Association Between Cerebral Microbleeds and Circulating Levels of Mid-Regional Pro-Adrenomedullin.

BACKGROUND: Mid-regional pro-adrenomedullin (MR-proADM) is a novel biomarker for cognitive decline based on its association with cerebral small vessel disease (SVD). Cerebral microbleeds (MBs) are characteristic of SVD; however, a direct association between MR-proADM and MBs has not been explored. OBJECTIVE: We aimed to examine whether circulating levels of MR-proADM are associated with the identification of MBs by brain magnetic resonance imaging (MRI) and whether this association could be linked with cognitive impairment. METHODS: In total, 214 participants (mean age: 75.9 years) without history of cerebral infarction or dementia were prospectively enrolled. All participants underwent brain MRI, higher cognitive function testing, blood biochemistry evaluation, lifestyle examination, and blood MR-proADM measurement using a time-resolved amplified cryptate emission technology assay. For between-group comparisons, the participants were divided into two groups according to whether their levels of MR-proADM were normal (< 0.65 nmol/L) or high (≥0.65 nmol/L). RESULTS: The mean MR-proADM level was 0.515±0.127 nmol/L. There were significant between-group differences in age, hypertension, and HbA1c levels (p < 0.05). In the high MR-proADM group, the MR-proADM level was associated with the identification of MBs on brain MR images and indications of mild cognitive impairment (MCI). In participants with ≥3 MBs and MCI, high MR-proADM levels remained a risk factor after multivariate adjustment (OR: 2.94; p < 0.05). CONCLUSION: High levels of MR-proADM may be a surrogate marker for the early detection of cognitive decline associated with the formation of cerebral MBs. This marker would be valuable during routine clinical examinations of geriatric patients.

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.

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

BACKGROUND: Recent 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. METHODS: A total of 151 participants were assessed for CD using the Mini-Mental State Examination (MMSE), and 34 participants were identified as showing CD. RESULTS: Among 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). CONCLUSIONS: The current study results suggest that the A/G ratio is related to cognitive decline and may reflect homeostatic alterations.

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

BACKGROUND: Oral 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. METHODS: A 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. RESULTS: In 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). CONCLUSIONS: The 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.

CD62-mediated activation of platelets in cerebral white matter lesions in patients with cognitive decline.

BACKGROUND: Vascular dementia is related to intracranial arteriosclerosis associated with deep white matter lesions (DWMLs). DWMLs have been linked to thrombogenesis due to sustained platelet activation; therefore, an accurate hematological marker is needed. This study was done to evaluate the usefulness of a new method to examine the function of activated platelets in order to assess DWMLs associated with cognitive decline. METHODS: A total of 143 individuals (70.4 ± 6.1 years old) who underwent hospital-based health screening using head MRI were evaluated. DWLs were evaluated on T2-weighted and FLAIR images by semi-quantitatively grading them from Grade 0 (none) to Grade 3 (severe) using the Fazekas classification. Cognitive function was evaluated using the MMSE and the word fluency test. Platelet activation was assessed using fluorescence-labeled anti-human platelet monoclonal antibodies and semi-quantitatively determining PAC-1- and CD62P-positive rates by flow cytometry. RESULTS: Significant increases in hypertension and CD62P levels were observed with increasing DWML grade (2.6% in Group 0, 3.1% in Group 1, 4.1% in Group 2, and 5.0% in Group 3). CD62P levels were defined as elevated when they were above the mean+2SD of the Grade 0 group, and the odds ratio of the Grade 2+3 group was 3.03. A significant negative correlation was observed between CD62P levels and word fluency tests or the MMSE score. CONCLUSION: Elevations in CD62P levels, which reflect platelet function activation, were associated with white matter lesions accompanied by a decline in cognitive function. CD62P levels may be useful as a sensitive clinical marker for the early detection of DWMLs with cognitive decline.