Aging trajectories of subscales in higher-level functional capacity among community-dwelling older Japanese adults: the Otassha study.

BACKGROUND: Maintaining higher-level functional capacity is important for independent living in older age. The aging trajectory of the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) has three patterns; however, the subscale patterns are unclear. AIMS: This study aimed to clarify the aging trajectory patterns of the TMIG-IC subscales among community-dwelling older Japanese. METHODS: Participants were 3,169 community-dwelling older Japanese who participated in the 2012-2022 mail survey of the Otassha study. The aging trajectory patterns of the TMIG-IC total and subscale scores for those aged 65-90 years were identified using group-based trajectory modeling. Further, the combination frequency of the subscale trajectory patterns was determined. RESULTS: Three patterns were identified: early-onset decreasing, late-onset decreasing, and high-stable. DISCUSSION: The instrumental activities of daily living (IADL) trajectory was maintained until approximately 80 years of age; however, chronic disease prevailed the most in the early-onset decreasing pattern. The early-onset decreasing pattern of intellectual activity (IA) was present in 25% of participants, showing impaired IA from 65 years of age. The late-onset decreasing pattern of social roles (SR) was present in 30% of participants, showing a sharp decline compared to other subscales. For many people, the patterns of decrease in SR and IA overlapped. CONCLUSIONS: To maintain higher-level functional capacity, interventions that include disease management and prevention of decline in IADL and increase the awareness of the social support provided throughout old age and interventions for people with an early decline in IA should be implemented.

Social isolation, regardless of living alone, is associated with mortality: the Otassha study.

Introduction: Social isolation has been recognized as a contributing factor to negative health outcomes. Although living alone is associated with health-related outcomes, existing findings are inconsistent. It is not the act of living alone that may predict poor health, but rather social isolation that can lead to increased mortality risk. This study investigated the combined associations of social isolation and living alone with mortality among community-dwelling older adults. Methods: We included older adults from Itabashi ward, Tokyo, who participated in comprehensive health checkups. Participants were categorized into four groups based on their social isolation status and living alone. The primary outcome was all-cause mortality, analyzed using Cox proportional hazards models. Results: Of the 1,106 participants (mean age 73, 42% male), 4.5% experienced both social isolation and living alone. This combination was associated with a worse prognosis regarding all-cause mortality (hazard ratio (HR): 2.08 [95% confidence interval (CI), 1.08-4. 00]). Those who were socially isolated but not living alone also showed a trend towards higher mortality risk (HR: 1.41 [95% CI, 0.90-2.20]). Contrastingly, those who were not socially isolated and lived alone did not show an increased mortality risk (HR: 0.81 [95% CI, 0.44-1.49]). Discussion and conclusion: Living alone is not inherently associated with a poor prognosis in older adults; however, social isolation was associated with a higher mortality risk. Healthcare providers should focus on enhancing social interactions and support for older adults because of their effects on health rather than solely addressing living arrangements to prevent adverse health events.

Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS): Revisiting the Meaning and Significance of the Method.

More than 5 years have passed since the Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS) method was proposed with the intention of evaluating the glymphatic system. This method is handy due to its noninvasiveness, provision of a simple index in a straightforward formula, and the possibility of retrospective analysis. Therefore, the ALPS method was adopted to evaluate the glymphatic system for many disorders in many studies. The purpose of this review is to look back and discuss the ALPS method at this moment.The ALPS-index was found to be an indicator of a number of conditions related to the glymphatic system. Thus, although this was expected in the original report, the results of the ALPS method are often interpreted as uniquely corresponding to the function of the glymphatic system. However, a number of subsequent studies have pointed out the problems on the data interpretation. As they rightly point out, a higher ALPS-index indicates predominant Brownian motion of water molecules in the radial direction at the lateral ventricular body level, no more and no less. Fortunately, the term "ALPS-index" has become common and is now known as a common term by many researchers. Therefore, the ALPS-index should simply be expressed as high or low, and whether it reflects a glymphatic system is better to be discussed carefully. In other words, when a decreased ALPS-index is observed, it should be expressed as "decreased ALPS-index" and not directly as "glymphatic dysfunction". Recently, various methods have been proposed to evaluate the glymphatic system. It has become clear that these methods also do not seem to reflect the entirety of the extremely complex glymphatic system. This means that it would be desirable to use various methods in combination to evaluate the glymphatic system in a comprehensive manner.

Association Between Ego-Resilience and Social Isolation Among Urban Older People.

Social isolation among older adults affects their physical and mental health. Ego-resilience is associated with flexible adaptation to various environments and acceptable behaviors. However, its association with social isolation among older people is unclear. Therefore, a health survey was conducted with 510 adults aged 65 years or older to assess social isolation, its associated factors, and ego resilience. The results showed that the social isolation group had a lower median ego-resiliency scale score (42.0) compared to the non-social isolation group (38.0). The social isolation group were mostly males without spouses, took time to move, had more depressive moods, and poorer subjective health status. The non-social isolated group had faster maximum walking speed. Low ego-resilience was newly identified as a factor associated with social isolation among older people, as were being male, having no spouse, and depressive symptoms. Mediation analysis revealed that ego-resilience affected social isolation and was partially mediated by depressive symptoms.

Three-year trajectories of social networks, face-to-face interactions, and non-face-to-face interactions among community-dwelling older adults in Japan during the COVID-19 pandemic: Otassha study.

OBJECTIVES: To investigate the trajectories of social networks and interactions among older Japanese individuals during the COVID-19 pandemic. STUDY DESIGN: We used data from a cohort of community-dwelling older individuals from the Otassha study's 2019-2022 survey. Participants comprised 606 older individuals who participated in the 2019 survey and were followed up at least once. MAIN OUTCOME MEASURES: Social networks were assessed using the Lubben Social Network Scale-6 (LSNS-6), whereas social interactions were assessed by the frequency of face-to-face or non-face-to-face contact with non-resident family members and friends. Trajectories of the LSNS-6 and face-to-face and non-face-to-face interactions were identified using group-based semiparametric mixture modeling. The trajectories of change in the LSNS-6 from 2019 were also identified. The factors associated with the changes in trajectory patterns were examined using logistic regression analysis. RESULTS: Three LSNS-6 trajectories were identified, with slightly decreasing patterns over time. Specifically, face-to-face interactions tended to decrease over time, whereas non-face-to-face interactions exhibited almost no change. The reduction in LSNS-6 in the decreased pattern failed to recover to its pre-pandemic level. The group of participants with the decreased pattern had a significantly higher proportion of people participating in group activities [odds ratio (95 % confidence interval): 2.27 (1.12-4.59)] and performing calisthenics twice a week than the group with the maintained pattern [2.08 (1.18-3.68)]. CONCLUSIONS: During the three years of the pandemic, no changes were observed in the social networks of community-dwelling older Japanese individuals.

Predicting the incidence of mild cognitive impairment with a computer-based cognitive assessment tool in community-dwelling older adults: The Otassha study.

This study examined the ability of a computer-based cognitive assessment tool (CompBased-CAT) to predict mild cognitive impairment (MCI) in community-dwelling older adults. A two-year longitudinal study was conducted using data from 2016 to 2018 from the Otassha study cohort of community-dwelling older adults. MCI was defined as a Mini-Mental Status Examination (MMSE) score of <27. The CompBased-CAT was used at baseline, with each subtest score converted into a Z-score. Subsequently, the total Z-scores were calculated. Participants were divided into robust and MCI groups, and all variables were compared using the t-test or χ2 test. Receiver operating characteristic (ROC) curves and logistic regression analyses were conducted, with MCI and total Z-scores as dependent and independent variables, respectively. Among the 455 participants (median age, 72 years; range, 65-89 years; 282 women and 173 men), 32 developed MCI after two years. The participants in the MCI group were significantly older. They had lower maximal gait speed, baseline MMSE scores, subtest Z-scores, and total Z-scores than those in the robust group. The area under the ROC curve was 0.79 (95% confidence interval: 0.70-0.87; P <0.01). The sensitivity was 0.76, and the specificity was 0.75. The logistic regression analysis showed an odds ratio of 1.34 (95% confidence interval: 1.18-1.52; P <0.01). This study showed that CompBased-CAT can detect MCI, which is an early stage of dementia. Thus, CompBased-CAT can be used in future community health checkups and events for older adults.

Development and validation of a rapid sarcopenia screening questionnaire: The Otassha study.

AIM: To develop a rapid and easy screening tool to detect sarcopenia. METHODS: In total, 683 community-dwelling older adults who participated in our cohort study, the "Otassha Study," in 2019, completely responded to a questionnaire, and were diagnosed with sarcopenia were included. Participants responded to a nine-item questionnaire, including candidate items for a new sarcopenia screening tool named rapid sarcopenia screening, based on items of the Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) questionnaire. To select appropriate items for the new screeening tool, multiple logistic regression analyses were performed, with sarcopenia as the dependent variable and questionnaire responses as independent variables. The area under the curve using 10 000 bootstraps was used to assess the rapid sarcopenia screening diagnostic ability for detecting sarcopenia. RESULTS: Responses to question nos 2 (how much can you squeeze a wet towel?), 5 (how much muscle strength do you think you have compared with that of people of your age and sex?), 7 (how fast do you usually walk?), and 9 (age-related item) were related to sarcopenia in multiple logistic regression analysis. The area under the curve of the total score of rapid sarcopenia screening was 0.82, 0.80, and 0.81 for men, women, and overall, respectively. At a cut-off value of 14/15, the sensitivity and specificity for sarcopenia detection were 0.73 and 0.73, respectively. CONCLUSIONS: The newly developed sarcopenia screening tool has a better diagnostic ability for sarcopenia than the SARC-F. Rapid sarcopenia screening does not require physical function measurements, making it a useful and accessible tool among older adults to detect sarcopenia. Geriatr Gerontol Int 2023; 23: 945-950.

Validation of self-reported articulatory oral motor skill against objectively measured repetitive articulatory rate in community-dwelling older Japanese adults: The Otassha Study.

AIM: To assess the validity of self-reported articulatory oral motor skill against objectively measured repetitive articulatory rate (oral diadochokinesis [oral-DDK]) as a gold standard index for articulatory oral motor skill in community-dwelling older Japanese adults. METHODS: This cross-sectional study included 607 Japanese adults (mean age = 73.9 years). A single-item self-report questionnaire for articulatory oral motor skill was developed. Study participants completed a 1-month-interval test-retest protocol to assess reliability of the questionnaire, and the protocol was tested by the kappa statistic. Oral-DDK with /ta/ (i.e., the number of repetitions of the monosyllable /ta/ per second) was measured during the on-site examination. Low oral-DDK performance was defined as <5.2 times/s in men and <5.4 times/s in women. Oral-DDK performance, oral functions other than articulatory oral motor skill, and physical frailty were compared in the groups with and without self-reported low articulatory oral motor skill as determined by the response to the questionnaire. RESULTS: Self-reported low articulatory oral motor skill was identified in 18.5% of the study population. The self-report questionnaire had good test-retest reliability, with a kappa statistic of 0.71. Self-reported low articulatory oral motor skill was significantly associated with a lower value of oral-DDK with /ta/ and a higher proportion of low oral-DDK performance, difficulties in chewing and swallowing, dry mouth, and physical frailty. Self-report had high specificity (83.1%) but low sensitivity (42.1%) for detecting low oral-DDK performance. CONCLUSIONS: A single-item self-report questionnaire for articulatory oral motor skill had acceptable test-retest reliability and was associated with objectively measured articulatory oral motor skill. Geriatr Gerontol Int 2023; 23: 729-735.

Social interaction trajectories and all-cause mortality in older adults: the Otassha study.

Introduction: This longitudinal study aimed to identify aging trajectory patterns of social interaction by sex and determine the association between these patterns and all-cause mortality. Methods: Participants were 4,065 community-dwelling older adults (1849 men) in Japan, aged 65-89 years, who responded twice or more to a mail survey conducted between 2012 and 2020. Social interaction was examined through the frequency of face-to-face and non-face-to-face contact with non-resident family and friends. The aging trajectories of the social interaction scores were identified using group-based trajectory modeling. Results: Two groups were identified among both men and women. Among men with high-frequency interaction, a rapid decrease in the frequency of social interaction was observed after 80 years of age. Conversely, among women, the frequency tended to remain the same, even after 80 years of age. The social interaction score among those aged 65 years in the low-frequency group was approximately 4 points for men and 6 points for women. Among men, no decrease was observed; however, it tended to decline after 85 years of age among women. Among men, the factors associated with the low-frequency group were instrumental activities of daily living score, perceived financial status, and social participation, while among women, they were self-rated health and social participation. The adjusted hazard ratio in the low-frequency group for all-cause mortality was 1.72 (95% confidence interval, 1.27-1.72) for men and 1.45 (95% confidence interval, 0.98-2.14) for women. Discussion: In the low-frequency group, men had a higher risk of all-cause mortality than women. Daily social interaction from mid-age is important to reduce the risk of social isolation and all-cause mortality in later life.

Evaluation of alterations in interstitial fluid dynamics in cases of whole-brain radiation using the diffusion-weighted image analysis along the perivascular space method.

In the current study, we assessed changes in interstitial fluid dynamics resulting after whole-brain radiotherapy using the diffusion-weighted image analysis along the perivascular space (DWI-ALPS) method, which is a simplified variation of the diffusion tensor image ALPS (DTI-ALPS) method using diffusion-weighted imaging (DWI) with orthogonal motion-probing gradients (MPGs). This retrospective study included 47 image sets from 22 patients who underwent whole-brain radiotherapy for brain tumors. The data for the normal control group comprised 105 image sets from 105 participants with no pathological changes. DWI was performed with the three MPGs applied in an orthogonal direction to the imaging plane, and apparent diffusion coefficient images for the x-, y-, and z-axes were retrospectively generated. The ALPS index was calculated to quantify interstitial fluid dynamics. The independent t-test was used to compare the ALPS index between normal controls and patients who underwent whole-brain radiotherapy. Patients were compared in all age groups and individual age groups (20-39, 40-59, and 60-84 years). We also examined the correlation between biologically equivalent doses (BEDs) and the ALPS index, as well as the correlation between white matter hyperintensity and the ALPS index. In the comparison of all age groups, the ALPS index was significantly lower (p < 0.001) in the postradiation group (1.32 ± 0.16) than in the control group (1.44 ± 0.17), suggesting that interstitial fluid dynamics were altered in patients following whole-brain radiotherapy. Significant age group differences were found (40-59 years: p < 0.01; 60-84 years: p < 0.001), along with a weak negative correlation between BEDs (r = -0.19) and significant correlations between white matter hyperintensity and the ALPS index (r = -0.46 for periventricular white matter, r = -0.38 for deep white matter). It was concluded that the ALPS method using DWI with orthogonal MPGs suggest alteration in interstitial fluid dynamics in patients after whole-brain radiotherapy. Further systematic prospective studies are required to investigate their association with cognitive symptoms.

Development of a multiple masticatory function model based on the evaluation of sarcopenia: A cross-sectional survey of the Otassha study.

OBJECTIVE: The masticatory function is intricately linked to several factors like natural teeth count, occlusion, masticatory muscles, and tongue coordination. This study's goal was to formulate a comprehensive masticatory function model, considering sarcopenia's conceptual structure, and subsequently validate its measurement efficacy. DESIGN: The study encompassed 753 participants (59.1 % women; mean age: 73.0 ± 5.1 years) from an urban community. The model amalgamated masseter muscle mass, occlusal force, and mixing ability. Based on the Asian Working Group for Sarcopenia 2019 classification, participants were categorized into a multiple masticatory dysfunction (MMD) or severe MMD (S-MMD) group. Logistic regression analysis gauged the model's validity, using serum albumin levels and self-reported chewing difficulties as dependent variables. RESULTS: Of the total, 61 (8.1 %) participants exhibited MMD, while 24 (3.2 %) had S-MMD. S-MMD was correlated with low serum albumin levels (odds ratio: 3.62; 95 % confidence interval: 1.07-12.29) and heightened self-reported chewing difficulties (odds ratio: 2.82; 95 % confidence interval: 1.09-7.28). CONCLUSIONS: Our multiple masticatory function model offers a straightforward approach for assessing MMD. Furthermore, the study establishes a link between S-MMD, nutritional vulnerability, and self-reported chewing challenges, thus affirming the model's credibility.

Serum levels of vitamin D and periodontal inflammation in community-dwelling older Japanese adults: The Otassha Study.

AIM: To evaluate the association between vitamin D status and periodontal inflammation as determined by the periodontal inflamed surface area (PISA) in community-dwelling older adults. MATERIALS AND METHODS: This cross-sectional study included 467 Japanese adults (mean age = 73.1 years) who underwent full-mouth periodontal examinations and measurements of serum levels of 25-hydroxyvitamin D (25(OH)D). We used linear regression and restricted cubic spline models to analyse the association between exposure (serum 25(OH)D) and outcome (PISA). RESULTS: The linear regression model showed that, after adjusting for potential confounders, participants in the lowest quartile of serum 25(OH)D had 41.0 mm2 more PISA (95% confidence interval [CI]: 4.6-77.5) than the reference group (the highest quartile of serum 25(OH)D). The spline model showed that the association between serum 25(OH)D and PISA was non-linear and restricted to the low 25(OH)D range. PISA initially sharply decreased as serum 25(OH)D increased, and then the decreasing trend slowed and plateaued. The inflection point with the minimum PISA value was a serum 25(OH)D level of 27.1 ng/mL, above which there was no decreasing trend in PISA with increasing serum 25(OH)D levels. CONCLUSIONS: Low vitamin D status had an L-shaped association with periodontal inflammation in this cohort of Japanese adults.

Impact of combinations of subscale declines in higher-level functional capacity on 8-year all-cause mortality among community-dwelling older Japanese adults.

BACKGROUND: The frequency of combined declines in domains of multi-faceted frailty and their impact on adverse health outcomes have not been adequately investigated. We aimed to examine the association between combined subscale declines in higher-level functional capacity and 8-year all-cause mortality among community-dwelling older Japanese individuals and the impact of multi-faceted frailty on mortality. MATERIALS AND METHODS: We administered a questionnaire to 7015 community-dwelling older adults aged 65-85 years. The higher-level functional capacity of the 3381 respondents was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Subscale decline was defined as (1) none, (2) only social role (SR), (3) only intellectual activity (IA), (4) SR and IA, (5) only instrumental activities of daily living (IADL), (6) IADL and SR, (7) IADL and IA, and (8) all. Associations between combined subscale declines and mortality were examined using adjusted Cox proportional hazards models. Follow-up was conducted from October 1, 2012, to death or November 1, 2020. RESULTS: The mortality rate was 16.7/1000 person-years. Moreover, 44% of respondents had declined SR, and half of them had multiple declines. Compared with no decline, SR (adjusted hazard ratio [HR]: 1.49, 95% confidence interval [CI]: 1.14-1.93), SR and IA (HR: 1.59, 95% CI: 1.16-2.17), IADL and SR (HR: 1.97, 95% CI: 1.31-2.99), and all-domain (HR: 2.72, 95% CI: 1.98-3.74) declines were significantly associated with higher mortality risks. CONCLUSIONS: Overlapping SR and IADL declines increased mortality risk, suggesting the importance of measuring social frailty and overlapping physical and social frailty.

Activity diversity is associated with the prevention of frailty in community-dwelling older adults: The Otassha Study.

Introduction: A prior study showed an association between diversity in daily activities (type, frequency, evenness) and frailty in older adults. However, the causality of this relationship is unclear. Therefore, this study aimed to clarify the relationship between activity diversity and frailty through a 2-year longitudinal study conducted among community-dwelling older adults. Methods: We evaluated data from the 2018 and 2020 waves of the Otassha Study. Frailty was assessed using the Cardiovascular Health Study criteria, with pre-frail and frail participants defined as frail and the other participants categorized into the robust group. We enrolled a total of 207 participants who were not frail at baseline. Activity type, frequency, and evenness scores were calculated using an Activity Diversity Questionnaire. The association between each activity diversity score and the incidence of frailty was evaluated using logistic regression modeling (each diversity score was entered the model after Z-transformation). Results: Of the 207 enrolled participants (median age, 73 years; age range, 65-91 years; 60.4% women), 64 (30.9%) had incident frailty during the follow-up period. A logistic regression analysis adjusting for sociodemographic and psychosomatic factors revealed odds ratios for activity type and evenness scores of 0.64 and 0.61, respectively (P < 0.05). These factors were significantly associated with the incidence of frailty. Discussion: Activity type and evenness (except frequency) within daily activities were predictors of frailty during 2 years of follow-up. Engagement in diverse activities appears to be more effective in preventing frailty than does engagement in a few activities.

[Sub-staff training program for community residents to provide community-based care services at day-care facilities].

Objectives　As the birthrate declines and the population ages, increase in the number of older adults certified as requiring long-term care and shortage of care staff are important issues to be considered. This study developed a sub-staff training program that trains community residents as sub-staff (paid auxiliary staff who possess knowledge and skills in care prevention and confidentiality) to provide care for enhancing independence of older adults with the support of staff in day-care facilities. The study also examined the program's feasibility and key factors, through the introduction of practical examples and surveys, for implementation in care prevention projects of local governments.Methods　The four-month training program included lectures on care prevention and provided job training to ensure participants understood the goals and contents of the care plan and learnt to provide care services with the assistance of facility staff. The training program was conducted at 14 facilities in Tokyo and Chiba from 2015 to 2017. The evaluation focused on the completion rate, change in understanding of care prevention and confidence regarding activities at the facility and in the community, participation in community activities after program completion, the psychological impact on care service recipients, and the perception of workload reduction by the facility staff.Results　A total of 96 out of 104 participants completed the training program (completion rate of 92.3%). The survey results showed that participants' confidence in activities at the facilities and understanding of care prevention increased significantly; 65.3% participated in new community activities after program completion, including activities at the facilities. The results of the survey of care service recipients showed that negative psychological effects did not increase among those who received care services from the participants compared to those who did not receive care from participants. Among the facility staff, 85.7% indicated that their workload had reduced after the community residents' participation in care services.Conclusion　The training program improved participants' confidence in care-related activities and their understanding of care prevention. More than half of them engaged in new community activities afterwards. Participants' provision of care services had a less negative impact on the service recipients and led to a reduction in workload for the facility staff. These results suggest high feasibility of the training program for care prevention projects.

Association between daily life walking speed and frailty measured by a smartphone application: a cross-sectional study.

OBJECTIVES: To assess whether frailty can be assessed using a smartphone and whether daily walking speed (DWS) is associated with frailty. DESIGN: Cross-sectional study. SETTING: Three prefectures (Kanagawa, Saitama and Tokyo) in Japan. PARTICIPANTS: The study enrolled 163 participants (65 in the robust group, 69 in the prefrailty group and 29 in the frailty group) by sending letters to house owners aged≥55 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The participants downloaded the DWS measurement application on their smartphones, which measured the daily walking (DW) parameters (DWS, step length and cadence) and the Kihon checklist for frailty assessment. The differences in the DW parameters between the robust, prefrailty and frailty groups were examined using one-way analysis of variance. We conducted logistic regression analysis for the Crude model (each DW parameter), model 1 (adjusted for the number of steps) and model 2 (model 1+age, sex and the number of chronic diseases). RESULTS: DWS was marginally significantly slower in the frailty group than in the prefrailty and robust group (robust 1.26 m/s vs prefrailty 1.25 m/s vs frailty 1.19 m/s, p=0.060). Step length was significantly smaller in the frailty group than in the robust group (robust 66.1 cm vs prefrailty 65.9 vs frailty 62.3 cm, p<0.01). Logistic regression analysis for the three models revealed that DWS was significantly associated with frailty. CONCLUSIONS: DWS measured using the smartphone application was associated with frailty. This was probably due to the shorter step length and body height seen in frail individuals.

An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent. OBJECTIVE: This protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS). METHODS: EPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area. RESULTS: This trial began data collection in September 2021 and is expected to be completed in October 2023. CONCLUSIONS: This study can provide useful data to understand the characteristics of EPI-589. TRIAL REGISTRATION: Japan Primary Registries Network jRCT2061210031; tinyurl.com/2p84emu6. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42032.

Effect of Temporal Sampling Rate on Estimates of the Perfusion Parameters for Patients with Moyamoya Disease Assessed with Simultaneous Multislice Dynamic Susceptibility Contrast-enhanced MR Imaging.

PURPOSE: The effect of temporal sampling rate (TSR) on perfusion parameters has not been fully investigated in Moyamoya disease (MMD); therefore, this study evaluated the influence of different TSRs on perfusion parameters quantitatively and qualitatively by applying simultaneous multi-slice (SMS) dynamic susceptibility contrast-enhanced MR imaging (DSC-MRI). METHODS: DSC-MRI datasets were acquired from 28 patients with MMD with a TSR of 0.5 s. Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and time to maximum tissue residue function (Tmax) were calculated for eight TSRs ranging from 0.5 to 4.0 s in 0.5-s increments that were subsampled from a TSR of 0.5 s datasets. Perfusion measurements and volume for chronic ischemic (Tmax ≥ 2 s) and non-ischemic (Tmax < 2 s) areas for each TSR were compared to measurements with a TSR of 0.5 s, as was visual perfusion map analysis. RESULTS: CBF, CBV, and Tmax values tended to be underestimated, whereas MTT and TTP values were less influenced, with a longer TSR. Although Tmax values were overestimated in the TSR of 1.0 s in non-ischemic areas, differences in perfusion measurements between the TSRs of 0.5 and 1.0 s were generally minimal. The volumes of the chronic ischemic areas with a TSR ≥ 3.0 s were significantly underestimated. In CBF and CBV maps, no significant deterioration was noted in image quality up to 3.0 and 2.5 s, respectively. The image quality of MTT, TTP, and Tmax maps for the TSR of 1.0 s was similar to that for the TSR of 0.5 s but was significantly deteriorated for the TSRs of ≥ 1.5 s. CONCLUSION: In the assessment of MMD by SMS DSC-MRI, application of TSRs of ≥ 1.5 s may lead to deterioration of the perfusion measurements; however, that was less influenced in TSRs of ≤ 1.0 s.

Population-based reference values for tongue pressure in Japanese older adults: A pooled analysis of over 5,000 participants.

PURPOSE: To establish age- and sex-specific population reference values for tongue pressure (TP) in community-dwelling Japanese older adults. METHODS: For this analysis, we pooled four population-based studies on community-dwelling adults aged ≥65 years that measured TP using a JMS tongue pressure measuring device. We calculated the means and deciles of TP per 5-year age group for each sex. We also estimated age trends in TP for men and women. RESULTS: In total, 5,083 individuals (2,150 men and 2,933 women, with a mean [standard deviation] age of 75.2 [6.5] years) were included in the present analysis. In male participants, the mean (standard deviation) TPs for ages 65-69, 70-74, 75-79, 80-84, and ≥85 years were 34.0 (8.4), 32.2 (8.1), 30.8 (8.3), 28.4 (8.9), and 24.4 (8.2) kPa, respectively. In female participants, the corresponding values were 31.5 (7.1), 30.5 (7.5), 29.6 (7.3), 28.4 (8.0), and 26.4 (7.6) kPa, respectively. For both sexes, there were significant declining trends in TP with advanced age. In addition, the interaction between age and sex had a significant effect on TP (regression coefficient [95% confidence interval] = -0.18 [-0.25 to -0.11] when age was modeled as a continuous variable and sex was modeled as a categorical variable [coded as 0=women, 1=men]). CONCLUSIONS: This study determined age- and sex-specific reference values for TP, presented as means and deciles, in community-dwelling Japanese older adults aged ≥65 years. This study also demonstrated sex differences in age-related declines in TP.