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Background: Recent studies have demonstrated an association between the gut microbiome and cognitive function. However, the associations between the gut microbiome and brain parenchyma damage, and their underlying mechanisms, remain unclear.Materials and Methods: We performed a cross-sectional sub-analysis using data from our prospective cohort study to determine the association between the gut microbiome and cerebral small vessel disease (SVD). We assessed patient demographics, risk factors, cognitive function, brain imaging, voxel-based specific regional analysis system for Alzheimer's Disease (VSRAD, indicating brain atrophy), and the gut microbiome as indicated by enterotypes and faecal microbiome metabolites. We then analysed the associations between total SVD scores, cognitive function, and the gut microbiome.Results: We analysed data from 87 patients without dementia or a history of stroke, 64 of whom exhibited mild cognitive impairment. Higher total SVD scores were associated with cognitive decline and behavioural and psychological symptoms. Compared with all other patients, patients with enterotype I (Bacteroides >30%) were more likely to have cognitive decline (median scores: Mini-Mental State Examination, 25 vs. 27, P = 0.047; Clinical Dementia Rating-Sum of Boxes, 1.5 vs. 0.5, P = 0.002) and present with cerebral SVD and high VSRAD scores (1.01 vs. 0.57, P = 0.012). Furthermore, faecal metabolites were significantly higher in patients with higher total SVD scores compared with those with lower scores. Multivariable logistic regression analyses indicated that certain gut microbiomes may double the risk of white matter hyperintensity.Conclusions: The gut microbiome is associated with cerebral SVD. [ABSTRACT FROM AUTHOR]

Since the operational definition of “cognitive frailty” was first proposed in 2013 by the International Academy of Nutrition and Aging and the International Association of Gerontology and Geriatrics, several studies have been carried out using this cognitive frailty model. In this review, we examined the available clinical and epidemiological evidence for cognitive frailty. Despite its low prevalence (1.0–1.8%) in the community setting, cognitive frailty has been associated with a high risk of disability, poor quality of life, and death; while cognitive frailty appears to be associated with a high risk of dementia, there is no clear evidence for this association. Again, while the prevalence of cognitive frailty appears to have increased in the clinical setting, to date, very few studies evaluated the impact of cognitive frailty. While a new definition of cognitive frailty was proposed in 2015 to incorporate “reversible” and “potential reversible” subtypes, there is a paucity of epidemiological evidence to support this definition. In conclusion, there is no consensus on the definition of cognitive frailty for use in clinical and community settings or on which measures to be used for detecting cognitive impairment. Further study is required to formulate effective preventive strategies for disability in the elderly. [ABSTRACT FROM AUTHOR]

Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor. We hypothesized that frail older adults would tend to have electrolyte imbalances because they should have many stressors together with fragile physiological systems. In this study, we aimed to determine whether older adults with higher Frailty Index scores have electrolyte imbalances and to establish which domains of the Frailty Index are correlated with electrolyte imbalances. A cross-sectional study. A total of 4204 older adults aged 70 years or over who visited the Japanese National Center for Geriatrics and Gerontology. We calculated the 50-item Frailty Index with the following domains: comorbidities, cognitive function and mood, basic and instrumental activities of daily living, physical function, nutrition, and fall risks from physical weakness and comorbidities. Participants were categorized into four groups: a non-frail group (Frailty Index ≤0.2), mildly frail group (0.20 < Frailty Index ≤0.3), moderately frail group (0.3 < Frailty Index ≤0.4), and severely frail group (0.4 < Frailty Index). Their serum sodium, potassium, calcium, and phosphorus concentrations were measured. A multiple regression model was used to explore the relationship of electrolyte imbalances with the Frailty Index and to determine which frailty domains are correlated with electrolyte imbalances. Compared with the non-frail group, the mildly and moderately frail groups tended to have hypernatremia and hypophosphatemia, whereas the severely frail group tended to have dysnatremia, hypokalemia, and hypophosphatemia. The estimated odds ratios increased by 15%–52% for each electrolyte imbalance as the Frailty Index increased by 0.1. The Frailty Index domains of cognitive function, activities of daily living, and nutrition were correlated with more than three kinds of electrolyte imbalances, the domains of physical function and fall risks from physical weakness were correlated with three kinds of electrolyte imbalances, and the domains of comorbidities and fall risks from comorbidities were correlated with two kinds of electrolyte imbalances. Older adults with higher Frailty Index scores tend to have electrolyte imbalances. • Older adults with higher Frailty Index scores tend to have electrolyte imbalances. • The older adults serum electrolyte concentration must be paid attention. • Electrolyte imbalances may participate in the mechanism of frail older adults. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Preventive strategy for falls in demented elderly is a clinical challenge. From early-stage of Alzheimer's disease (AD), patients show impaired balance and gait. The purpose of this study is to determine whether regional white matter lesions (WMLs) can predict balance/gait disturbance and falls in elderly with amnestic mild cognitive impairment (aMCI) or AD. Design: Cross-sectional. Settings: Hospital out-patient clinic. Participants: One hundred sixty-three patients diagnosed with aMCI or AD were classified into groups having experienced falls (n = 63) or not (n = 100) in the previous year. Measurements: Cognition, depression, behavior and psychological symptoms of dementia, medication, and balance/gait function were evaluated. Regional WMLs were visually analyzed as periventricular hyperintensity in frontal caps, bands, and occipital caps, and as deep white matter hyperintensity in frontal, parietal, temporal, and occipital lobes, basal ganglia, thalamus, and brain stem. Brain atrophy was linearly measured. Results: The fallers had a greater volume of WMLs and their posture/gait performance tended to be worse than nonfallers. Several WMLs in particular brain regions were closely associated with balance and gait impairment. Besides polypharmacy, periventricular hyperintensity in frontal caps and occipital WMLs were strong predictors for falls, even after potential risk factors for falls were considered. Conclusions: Regional white matter burden, independent of cognitive decline, correlates with balance/gait disturbance and predicts falls in elderly with aMCI and AD. Careful insight into regional WMLs on brain magnetic resonance may greatly help to diagnose demented elderly with a higher risk of falls. [Copyright &y& Elsevier]

Abstract: Background: Intima-media thickness (IMT) of the carotid artery, flow-mediated dilation (FMD) of the brachial artery, and pulse wave velocity of the central artery (PWV) have been widely used to evaluate progression of atherosclerosis. Our previous work has revealed that IMT, FMD and PWV are related to each other, and the combination of these measurements was useful in identifying patients with atherosclerotic disease. The aim of the present study was to investigate whether combination of these measurements would predict future cardiovascular events better than each test alone. Methods and results: From November 2000 to March 2008, 274 consecutive elderly subjects (men/women; 114/160, mean age; 71 ± 12 years) were enrolled in this study. We measured IMT, FMD, and PWV in all of these subjects and followed them for a mean of 41 ± 28 months. During the follow-up period, vascular events occurred in 42 patients (15.3%). IMT (hazard ratio = 1.28 [95%CI, 1.09–1.50], p = 0.002 per 0.1 mm increase in mean IMT) and brachial-ankle (ba) PWV (hazard ratio = 1.06 [95%CI, 1.01–1.10], p = 0.015 per 1 m/s increase in baPWV) were independent predictors of future vascular events by Cox proportional hazard analysis, although FMD did not reach statistical significance (hazard ratio = 0.85 [95%CI, 0.72–1.01], p = 0.062 per 1% increase in %FMD). Importantly, the number of tests showing results in the worst tertile was a more powerful predictor (hazard ratio = 2.21 [95%CI, 1.42–3.43], p = 0.0004 for number of tests showing worst tertile) of future vascular events than either IMT, baPWV, or FMD alone. When both IMT and baPWV (with respective cut-off values of 0.98 mm and 19.1 m/s) were taken into consideration, the efficacy increased as compared with each test alone (odds ratio 4.9). Conclusion: These results indicate that IMT and baPWV, especially when combined, are useful in predicting future vascular events in elderly subjects. [Copyright &y& Elsevier]

Abstract: Objectives: Physicians are uncertain about what medical services should be provided to older and/or disabled patients. Better understanding of health outcome prioritization among health care providers and recipients may help the process of decision- and policy-making. For this purpose, surveys were conducted on priorities of health care outcomes for the elderly. Design: Survey research. Setting: Four groups of health care providers and four groups of health care recipients. Participants: A total of 2512 health care providers and 4277 recipients. Measurements: Questionnaires were sent to more than 8000 health care providers and more than 9000 health care recipients: geriatricians, physicians who commonly see older patients or work in long term care facilities, staff members and participants in adult day care, patients in outpatient geriatric clinics, family members of patients with dementia, and community-dwelling older adults. The questionnaire asked the subjects to rank 12 measures of health care outcomes. Results: The mean response rate was 49%. All health care provider groups considered “improvement of quality of life” the most important. In contrast, in health care recipient groups, “effective treatment of illness,” “improvement of physical function,” and “reduction of carer burden” were given high priority, whereas “improvement of quality of life” was perceived as less important. All the groups, including health care providers and recipients, ranked “reduction of mortality” the least important, followed by “avoiding institutional care.” Stratification analysis showed that the results did not differ by sex, nursing care level, or the existence of relatives who required nursing care, whereas age slightly influenced the order of high-ranked measures. Conclusion: Priorities of health care services and their differences between providers and recipients should be taken into account in the health care of older patients and the design of health care policies and research. [Copyright &y& Elsevier]

Abstract: Objective: Effects of potent free radical scavenger, edaravone, on oxidative stress-induced endothelial damage and early atherosclerosis were investigated using animal models and cultured cells. Methods and results: Endothelial apoptosis was induced by 5-min intra-arterial exposure of a rat carotid artery with 0.01mmol/L H2O2. Edaravone treatment (10mg/kg i.p.) for 3 days suppressed endothelial apoptosis, as evaluated by chromatin staining of en face specimens at 24h, by approximately 40%. Similarly, edaravone dose-dependently inhibited H2O2-induce apoptosis of cultured endothelial cells in parallel with the inhibition of 8-isoprostane formation, 4-hydroxy-2-nonenal (4-HNE) accumulation and VCAM-1 expression. Next, apolipoprotein-E knockout mice were fed a high-cholesterol diet for 4 weeks with edaravone (10mg/kg i.p.) or vehicle treatment. Edaravone treatment decreased atherosclerotic lesions in the aortic sinus (0.18±0.01 to 0.09±0.01mm2, P <0.001) and descending aorta (5.09±0.86 to 1.75±0.41mm2, P <0.05), as evaluated by oil red O staining without influence on plasma lipid concentrations or blood pressure. Dihydroethidium labeling and cytochrome c reduction assay showed that superoxide anions in the aorta were suppressed by edaravone. Also, plasma 8-isoprostane concentrations and aortic nitrotyrosine, 4-HNE and VCAM-1 contents were decreased by edaravone treatment. Conclusions: These results suggest that edaravone may be a useful therapeutic tool for early atherosclerosis, pending the clinical efficacy. [Copyright &y& Elsevier]

Flow-mediated dilation (FMD) of the brachial artery, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) have been shown to be good surrogate markers of clinical atherosclerosis. We determined the interrelation between these measurements, and examined whether their combination would be of clinical significance. One hundred and thirty-five consecutive subjects (79 women/56 men) were enrolled, including 110 patients with risk factors for atherosclerosis, and 33 patients with atherosclerotic disease such as coronary heart disease, stroke or arteriosclerosis obliterans. IMT and plaque formation of the carotid artery and FMD of the brachial artery were assessed using ultrasonography. Brachial-ankle PWV (baPWV) was measured using an automated device (form ABI/PWV, Colin). Age, FMD, IMT and PWV were significantly correlated with each other. Multivariate analysis revealed an independent correlation between the parameters except for FMD, and all four parameters were independently correlated with each other in subjects <70 years. Next, we classified the subjects by tertile according to the values of FMD, IMT and PWV. Each of the worst tertiles was associated with a higher prevalence of atherosclerotic disease and carotid plaques compared to the other tertiles. Moreover, subjects with the worst tertiles of all three measurements had a markedly higher prevalence of atherosclerotic disease and carotid plaques. These results suggest that FMD, IMT and PWV are related to each other, but the combination of these measurements will be of stronger clinical relevance. [Copyright &y& Elsevier]

Tests the hypothesis that acute intake of red wine may exert a positive effect on flow-mediated vasodilatation in men. Improvement in endothelium-dependent vasodilatation after acute intake of red wine or red wine without alcohol in men; Constituents of red wine that help improve endothelial function.

Objectives To validate the ability of the total Kihon checklist (t-KCL) score to predict the incidence of dependency or death within 3 years in a community-dwelling older population. Design Population-based longitudinal observational study. Setting Town of Higashi-ura, Japan. Participants A total of 5542 independent seniors who were residents in the town of Higashi-ura. Measurements The KCL questionnaire was sent to independent older residents. Based on our previous report, those with a t-KCL score of 0-3 were classified as robust, 4-7 as pre-frail, and 8 + as frail. The incidence of dependency or death was observed over 3 years. Dependency was defined as a new certification for long-term care insurance (LTCI) service need. Information regarding LTCI certification or death was obtained from the municipal government. Results Of 8091 independent older adults, 5542 seniors completed the KCL questionnaire. Based on the t-KCL score, they were classified into 3 groups: 2962 (53.4%) as robust, 1625 (29.3%) as pre-frail, and 955 (17.2%) as frail. Over the 3 years, 510 seniors (9.2%) had new LTCI certifications and 170 (3.1%) died. Cox regression analysis adjusted for age and sex showed that the classification of frailty status by t-KCL score was significantly associated with the incidence of dependency both in the pre-frail and the frail [hazard ratios (HRs): 2.027 and 4.768; 95% confidence intervals (CIs): 1.575-2.608 and 3.733-6.089, respectively]. On the other hand, the ability to predict death was significant, but only in the frail group (HR: 2.830; 95% CI: 1.952-4.104). Conclusion The classification of frailty status by t-KCL score could be a significant tool to predict the incidences of dependency and mortality in older adults. [ABSTRACT FROM AUTHOR]

Objectives We investigated the differences in the physical function test results across stages from normal cognition (NC) to moderate Alzheimer disease (AD) and how risk factors of physical function decline are correlated with the physical function test results. Design A cross-sectional study of outpatients at the Memory Disorder Outpatient Center of Japan's National Center of Geriatrics and Gerontology. Participants We enrolled 882 individuals aged ≥65 diagnosed with NC (n = 210), amnestic mild cognitive impairment (aMCI; n = 273), mild AD (n = 181) or moderate AD (n = 197). Measurements We measured the participants' results for functional reach (FR), the one-leg standing (OLS) test, the Timed Up and Go (TUG) test, tandem gait (TG), and grip strength (GS). A one-way analysis of covariance (ANCOVA) was used to identify significant differences among the groups' results on the physical function tests, controlling for age, sex, educational year, Mini-Nutritional Assessment, senior activity and exercise frequency, low-density lipoprotein, body mass index, free-fat mass index, and assistance for the TUG test. Multiple regression analysis was also used to investigate the correlation between these covariates and physical function tests results. Results The ANCOVA showed that FR, OLS, and TG were significantly worse among the individuals with aMCI, mild AD, or moderate AD compared with NC. However, TUG was significantly worse only in the moderate AD group compared with the NC, aMCI, and mild AD group. Multiple regression analysis showed that aging was correlated with poorer scores on all physical function tests, women had poorer scores on FR and GS than men, and low frequency of senior activity was significantly correlated with poorer scores on FR, OLS, and TG. Conclusion Postural impairment and instability on TG was seen in earlier AD stages compared with instability on TUG. As were the covariates of age and sex, senior activity frequency was significantly related to 2 or more physical function tests. [ABSTRACT FROM AUTHOR]