Plasma Homocysteine and Risk of Coexisting Silent Brain Infarction in Alzheimer’s Disease

Matsui, Toshifumi; Nemoto, Miyako; Maruyama, Masahiro; Yuzuriha, Takefumi; Yao, Hiroshi; Tanji, Haruko; Ootsuki, Mari; Tomita, Naoki; Matsushita, Satoru; Higuchi, Susumu; Yoshida, Yo; Seki, Takashi; Iwasaki, Katsunori; Furukawa, Koichi; Arai, Hiroyuki

doi:10.1159/000092316

Cited by 23 publications

(11 citation statements)

References 43 publications

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“…However, 13 of the 70 subjects had SBI at baseline, with the majority being lacunar infarcts. There have been several reports showing an association between homocysteine levels and the number and volume of SBIs [5,21]. Analysis of SBI in our data did not yield further support for this observation.…”

Section: Discussioncontrasting

confidence: 88%

Elevated Plasma Homocysteine Is Associated with Increased Brain Atrophy Rates in Older Subjects with Mild Hypertension

Narayan¹,

Firbank²,

Saxby³

et al. 2011

Dement Geriatr Cogn Disord

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We determined using serial MR imaging whether raised plasma homocysteine levels are associated with increased brain atrophy, white matter lesion (WML) progression or incidence of silent brain infarcts (SBIs) in older hypertensive subjects. Brain atrophy rates (0.58 ± 0.48% per year, mean ± SD) were significantly correlated with homocysteine (β = 0.46, p = 0.001 homocysteine; β = 0.44, p = 0.007 homocysteine/folate/B12 models) but not with folate or B12 levels. Progression of WML (0.08 ± 0.16%) was not associated with homocysteine level (B = 0.01, p = 0.29). New SBIs were uncommon. In older hypertensive individuals, plasma homocysteine levels are associated with increased rates of whole-brain atrophy but not WML progression.

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Section: Discussioncontrasting

confidence: 88%

Elevated Plasma Homocysteine Is Associated with Increased Brain Atrophy Rates in Older Subjects with Mild Hypertension

Narayan¹,

Firbank²,

Saxby³

et al. 2011

Dement Geriatr Cogn Disord

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“…Prevalence of silent brain infarcts (8%-28%) increases with age and is higher in those with a history of stroke or dementia. [1][2][3] Presence of silent brain infarcts increases risk of subsequent stroke and significantly increases the risk of cognitive impairment. 4,5 Cardiovascular risk factors known to increase the risk of stroke are also associated with silent brain infarcts 1 ; thus, timely institution of preventive treatment strategies in individuals with "silent strokes" may be critical for reducing risk of subsequent stroke and dementia.…”

mentioning

confidence: 99%

Silent Stroke

Saini

Ikram

Hilal

et al. 2012

Stroke

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Background and Purpose— The prevalence of silent brain infarcts varies from 8% to 28% in the general elderly population. Silent brain infarcts are associated with increased risk of subsequent stroke and cognitive dysfunction. By definition, silent strokes lack clinically overt stroke-like symptoms and fail to come to clinical attention; however, impaired recall of symptoms may be a potential confounder. Our aim is to report a series of patients with incidentally detected acute and subacute strokes and examine whether they were truly asymptomatic. Methods— Subjects included in this study were drawn from ongoing dementia research studies at the Memory Ageing and Cognition Center, in which all participants underwent a cranial MRI. Incidental hyperintense lesions on diffusion-weighted imaging with corresponding apparent diffusion coefficient defects indicative of acute/subacute silent stroke were identified. Clinical data for individuals with incidental hyperintense lesions on diffusion-weighted imaging were collated. Results— Six of 649 subjects had incidental hyperintense lesions on diffusion-weighted imaging; on retrospective questioning, 3 recalled symptoms temporally correlated with MRI lesions, which had been reported to but ignored by family members. Two subjects had focal neurological signs. A majority of the subjects with incidental hyperintense lesions on diffusion-weighted imaging had significant cognitive impairment. Conclusions— A significant number of strokes may be “silent” due to lack of awareness of stroke-like symptoms in the elderly and their families. Enhanced stroke prevention education strategies are needed for the elderly population and, in particular, for their families.

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“…Higher plasma tHcy levels appear to be associated with an increased risk of silent brain infarction on brain MRI,15 and with moderate-to-severe WMC on brain computed tomography (CT) in individuals with AD 16. Homocysteine has been shown to potentiate amyloid beta-peptide-mediated toxicity in primary neuronal cultures 17.…”

Section: Introductionmentioning

confidence: 99%

Plasma Total Homocysteine Levels are not Associated with Medial Temporal Lobe Atrophy, but with White Matter Changes in Alzheimer's Disease

Kim

Choi

et al. 2009

J Clin Neurol

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Background and purposeElevated plasma total homocysteine (tHcy) levels are reported to be associated with an increased risk of Alzheimer's disease (AD). However, the mechanism by which homocysteine contributes to the pathogenesis of AD is as yet unknown. The aim of this study was to elucidate the relationship between white matter changes (WMC) and medial temporal lobe atrophy (MTA) on brain magnetic resonance imaging (MRI), and plasma levels of tHcy in AD patients.MethodsSeventy-two patients with a clinical diagnosis of probable AD were recruited to the study. Plasma tHcy levels, vascular risk factors, and WMC and MTA on brain MRI were evaluated in all patients. The AD patients were classified into two groups: those with no or minimal WMC (69.2±8.8 years, mean±SD, n=36) and those with moderate-to-severe WMC (74.6±4.6 years, n=36) on brain MRI.ResultsIn a univariate logistic regression analysis, the risk of moderate-to-severe WMC in AD was significantly associated with increasing age, female gender, lower education level, hypertension, high plasma tHcy levels, and lower Mini-Mental State Examination (MMSE) score. Multivariate logistic regression analysis revealed only high plasma tHcy as the independent and significant risk factor for moderate-to-severe WMC [odds ratio (OR; adjusted for age, gender, education level, MMSE score, and hypertension comparing the top tertile - tHcy levels ≥12.9 µmol/L - with the bottom tertile - tHcy levels ≤9.4 µmol/L)=7.35; 95% confidence interval, confidence interval=1.36-39.84; p=0.02], and age as a borderline significant risk factor (OR=1.08, 95% CI=0.99-1.19, p=0.09) in AD patients. Plasma tHcy levels were not correlated significantly with either right or left MTA.ConclusionsOur results suggest that the vascular pathway mediates the association between elevated plasma tHcy levels and AD.

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Plasma Homocysteine and Risk of Coexisting Silent Brain Infarction in Alzheimer’s Disease

Cited by 23 publications

References 43 publications

Elevated Plasma Homocysteine Is Associated with Increased Brain Atrophy Rates in Older Subjects with Mild Hypertension

Elevated Plasma Homocysteine Is Associated with Increased Brain Atrophy Rates in Older Subjects with Mild Hypertension

Silent Stroke

Plasma Total Homocysteine Levels are not Associated with Medial Temporal Lobe Atrophy, but with White Matter Changes in Alzheimer's Disease

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