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Background: Periodontal disease (PeD) is a risk factor of Alzheimer's disease and is associated with cognitive decline in older adults. However, the relationships between subitems of neuropsychological tests and PeD have not been fully clarified., Objective: To evaluate associations between PeD and subitems of neuropsychological tests., Methods: We performed a cross-sectional analysis of data of 183 participants (women: 50%, mean age: 79 years) from a clinical study. We enrolled patients who visited our memory clinic and assessed demographics, dementia-related risk factors, neuropsychological tests, brain magnetic resonance images, and a dental screening check. We evaluated the relationships between cognitive function and PeD using multivariable logistic regression analyses., Results: Participants with dementia were less likely to make periodical visits to the dentist, had fewer teeth, had less frequent tooth brushing habits, and were more likely to have PeD. Impaired cognitive function was significantly associated with an increasing degree of PeD. In multivariable logistic regression analyses, impaired visuospatial function and attention were associated with twice the risk of moderate or severe PeD compared with individuals with preserved visuospatial function and attention (odds ratio: 2.11, 95% confidence interval: 1.04-4.29, p = 0.037). Impaired word recall and recognition and following commands were associated with increased risk of PeD (odds ratio: 2.80, 95% confidence interval: 1.41-5.32, p = 0.003)., Conclusions: Cognitive decline, such as impaired visuospatial function, attention, word recall and recognition, and inability to follow commands were independently and strongly associated with PeD. These items can be assessed easily on a daily basis.

Aims/introduction: To investigate the changes in the glycated hemoglobin (HbA1c) levels and the relative status of the glycemic control related to the new glycemic targets recommended by the Japan Diabetes Society/Japan Geriatrics Society Joint Committee in 2016 in patients with diabetes mellitus visiting a memory clinic from 2012 to 2020., Materials and Methods: This cross-sectional study included 1,436 patients aged ≥65 years with diabetes. Patients were categorized into three categories as follows: category I, intact cognitive function and activities of daily living (ADL); category II, mild cognitive deficits or impaired instrumental ADL; and category III, moderate to severe cognitive impairment or impaired basic ADL. Trends in HbA1c levels, glycemic control status (optimally/poorly/excessively controlled) and proportion of individuals receiving drugs potentially associated with severe hypoglycemia among all patients and categories (I, II or III) from 2012 to 2020 were examined using linear, logistic and multinominal logistic regression models adjusted for confounding factors., Results: Between 2012 and 2020, the HbA1c levels, as well as the proportion of patients with poor glycemic control, increased, whereas the proportion of patients with excessive glycemic control and those receiving drugs potentially associated with severe hypoglycemia decreased., Conclusions: Increased levels of HbA1c and decreased proportions of individuals under excessive glycemic control might reflect recent treatment strategies that avoid hypoglycemia in older patients. Given the adverse complications associated with hyperglycemia, more flexible and individualized glycemic targets based on comprehensive assessments, including vascular complications and comorbidities, might be necessary., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aim: Olfactory impairment is associated with cognitive impairment. However, differences between subjective and objective olfactory impairment measurements in older adults and their relationship with cognitive impairment are unclear., Methods: We assessed the relationship between cognitive and olfactory impairments via a single-center observational study in 2020. Forty-seven individuals who visited our memory clinic were enrolled and asked to complete objective and subjective olfactory tests. Participants had dementia, mild cognitive impairment, or normal cognition. We administered the Open Essence (a simple card-type odor identification test) and self-administered odor questionnaire to assess objective and subjective olfaction, respectively, and the Mini-Mental State Examination to assess cognitive function., Results: Older age was related to decreased Open Essence scores (P < 0.001). Compared with the mild cognitive impairment and normal cognition groups, the dementia group had significantly lower Open Essence scores (P < 0.001). Cognitive impairment was also associated with decreased Open Essence scores after adjusting for age, sex, and education (P < 0.001). Participants with dementia did not obtain lower self-administered odor questionnaire scores than those with normal cognition, and they tended to be unaware of their olfactory impairment., Conclusion: Open Essence scores significantly decreased according to the degree of cognitive impairment. Participants with dementia were unaware of their olfactory impairment, as indicated by odor questionnaire scores. Objective and subjective scores of olfaction differed in participants with dementia. Concomitant assessment of objective and subjective olfaction is useful to screen older adults with both olfactory and cognitive impairments. Geriatr Gerontol Int 2022; 22: 924-929., (© 2022 Japan Geriatrics Society.)

Background & Aims: While cross-sectional studies report associations between behavioral and psychological symptoms of dementia (BPSD) and nutritional status as a modifiable factor, their causal relationship remains unclear. Therefore, this study investigated the impact of nutritional status on BPSD., Methods: This study included women with mild cognitive impairment (MCI) and early-stage Alzheimer's disease (AD) from Memory Clinic, National Center for Geriatrics and Gerontology. The participants were assessed for nutritional status and BPSD using the Mini Nutritional Assessment Short-Form (MNA-SF) and the Dementia Behavior Disturbance Scale (DBD), respectively. Based on their MNA-SF scores, the subjects were classified as well-nourished, at risk of malnutrition, or malnourished. Nutritional status and change in BPSD was examined for association by univariate and multivariate linear regression analyses., Results: This study analyzed 181 women (79 with MCI and 102 with early-stage AD). The multivariate analysis showed that the malnourished subjects or those at risk of malnutrition (54.1%) were significantly associated with increased DBD scores (β = 0.255, P = 0.003) during follow-up. In addition, multivariate regression analysis incorporating change in DBD sub-score as a dependent variable showed that the malnourished subjects or those at risk of malnutrition were associated with increased DBD sub-scores for "verbal aggressiveness/emotional disinhibition" (β = 0.247, P = 0.005)., Conclusions: Poor nutritional status increased BPSD, especially verbal aggressiveness/emotional disinhibition, in those with MCI and early-stage AD during 2.5-year follow-up. Patients with MCI and early-stage AD may need to be assessed for nutritional status from early on, at the onset of mild cognitive decline, and require intervention to prevent worsening of BPSD. Further intervention studies in large prospective cohorts are needed to establish nutritional measures to prevent progression of BPSD in older adults with cognitive impairment., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: White matter hyperintensity (WMH), defined as abnormal signals on magnetic resonance imaging (MRI), is an important clinical indicator of aging and dementia. Although MRI image analysis software can automatically detect WMH, the quantitative accuracy of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) is unknown., Materials and Methods: This study was a sub-analysis of MRI data from an ongoing hospital-based prospective cohort study (the Gimlet study). Between March 2016 and March 2017, we enrolled patients who visited our memory clinic and agreed to undergo medical assessments of cognitive function and fecal examination to study the gut microbiome. Participants with a history of stroke were excluded. WMH was independently quantitatively analyzed using two MRI imaging analysis software modalities: SNIPER and FUSION. Intraclass correlation coefficients and the mean difference in volume were calculated and compared between modalities., Results: The data of 87 patients (49 women, mean age 74.8 ± 7.9 years) were analyzed. Both total WMH and DWMH volumes obtained using FUSION were greater (p < 0.001), and PVH volume was smaller (p < 0.001) than those obtained using SNIPER. Intraclass correlation coefficients for the lesion measurements of WMH, PVH, and DWMH between the different software were 0.726 (p < 0.001), 0.673 (p < 0.001), and 0.048 (p = 0.231), respectively., Conclusions: There were significant differences in the quantitative data of WMH between the two MRI imaging analysis software modalities. Thus, care should be taken for quantitative assessments of WMH., Competing Interests: Declaration of Competing Interest Dr. Saji received grants from the Grant-in-Aid for Scientific Research (C) and JSPS KAKENHI (Grant 20k07861), as well as research funds from the Comprehensive Research on Aging and Health program at the Japan Agency for Medical Research and Development (AMED). Dr. Saji received grants from the NARO Bio-oriented Technology Research Advancement Institution Project (for advanced integration research within agriculture and interdisciplinary fields), the Research Funding of Longevity Sciences from the NCGG, the Danone Institute of Japan Foundation, the Honjo International Scholarship Foundation, and the BMS/Pfizer Japan Thrombosis Investigator-initiated Research Program. These funders were not involved in the design, conduct, or publication of this work. All other authors have no actual or potential conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective Dementia with Lewy bodies (DLB) is the second-most common form of neurodegenerative dementia after Alzheimer's disease (AD). Falls are a vital prognostic factor in patients with dementia and are a characteristic feature of DLB. This study investigated the screening potential of the fall risk evaluation for DLB and compared it with that of AD to facilitate an accurate diagnosis. Methods We enrolled patients diagnosed with DLB (n=410) and AD (n=2,683) and categorized the participants into 3 groups depending on their physical ability, age, cognitive function, and fall events. Using the Fall Risk Index-21 (FRI-21) questionnaire, we evaluated and comparatively analyzed the fall risk between DLB and AD patients in three defined groups of participants. Results The FRI-21 score was significantly higher in DLB patients than in AD patients in every group. Using this score, we were able to distinguish between DLB and AD patients in each group. Among the three groups, the group with a young age, relatively mild cognitive dysfunction, and no fall events exhibited the best specificity for DLB (0.895). Conclusions The FRI-21 is a useful tool for screening for DLB and differentiating it from AD. This questionnaire can be used at a relatively early stage of the disease in young patients with mild cognitive dysfunction and no history of falling. These preliminary results need to be validated in an interventional study to evaluate the effectiveness of rehabilitative measures and daily environmental changes carried out to prevent falls using this tool.

Objective: Previous studies have shown associations between the gut microbiota, microbial metabolites, and cognitive decline. However, the effect of the dietary composition on such associations has not been fully investigated. The aims of this study were to evaluate the relationships between adherence to a Japanese-style diet, the gut microbiota, and cognitive decline. Furthermore, we aimed to evaluate the three forms of the Japanese diet index (JDI; the conventional [JDI 9 ], updated [JDI 12 ], and a newly modified JDI) to determine which would show the closest relationships with cognition and the gut microbiota., Methods: We performed a cross-sectional subanalysis of data from a prospective hospital-based cohort study. We assessed the patients' demographic characteristics, dietary composition, risk factors, cognitive function, brain imaging, gut microbiome, and microbial metabolites. On the basis of previous studies, a nine-component traditional JDI (JDI 9 ), a 12-component modern JDI (JDI 12 ), and a 12-component revised JDI (rJDI 12 ), were defined. We evaluated the relationships between the JDI scores, cognitive function, and the gut microbiome and microbial metabolites using multivariable logistic regression analyses., Results: We analyzed data from 85 eligible participants (61% women; mean age: 74.6 ± 7.4 y). Compared with participants who had dementia, those without dementia were more likely to consume foods in the JDI 12 , including fish and shellfish (64.5 versus 39.1%, P = 0.048), mushrooms (61.3 versus 30.4%, P = 0.015), soybeans and soybean-derived foods (62.9 versus 30.4%, P = 0.013), and coffee (71 versus 43.5%, P = 0.024). There were non-significant trends toward lower fecal concentrations of gut microbial metabolites in participants with a more traditional Japanese diet. Participants with dementia had lower JDI scores than those without dementia (dementia versus non-dementia, median JDI 9 score: 5 versus 7, P = 0.049; JDI 12 : 7 versus 8, P = 0.017; and rJDI 12 : 7 versus 9, P = 0.006, respectively)., Conclusions: Adherence to a traditional Japanese diet was found to be inversely associated with cognitive decline and tended to be associated with lower concentrations of gut microbial metabolites., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

A lower body mass is associated with the progression of Alzheimer's disease (AD) and the risk of mortality in patients with AD; however, evidence of genetic determinants of decreased body mass in cognitively impaired older adults is limited. We therefore investigated the genetic effect of APOE-ε4 on body composition in older adults with mild cognitive impairment (MCI) and early-to-moderate-stage AD. A total of 1631 outpatients (aged 65-89 years) with MCI and early-to-moderate-stage AD were evaluated for the association between body composition and APOE-ε4 status. After adjusting for covariates, including cognitive function evaluated with the Mini-Mental State Examination, the presence of the APOE-ε4 was associated with lower weight (β = -1.116 ± 0.468 kg per presence, p = 0.017), fat mass (β = -1.196 ± 0.401 kg per presence, p = 0.003), and percentage of body fat (β = -1.700 ± 0.539% per presence, p = 0.002) in women but not in men. Additionally, the impact of APOE-ε4 on measures of body composition in women was more remarkable in MCI than in AD patients. The presence of the APOE-ε4 allele was associated with lower fat mass, particularly in women with MCI, independent of cognitive decline.

Background: With increasingly aging societies, a comprehensive strategy for dementia research is important. The Organized Registration for the Assessment of dementia by the Nationwide General consortium toward Effective treatment (ORANGE) Registry is the first longitudinal multicenter prospective trial-ready cohort in Japan., Objective: To establish a large cohort for use in clinical trials and research in Japan., Methods: This registry, based on communities, hospitals, and nursing homes, covers three dementia stages (preclinical, mild cognitive impairment [MCI], and advanced dementia), and includes more than 30 hospitals. We analyzed enrollment and 1-year follow-up data for disease progression., Results: There were 1450 registered patients (649 men, 801 women; mean age, 77.92±6.70 years; mean Mini-Mental State Examination [MMSE] score, 25.19±2.76). The conversion rates from MCI to dementia and MCI to normal were 14.3% and 1.1%, respectively. High Clinical Dementia Rating score (odds ratio [OR] = 11.085, 95% confidence interval [CI]:1.619-75.913, p = 0.014), low MMSE score (OR = 0.835, 95% CI: 0.761-0.917, p < 0.001), high Geriatric Depression Scale score (OR = 1.093, 95% CI: 1.005-1.189, p = 0.038), and low body mass index (OR = 0.895, 95% CI: 0.829-0.967, p = 0.005) at enrollment were significant factors for conversion., Conclusion: The ORANGE MCI Registry is an established registry that facilitates creation of trial-ready cohorts to accelerate promotion of clinical trials with low reversion rates as it originates from a hospital. One-year follow-up analysis suggested assessing various factors for conversion risk. Further analyses will be possible in future with registry expansion. We will continue to refine this registry, including how it can be used more efficiently.

Objective: The influence of living alone on multiple food and nutrition behaviors across a range of ages and genders has not been sufficiently investigated. Moreover, to our knowledge, no studies have described both dietary status and medical examination findings in persons living alone. Among individuals who attended a health checkup in a rural town in Japan, we investigated dietary habits and medical examination findings in persons living alone and those living with one or more other persons., Methods: The participants in this investigation were 501 community-dwelling individuals aged 40 to 91 y (mean, 63.8 ± 9.9 y). Thirty-four (16.4%) of the 207 men and 45 (15.3%) of the 294 women lived alone. Dietary intake frequency of 28 types of foods and drinks, including various vegetables, fruits, meat, seafood, and dairy products, was investigated based on responses to a self-completed questionnaire. During the physical examination, body weight, body mass index, body fat percentage, and blood pressure (systolic and diastolic) were measured. Blood examination included red blood cell count, white blood cell count, platelet count, hemoglobin, hematocrit, total protein, albumin/globulin ratio, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, creatinine, blood urea nitrogen, uric acid, and serum calcium., Results: Multivariate analysis revealed that living alone independently was associated with a reduced intake frequency of various vegetables and seafood, especially in men. Diastolic blood pressure and triglyceride levels were significantly higher in men living alone than in men living with other persons. The albumin/globulin ratio in women living alone was significantly lower than in women living with other persons., Conclusions: It was found that living alone was associated not only with a reduced quality of dietary intake but also with an unfavorable trend in some of the medical examination findings., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Relationships between hearing impairment (HI) and dementia have been reported in elderly adults, and there is growing evidence that HI is an independent modifiable risk factor for dementia. However, there is insufficient evidence to recommend the use of hearing aids to reduce the risk of cognitive decline. To address these issues, we are currently conducting an observational study in cooperation with neurologists, gerontologists, and otorhinologists to investigate the association between cognitive function and HI in elderly adults. As part of this study, we also investigated this association using data from healthcare check-up programs for community dwellers. We analyzed the data of 1602 eligible community-dwellers. Hearing aid users were older and less likely to exhibit cognitive impairment than non-hearing aid users. Multivariate logistic regression analysis showed that HI was independently associated with an inability to draw a clock correctly (odds ratio 1.60, 95% confidence interval 1.12-2.26). Compared with those in Western countries, the usage rate of hearing aids in Japan is lower, although the rate of elderly adults presenting with HI is similar to those in Western countries. Both otorhinologists and geriatricians should be aware of the potential presence of HI in elderly adults.

Background: Hearing impairment (HI) is associated with dementia. However, the cognitive screening tasks effective in older community dwellers presenting with HI are unclear., Methods: We retrospectively and cross-sectionally investigated the associations between HI and cognitive function assessed with screening tasks using data from two healthcare check-up programs for community dwellers ≥65 years old in 2018. We examined demographics, risk factors, cognitive function, hearing condition, lifestyles, and self-care levels. Cognitive function was assessed using the clock drawing task and the delayed three words recall task. Hearing condition was assessed using questionnaires on the use of hearing aids and HI during conversation situations. Multivariate analysis was used to identify independent associations between HI and cognitive assessment tasks., Results: We analyzed 1602 eligible participants (61.9% women; 74.3 ± 6.5 years old). Hearing aid users (n = 90) were older (80 vs. 73 years, respectively; p < 0.001) and less likely to draw the clock correctly (71.1% vs. 80.1% years, respectively; p = 0.044) than non-hearing aid users. Multivariate logistic regression analysis showed that HI was associated with inability to draw the clock correctly (odds ratio 1.60, 95% confidence interval 1.12-2.26; p = 0.011), independent of age, living alone, memory impairment, and impaired self-care levels., Conclusion: Hearing impairment is independently associated with cognitive decline assessed by the clock drawing task. The clock drawing task may be useful for identifying an increased risk of dementia in older subjects presenting with HI., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declarations of Competing Interest Dr Saji has received grants from the Grant-in-Aid for Scientific Research (C), JSPS KAKENHI (grant 20k07861), grants from the NARO Bio-oriented Technology Research Advancement Institution Project (advanced integration research for agriculture and interdisciplinary fields), grants from the Danone Institute of Japan Foundation, grants from the Honjo International Scholarship Foundation, and the BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program. Dr Saji, Dr Niida, and Dr Sakurai have received research grants from the Research Funding of Longevity Sciences from the National Center for Geriatrics and Gerontology. Dr Saji, Dr Toba, and Dr Sakurai have received research funds for Comprehensive Research on Aging and Health from the Japan Agency for Medical Research and Development (AMED). Dr Tsuduki has received grants from the NARO Bio-oriented Technology Research Advancement Institution Project (advanced integration research for agriculture and interdisciplinary fields)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Dysregulation of the gut microbiome is associated with dementia. However, the relationship between microbiome-associated metabolites and dementia has yet to be identified. Outpatients visiting a memory clinic in Japan enrolled in this cross-sectional study; 107 subjects were eligible for the study, 25 of which had dementia. We collected demographics, activities of daily living, risk factors, cognitive function, and brain imaging data. The gut microbiome was assessed using terminal restriction fragment length polymorphism analysis. Concentrations of faecal metabolite were measured. We used multivariable logistic regression analyses to identify whether metabolites were independently related to dementia. The concentrations of metabolites were significantly different between subjects with and those without dementia. Every 1 standard deviation increment in faecal ammonia concentration was associated with around a 1.6-fold risk for the presence of dementia. A higher faecal lactic acid concentration was related to a lower risk of dementia, by around 60%. A combination of higher faecal ammonia and lactic acid concentrations was indicative of the presence of dementia, and had a similar predictive value as traditional biomarkers of dementia. Thus, faecal ammonia and lactic acid are related to dementia, independently of the other risk factors for dementia and dysregulation of the gut microbiome.

Dysregulation of the gut microbiome is associated with several life-threatening conditions, and might therefore represent a useful target for the prevention of dementia. However, the relationship between the gut microbiome and dementia has not yet been fully elucidated. Here, we recruited outpatients visiting our memory clinic to participate in this study. Information for patient demographics, various risk factors, and daily activities was collected, and cognitive function was assessed using neuropsychological tests and magnetic resonance imaging scans. Fecal samples were obtained, and the gut microbiome was assessed by terminal restriction fragment length polymorphism (T-RFLP) analysis, one of the most well-established and reliable 16S ribosomal RNA-based methods for classifying gut microbiota. Multivariable logistic regression models were used to identify factors independently associated with dementia and mild cognitive impairment. Graphical modelling was used to illustrate mutual associations. We analyzed 128 eligible patients (female: 59%, mean age: 74.2±8.7 years, mean Mini Mental State Examination score 24). Multivariable analyses showed that enterotype I and enterotype III bacteria were strongly associated with dementia, independent of traditional dementia biomarkers. Further studies investigating metabolites of gut microbes are needed to determine the mechanism underlying this association.

Dysregulation of the gut microbiome is associated with several life-threatening conditions and thus might represent a useful target for the prevention of dementia. However, the relationship between the gut microbial population and dementia has not yet been fully clarified. We recruited outpatients visiting our memory clinic to participate in this study. Information on patient demographics, risk factors, and activities of daily living was collected, and cognitive function was assessed using neuropsychological tests and brain magnetic resonance imaging scans. Faecal samples were obtained, and the gut microbiome was assessed by terminal restriction fragment length polymorphism (T-RFLP) analysis, one of the most well-established and reliable 16S ribosomal RNA-based methods for classifying gut microbiota. Patients were divided into two groups, demented and non-demented. Multivariable logistic regression models were used to identify the variables independently associated with dementia. The T-RFLP analysis revealed differences in the composition of the gut microbiome: the number of Bacteroides (enterotype I) was lower and the number of 'other' bacteria (enterotype III) was higher in demented than non-demented patients. Multivariable analyses showed that the populations of enterotype I and enterotype III bacteria were strongly associated with dementia, independent of the traditional dementia biomarkers. Further studies of the metabolites of gut microbes are needed to determine the mechanism underlying this association.

Background: The mechanism of progressive neurological deficit in patients with recent small subcortical infarcts has not yet been clarified. Inflammatory biomarkers and the use of cilostazol may be associated with this phenomenon., Methods: Between May 2013 and April 2014, we evaluated consecutive first-ever patients with stroke due to recent small subcortical infarcts within 48 hours of onset. We divided patients into 2 groups according to the use of antiplatelet agents (cilostazol with or without aspirin versus aspirin alone). Plasma biomarkers such as matrix metalloproteinase-9, interleukin-6, high sensitive C-reactive protein, and amyloid β precursor protein (APP770, indicating endothelial dysfunction) were measured twice: (1) within 24 hours; and (2) 1 week after their admission. Multivariable logistic regression analyses were performed to identify the variables independently associated with progressive neurological deficit and poor functional outcome., Results: We analyzed 41 patients (male: 63.4%, mean age: 70.8 years). Most of the patients (90%) who were treated with cilostazol were concomitantly treated with aspirin. Matrix metalloproteinase-9 and high sensitive C-reactive protein were higher in patients with progressive neurological deficit compared with those without. APP770 were more likely to be decreased in cilostazol group compared with aspirin group. Multivariable analyses show that traditional risk factors such as age and National Institutes of Health Stroke Scale scores were independently associated with both progressive neurological deficit and poor functional outcome., Conclusions: Inflammatory biomarkers may be associated with progressive neurological deficit. Early initiation of cilostazol may decrease the levels of plasma biomarkers., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to determine whether pulse wave velocity (PWV), a marker of vascular endothelial impairment and arteriosclerosis, predicts future ischemic stroke in patients who developed acute lacunar infarction. Patients with a first-ever ischemic stroke due to acute lacunar infarction were enrolled in this study. An oscillometric device (Form PWV/ABI; Omron Colin, Tokyo, Japan) was used to measure brachial-ankle PWV 1 week after stroke onset. Patients were followed for at least 5 years. The main end point of the study was recurrent ischemic stroke. Event-free survival was analyzed using Kaplan-Meier plots and log-rank tests. The risk of recurrent ischemic stroke was estimated using the Cox proportional-hazards model. Of the 156 patients (61% male, mean age: 69.2±11.3 years) assessed in this study, 29 developed recurrent ischemic stroke. The median brachial-ankle PWV value was 20.4 m s -1 . Patients with high PWV values had a greater risk of recurrent ischemic stroke than patients with low PWV values (28% vs. 15%, P=0.08). Kaplan-Meier curve analysis showed that patients with high PWV values had a less favorable (that is, free of recurrent ischemic stroke) survival time (P=0.015). A multivariate Cox proportional-hazards model identified high PWV as an independent predictor of recurrent ischemic stroke after adjusting for age, sex and blood pressure (hazard ratio 2.35, 95% confidence interval, 1.02-5.70, P=0.044). In patients with acute lacunar infarction, a high PWV predicts a twofold greater risk of future ischemic stroke, independent of patient age, sex and blood pressure levels.

Background: Weight loss is frequently observed in patients with Alzheimer's disease (AD); however, the underlying mechanisms are not well understood., Objects: To clarify the associations between nutritional status and AD-related brain changes using Pittsburgh Compound-B (PiB)-PET, fluorodeoxyglucose (FDG)-PET, and structural MRI., Methods: The subjects were 34 amyloid-β (Aβ)-positive individuals with mild cognitive impairment or early AD (prodromal/early AD), and 55 Aβ-negative cognitively normal (CN) subjects who attended the Multimodal Neuroimaging for AD Diagnosis (MULNIAD) study. Nutritional status of the subjects was assessed by body mass index and waist to height ratio (waist circumference/height). The associations between nutritional status and brain changes were examined by multiple regression analysis using statistical parametric mapping., Results: In the prodromal/early AD group, nutritional status was significantly positively correlated with regional cerebral glucose metabolism (rCGM) in the medial prefrontal cortices, while different topographical associations were seen in the CN group, suggesting these changes were AD-specific. Aβ deposition and gray matter volume were not significantly associated with nutritional status. Sub-analysis in the prodromal/early AD group demonstrated that fat mass index, but not fat-free mass index, was positively correlated with rCGM in the medial prefrontal areas., Conclusion: This present study provides preliminary results suggesting that hypometabolism in the medial prefrontal areas is specifically associated with AD-related weight loss, and decrease in fat mass may have a key role.

The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2-4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.

Background: Hereditary cerebellar ataxia constitutes a heterogeneous group of neurodegenerative disorders, occasionally accompanied by other neurological features. Genetic defects remain to be elucidated in approximately 40% of hereditary cerebellar ataxia cases in Japan. We attempted to identify the gene responsible for autosomal recessive cerebellar ataxia with intellectual disability., Methods: The present study involved three patients in a consanguineous Japanese family. Neurological examination and gene analyses were performed in all family members. We performed genome-wide linkage analysis including single nucleotide polymorphism arrays, copy-number variation analysis and whole exome sequencing. To clarify the functional alteration resulting from the identified mutation, we performed cell viability assay of cultured cells expressing mutant protein., Results: One homozygous region shared among the three patients on chromosomes 2p16.1-2q12.3 was identified. Using whole exome sequencing, six homozygous variants in genes in the region were detected. Only one variant, VWA3B c.A1865C, results in a change of a highly conserved amino acid (p.K622T) and was not present in control samples. VWA3B encodes a von Willebrand Factor A Domain-Containing Protein 3B with ubiquitous expression, including the cerebellum. The viability of cultured cells expressing the specific K622T mutation was proved to decrease through the activation of apoptotic pathway., Conclusions: Mutated VWA3B was found to be likely associated with cerebellar degeneration with intellectual disability. Although a rare cause of cerebellar degeneration, these findings indicate a critical role for VWA3B in the apoptosis pathway in neuronal tissues., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Cerebral small vessel diseases, including silent lacunar infarcts, white matter hyperintensities, and microbleeds, pose a risk for cerebrovascular disease, cognitive impairment, and the geriatric syndrome via effects on arterial stiffness. However, the vascular, physiological, and metabolic roles of arterial stiffness in cerebral small vessel diseases remain unclear., Summary: Arterial stiffness can be assessed using various indicators such as the ankle-brachial index, pulse wave velocity, cardio-ankle vascular index, and augmentation index. Arterial stiffness is independently associated with all components of cerebral small vessel disease including silent lacunar infarcts, white matter hyperintensities, and microbleeds, although there are some methodological differences between the various surrogate markers. Evidence of arterial stiffness indicates microvessel arteriosclerosis presenting with vascular endothelial dysfunction. Further, vascular narrowing due to atherosclerosis and vascular stiffness due to lipohyalinosis can accelerate the pulse waves. This hemodynamic stress, pulsatile pressure, or blood pressure variability can cause a 'tsunami effect' towards the cerebral parenchyma and lead to cerebral small vessel disease. Previous studies have shown that silent lacunar infarcts and white matter hyperintensities are strongly associated with arterial stiffness. However, the association between microbleeds and arterial stiffness remains controversial, as there are two vessel mechanisms related to microbleeds: cerebral amyloid angiopathy and hypertensive small vessel disease., Key Messages: Cerebral small vessel disease with associated arterial stiffness is a risk factor for silent cerebral lesions, stroke, and cognitive impairment. Improvement of the living environment, management of risk factors, and innovation and development of novel drugs that improve arterial stiffness may suppress the progression of cerebral small vessel disease, and may reduce the risk for stroke and dementia.

Frailty is a predictor of functional decline, falls, hospitalization, and mortality. Fried et al. developed the frailty index, which include 5 simple items: weight loss, weakness, exhaustion, slowness, and low activity. Likewise, sarcopenia indicates an age-related decline in skeletal muscle mass as well as muscle function, which may result in reduced physical capability, poorer quality of life, impaired cardiopulmonary performance, unfavorable metabolic effects, falls, disability, and mortality. Both frailty and sarcopenia could be associated with mild cognitive impairment which leads to dementia. Thus, early initiation of a comprehensive geriatric health examination and a multidomain intervention such as diet, exercise, cognitive training, and vascular risk monitoring may be useful to prevent frailty and sarcopenia in community-dwelling older adults.

Background and Purpose: Hyperintense vessels (HV) detected on fluid-attenuated inversion recovery (FLAIR) in patients with acute ischemic stroke (AIS) indicate cerebral hypoperfusion. However, the clinical meaning of changes in HV is yet to be clarified. Here, we investigated serial changes to HV in patients with AIS who received tissue plasminogen activator (t-PA) therapy., Methods: We studied t-PA patients presenting with HV on FLAIR in the middle cerebral artery territory. Patients underwent brain MRI 1 h before and after t-PA infusion. HV scores (range 1-7) were evaluated according to Alberta Stroke Program Early Computed Tomography Score territories, and then by subtracting HV scores at 1 h after t-PA infusion from those on admission, with a result of >1 defined as decrease in HV score (DHV). Patients were divided into 2 groups based on the presence or absence of DHV. Multivariate logistic regression analysis was conducted to identify variables independently associated with good outcome (modified Rankin Scale score at 90 days after stroke onset of 0-1)., Results: A total of 118 consecutive patients were enrolled (73 men; mean age 76 ± 9.7; median initial National Institutes of Health Stroke Scale (NIHSS) 13; median initial HV score 5), of whom 52 (44%) had DHV. Patients with DHV showed a significantly lower NIHSS time course (p < 0.001) and significantly smaller infarct volume time course (p < 0.001) compared to those without DHV. Multivariate analysis showed that DHV was independently associated with good outcome (OR 3.89; 95% CI 1.55-9.77; p < 0.01). The sensitivity and specificity of DHV for good outcome were 70 and 68%, respectively., Conclusion: A DHV on FLAIR predicts good outcome in patients receiving t-PA., (© 2016 S. Karger AG, Basel.)

White matter hyperintensities (WMH) are defined as cerebral white matter changes presumed to be of vascular origin, bilateral and mostly symmetrical. They can appear as hyperintense on T2-weighted and fluid-attenuated inversion recovery sequences, and as isointense or hypointense on T1-weighted magnetic resonance imaging of the brain. WMH have been focused on because of their clinical importance as a risk factor for cerebrovascular diseases and cognitive impairment. WMH are associated with geriatric syndrome, which is defined by clinical symptoms characteristic of older adults, including cognitive and functional impairment and falls. Cerebral small vessel diseases, such as WMH, might play an important role as risk factors for cerebrovascular diseases, cognitive impairment and geriatric syndrome through the mechanism of arterial stiffness. However, the vascular, physiological and metabolic roles of arterial stiffness remain unclear. Basically, arterial stiffness indicates microvessel arteriosclerosis presenting with vascular endothelial dysfunction. These changes might arise from hemodynamic stress as a result of a "tsunami effect" on cerebral parenchyma. In the present article, we review the clinical characteristics of WMH, focusing particularly on two associations: (i) those between cerebral small vessel diseases including WMH and arterial stiffness; and (ii) those between WMH and geriatric syndrome., (© 2015 Japan Geriatrics Society.)

Background: Cerebral small-vessel disease (SVD) is associated with renal dysfunction such as chronic kidney disease. Although cerebral microbleeds (CMBs) are common in patients with acute lacunar infarcts (ALI), the association between renal dysfunction and CMBs in such patients remains unclear., Methods: Between April 2007 and March 2013, we evaluated consecutive first-ever ALI patients, who were admitted to our hospital within 24 hours of stroke onset. CMBs were defined as focal areas of signal loss in brain parenchyma less than 5 mm on T2(∗)-weighted gradient-echo imaging. Renal dysfunction was defined as an estimated glomerular filtration rate less than 60 mL/minute/1.73 m(2) on admission. Correlations between renal dysfunction and the presence (model 1) and location of CMBs (model 2; any deep or infratentorial CMBs) were determined by multivariable logistic regression analyses., Results: Among 152 patients (33.6% men; mean age, 67.6 years), 53 had CMBs. Patients with CMBs were older (69.9 versus 66.3 years, P = .03) and had a higher frequency of white matter hyperintensity (WMH; 62.3% versus 25.3%, P < .001), silent lacunar infarcts (SLI; 75.5% versus 43.3%, P < .001), and renal dysfunction (41.5% versus 22.2%, P = .015) than those without CMBs. On multivariable analyses, renal dysfunction (odds ratio, 95% confidence interval; model 1: 2.38, 1.02-5.66; model 2: 2.78, 1.16-6.81), WMH (3.87, 1.76-8.80; 3.72, 1.64-8.71), SLI (3.85, 1.71-9.14; 4.20, 1.77-10.8), and diabetes mellitus (.26, .09-.63; .24, .08-.63) were independently associated with CMBs., Conclusions: In patients with ALI, renal dysfunction was positively associated with CMBs independent of cerebral SVD., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) are surrogate markers of arteriosclerosis. However, their roles in patients with acute ischemic stroke remain unclear. From October 2003 to September 2011, we enrolled patients with arteriosclerotic ischemic stroke (AIS) exhibiting large infarcts attributed to large-artery atherosclerosis (LAA) or deep subcortical infarcts (mainly lacunar infarcts) attributed to small-artery disease (SAD). Outpatients without a history of stroke served as controls (CTL). We divided the study period into two terms and assessed patients using two different oscillometric devices (Form PWV/ABI, Omron Colin; and VaSera VS-1500, Fukuda Denshi) in each term. One-way analysis of variance and age- and sex-adjusted analysis of covariance were used to compare the three groups. We analyzed 842 patients. The ABI was significantly lower in the LAA (n = 102) group than in the SAD (n = 280) and CTL (n = 460) groups. The baPWV was significantly higher in the LAA and SAD groups than in the CTL group. The CAVI gradually increased in the order of CTL, SAD and LAA. The cutoff values of baPWV and CAVI for detection of AIS were 18.3 m s(-1) (odds ratio (OR): 6.09, 95% confidence interval (CI): 3.97-9.62, P < 0.01) and 9.5 (OR: 1.44, 95% CI: 1.24-1.70, P < 0.001), respectively. Among the three indicators, a lower ABI indicated advanced atherosclerosis associated with LAA, and an increased baPWV more closely indicated AIS. An increased CAVI may indicate the degree of vessel stiffness due to arteriosclerosis.

Background: Whether brain natriuretic peptide (BNP) levels are associated with early recurrent stroke in cardioembolic stroke patients was investigated., Methods: From January 2010 to March 2014, consecutive patients within 24 hours of onset of cardioembolic stroke were prospectively enrolled, and admission plasma BNP levels were measured. Recurrent stroke was identified as the occurrence of additional neurologic deficits and the appearance of a new infarct on neuroimaging. Patients were divided into 2 groups: the recurrence group and the nonrecurrence group. Factors associated with stroke recurrence were investigated by multiple logistic regression analysis., Results: A total of 348 patients were included; 17 patients (5%) had recurrent stroke during hospitalization. The median interval from stroke onset to recurrent stroke was 4 days (range, 0-30). BNP levels were significantly higher in the recurrence group than in the nonrecurrence group (304.1 vs. 206.5 pg/mL, P = .029). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the recurrence group from the nonrecurrence group were 255.0 pg/mL, 76%, and 60%, respectively. On multivariate analysis after adjustment for confounders, plasma BNP ≥ 255.0 pg/mL (odds ratio, 5.21; 95% confidence interval, 1.63-16.72; P = .005) was independently associated with recurrent stroke during hospitalization in cardioembolic stroke patients., Conclusions: Plasma BNP could be a useful marker for predicting early recurrent stroke during hospitalization in cardioembolic stroke patients., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Intravenous thrombolysis using the tissue-type plasminogen activator (t-PA) is contraindicated for patients with a history of intracerebral hemorrhage (ICH). T2*-weighted magnetic resonance imaging (MRI) is able to detect asymptomatic ICH. If there is an association between asymptomatic ICH on T2* before t-PA therapy and ICH after t-PA therapy, we may be able to take preventive measures before starting t-PA therapy in patients with MRI-proven hemorrhage. The aim of the present study was to investigate whether asymptomatic ICH seen on T2* increases the risk of new ICH after t-PA therapy., Methods: Patients who had consecutive stroke treated with t-PA between October 2005 and November 2013 were enrolled. A hypointense T2* signal with a diameter >5 mm was defined as asymptomatic ICH before t-PA therapy. The presence of new ICH at 24 h after t-PA therapy was assessed using T2*. Symptomatic ICH (sICH) was defined as new ICH combined with an increase in the National Institutes of Health Stroke Scale score ≥4. At 3 months after onset, good and poor outcomes were defined as modified Rankin Scale (mRS) scores of 0-1 and 4-6, respectively., Results: Of 300 patients (age 77 [68-83] years; 173 [58%] males), 25 (8%) had an asymptomatic ICH on T2* before t-PA therapy. Eleven (45%) patients showed an isolated asymptomatic ICH. Three (12%) patients had a round hypointense lesion similar to microbleeds. Nine (36%) patients had a hemorrhagic transformation within a prior infarcted area. Multiple asymptomatic ICHs were seen in 2 (8%) patients. The rates of good and poor outcomes at 3 months were 24 and 59% of patients with asymptomatic ICH and 38 and 41% of patients without asymptomatic ICH (p = 0.300 and 0.202, respectively). At 24 h after t-PA therapy, 11 (44%) of the 25 patients with asymptomatic ICH before t-PA therapy and 87 (32%) of 275 without asymptomatic ICH had new ICH (p = 0.265). Only 1 (4%) of 25 patients with asymptomatic ICH before t-PA therapy and 6 (2%) of 275 without asymptomatic ICH had sICH within 24 h (p = 0.460). On multivariate logistic regression analysis, neither new ICH (odds, 1.19; 95% CI, 0.40-3.54, p = 0.753) nor sICH (odds, 0.95; 95% CI, 0.08-11.90, p = 0.970) was related to asymptomatic ICH on T2* before t-PA therapy., Conclusion: The presence of T2* hypointensity as a marker of asymptomatic ICH may not be associated with new ICH and sICH after t-PA therapy., (© 2014 S. Karger AG, Basel.)

Transient neurological attacks (TNAs) are attacks with temporary (< 24 h) neurological symptoms, and reported in 1975. Ischemic cerebral infarction often occurres after transient neurological symptoms which are not sometimes involved in transient ischemic attack (TIA) criteria. The purpose of this study was to clarity transient neurological symptoms before the onset of ischemic stroke. Consecutive acute stroke and TIA patients within 7 days of onset between July 2011 and December 2012 were studied. Questionnaire survey of transient neurological symptoms was done and we investigated the history of transient neurological symptoms and divided the patients into three groups, TIA group (history of TIA), TNAs group (history of TNAs), and no past history group. We compared clinical characteristics, the rate of posterior circulation lesions, and number of attacks among three groups. 184 patients (male 112 patients, mean 73 years old) were enrolled into the present study. TNAs group had 13 (7%) patients, and TIA had 20 (11%). Neurological symptoms of TNAs group were 5 (38%) transient dizziness, 3 (23%) disturbance of consciousness, 2 (23%) weakness of legs, 1 (8%) sensory disturbance of legs, 1 (8%) gait disturbance, and 1 (8%) sensory disturbance of lips. Five (38%) TNAs group had multiple attacks. In 33 transient neurological symptom patients, 17 (52%) patients did not have hospital visit, and 7 (21%) patient did not have antiplatelet and anticoagulant drug. TNAs group more frequently had hyperlipidemia, diabetes mellitus, and posterior circulation lesions among three groups. 20% posterior circulation lesion patients had TNAs history, and posterior circulation might be examined in TNAs patients.

The frequency and clinical characteristics of intractable hiccups due to the medullary infarction is unknown. The aim of this study was to identify the lesions of hiccups using by brain MRI. Ninety acute medullary patients admitted to our stroke center within 14 days of stroke onset between April 2004 and August 2012 were retrospectively studied. We evaluated clinical characteristics and the frequency of the patients causing intractable hiccups among acute medullary stroke patients. We divided the patients into two groups, intractable hiccups group, and not hiccups group. Of 90 patients, five (5.5%) had intractable hiccups. Hiccups group had more frequently involved right middle medullary lesion than not hiccups group (hiccups group vs. not hiccups group; (60% vs. 4%, p < 0.001). In 16 cases reported the lesion of intractable hiccups, the right middle medullary lesion was 11 cases. We suspected that the lesion of the intractable hiccups was associated with the right middle medullary.

Background and Purpose: It is unknown whether new-extraischemic microbleeds (new-EMBs) develop rapidly after tissue-type plasminogen activator (tPA) infusion. We hypothesized that new-EMBs may develop rapidly after tPA infusion using T2*-weighted MRI (T2*) and investigated the frequency and clinical factors associated with new-EMBs., Methods: Patients with acute stroke within 3 hours of onset who were treated with tissue-type plasminogen activator (tPA) were studied prospectively. T2* was performed before and 24 hours after tPA therapy. Independent clinical factors associated with new-EMBs development were examined using multivariate logistic regression analysis., Results: A total of 224 patients (121 men; mean age, 76.2±10.6 years) were enrolled in the present study. MBs before tPA infusion were observed in 72 (32.1%) patients. Within 24 hours after tPA infusion, 6 (2.7%) patients had symptomatic intracranial hemorrhage (extraischemic [n=4], and hemorrhagic transformation [n=2]). Follow-up T2* revealed asymptomatic new-EMBs in 11 (4.9%) patients and hemorrhagic transformation in the infarcted area in 65 (29.0%). The total and mean number of new-EMBs were 23 and 1.6±1.3, respectively. Patients with new-EMBs more frequently had symptomatic extraischemic hemorrhage than those without new-EMBs (27.3% [3/11] versus 0.5% [1/213]; P=0.0003). However, the frequency of hemorrhagic transformation was not different between patients with and without new-EMBs (27.3% versus 29.1%; P=0.9999). Multivariate logistic regression demonstrated that the presence of MBs before tPA infusion was the only independent factor associated with new-EMBs (odds ratio, 10.6; 95% confidence interval, 20.68-54.279; P=0.0046)., Conclusions: New-EMBs occurred rapidly after tPA infusion in 4.9% of patients. The presence of MBs before tPA therapy was associated with new-EMBs. Patients with new-EMBs are likely to have symptomatic extraischemic hemorrhage.

Lacunar infarction (LI) remains an important stroke subtype in Japan. The aim of this study was to investigate the characteristics of outcome determinants in LI. This study was a single center observational study and included 163 consecutive patients (108 male, 55 female; mean age 69 years). The National Institutes of Health Stroke Scale (NIHSS) score on admission and the modified Rankin scale (mRS) score at discharge were used to evaluate stroke severity. We determined the location of the infarct, the grade of white matter hyperintensity (WMH), and the prevalence of silent brain infarcts, hypertension, hypercholesterolemia, diabetes mellitus, ischemic heart disease, and smoking. We compared 2 groups, good outcome (mRS score 0-2) and poor outcome (mRS score 3-5), using multiple logistic regression analysis. We found significant differences between the 2 groups according to female sex (P = .04), WMH (P = .04), and NIHSS score (P < .001). After multivariate analysis, female sex (odds ratio [OR] = 3.4, 95% confidence interval [CI] = 1.1-11.4; P = .03), and NIHSS score (OR = 2.3, 95% CI = 1.7-3.3; P < .001) were independently associated with poor outcome. Elderly onset, poor outcome, and hypercholesterolemia were more common in female patients, whereas smoking was more prevalent in males. Our data indicate that sex differences exist in Japanese LI patients with regard to risk factors and outcome. The treatment of risk factors based on sex differences is important to the management of LI., (Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Age is an important factor correlated with stroke prevalence and independently influences stroke outcome especially in Japanese longevity society. To re-evaluate the characteristics of acute ischemic stroke in the old-old, analyses of clinical data on 426 patients registered at a Japanese tertiary emergency hospital were performed under appropriate statistical methods. Clinical features, stroke subtypes, current-known risk factors for stroke, time from onset to arrival, the National Institute of Health Stroke scale (NIHSS) score on admission, length of hospital stay, modified Rankin Scale (mRS) at discharge were compared between two stratified groups by age-at-onset (≧75 and < 75 years old). Significant differences were demonstrated in categories of sex, NIHSS score, length of hospital stay and m-RS. Current-known risk factors for stroke except atrial fibrillation were not prominent in the elderly group. Our study revealed that clinical phenotype and outcome in stroke patients would have been modified and re-evaluation of risk factors is necessary for prevention of ischemic stroke in Japanese longevity society.

A 72-year-old male with liver cirrhosis and hepatocellular carcinoma experienced general fatigue. Four days later he was admitted to our hospital because of dizziness, dysbasia and left facial palsy (day 1). On day 6, a neurological examination revealed left trigeminal neuralgia, left medial longitudinal fasciculus (MLF) syndrome, skew deviation, hypacusia, tongue deviation and left limb ataxia. Magnetic resonance imaging of the brain including diffusion-weighted imaging showed previous lacunar infarctions at the left thalamus and pons. The immunological investigation for viral infection in his serum samples showed high titers of IgM antibody against cytomegalovirus (CMV). Cerebrospinal fluid (CSF) investigation revealed mononuclear pleocytosis, elevated protein levels and high titers of IgG antibody against the varicella-zoster virus (VZV). Anti-CMV antibody measurement and CMV-DNA detection by the polymerase chain reaction in CSF revealed that the central nervous system (CNS) was not infected by CMV. We diagnosed this case as brainstem encephalitis following multiple cranial neuropathy associated with CMV and VZV infections. The neurological symptoms gradually improved with aciclovir and prednisolone therapy. The titers of antibody for CMV in his serum samples normalized 4 months later after onset. Although there was no evidence of CMV infection in the CNS was obtained, parainfection or autoimmune mediated responses followed by viral infections might have led to brainstem encephalitis with multiple cranial nerve involvements in our patient.

A 76-year-old woman developed fever and consciousness disturbance. The next day, she became delirious and was brought to our hospital. On arrival, she was unconscious and showed hypopnea and hypotension. She was immediately intubated and placed on a respirator. CSF protein was 65.8 mg/dl with 1 cell/microl, and no oligoclonal bands were present. An electroencephalogram showed diffuse theta background activity without epileptic discharges. A nerve conduction study showed damaged motor and sensory peripheral nerve functions in the upper and lower limbs. The neurological findings showed no improvement after methylprednisolone pulse therapy and administration of intravenous immunoglobulin. Magnetic resonance imaging of the brain, including diffusion-weighted images showed bilateral symmetric lesions in the thalamus, globus pallidus and pontine tegmentum. These radiologic findings are not typically, but are similar to those of acute necrotizing encephalopathy (ANE) of childhood as proposed by Mizuguchi et al. After 10 months, brain MRI showed bilateral brain atrophy and a reduction of the abnormal thalamic lesions. There are very few reports of adult cases of ANE, in which, pathologically, local breakdown of the blood-brain-barrier causes acute edema and necrosis involving both gray and white matter. ANE is thought a proinflammatory cytokine-related disease. In our case, the concentrations of some cytokines (IL-6, IL-10) were elevated in serum and cerebrospinal fluid, which might suggest a relationship with them and local breakdown of the blood-brain-barrier in the thalamus.

We reported a 60-year-old woman who suffered from isolated neurosarcodosis. She was presenting comprehensive dysfunction and intermittent high fever. In several months she gradually developed dysorientation, amnesia, dementia. However, no focal sign such as paralysis or sensory disturbance was demonstrated. Her blood chemistry showed normal including ACE (angiotensin converting enzyme) and lysozyme. Cerebrospinal fluid revealed elevated mononuclear cells, protein, and decreased glucose level. At first we treated with antibiotics including antiviral drugs in suspect of the infectious encephalomeningitis. But no improvement was observed. The elevation of ACE in spinal fluid made us suspect of neurosarcoidosis. So intravenous predonizoron (1,000 mg) was given, improving. Her high fever and mental disturbance improved. Second spinal fluid showed improvement. During the course her brain MRI revealed new bilateral diffuse confluent high intensity lesions at the deep white matters. Brain biopsy of deep matter at the right anterior lobe showed noncaseating granuloma. Since systemic work-up to detect sarcoidosis did not reveal lesions other than CNS, we considered this patient as having isolated CNS sarcoidosis.