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Background: Participant eligibility for the A4 Study was determined by amyloid PET imaging. Given the disadvantages of amyloid PET imaging in accessibility and cost, blood-based biomarkers may serve as a sufficient biomarker and more cost-effective screening tool for patient enrollment into preclinical AD trials. Objective: To determine if a blood-based screening test can adequately identify amyloid burden in participants screened into a preclinical AD trial. Methods: In this cross-sectional study, 224 participants from the A4 Study received an amyloid PET scan (18Florbetapir) within 90 days of blood sample collection. Blood samples from all study participants were processed within 2 h after phlebotomy. Plasma amyloid measures were quantified by Shimazdu and C2 N Diagnostics using mass spectrometry-based platforms. A corresponding subset of blood samples (n = 100) was processed within 24 h after phlebotomy and analyzed by C2 N. Results: Plasma Aβ42/Aβ40 demonstrated the highest association for Aβ accumulation in the brain with an AUC 0.76 (95%CI = 0.69, 0.82) at C2 N and 0.80 (95%CI = 0.75, 0.86) at Shimadzu. Blood samples processed to plasma within 2 h after phlebotomy provided a better prediction of amyloid PET status than blood samples processed within 24 h (AUC 0.80 versus 0.64; p

Background and Objectives Readmission-related healthcare reforms have shifted their focus from all-cause readmissions (ACR) to potentially avoidable readmissions (PAR). However, little is known about the utility of analytic tools from administrative data in predicting PAR. This study determined whether 30-day ACR or 30-day PAR is more predictable using tools that assess frailty, comorbidities, and activities of daily living (ADL) from administrative data. Research Design and Methods This retrospective cohort study was conducted at a large general acute care hospital in Tokyo, Japan. We analyzed patients aged ≥70 years who had been admitted to and discharged from the subject hospital between July 2016 and February 2021. Using administrative data, we assessed each patient’s Hospital Frailty Risk Score, Charlson Comorbidity Index, and Barthel Index on admission. To determine the influence of each tool on readmission predictions, we constructed logistic regression models with different combinations of independent variables for predicting unplanned ACR and PAR within 30 days of discharge. Results Among 16,313 study patients, 4.1% experienced 30-day ACR and 1.8% experienced 30-day PAR. The full model (including sex, age, annual household income, frailty, comorbidities, and ADL as independent variables) for 30-day PAR showed better discrimination (C-statistic: 0.79, 95% confidence interval: 0.77-0.82) than the full model for 30-day ACR (0.73, 0.71-0.75). The other prediction models for 30-day PAR also had consistently better discrimination than their corresponding models for 30-day ACR. Discussion and Implications PAR is more predictable than ACR when using tools that assess frailty, comorbidities, and ADL from administrative data. Our PAR prediction model may contribute to the accurate identification of at-risk patients in clinical settings who would benefit from transitional care interventions.

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

Community settings often need simple screening, rather than detailed tests, to identify cognitive impairment. This study aimed to develop models to screen older adults with cognitive impairment.This study used data from the Integrated Research Initiative for Living Well with Dementia Cohort Study and included 5830 older adults. Individuals were considered cognitively impaired if their Mini-Mental State Examination score was less than 24. Three screening models were developed: the simple model (age, sex, and education), the base model comprising 13 candidate variables available in the questionnaire, and the enhanced model, where grip strength and gait speed were added to the base model. We performed binary logistic regression analysis with stepwise backward elimination (P 0.1 for retention in the model) to develop each model. Then, we calculated integer scores from coefficients to develop score-based models. The area under the receiver operating characteristic curve (AUC) was used to evaluate discrimination.Participants with cognitive impairment accounted for 4.0% (n = 233) of the total. The score-based simple model comprised three variables (AUC = 0.72, sensitivity: 72%, specificity: 61%). The score-based base model included nine variables (AUC = 0.76, sensitivity: 70%, specificity: 67%). The score-based enhanced model comprised eight variables, including grip strength and gait speed (AUC = 0.79, sensitivity: 73%, specificity: 70%).This study developed three screening models with acceptable discriminant validity for cognitive impairment. These models comprised simple questionnaire-based items and common physical performance measurements. These models could enable screening of older adults suspected of cognitive impairment without the need to conduct cognitive tests in community settings. Geriatr Gerontol Int 2022; 22: 292-297.

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.To establish a large cohort for use in clinical trials and research in Japan.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.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.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.

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.

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 significantlycorrelatedwithgutmicrobialmetabolites.MultivariableanalysesrevealedthatahigherplasmaNfLconcentration 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.

During the last three decades, Japan has become one of the world's top countries for longevity, and the increase in average life expectancy is accompanied by a sharp rise in older population 65 years of age and above to ∼28%. This study aimed to examine the changes in major health-related measures, including a physical constitution, physical function, and functional capacity of community-dwelling Japanese older people in the last decade. From the data of 13 longitudinal cohort studies on aging conducted in Japan with a total of 13,441 older subjects, this study analyzed the changes in six indices that are related to health and functioning of the older people; height, weight, body mass index, walking speed, grip strength, and instrumental activity of daily living, between 2007 (±2 years) and 2017 (±2 years). Comparison of data for the two periods between subjects matched for age group and gender evidently showed better health status and a slower decline in most of the health-related measures in 2017 compared to a decade ago. The results of this study indicate that the phenomenon of “rejuvenation” is occurring among the new generation of Japanese older adults, and the importance of this older population as a social resource in the super-aged society should be reacknowledged.

Background There is a dearth of longitudinal data on body composition, function, and physical performance in persons with Alzheimer's disease (AD). Objectives The aim was to describe the trajectories of function, body composition, and physical performance in older adults with AD. Methods In this retrospective cohort study, data were collected from older adults (n=1402) diagnosed with AD (mean age: 78.1 y old, women: 69.3%). Cognitive function was assessed using the mini-mental state examination. Proxy-reported instrumental and basic activities of daily living were assessed using the Lawton and Barthel indexes. Body composition was assessed using bioelectrical impedance analysis. Physical performance was assessed using the timed up and go test and grip strength. Results Median (interquartile range) of follow-up time was 2.2 (1.2 to 3.6) years. Participants' mini-mental state examination score, Barthel index, and Lawton index declined over time. Skeletal muscle mass index and physical performance (timed up and go test and grip strength) decreased, while fat mass index increased with time. No significant changes or slight decline in weight and body mass index was observed. Conclusions Muscle mass and physical performance are likely to decline in older adults with AD. Clinicians should assess muscle mass and physical performance trajectories regularly in these patients and intervene appropriately.

Objective: To examine whether age-specific prevalence of frailty in Japan changed between 2012 and 2017. Design: This study performed meta-analyses of data collected from 2012 to 2017 using the Integrated Longitudinal Studies on Aging in Japan (ILSA-J), a collection of representative Japanese cohort studies. Setting: The ILSA-J studies were conducted on community-living older adults. Participants: ILSA-J studies were considered eligible for analysis if they assessed physical frailty status and presence of frailty in the sample. Seven studies were analyzed for 2012 (±1 year; n = 10312) and eight studies were analyzed for 2017 (±1 year; n = 7010). Five studies were analyzed for both 2012 and 2017. Measurements: The study assessed the prevalence of frailty and frailty status according to 5 criteria: slowness, weakness, low activity, exhaustion, and weight loss.Results: The overall prevalence of physical frailty was 7.0% in 2012 and 5.3% in 2017. The prevalence of frailty, especially in people 70 years and older, tended to decrease in 2017 compared to 2012. Slight decreases were found in the prevalence of frailty subitems including weight loss, slowness, exhaustion, and low activity between 2012 and 2017, but change in the prevalence of weakness was weaker than other components. Conclusions: The prevalence of physical frailty decreased from 2012 to 2017. There are age- and gender-related variations in the decrease of each component of frailty.

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.

Key Points Question How well does plasma amyloid-β 42/40 (Aβ42/40), measured using 8 different assays, detect brain Aβ pathology in the early stages of Alzheimer disease? Findings In this study, including 408 participants from 2 independent cohorts (BioFINDER and Alzheimer Disease Neuroimaging Initiative), plasma Aβ42/40 quantified using certain mass spectrometry–based methods showed better discriminative accuracy than immunoassays when identifying individuals with abnormal intracerebral Aβ status according to cerebrospinal fluid Aβ42/40 levels and Aβ positron emission tomography. Meaning Certain mass spectrometry–based plasma tests might have sufficient performance to detect brain Aβ pathology in Alzheimer disease., This cross-sectional study compares the performance of plasma amyloid-β 42/40 (Aβ42/40) measured using 8 different Aβ assays and methods in detecting abnormal brain Aβ status in patients with early Alzheimer disease., Importance Blood-based tests for brain amyloid-β (Aβ) pathology are needed for widespread implementation of Alzheimer disease (AD) biomarkers in clinical care and to facilitate patient screening and monitoring of treatment responses in clinical trials. Objective To compare the performance of plasma Aβ42/40 measured using 8 different Aβ assays when detecting abnormal brain Aβ status in patients with early AD. Design, Setting, and Participants This study included 182 cognitively unimpaired participants and 104 patients with mild cognitive impairment from the BioFINDER cohort who were enrolled at 3 different hospitals in Sweden and underwent Aβ positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) and plasma collection from 2010 to 2014. Plasma Aβ42/40 was measured using an immunoprecipitation-coupled mass spectrometry developed at Washington University (IP-MS-WashU), antibody-free liquid chromatography MS developed by Araclon (LC-MS-Arc), and immunoassays from Roche Diagnostics (IA-Elc); Euroimmun (IA-EI); and Amsterdam University Medical Center, ADx Neurosciences, and Quanterix (IA-N4PE). Plasma Aβ42/40 was also measured using an IP-MS–based method from Shimadzu in 200 participants (IP-MS-Shim) and an IP-MS–based method from the University of Gothenburg (IP-MS-UGOT) and another immunoassay from Quanterix (IA-Quan) among 227 participants. For validation, 122 participants (51 cognitively normal, 51 with mild cognitive impairment, and 20 with AD dementia) were included from the Alzheimer Disease Neuroimaging Initiative who underwent Aβ-PET and plasma Aβ assessments using IP-MS-WashU, IP-MS-Shim, IP-MS-UGOT, IA-Elc, IA-N4PE, and IA-Quan assays. Main Outcomes and Measures Discriminative accuracy of plasma Aβ42/40 quantified using 8 different assays for abnormal CSF Aβ42/40 and Aβ-PET status. Results A total of 408 participants were included in this study. In the BioFINDER cohort, the mean (SD) age was 71.6 (5.6) years and 49.3% of the cohort were women. When identifying participants with abnormal CSF Aβ42/40 in the whole cohort, plasma IP-MS-WashU Aβ42/40 showed significantly higher accuracy (area under the receiver operating characteristic curve [AUC], 0.86; 95% CI, 0.81-0.90) than LC-MS-Arc Aβ42/40, IA-Elc Aβ42/40, IA-EI Aβ42/40, and IA-N4PE Aβ42/40 (AUC range, 0.69-0.78; P

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.

Background Pulmonary arterial hypertension (PAH) remains a life-threatening condition, despite modern therapies. We prospectively investigated the therapeutic health-related quality of life (HRQOL) effects of goal-oriented sequential combination therapy based on exercise capacity in patients newly diagnosed with PAH. Methods To examine the changes in HRQOL in PAH patients, we treated 30 patients newly diagnosed with PAH with goal-oriented sequential combination therapy based on exercise capacity. We monitored exercise capacity by cardiopulmonary exercise testing and observed the benefit of using a peak VO2 cut-off of 15 mL/kg/min to guide combination therapy. First-line treatment was an endothelin receptor antagonist (ERA); second-line treatment was the addition of a phosphodiesterase-5 inhibitor (PDE-5I). At baseline and at 3, 6, and 12 months, HRQOL was evaluated by using the eight-item Medical Outcomes Survey Short Form Health Survey. Results At 12 months, 100% of PAH patients were receiving an ERA, and 82% an ERA + PDE-5I. The mean physical component summary (PCS) score was 33.5 at baseline, 41.2 at 3 months, 40.8 at 6 months, and 42.0 at 12 months, and the mean mental component summary (MCS) scores were 45.6, 47.0, 50.0, and 50.1, respectively. PCS score was significantly greater at 3 months than at baseline (P = 0.035). MCS score was comparable at 3 months and at baseline, but was significantly greater at 6 and 12 months than at baseline (P = 0.033, P = 0.028, respectively). Thus, PCS score improved soon after initiation of therapy, and MCS score improved later. Conclusions Together, these results suggest that goal-oriented sequential combination therapy based on exercise capacity improves HRQOL in patients with PAH.

Aim There are few studies concerning the classification of fall risk by nurses without established fall risk assessment tools. In the present study, clinical classification of fall risk using visually obtained information was compared with the assessment of fall risk in order to evaluate the rationale and validity of the clinical classification of fall risk by nurses. Methods New patients who visited the center of comprehensive care and research for memory disorders at the National Center for Geriatrics and Gerontology were enrolled in the present study.Day-shift nurses separately recorded the clinical classification of fall risks through visually obtained information during the 10-minutes waiting time for outpatients.Fall risk assessments such as the Fall Risk Index and Timed Up & Go test, were performed by non-nurse medical staffs. Data were analyzed by an independent researcher who was not involved in obtaining clinical information. Results Nurse's clinical classification of fall risk using visually obtained information correlated well with Fall Risk Index, Timed Up & Go test, One-leg Standing test and Dorsiflex meter. In addition, subjects classified as having high fall risk were more frequently judged to be frail than classes of moderate or little fall-risk. Conclusion Nurse's clinical classification of fall risk using visually obtained information was judged on their integrated impression including their evaluation of the muscle strength, gait speed and balance.

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.

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

Aim The aim of this study was to examine the ability of a group-based multi-component psycho-educational intervention (GMC-PEI) to reduce depression, and improve caregiving appraisals, coping skills of informal caregivers and the condition of people with dementia. Methods In this randomized controlled and blinded trial, we enrolled 54 informal caregivers of people with dementia visiting the Japan National Center of Geriatrics and Gerontology, and divided them into GMC-PEI and control groups. The intervention group received a 12-week GMC-PEI program that included six 2-h structured sessions to enhance their knowledge of dementia, caregiving skills and coping skills. The control group received leaflets containing information about dementia. We evaluated caregivers' depression, caregiving time, subjective burden, caregiving appraisal and care coping skills. We also evaluated people with dementia at baseline and 12 weeks, and reassessed 20 participants from the intervention group at 24 and 48 weeks. Results The GMC-PEI significantly improved depression, positive appraisals of fulfillment in caregiving, affection for care recipients, self-growth and coping skills, such as seeking formal support. Depression, fulfillment and affection for people with dementia showed a peak improvement at 24 weeks; formal support-seeking showed a linear improvement throughout the 48-week follow-up period. Conclusions The group-based multi-component psycho-educational intervention reduced depression, improved self-appraisal and enhanced coping skills in caregivers. However, emotional enhancements dissipated sooner than support-seeking skills, suggesting that caregivers should be reviewed every 12-24 weeks. Geriatr Gerontol Int 2021; 21: 561-567.

Background 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. Methods We performed a cross-sectional sub-analysis of data from our prospective hospital-based cohort study (the Gimlet study) to evaluate the relationships between dietary composition, cognitive decline, and the gut microbiota. All the participants of the Gimlet study had been provided with information regarding this sub-study in 2018. Patients were excluded if they were unable to provide sufficient data in the questionnaire regarding their dietary composition. We assessed their demographics, dietary composition, risk factors, cognitive function, results of brain imaging, gut microbiome, and microbial metabolites. On the basis of previous studies, a nine-component traditional Japanese diet index (JDI9), a 12-component modern JDI (JDI12), and a 12-component revised JDI (rJDI12), were defined. Higher JDI scores indicated greater conformity to the traditional Japanese diet. We then 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 patients (61% women; mean age: 74.6 ± 7.4 years; mean Mini-Mental State Examination score: 24 ± 5). Compared with participants with dementia, those without dementia were more likely to consume foods in the JDI12, including fish and shellfish (64.5% vs. 39.1%, P = 0.048), mushrooms (61.3% vs. 30.4%, P = 0.015), soybeans and soybean-derived foods (62.9% vs. 30.4%, P = 0.013), and coffee (71.0% vs. 43.5%, P = 0.024). There were non-significant trends towards lower fecal concentrations of gut microbial metabolites in participants with a more traditional Japanese diet. Participants with dementia had lower JDI9, JDI12, and rJDI12 scores than participants without dementia (dementia vs. non-dementia, median JDI9 score: 5 vs. 7, P = 0.049; JDI12: 7 vs. 8, P = 0.017; and rJDI12: 7 vs. 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. Trial registration: UMIN000031851.

Introduction Understanding the association between cognitive impairment severity and potentially avoidable readmissions (PARs) in older patients may facilitate the identification of at‐risk individuals who would benefit from readmission prevention measures. Methods This retrospective cohort study was conducted using claims data linked with routinely collected cognitive impairment assessment results from a general acute care hospital in Tokyo, Japan. Patients were 65 years or age or older who were discharged from the subject hospital to home or a facility between July 2016 and September 2018. Results A multivariable logistic regression analysis adjusted for covariates showed that the odds of PARs within 90 days to the subject hospital for patients with moderate and severe cognitive impairment were 1.418 times (95% confidence interval: 1.005‐2.002) and 2.212 times (95% confidence interval: 1.206‐4.058) higher, respectively, that for patients with normal cognition. Discussion Older inpatients with later‐stage cognitive impairment may represent a suitable target population for transitional care programs aimed at reducing readmissions.

Background Mild hyponatremia (serum sodium 130–135 mEq/L) is a common electrolyte disorder in the elderly. However, its association with both sarcopenia and cognitive function remains to be clarified. Therefore, here we investigated the association of mild hyponatremia with skeletal muscle mass, physical function, and cognitive function in the elderly. Methods We enrolled 75 participants with mild hyponatremia and 2907 with normonatremia (serum sodium, 136–145 mEq/L) aged ≥70 years who visited the Memory Disorder Outpatient Center of Japan’s National Center for Geriatrics and Gerontology. Skeletal muscle mass index (SMI), grip strength (GS), walking speed (WS), one-leg standing (OLS) test times, and neuropsychological test scores were determined. Results One-way analysis of covariance showed that elderly participants with mild hyponatremia had lower SMI (7.1 ± 0.2, 7.2 ± 0.2 kg/m2, p = 0.04), weaker GS (19.1 ± 1.9 vs 21.4 ± 1.8 kg, p = 0.01), slower WS (0.9 ± 0.1 vs 1.1 ± 0.1 m/s, p = 0.001), and higher GDS- 15 score (6.4 ± 0.9 vs 5.2 ± 0.9, p = 0.002) than those with normonatremia. Multiple logistic regression analysis indicated that mild hyponatremia was independently associated with sarcopenia (odds ratio [OR]: 2.2, p = 0.02), slower WS (OR: 5.3, p = 0.04) and shorter OLS time (OR: 2.5, p = 0.02) as well as with severe depressive mood (OR: 2.6 p = 0.006) but not with SMI (OR: 1.6, p = 0.2) or GS (OR: 1.9, p = 0.09). Conclusions Our results suggest that elderly people with even mild hyponatremia had physical function impairment and depressive mood.

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.

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 [JDIWe 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 (JDIWe 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 JDIAdherence 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.

The goal of dementia treatment is to improve the quality of life for both people with dementia and their families. Rehabilitation as a non-pharmacological approach, coordinated with pharmacological treatment, aims to allow patients to live better by slowing the progression, and relieving the behavioral and psychological symptoms of dementia. In dementia, the manifestation of symptoms caused by neurological impairment is modified by various factors; thus, multidimensional assessment and approaches are effective based on the concept of the International Classification of Functioning, which emphasizes the healthy components of every person's functioning. Regarding the process of rehabilitation, every person with dementia should take initiative throughout the course of rehabilitation, and shared decision-making is a fundamental requirement at every phase of intervention. The needs of rehabilitation differ depending on the stage of dementia. In the early stages, cognitive rehabilitation is needed, and interventions are carried out using preserved functions and compensatory strategies. As the disease progresses, capacities of instrumental and then basic activities of daily living deteriorate, and interventions need to be tailor-made and carried out in the context of actual living situations. In the early-to-moderate stages, prevention and management of behavioral and psychological symptoms of dementia are required. In the interventions to alleviate behavioral and psychological symptoms of dementia, it is critical to consider the individual and the meaning behind his/her behaviors from a holistic perspective. Family carers also need support, and education to learn coping strategies can be beneficial for both people with dementia and their carers. Rehabilitation can empower people with dementia and their families to live better with dementia. Geriatr Gerontol Int 2018; 18: 1529-1536.

AIM The present study aimed to: (i) examine the reliability and validity of the Dementia Assessment Sheet for Community-based Integrated Care System 21-items for classifying patients to the appropriate categories for glycemic targets in older patients; and (ii) develop a short version of the tool and examine its reliability and validity. METHODS A total of 410 older individuals were recruited for this multicenter cross-sectional study. We classified them into three categories used for determining the glycemic target in older patients in Japan based on cognitive functions and activities of daily living. Exploratory factor analyses were used to select the eight items of the shorter version. The reliability and validity of the assessment tools were assessed using Cronbach's alpha coefficients and receiver operating characteristic analyses, respectively. RESULTS The Dementia Assessment Sheet for Community-based Integrated Care System 21-items had three latent factors: cognitive function, instrumental activities of daily living and basic activities of daily living. The Dementia Assessment Sheet for Community-based Integrated Care System 8-items was developed based on each factor load quantity and was confirmed to have a strong correlation with the original version (r = 0.965, P

Aim Physical and cognitive functions are mutually associated. However, it is unknown which markers of physical functions or body composition are most strongly associated with cognition. Here, we explored the association between body composition/physical performance and comprehensive neuropsychological assessments in an effort to identify reliable markers of cognition among factors in body composition/physical performance, including both usual and maximum gait speeds. Methods We examined a total of 161 Japanese individuals (71 men, 90 women; aged 76.3 ± 7.2 years) with a Clinical Dementia Rating of 0.5 and a Mini-Mental State Examination score >24. A battery of neuropsychological assessments, physical functional assessments and measurements of body composition was carried out. We conducted a multiple regression analysis to investigate the associations between cognitive performance and the factors in body composition and physical performance with adjustments for age, sex, and number of school years. Results Maximum gait speed was the factor most widely associated with cognitive performance among the factors of body composition and physical performance. Conclusion Maximum gait speed might be the best marker for cognition in this population of older individuals. Geriatr Gerontol Int 2018; 18: 1323-1329.

BackgroundAlthough research indicates that a physically active lifestyle has the potential to prevent cognitive decline and dementia, the optimal type of physical activity/exercise remains unclear. The present study aimed to determine the cognitive benefits of a golf-training programme in community-dwelling older adults.MethodsWe conducted a randomised controlled trial between August 2016 and June 2017 at a general golf course. Participants included 106 Japanese adults aged 65 and older. Participants were randomly assigned to either a 24-week (90–120 min sessions/week) golf-training group or a health education control group. Postintervention changes in Mini-mental State Examination (MMSE) and National Centre for Geriatrics and Gerontology-Functional Assessment Tool scores were regarded as primary outcome measures. Secondary outcome measures included changes in physical performance and Geriatric Depression Scale (GDS) scores.ResultsA total of 100 participants (golf training, n=53; control, n=47) completed the assessments after the 24-week intervention period. The adherence to the golf programme was 96.2% (51/53 participants). Analysis using linear mixed models revealed that the golf training group exhibited significantly greater improvements in immediate logical memory (p=0.033), delayed logical memory (p=0.009) and composite logical memory (p=0.013) scores than the control group. However, no significant changes in MMSE, word memory, Trail Making Test or Symbol Digital Substitution Test scores were observed. In addition, no significant changes in grip strength, walking speed or GDS were observed.ConclusionsGolf-based exercise interventions may improve logical memory in older adults, but no significant changes in other cognitive tests. Further follow-up investigations are required to determine whether the observed effects are associated with delayed onset of mild cognitive impairment or Alzheimer’s disease in older adults.Trial registration numberUMIN-CTR UMIN000024797; Pre-results.

The Kihon Checklist (KCL) is a structured questionnaire consisting of 7 domains to assess seniors’ function in daily living. The aim of this study was to examine which domains of the KCL can predict incident dependency and mortality. The municipality sent a KCL questionnaire to independent seniors in Higashi-ura Town and collected the answers of the 5542 seniors who provided complete answers. Their incident dependency and mortality were followed-up for 2.5 years. A Cox proportional hazard model indicated that meeting any of the criteria in instrumental activities of daily living, physical, nutrition, and mood domains significantly predicted the risk of dependency, whereas meeting any of the criteria in physical, nutrition and socialization domains significantly predicted the risk of mortality. Category assessment by the KCL could be useful to predict incident dependency and all-cause mortality.

The number of people with dementia in Japan is ever-increasing. In 2020, 6 million people lived with dementia. The number is expected to increase to 9 million in 2040. This means that a person with dementia will be supported by three working people. To prepare for the big wave of dementia, Japan released the New Orange Plan in January 2015. In 2019, the Framework for Promoting Dementia Care was issued by the Japanese cabinet in which prevention and the opportunity for persons with dementia to age in place were set as the main goals. This framework requires all ministries to promote people’s awareness about individuals with cognitive impairment. The educational targets include taxi drivers, retail shop clerks, bankers, police, and people working in the criminal justice system. I will discuss the New Framework which has potential to assist the country in supporting people living with dementia.

Left main coronary artery (LMCA) disease due to external compression by a dilated main pulmonary artery (MPA) is an uncommon clinical entity. Here, we describe a 52-year-old woman with pulmonary arterial hypertension (PAH) and anteroseptal old myocardial infarction (OMI). The cause of the OMI was external compression of the LMCA by the dilated MPA and aneurysm of the left coronary sinus of Valsalva. The patient’s sister (aged 56 years) had also been diagnosed with PAH and both women had a novel heterozygous splicing mutation, IVS2-2A > G (c.374-2A > G in NM_001456), in the filamin A (FLNA) gene. To our knowledge, this is the first report of HPAH which is likely to be due to FLNA mutation and compression of the LMCA between a dilated MPA and aneurysm of the left coronary sinus of Valsalva.