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Aim: To examine cross‐sectional associations between continuous glucose monitoring (CGM)‐derived metrics and cerebral small vessel disease (SVD) in older adults with type 2 diabetes. Materials and Methods: In total, 80 patients with type 2 diabetes aged ≥70 years were analysed. Participants underwent CGM for 14 days. From the CGM data, we derived mean sensor glucose, percentage glucose coefficient of variation, mean amplitude of glucose excursion, time in range (TIR, 70‐180 mg/dl), time above range (TAR) and time below range metrics, glycaemia risk index and high/low blood glucose index. The presence of cerebral SVD, including lacunes, microbleeds, enlarged perivascular spaces and white matter hyperintensities, was assessed, and the total number of these findings comprised the total cerebral SVD score (0‐4). Ordinal logistic regression analyses were performed to examine the association of CGM‐derived metrics with the total SVD score. Results: The median SVD score was 1 (interquartile range 0‐2). Higher hyperglycaemic metrics, including mean sensor glucose, TAR >180 mg/dl, TAR >250 mg/dl, and high blood glucose index and glycaemia risk index, were associated with a higher total SVD score. In contrast, a higher TIR (per 10% increase) was associated with a lower total SVD score (odds ratio 0.73, 95% confidence interval 0.56‐0.95). Glycated haemoglobin, percentage glucose coefficient of variation, mean amplitude of glucose excursions, time below range and low blood glucose index were not associated with total cerebral SVD scores. Conclusions: The hyperglycaemia metrics and TIR, derived from CGM, were associated with cerebral SVD in older adults with type 2 diabetes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. • The longitudinal association between nutritional status and BPSD still remains poorly understood. • Poor nutritional status was associated with worsening of BPSD, especially verbal aggressiveness/emotional disinhibition. • Nutritional status should be assessed and managed from MCI and early-stage AD to prevent worsening of BPSD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and lipopolysaccharides (LPS; molecules of the outer membrane of gram-negative bacteria) remain controversial.Objective: To evaluate associations between plasma LPS, gut microbiota, and cognitive function.Methods: We performed a cross-sectional sub-analysis of data of 127 participants (women: 58%, mean age: 76 years) from our prospective cohort study regarding the relationship between gut microbiota and cognitive function. We enrolled patients who visited our memory clinic and assessed demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites. We evaluated relationships between cognitive decline and plasma LPS using multivariable logistic regression analyses.Results: Plasma LPS concentration increased with increasing degree of cognitive decline and total cerebral small vessel disease (SVD) score (Kruskal-Wallis test; p = 0.016 and 0.007, respectively). Participants with high plasma LPS concentrations tended to have lower concentrations of gut microbial metabolites, such as lactic acid and acetic acid, and were less likely to consume fish and shellfish (44.7% versus 69.6%, p = 0.027) than those with low plasma LPS concentrations. Multivariable analyses revealed that plasma LPS concentration was independently associated with the presence of mild cognitive impairment in participants without dementia (odds ratio: 2.09, 95% confidence interval: 1.14-3.84, p = 0.007).Conclusion: In this preliminary study, plasma LPS concentration was associated with both cognitive decline and cerebral SVD and significantly correlated with beneficial gut microbial metabolites. Plasma LPS may be a risk factor for cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and neurofilament light chain (NfL; a disease-nonspecific biomarker of neural damage) remain controversial.Objective: To evaluate the associations between plasma NfL, gut microbiota, and cognitive function.Methods: We performed a cross-sectional sub-analysis of data from our prospective cohort study that was designed to investigate the relationship between gut microbiota and cognitive function. Patients who visited our memory clinic were enrolled and demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites were assessed. We evaluated the relationships between the gut microbiome, microbial metabolites, and plasma NfL. Moreover, the relationships between plasma NfL and cognitive function were assessed using multivariable logistic regression analyses.Results: We analyzed 128 participants (women: 59%, mean age: 74 years). Participants with high (above the median) plasma NfL concentrations tended to be older, women, and hypertensive and have a history of stroke, chronic kidney disease, and dementia. Plasma NfL was also associated with cerebral small vessel disease. However, plasma NfL levels were not significantly correlated with gut microbial metabolites. Multivariable analyses revealed that a higher plasma NfL concentration was independently associated with the presence of dementia (odds ratio: 9.94, 95% confidence interval: 2.75-48.2, p < 0.001).Conclusion: High plasma NfL concentration was independently associated with the presence of dementia as previously reported. However, plasma NfL levels were not significantly correlated with gut microbial metabolites in this preliminary study. [ABSTRACT FROM AUTHOR]

Background: Very few studies have investigated the impact of cognitive frailty in clinical settings, especially in memory clinic populations.Objective: To examine the impact of cognitive frailty on activities of daily living (ADL), cognitive function, and conversion to dementia among memory clinic patients with mild cognitive impairment (MCI).Methods: The subjects of this retrospective study were 248 MCI patients (mean age, 76.3±5.4 years; females, 60.9%). All subjects completed a comprehensive geriatric assessment at baseline and at least one assessment during 3-year follow-up. Frailty was defined by generating a frailty index (FI), and MCI patients with frailty (FI≥0.25) were considered to represent cognitive frailty. As primary outcomes, the Barthel Index, Mini-Mental State Examination, and incident dementia were evaluated during follow-up. At baseline, patients were assessed for apolipoprotein E (APOE) phenotype. A linear mixed model, as well as a Cox proportional hazards regression model with adjustment for confounding variables, was performed.Results: Of these patients, 75 (30.2%) were classified as cognitive frail. APOEɛ4 carriers accounted for 26.7% of those with cognitive frailty and 44.5% of those without (p = 0.008). Cognitive frail patients showed a faster ADL decline (estimate, -1.04; standard error, 0.38; p = 0.007) than patients without cognitive frailty. Cognitive frailty was not associated with cognitive decline and incident dementia.Conclusion: Our findings demonstrated cognitive frailty increases the risk of dependence but not cognitive outcomes. Cognitive frailty may have heterogeneous conditions, including APOEɛ4-related pathologies, which may affect the cognitive trajectories of patients with MCI. [ABSTRACT FROM AUTHOR]

Recent studies have revealed an association between the dysregulation of the gut microbiome and dementia. However, whether this dysregulation is associated with mild cognitive impairment (MCI), an early stage of cognitive decline, in patients without dementia remains unclear. We performed a cross-sectional analysis to determine the association between the gut microbiome and MCI. Data, including patient demographics, risk factors, cognitive function, and brain imaging, were collected. The gut microbiome was assessed through terminal restriction fragment length polymorphism analysis. Multivariable logistic regression models were used to identify factors independently associated with MCI. Graphical modelling was used to illustrate mutual associations between MCI and identified factors. We analysed 82 patients, 61 of whom exhibited MCI. Patients with MCI had a higher prevalence of Bacteroides. Furthermore, patients with more Bacteroides were more likely to present with white matter hyperintensity and high voxel-based specific regional analysis system for Alzheimer's Disease (VSRAD) scores, indicating cortical and hippocampal atrophy. A multivariable logistic regression analysis revealed that a greater prevalence of Bacteroides was independently associated with MCI. Graphical modelling also showed a close association between Bacteroides and MCI. In conclusion, an increased prevalence of Bacteroides is independently associated with the presence of MCI in patients without dementia. [ABSTRACT FROM AUTHOR]

Background: Cognitive frailty (CF) is defined as simultaneous presence of physical frailty (PF) and cognitive impairment among older adults without dementia. Although white matter hyperintensities (WMH) as expressions of cerebral small vessel disease are associated with physical and cognitive decline and could manifest as CF, this association remains yet to be clarified.Objects: To clarify the association between CF and WMH among memory clinic patients.Methods: The subjects of this cross-sectional study were 121 cognitively normal (CN) and 212 mildly cognitively impaired (MCI) patients who presented to the Memory Clinic at the National Center for Geriatrics and Gerontology of Japan. PF status was defined based on the definition proposed by Fried and colleagues. CF was defined as simultaneous presence of pre-PF or PF and MCI. WMH volumes were measured using an automatic segmentation application. Multiple liner regression analyses with adjustment for cardiovascular risk factors were performed.Results: Of all subjects, 77 (63.6%) and 22 (18.2%) CN patients and 132 (62.3%) and 65 (30.7%) MCI patients were categorized into pre-PF and PF, respectively. Multiple liner regression analysis showed that those with CF had higher WMH volumes than those without (β= 0.23). When categorized into six groups according to PF and cognitive status, the PF/CN (β= 0.15), pre-PF/MCI (β= 0.41), and PF/MCI (β= 0.34) groups had higher WMH volumes than the non-PF/CN group.Conclusions: This study showed increased WMH volumes in CF and PF, indicating that WMH could be one of the key underlying brain pathologies of CF. [ABSTRACT FROM AUTHOR]

Background/Aims: Behavioral and psychological symptoms of dementia (BPSD) are exhibited in most patients with Alzheimer disease (AD). Although white matter hyperintensity (WMH) is often observed with AD, the precise role of WMH in BPSD remains unclear. The current study aimed to identify the impact of regional WMH on specific features of BPSD in persons with mild to moderate AD and amnestic mild cognitive impairment (aMCI). Methods: A sample of 256 female outpatients with AD (n = 217) and aMCI (n = 39) were recruited. We assessed BPSD using the Dementia Behavior Disturbance Scale. WMH and brain atrophy were evaluated using an automatic segmentation program. Regional WMH was evaluated as periventricular hyperintensity (PVH) and deep WMH in frontal, temporal, occipital, and parietal lobes. Results: Whole-brain WMH was associated with verbal aggressiveness. In multivariate analysis, PVH in the frontal lobe was independently associated with verbal aggressiveness after adjustment for brain atrophy and clinical confounders. Conclusion: The current results indicated that PVH in the frontal lobe was independently associated with verbal aggressiveness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Instrumental activities of daily living (IADL) start to decline during the progression of amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD). Cognitive and physical decline are involved in the loss of functional independence. However, little is known about AD-related neural change that leads to IADL impairment. The purpose of this study was to clarify the effects of regional white matter hyperintensity (WMH) on IADL impairment in persons with AD and aMCI. Methods: The participants were 347 female subjects aged 65–85 years diagnosed with AD (n = 227), aMCI (n = 44) or normal cognition (n = 76). IADL was assessed by the Lawton Index. Cognition, mood and mobility function were evaluated by comprehensive geriatric assessment batteries. WMH and brain atrophy were analyzed with brain magnetic resonance imaging, using an automatic segmentation program. Regional WMH was measured in the frontal, temporal, occipital and parietal lobes. Results: Ability to carry out IADL of shopping, food preparation, mode of transportation, responsibility for own medication, and ability to handle finances was obviously impaired in the early stage of AD. Frontal WMH was specifically associated with disability to do shopping and food preparation even after adjusting for several confounders including brain atrophy. Conclusions: IADL subcategories were differentially impaired along with cognitive status in persons with AD and aMCI. Frontal WMH was an important predictor of impaired ability to do shopping and food preparation. A preventive strategy for WMH might lead to suppression of IADL disability and slow the progression of AD. [ABSTRACT FROM AUTHOR]

Background: Urinary incontinence (UI) is frequently observed in patients with Alzheimer's disease (AD). Although previous works highlight the association between frontal lobe-related function and UI, causal relationship is unclear.Objects: To clarify the longitudinal association between frontal lobe function and the incidence of UI at 1 year in patients with AD.Methods: The subjects were 215 continent AD patients who attended the Memory Clinic of the National Center for Geriatrics and Gerontology of Japan during the period from March 2011 to December 2014. The absence or presence of UI was operationally assigned by the dementia behavior disturbance scale subscale, which was completed by the patients' caregivers. Frontal lobe function was assessed using the Frontal Assessment Battery (FAB). Other confounding factors including demographic data, cognitive status, vitality, mood, physical performance, and use of medication (cholinesterase inhibitors, calcium channel blockers [CCBs], diuretics, alpha blockers and anticholinergic drugs) were assessed.Results: During 1-year follow up (mean: 377.4±83.7 days), the incidence of UI was 12.1% (n = 26). Patients with UI had significantly lower FAB performance at baseline (no UI versus UI = 9.3±2.8 versus 7.8±2.7). In multivariate analysis, stepwise logistic regression analysis demonstrated that FAB (odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.66-0.94) and the use of CCB (OR = 2.72, 95% CI = 1.09-6.77) were significantly associated with UI at 1 year.Conclusion: The results of study indicate that frontal lobe dysfunction is predictor for UI in patients with AD. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to clarify the effect of glucose profiles after stroke, which was assessed by a continuous glucose monitoring (CGM) device. Methods: Acute ischemic stroke patients within 24 h of onset were prospectively studied. CGM was performed for 72 h after admission. CGM parameters were evaluated as follows: (1) mean glucose level, (2) area under the curve (AUC) for glucose level >140mg/dland (3) SDofthe glucose level. Infarct volume was measured at admission and 24 and 72 h after admission using diffusion-weighted imaging. CGM data and infarct volume growth were compared at 24 and 72 h. Results: Seventy-eight patients were enrolled in the present study. Spearman's rank correlation coefficients showed that both the mean glucose level (r = 0.433, p < 0.001 for 24 h; r = 0.308, p = 0.006 for 72 h) and AUC > 140 mg/dl (r = 0.417, p < 0.001 for 24 h; r = 0.277, p = 0.014 for 72 h) were significantly correlated with acute infarct volume growth. The SD of the glucose level was associated with infarct volume growth at 24 h (r = 0.303, p = 0.007), but not 72 h (r = 0.195, p = 0.088). Conclusion: Post-stroke hyperglycemia was associated with infarct volume growth during the acute phase of ischemic stroke. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic telangiectasia (HHT) occasionally can be discovered in patients with cerebrovascular disease. Pulmonary arteriovenous malformation (PAVM) is one of the complications in HHT and occasionally is causative for life-threatening embolic stroke. Several genetic defects have been reported in patients with HHT. The broad spectrum of phenotype and intrafamilial phenotype variations, including age-at-onset of vascular events, often make an early diagnosis difficult. We present here a Japanese family with a novel intronic heterozygous mutation of ENG , which was identified using whole exome sequencing (WES). The intronic mutation, IVS3 + 4delAGTG, results in in-frame deletion of exon 3 and would produce a shorter ENG protein lacking the extracellular forty-seven amino acid sequences, which is located within the orphan domain. Our findings highlight the importance of the domain for the downstream signaling pathway of transforming growth factor-beta and bone morphogenesis protein superfamily receptors. Considering the phenotype variations and the available treatment for vascular complications, an early diagnosis using genetic testing, including WES, should be considered for individuals at risk of HHT. [ABSTRACT FROM AUTHOR]

Purpose: To examine whether Functional Independence Measure (FIM) scores on admission can predict the future care levels of patients after acute stroke. Methods: In this multicenter retrospective cohort study, we enrolled post-acute stroke patients and assessed stroke subtypes, self-care abilities using FIM scores, and discharge destination. Patients' care levels were assessed according to the Long-Term Care Insurance (LTCI) system (0-5: slight impairment to bedridden), the national insurance plan for care in Japan, at discharge. We divided patients into two groups according to LTCI care levels (0-2 versus 3-5) to compare their clinical characteristics using multivariate logistic regression analysis. The trial was registered with the UMIN Clinical Trials Registry (UMIN000012653). Results: Of the 1261 patients (47% female, mean age 75 years), 492 (39%) fulfilled LTCI care levels 0-2. FIM scores on admission were significantly correlated with LTCI care levels ( p < 0.001). On multivariate analysis, age and FIM scores on admission were found to be independent predictors of LTCI care levels 0-2. Conclusions: FIM scores on admission after stroke can independently predict later care requirements. Early prediction of LTCI care levels may contribute to the early supported discharge and improve the efficiency of healthcare planning. [ABSTRACT FROM AUTHOR]

Background and Purpose: The purpose of the present study was to test the hypothesis that plasma brain natriuretic peptide (BNP) is associated with short-term mortality after intracerebral hemorrhage (ICH). Methods: We prospectively enrolled 271 patients (median age 72 years; 109 females) who were admitted within 24 h of ICH onset between April 2007 and July 2011 and in whom plasma BNP levels were measured upon admission. The patients were assigned to two groups according to survival within 1 month of ICH. Factors associated with mortality were determined by multivariate logistic regression analysis. Results: Within 1 month of ICH, 48 (17.7%) of the 271 enrolled patients died. The median (interquartile range) level of plasma BNP was significantly higher in the group of non-survivors than in the group of survivors [102.5 (48.7-205.0) vs. 32.4 (17.3-85.0) pg/ml; p < 0.001]. A cutoff BNP level of 60.0 pg/ml could predict death within 1 month of ICH. Multivariate logistic regression analysis showed that a plasma BNP of >60.0 pg/ml (OR 4.7; 95% CI 1.43-15.63; p = 0.011) was independently associated with mortality within 1 month after ICH. Conclusions: A high BNP level upon admission is associated with mortality within 1 month after ICH. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Purpose: We investigated whether brain natriuretic peptide (BNP) can serve as a biological marker of long-term mortality in ischemic stroke survivors. Methods: Consecutive patients with ischemic stroke within 24 h of onset from April 2007 to December 2010 were prospectively enrolled, and admission plasma BNP levels were measured. Survivors were followed up until 1 year after stroke onset. Patients were divided into two groups: the deceased group and the surviving group. The factors associated with long-term mortality were investigated by multiple logistic regression analysis. Results: A total of 736 patients who were alive at hospital discharge were included; 130 (17.7%) patients died. On multivariate analysis, age >75 years (odds ratio, OR, 2.83; 95% CI, 1.74-4.60, p = 0.0001), dialysis-dependent chronic renal failure (OR, 5.99; 95% CI, 2.18-16.47, p = 0.0005), modified Rankin Scale score >3 at discharge (OR, 4.41; 95% CI, 2.76-7.05, p < 0.0001), and plasma BNP >100.0 pg/ml (OR, 3.94; 95% CI, 2.31-6.73, p < 0.0001) were found to be independently associated with long-term mortality. We developed a risk score from 4 variables (each variable: 1 point, total score: 0-4 points). The mortality rates were 2% with a score of 0, 9% with a score of 1, 27% with a score of 2 and 50% with a score ≥3. Conclusions: The risk score, composed of clinical parameters and BNP, may predict long-term mortality in ischemic stroke survivors. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]