based Sample of Elderly People – The 3C Dijon Study

Association of plasma homocysteine concentration with cerebral white matter hyperintensity on magnetic resonance images in stroke patients

Homocysteine inhibits neoangiogenesis in mice through blockade of annexin A2–dependent fibrinolysis

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