Etsuko Ozaki

Intracranial deep white matter lesions (DWLs) are associated with chronic kidney disease (CKD) and cognitive impairment: a 5-year follow-up magnetic resonance imaging (MRI) study.

Stroke incidence and cognitive decline are related to progression of arteriosclerosis in intracranial DWLs. However, the relationships between DWLs and factors associated with their progression, including CKD, have not been fully elucidated using longitudinal MRI. Of 291 individuals (184 males, 107 females; age 66.9 ± 6.1 years) who had voluntarily participated in a hospital-based health check-up and underwent repeated brain MRI scans in 2003 and 2008, 273 were evaluated in this study. The DWL group included those having DWL without progression, and the DWL progression (DWLP) group included those having an increase in grade number according to the Fazekas classification. Unimpaired age-matched subjects with no brain MRI abnormalities constituted Group C. The Mini-Mental State Examination (MMSE) and verbal fluency tasks were used for objective cognitive evaluations according to the MR evaluation schedule in 2008. Associations between DWLs and vascular risk factors were examined. DWLP occurred in 9.2% of subjects. Compared to Group C subjects, DWL and DWLP group subjects had high odds ratios (ORs) for hypertension (HT) (2.23 and 2.92, respectively) and CKD (1.40 and 2.41, respectively). After adjustment for potential confounders, the ORs of CKD for DWLs remained significant (1.13 and 1.43, p<0.05). DWLs and DWLP were associated with low cognitive scale scores and increased CKD. In conclusion, CKD was associated with DWLs and DWLP as an independent risk factor and a lower level of cognitive function 5 years after CKD was identified. Successful CKD therapy may be expected to prevent DWLP.

Relationship between Cnm‐positive Streptococcus mutans and cerebral microbleeds in humans

OBJECTIVE Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus mutans carrying the collagen-binding Cnm gene. However, the relationship between cerebral microbleeds and oral hygiene, with a focus on Cnm gene-positive S. mutans infection, remains unclear. MATERIAL AND METHODS One hundred and thirty-nine subjects participated. The presence or absence of Cnm-positive S. mutans and its collagen-binding activity were investigated using saliva samples, and relationship with cerebral microbleeds detected on MRI investigated, including clinical information and oral parameters. RESULTS Fifty-one subjects were identified as Cnm-positive S. mutans carriers (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly larger number of subjects carried Cnm-positive S. mutans in the cerebral microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral microbleeds in the Cnm-positive group was 14.4. Regarding the presence of cerebral microbleeds, no significant differences were noted in the number of remaining teeth, dental caries, or in classic arteriosclerosis risk factors. CONCLUSIONS The occurrence of cerebral microbleeds was higher in subjects carrying Cnm-positive S. mutans, indicating that the presence of Cnm-positive S. mutans increases cerebral microbleeds, and is an independent risk for the development of cerebrovascular disorders.

Validity of self-reported number of teeth and oral health variables.

BackgroundOral condition and number of teeth were investigated by questionnaire in the Japan Multi-Institutional Collaborative Cohort (J-MICC Study). The aim of the present study was to assess the validity of the tooth number measure by comparing the self-reported number of teeth with the number of teeth determined at clinical dental examination.MethodsA self-administered questionnaire and dental examination were performed by 1275 participants of a company medical examination who requested dental check-up and 377 subjects of the J-MICC study. The validity of the tooth number measure was assessed by comparing the self-reported number of teeth with that determined at clinical examination. Spearman’s rank correlation coefficient was calculated to quantitatively evaluate the validity.ResultsIn males, the mean clinically-examined and self-reported numbers of teeth were 26.5 and 24.8 teeth, respectively. In females, the mean clinically-examined and self-reported numbers of teeth were 26.4 and 25.5 teeth, respectively. There was a tendency toward underestimation of the number of natural teeth by self-reporting. A significant correlation was observed between the clinically-examined and self-reported numbers of teeth in total (ρ = 0.69) and both males (ρ = 0.70) and females (ρ = 0.67).ConclusionsThe self-reported oral health variables were valid and reflected clinical status. Further revision of the question on the remaining tooth in the questionnaire improves the validity of self-reported number of teeth.

Oral Cnm - positive Streptococcus Mutans Expressing Collagen Binding Activity is a Risk Factor for Cerebral Microbleeds and Cognitive Impairment

Cerebral microbleeds (CMBs) are an important risk factor for stroke and dementia. We have shown that the collagen binding surface Cnm protein expressed on cnm-positive Streptococcus mutans is involved in the development of CMBs. However, whether the collagen binding activity of cnm-positive S. mutans is related to the nature of the CMBs or to cognitive impairment is unclear. Two-hundred seventy nine community residents (70.0 years) were examined for the presence or absence of cnm-positive S. mutans in the saliva by PCR and collagen binding activity, CMBs, and cognitive function were evaluated. Cnm-positive S. mutans was detected more often among subjects with CMBs (p < 0.01) than those without. The risk of CMBs was significantly higher (odds ratio = 14.3) in the group with S. mutans expressing collagen binding activity, as compared to the group without that finding. Deep CMBs were more frequent (67%) and cognitive function was lower among subjects with cnm-positive S. mutans expressing collagen binding activity. This work supports the role of oral health in stroke and dementia and proposes a molecular mechanism for the interaction.

Nationwide hospital‐based survey of idiopathic normal pressure hydrocephalus in Japan: Epidemiological and clinical characteristics

There have been no nationwide epidemiological studies of idiopathic normal pressure hydrocephalus (iNPH) in Japan. Therefore, a nationwide epidemiologic survey of iNPH was performed to determine the number of cases and clinical characteristics by sex and diagnostic level.

Determinants of brachial-ankle pulse wave velocity in a Japanese population: a cohort study.

Abstract Arterial stiffness is one of the biggest predictors of coronary heart disease (CHD). We evaluated whether brachial–ankle pulse wave velocity (baPWV) and augmentation index (AI) are correlated with risk factors of CHD. All of the 528 participants (270 males and 258 females) in this study were healthy workers aged from 36 to 69 (mean age: 47.9 ± 8.1 years). The Framingham Risk Score (FRS) showed a good correlation with baPWV (r = 0.53, p < 0.01), indicating that FRS is also applicable as an index of arterial stiffness in Japanese people. Blood pressures were well controlled in patients with medical treatment for hypertension; however, vessels remained relatively still stiff, whereas the AI was considerably low. Multivariate linear regression analysis showed that factors of such as FRS, body mass index, alcohol consumption and AI P75 were significantly correlated with baPWV.

Gene-gene combination effect and interactions among ABCA1, APOA1, SR-B1, and CETP polymorphisms for serum high-density lipoprotein-cholesterol in the Japanese population.

Background/Objective Gene-gene interactions in the reverse cholesterol transport system for high-density lipoprotein-cholesterol (HDL-C) are poorly understood. The present study observed gene-gene combination effect and interactions between single nucleotide polymorphisms (SNPs) in ABCA1, APOA1, SR-B1, and CETP in serum HDL-C from a cross-sectional study in the Japanese population. Methods The study population comprised 1,535 men and 1,515 women aged 35–69 years who were enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We selected 13 SNPs in the ABCA1, APOA1, CETP, and SR-B1 genes in the reverse cholesterol transport system. The effects of genetic and environmental factors were assessed using general linear and logistic regression models after adjusting for age, sex, and region. Principal Findings Alcohol consumption and daily activity were positively associated with HDL-C levels, whereas smoking had a negative relationship. The T allele of CETP, rs3764261, was correlated with higher HDL-C levels and had the highest coefficient (2.93 mg/dL/allele) among the 13 SNPs, which was statistically significant after applying the Bonferroni correction (p<0.001). Gene-gene combination analysis revealed that CETP rs3764261 was associated with high HDL-C levels with any combination of SNPs from ABCA1, APOA1, and SR-B1, although no gene-gene interaction was apparent. An increasing trend for serum HDL-C was also observed with an increasing number of alleles (p<0.001). Conclusions The present study identified a multiplier effect from a polymorphism in CETP with ABCA1, APOA1, and SR-B1, as well as a dose-dependence according to the number of alleles present.

Ventricular Temperatures in Idiopathic Normal Pressure Hydrocephalus (iNPH) Measured with DWI-based MR Thermometry.

PURPOSE The brain produces intense heat as a result of cerebral metabolism and cerebral blood flow, and the generated heat is removed mainly through circulation of the intracranial blood vessels and cerebrospinal fluid (CSF). Because magnetic resonance (MR) images are constructed from analysis of the spin of various molecules, the diffusion coefficient can be used as a parameter that reflects the temperature of water molecules. We used diffusion-weighted imaging (DWI)-based MR imaging to measure the temperature of the CSF around the lateral ventricles in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS Our study included 33 cases of iNPH (Group N, mean age, 75.1 years) and 40 age-matched controls (Group C, mean age, 74.5 years). We calculated CSF temperature in the ventricular domain using the conversion formula to evaluate the feasibility of iNPH study. RESULTS The mean temperatures were significantly higher in Group N (37.6°C ± 0.4°C) than Group C (36.7°C ± 0.5°C; P < 0.01). The cut-off value of 37.2°C (more than the mean + 2 standard deviations [SD] of the values in Group C) showed sensitivity of 72.4% and specificity of 77.5% for distinguishing the 2 groups. We confirmed improved CSF temperature in the lateral ventricles in all patients examined both before and after shunting. CONCLUSIONS Elevated ventricular temperatures in patients with iNPH (Group N) may represent a disturbance in heat balance. Our results showed that thermometry using DWI-based MR imaging can help in the noninvasive and consistent evaluation of CSF temperature and may thus provide a useful supplementary brain biomarker for iNPH.

Association between loss of bone mass due to short sleep and leptin-sympathetic nervous system activity

BACKGROUND Sleep has been reported to be an important factor in bone metabolism, and sympathetic nervous system activity has been reported to regulate bone metabolism. In this study, we evaluated the association between sleep, sympathetic nervous system activity, and bone mass. METHODS The study subjects were 221 individuals (108 males; 113 females; mean age: 55.1±7.0years) divided into two groups: those who slept for less than 6h a day (short sleep [SS] group), and those who slept 6h or longer (normal sleep [NS] group). The groups were compared with regard to lifestyle, cortical bone thickness, cancellous bone density, bone metabolism markers, blood leptin levels, and sympathetic nervous system activity as evaluated by heart rate variability analysis. RESULTS Significant differences were observed between the two groups in cortical bone thickness, blood TRACP-5b, and leptin levels. The L/H ratio (an index of sympathetic nervous system activity) was higher in the SS group than in the NS group. Significant negative correlations were observed between cortical bone thickness and both the L/H ratio and leptin levels, and a significant positive correlation was observed between the L/H ratio and leptin levels. CONCLUSIONS Short sleep was associated with a decline in cortical bone thickness due to the promotion of bone resorption and sympathetic nervous system hyperactivity in the middle-aged group. Leptin levels and cortical bone thickness were found to be closely related, suggesting that cortical bone mass may be regulated via interaction with the leptin-sympathetic nervous system.

Serum albumin to globulin ratio is related to cognitive decline via reflection of homeostasis: a nested case-control study

BackgroundRecent research suggests that several pathogenetic factors, including aging, genetics, inflammation, dyslipidemia, diabetes, and infectious diseases, influence cognitive decline (CD) risk. However, no definitive candidate causes have been identified. The present study evaluated whether certain serum parameters predict CD.MethodsA total of 151 participants were assessed for CD using the Mini-Mental State Examination (MMSE), and 34 participants were identified as showing CD.ResultsAmong CD predictive risk factors, Helicobacter pylori seropositivity was significantly predictive of CD risk, more so than classical risk factors, including white matter lesions and arterial stiffness [adjusted odds ratio (OR) = 4.786, 95% confidence interval (CI) = 1.710–13.39]. A multivariate analysis indicated that the albumin to globulin (A/G) ratio was the only factor that significantly lowered CD risk (OR = 0.092, 95% CI = 0.010–0.887). A/G ratio also was positively correlated with MMSE scores and negatively correlated with disruption of homeostatic factors (i.e., non-high-density lipoprotein, hemoglobin A1c, and high-sensitive C-reactive protein).ConclusionsThe current study results suggest that the A/G ratio is related to cognitive decline and may reflect homeostatic alterations.