Cerebral microbleeds in vascular dementia from clinical aspects to host-microbial interaction.

Vascular dementia is the second leading cause of dementia after Alzheimer's disease in the elderly population worldwide. Cerebral microbleeds (CMBs) are frequently observed in MRI of elderly subjects and considered as a possible surrogate marker. The number and location of CMBs reflect the severity of diseases and the underlying pathologies may involve cerebral amyloid angiopathy or hypertensive vasculopathy. Accumulating evidence demonstrated the clinicopathological discrepancies of CMBs, the clinical significance of CMBs associated with other MRI markers of cerebral small vessel disease, cognitive impairments, serum, and cerebrospinal fluid biomarkers. Moreover, emerging evidence has shown that genetic factors and gene-environmental interactions might shed light on the underlying etiologies of CMBs, focusing on blood-brain-barrier and inflammation. In this review, we introduce recent genetic and microbiome studies as a cutting-edge approach to figure out the etiology of CMBs through the "microbe-brain-oral axis" and "microbiome-brain-gut axis." Finally, we propose novel concepts, "microvascular matrisome" and "imbalanced proteostasis," which may provide better perspectives for elucidating the pathophysiology of CMBs and future development of therapeutics for vascular dementia using CMBs as a surrogate marker.

[Meningovascular neurosyphilis as the cause of ischemic cerebrovascular disease in a young man]. / Meningovascularis neurosyphilis miatti fiatalkori ischaemiás cerebrovascularis betegség.

Authors report a case of a 35-year-old male with right-sided mild paresis, incontinence, dysexecutive syndrome, short-term memory loss and behavioral changes. Bilateral cerebral infarcts in the region of the caudate nuclei and the adjacent white matter were proved by brain MRI and multiple stenoses of the branches of Willis-circle were confirmed by MR angiography. Elevated protein level and pleocytosis were found in the cerebrospinal fluid with intrathecal IgG synthesis. Serum rapid plasma reagin, Treponema pallidum Particle Agglutination test, Treponema pallidum ELISA, liquor Venereal Disease Research Laboratory tests were positive. Meningovascular neurosyphilis was diagnosed. 24M U/day intravenous penicillin-G treatment was given for 14 days. The patient has vascular dementia due to the bilateral strategic infarcts disconnecting the prefrontal circuits; his symptoms are similar to general paresis. Laboratory and radiologic improvement was observed. Still, the patient have severe residual cognitive decline.

High prevalence of Chlamydia pneumoniae antibodies and increased high-sensitive C-reactive protein in patients with vascular dementia.

OBJECTIVES: To determine the relationships between Chlamydia pneumoniae infection, carotid atherosclerosis, and dyslipidemia in patients with vascular dementia (VaD) and Alzheimer's disease (AD). DESIGN: Case control study. SETTING: Showa University Karasuyama Hospital, Tokyo, Japan. PARTICIPANTS: One hundred twenty-four elderly subjects: 31 with VaD, 61 with AD, and 32 age-matched controls without dementia. MEASUREMENTS: Presence of antibodies to C. pneumoniae (immunoglobulin G (IgG) and IgA), the serum concentrations of high-sensitive C-reactive protein (hs-CRP) and atherogenic lipoproteins, and the carotid artery intima-media thickness (IMT) and plaques were determined. RESULTS: Age; body mass index; systolic and diastolic blood pressures; and fasting plasma glucose, hemoglobin A(1c), high-density lipoprotein cholesterol, and apolipoprotein A-I, B, and E concentrations did not differ significantly between the three groups, but the mean IMT and frequency of atherosclerotic plaques in the carotid arteries, as well as the serum concentrations of low-density lipoprotein cholesterol (LDL-C), lipoprotein(a), and lipid peroxides were significantly greater in VaD patients than in AD patients or nondemented controls. Hs-CRP concentrations and prevalence of C. pneumoniae IgG and IgA antibodies also were significantly higher in VaD patients than in AD patients and nondemented controls. Multiple logistic regression analysis revealed that carotid IMT and plaques, LDL-C, lipid peroxides, hs-CRP, and IgG and IgA C. pneumoniae seropositivity were independent risk factors for VaD. CONCLUSION: These results suggest that carotid atherosclerosis, atherogenic lipoproteins, and C. pneumoniae infection (as documented by the IgG and IgA seropositivity together with increased hs-CRP) may be VaD risk factors.

Lack of association between vascular dementia and Chlamydia pneumoniae infection: a case-control study.

BACKGROUND: Chronic inflammation appears to play a role in the pathogenesis of vascular dementia. Given the association between Chlamydia pneumoniae and stroke, the possibility exists that previous exposure to C. pneumoniae may play a role in vascular dementia. The objective of this study was to determine if there was an association between serological evidence of C. pneumoniae infection or inflammatory markers with vascular dementia. METHODS: 28 case-patients with vascular dementia at a geriatric clinic and 24 caregiver-controls were tested for C. pneumoniae IgG and IgA antibodies. The association between vascular dementia and C. pneumoniae titres as well as inflammatory markers was estimated by using both conditional logistic regression and stratified logistic regression. RESULTS: When matched cases were compared to controls, there was no significant difference in elevated C. pneumoniae specific IgG antibodies (titre >or= 1:32), odds ratio [OR] 1.3 (95% confidence intervals [CI] 0.3 to 6.0), p = 0.71, or in elevated C. pneumoniae specific IgA antibodies (titre >or= 1:16), OR 2.0 (95%CI 0.5 to 8.0), p = 0.33 indicative of past or persistent C. pneumoniae infection. Similarly, no difference in high IgG or IgA antibody levels (IgG titre >or= 1:512 or IgA titre >or= 1:64) between the two groups, indicative of recent C. pneumoniae infection, was found, OR 0.4 (95%CI 0.1 to 2.1), p = 0.27. For C-reactive protein (CRP), the mean difference between 18 matched pairs (case - control) was - 3.33 mg/L. There was no significant difference between cases and controls when comparing log transformed values, OR 0.03 (95%CI 0.00 to 2.89), p = 0.13 or comparing CRP values above or below the median, OR 0.8 (95%CI 0.2 to 3.4), p = 0.71. For fibrinogen, the mean difference between pairs (case - control) was -0.07 g/L. There was no statistical difference between cases and controls when comparing log transformed values, OR 0.6 (95%CI 0.0 to 31.2), p = 0.79 or between fibrinogen values above and below the median, OR = 0.5 (95%CI 0.1 to 2.0), p = 0.50. CONCLUSION: We found no evidence for a significant association between C. pneumoniae infection, inflammatory markers such as CRP and fibrinogen, and vascular dementia.

Absence of Chlamydia pneumoniae in brain of vascular dementia patients.

We recently detected cytomegalovirus (CMV) in brains of 83% of vascular dementia (VaD) patients and 34% of age-matched normal people. Since CMV and also Chlamydia pneumoniae (Cpn) have been found in some studies to be associated with coronary artery disease (which shares several risk factors with VaD), we sought Cpn DNA in VaD brain DNA. We examined brain specimens from 19 VaD patients, 16 elderly normal people and four Alzheimer's disease (AD) patients for the presence of a sequence in the Cpn gene for rRNA, using polymerase chain reaction (PCR) and taking stringent precautions against contamination. We did not detect Cpn DNA in any of the brain specimens, the sensitivity of detection being 10 copies or fewer bacterial DNA sequences per tube or, in terms of infectious units (IFU), 0.025 IFU. Our results do not support a role for Cpn in the aetiology of VaD, either in the 83% of patients in whose brains we detected CMV, or in the remaining 17% without CMV in brain.