Japan-Multimodal Intervention Trial for the Prevention of Dementia: A randomized controlled trial.

INTRODUCTION: We examined the efficacy of a multidomain intervention in preventing cognitive decline among Japanese older adults with mild cognitive impairment (MCI). METHODS: Participants aged 65-85 years with MCI were randomized into intervention (management of vascular risk factors, exercise, nutritional counseling, and cognitive training) and control groups. The primary outcome was changes in the cognitive composite score over a period of 18 months. RESULTS: Of 531 participants, 406 completed the trial. The between-group difference in composite score changes was 0.047 (95% CI: -0.029 to 0.124). Secondary analyses indicated positive impacts of interventions on several secondary health outcomes. The interventions appeared to be particularly effective for individuals with high attendance during exercise sessions and those with the apolipoprotein E ε4 allele and elevated plasma glial fibrillary acidic protein levels. DISCUSSION: The multidomain intervention showed no efficacy in preventing cognitive decline. Further research on more efficient strategies and suitable target populations is required. HIGHLIGHTS: This trial evaluated the efficacy of multidomain intervention in individuals with MCI. The trial did not show a significant difference in preplanned cognitive outcomes. Interventions had positive effects on a wide range of secondary health outcomes. Those with adequate adherence or high risk of dementia benefited from interventions.

A study on the estimation of area of origin of swing cast-off pattern.

In bloodstain pattern analysis (BPA), a field of forensic science, there has been active discussion on the estimation of the area of origin of impact spatter. However, there is no established methodology to quantitatively analyze the area of origin of a swing cast-off pattern. To quantitatively analyze the methodology of previous research on estimation of area of origin, a device for generating uniform swing cast-off patterns was produced. Using artificial blood, 10 swing cast-off patterns were generated on porous paper; in each, 10 blood drops were selected for the calculation of the impact angle. Hemospat software was used for individual bloodstain analysis, and an open source code was used for estimation of area of origin. Under the same conditions, an additional 10 swing cast-off patterns were generated, and quantitative analysis was performed using trigonometric functions and an adjustment formula that minimized errors in calculating the impact angle. The adjustment formula was corrected to calculate the impact angle for the bloodstains on the porous surface. As uncertainty decreases, the error increases, and the point at which both uncertainty and error can be minimized is calculated as 75%. The existing formula included the trajectory in the estimated likelihood range in 75% of samples. When the adjustment formula was applied, the accuracy was improved, with the trajectory included in the area with a 90% likelihood.

An analysis of the contents of the young-onset dementia helpline: profiles of clients who consulted the helpline themselves.

BACKGROUND: Young-onset dementia (YOD) community care requires personalised approaches. Yet, the specific details of YOD consultations are unclear. This study explored how initial consultations correlate with client profiles. METHODS: Data from regional YOD helplines were used to analyze the main characteristics of people living with YOD or who had concerns about the possibility of YOD (n = 132). Among several categorical variables, the following were used for analysis: age group, sex, type of living arrangement, employment status, presence of dementia, and content of the consultation. To identify groups of items that frequently occur together, strongly connected rules were identified using association rule analysis with the a priori algorithm. To focus on the characteristics of clients, rules related to client characteristics were extracted based on the type of consultation. RESULTS: A total of 51 rules were identified for the consultations. These rules fell into two categories: (1) consultations for medical matters, which mainly involved employed individuals with undiagnosed dementia, and (2) other consultations on daily life or work, which mainly involved individuals diagnosed with dementia and were characterised by the influence of sex. These rules indicate the importance of medical involvement in confirming the diagnosis and specific individualised care following diagnosis for people living with YOD. CONCLUSION: Clients with or without a dementia diagnosis were consulted differently in the YOD helplines. Before receiving a diagnosis, medical matters were the main theme of consultations, whereas after receiving a diagnosis, adjustments to daily life or work were the main themes. The results of this study suggest that the needs of people living with YOD and the services they require may vary depending on their backgrounds.

Investigation on Contact Properties of 2D van der Waals Semimetallic 1T-TiS2/MoS2 Heterojunctions.

Two-dimensional transition metal dichalcogenides (2D TMDCs) are considered promising alternatives to Si as channel materials because of the possibility of retaining their superior electronic transport properties even at atomic body thicknesses. However, the realization of high-performance 2D TMDC field-effect transistors remains a challenge owing to Fermi-level pinning (FLP) caused by gap states and the inherent high Schottky barrier height (SBH) within the metal contact and channel layer. This study demonstrates that high-quality van der Waals (vdW) heterojunction-based contacts can be formed by depositing semimetallic TiS2 onto monolayer (ML) MoS2. After confirming the successful formation of a TiS2/ML MoS2 heterojunction, the contact properties of vdW semimetal TiS2 were thoroughly investigated. With clean interfaces of the TiS2/ML MoS2 heterojunctions, atomic-layer-deposited TiS2 can induce gap-state saturation and suppress FLP. Consequently, compared with conventional evaporated metal electrodes, the TiS2/ML MoS2 heterojunctions exhibit a lower SBH of 8.54 meV and better contact properties. This, in turn, substantially improves the overall performance of the device, including its on-current, subthreshold swing, and threshold voltage. Furthermore, we believe that our proposed strategy for vdW-based contact formation will contribute to the development of 2D materials used in next-generation electronics.

Association between the perceived value of adopting new behaviors and depressive symptoms among older adults.

Early preventive measures against depression have become important with unprecedented global aging. Increase in one's perceived value (PV) may correspond to better mental health outcomes. This cross-sectional observation study aimed to clarify whether the PV of adopting new behaviors is associated with depressive symptoms. The participants were 5266 community-dwelling older adults aged ≥ 65 years. We developed a questionnaire to measure the PV of adopting new behaviors, specifically activities beneficial for preventing depressive symptoms (physical, cognitive, and social activities) in older adults. The questionnaire asked whether adopting the ten selected behaviors was valuable. The scores were added, and the total score ranged from - 20 to 20. The odds ratios (OR) of depressive symptoms were calculated using binomial logistic regression according to the PV score quartiles. Depressive symptoms were reported by 595 (11.3%) participants. After adjusting for potential confounders, higher quartiles of PV scores were significantly associated with lower prevalence of depressive symptoms: vs Q1; Q2 OR 0.76 (95% confidence interval: 0.59-0.97); Q3 0.67 (0.51-0.87); Q4 0.54 (0.40-0.73) (P for trend < .001). Having a higher PV of adopting new behaviors may prevent depressive symptoms among older adults. Healthcare professionals need to pay attention to poor value orientation among older adults.

Lifetime Physical Activity and Late-Life Mild Cognitive Impairment in Community-Dwelling Older Adults.

OBJECTIVES: Regular physical activity throughout life is generally recommended to prevent dementia; however, there is little evidence regarding the association between lifetime physical activity and mild cognitive impairment (MCI), which often precedes dementia. This study aimed to examine the association of lifetime physical activity and their transitions with late-life MCI. DESIGN: A population-based case-control study. SETTING AND PARTICIPANTS: A total of 2968 Japanese community-dwelling older adults aged ≥70 years without dementia. METHODS: We evaluated the participants' early-, mid-, and late-life physical activity habits and categorized their transitions across life stages. Cognitive functions in late life were assessed for memory, attention, executive function, and processing speed; functional impairment in one or more cognitive domains was defined as MCI. RESULTS: Regular physical activity in early life was not significantly associated with late-life MCI [odds ratio (OR), 0.80; 95% CI, 0.63-1.02], although those in mid-life (OR, 0.64; 95% CI, 0.51-0.81) and late-life (OR, 0.74; 95% CI, 0.59-0.91) were associated with lower odds of late-life MCI. Compared with nonexercisers, participants who acquired new habits of physical activity during mid- or late-life (OR, 0.71; 95% CI, 0.55-0.91) and those who maintained physical activity throughout their life span (OR, 0.61; 95% CI, 0.42-0.87) had lower odds of late-life MCI; those who stopped regular activity during mid- or late-life did not (OR, 0.79; 95% CI, 0.58-1.06). CONCLUSIONS AND IMPLICATIONS: While physical activity throughout the life span is associated with the lowest odds of MCI, starting regular physical activity, even later in life, confers a benefit and should be encouraged as a "lifelong approach" to MCI risk reduction.

Proposal for priority emerging pollutants in the Nakdong river, Korea: Application of EU watch list mechanisms.

The Nakdong River, the longest in Korea, has received numerous pollutants from heavily industrialized and densely populated areas while being used as a drinking water source. A number of research have reported occurrences of emerging pollutants (EPs) in the river. The results requested efficient monitoring and systematic management strategies such as EU watch list under Water Framework Directive. The aim of this study is to propose a watch list through preliminary monitoring of the river and risk-based prioritization approach. As candidates for monitoring target, 632 substances were selected based on literature and database searches. Among them, 175 substances were subjected to target screening method whereas 457 were evaluated via suspect screening. A risk-based prioritization was applied to substances quantified through target screening based on concentrations, and a scoring-based prioritization was applied to substances tentatively identified through suspect screening. Sampling campaigns (n = 12) were conducted from October 2020 to September 2021, at 8 sampling sites along the river. As a result, 130 target substances were quantified above the LOQ. Among the 21 substances whose priority score was assigned through risk-based prioritization, telmisartan and iprobenfos were identified with very high environmental risk while candesartan, TBEP, imidacloprid, azithromycin and clotrimazole were classified with high or intermediate risk. As result of the scoring system for 39 tentatively identified substances, 6 substances (benzophenone, caprolactam, metolachlor oxanilic acid, heptaethylene glycol, octaethylene glycol and pentaethylene glycol), which were then confirmed with reference standards, showed a potential environmental risk. Those substances prioritized through target and suspect screening followed by scoring systems can be a subset for the watch list and potential targets for nationwide water quality monitoring program in the future.

Physical frailty and survival time after the onset of functional disability: Is there a sex difference?

BACKGROUND: Physical frailty accelerates the timing of both subsequent disability and death; however, evidence regarding the impact of frailty on the period from disability onset to death and sex differences of this impact is lacking. The aim of this study was to examine the relationship among physical frailty, disability, death, and sex differences. METHODS: This Japanese cohort study included 10,524 community-dwelling people aged ≥65 years. Physical frailty was operationalized by key phenotypes as per Fried's criteria (slowness, weakness, exhaustion, weight loss, and low activity) at baseline. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for disability onset and post-disability survival according to the frailty status. RESULTS: During a 5-year follow-up, the risk of disability onset for pre-frailty (HR: 1.74, 95% CI: 1.51-2.00) and frailty (HR: 3.27, 95% CI: 2.77-3.87) were significantly higher than that for robust people. Furthermore, among participants who developed disabilities within 5 years (n = 1481), the risk of post-disability death for pre-frailty was not different from that for robust (HR: 1.49, 95% CI: 0.99-2.24), but frailty showed a higher risk of post-disability death than did robust people. (HR: 1.75, 95% CI: 1.13-2.72). In the sex-stratified analysis, although the female group showed no association between frailty status and post-disability death (HR: 1.21, 95% CI: 0.63-2.33 in pre-frailty; HR: 1.24, 95% CI: 0.60-2.57 in frailty), the male group showed higher risk of post-disability death in both pre-frailty (HR: 1.74, 95% CI: 1.03-2.96) and frailty (HR: 2.32, 95% CI: 1.32-4.09). CONCLUSIONS: Physical frailty shortens the period from disability onset to death. Additionally, the impact of frailty on post-disability death is greater for males than for females. Our findings suggest that physical frailty is an important clinical indicator distinct from disability and that interventions to prevent and address frailty in men need further investigation.

Preliminary analysis of predicting the first recurrence in patients with neovascular age-related macular degeneration using deep learning.

BACKGROUND: To predict, using deep learning, the first recurrence in patients with neovascular age-related macular degeneration (nAMD) after three monthly loading injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: Optical coherence tomography (OCT) images were obtained at baseline and after the loading phase. The first recurrence was defined as the initial appearance of a new retinal hemorrhage or intra/subretinal fluid accumulation after the initial resolution of exudative changes after three loading injections. Standard U-Net architecture was used to identify the three retinal fluid compartments, which include pigment epithelial detachment, subretinal fluid, and intraretinal fluid. To predict the first recurrence of nAMD, classification learning was conducted to determine whether the first recurrence occurred within three months after the loading phase. The recurrence classification architecture was built using ResNet50. The model with retinal regions of interest of the entire region and fluid region on OCT at baseline and after the loading phase is presented. RESULTS: A total of 1,444 eyes of 1,302 patients were included. The mean duration until the first recurrence after the loading phase was 8.20 ± 15.56 months. The recurrence classification system revealed that the model with the fluid region of OCT after the loading phase provided the highest classification performance, with an area under the receiver operating characteristic curve (AUC) of 0.725 ± 0.012. Heatmap analysis revealed that three pathological fluids, subsided choroidal neovascularization lesions, and hyperreflective foci were important areas for the first recurrence. CONCLUSIONS: The deep learning algorithm allowed for the prediction of the first recurrence for three months after the loading phase with adequate feasibility. An automated prediction system may assist in establishing patient-specific treatment plans and the provision of individualized medical care for patients with nAMD.

Acupuncture for patients with insomnia and predictors of treatment response: a chart review.

BACKGROUND: Acupuncture is a potentially effective non-pharmacological treatment for insomnia. OBJECTIVE: We observed the responses of patients with insomnia to acupuncture in routine clinical practice. In addition, we explored patient characteristics that might affect the treatment response to acupuncture for insomnia. METHODS: Medical records of patients with insomnia in a Korean medicine clinic with baseline Insomnia Severity Index (ISI) scores ⩾8 and Pittsburgh Sleep Quality Index (PSQI) scores ⩾5 were reviewed. Acupuncture was applied at ST43, GB41, ST41, SI5, HT3, KI10, HT7 and ST3, for 1-2 months. The ISI and PSQI were measured monthly to assess insomnia severity. The effect of acupuncture over time was analyzed using a multilevel linear model for repeated measures. In addition, logistic regression was used to explore predictors of treatment response. RESULTS: A total of 91 patients with insomnia aged 59.2 ± 12.5 years (mean ± standard deviation (SD)) (90.1% female) were included in the analysis. After the acupuncture treatment, ISI scores were significantly reduced by -3.75 (95% confidence interval (CI) = -4.99, -2.50) and -4.69 (95% CI = -6.22, -3.16) after the first and second month, respectively. The PSQI global scores also improved, and sleep duration showed a tendency to increase by 0.35 h (95% CI = -0.17, 0.86) after acupuncture treatment. Three cases of mild fatigue were reported. In addition, higher baseline pain/discomfort predicted a greater likelihood of response after acupuncture treatment (odds ratio (OR) = 1.66, 95% CI = 1.10, 2.60). CONCLUSION: In a real-world setting, the insomnia of outpatients in a clinic was slightly alleviated after acupuncture treatment. These findings require validation by randomized controlled trials.

Neurophysiological markers in community-dwelling older adults with mild cognitive impairment: an EEG study.

BACKGROUND: Neurodegeneration and structural changes in the brain due to amyloid deposition have been observed even in individuals with mild cognitive impairment (MCI). EEG measurement is considered an effective tool because it is noninvasive, has few restrictions on the measurement environment, and is simple and easy to use. In this study, we investigated the neurophysiological characteristics of community-dwelling older adults with MCI using EEG. METHODS: Demographic characteristics, cognitive function, physical function, resting-state MRI and electroencephalogram (rs-EEG), event-related potentials (ERPs) during Simon tasks, and task proportion of correct responses and reaction times (RTs) were obtained from 402 healthy controls (HC) and 47 MCI participants. We introduced exact low-resolution brain electromagnetic tomography-independent component analysis (eLORETA-ICA) to assess the rs-EEG network in community-dwelling older adults with MCI. RESULTS: A lower proportion of correct responses to the Simon task and slower RTs were observed in the MCI group (p < 0.01). Despite no difference in brain volume between the HC and MCI groups, significant decreases in dorsal attention network (DAN) activity (p < 0.05) and N2 amplitude of ERP (p < 0.001) were observed in the MCI group. Moreover, DAN activity demonstrated a correlation with education (Rs = 0.32, p = 0.027), global cognitive function (Rs = 0.32, p = 0.030), and processing speed (Rs = 0.37, p = 0.010) in the MCI group. The discrimination accuracy for MCI with the addition of the eLORETA-ICA network ranged from 0.7817 to 0.7929, and the area under the curve ranged from 0.8492 to 0.8495. CONCLUSIONS: The eLORETA-ICA approach of rs-EEG using noninvasive and relatively inexpensive EEG demonstrates specific changes in elders with MCI. It may provide a simple and valid assessment method with few restrictions on the measurement environment and may be useful for early detection of MCI in community-dwelling older adults.

Developing a predictive model for mortality in patients with cognitive impairment.

OBJECTIVES: We developed a predictive model for all-cause mortality and examined the risk factors for cause-specific mortality among people with cognitive impairment in a Japanese memory clinic-based cohort (2010-2018). METHODS: This retrospective cohort study included people aged ≥65 years with mild cognitive impairment or dementia. The survival status was assessed based on the response of participants or their close relatives via a postal survey. Potential predictors including demographic and lifestyle-related factors, functional status, and behavioral and psychological status were assessed at the first visit at the memory clinic. A backward stepwise Cox regression model was used to select predictors, and a predictive model was developed using a regression coefficient-based scoring approach. The discrimination and calibration were assessed via Harrell's C-statistic and a calibration plot, respectively. RESULTS: A total of 2610 patients aged ≥65 years (men, 38.3%) were analyzed. Over a mean follow-up of 4.1 years, 544 patients (20.8%) died. Nine predictors were selected from the sociodemographic and clinical variables: age, sex, body mass index, gait performance, physical activity, and ability for instrumental activities of daily living, cognitive function, and self-reported comorbidities (pulmonary disease and diabetes). The model showed good discrimination and calibration for 1-5-year mortality (Harrell's C-statistic, 0.739-0.779). Some predictors were specifically associated with cause-specific mortality. CONCLUSIONS: This predictive model has good discriminative ability for 1- to 5-year mortality and can be easily implemented for people with mild cognitive impairment and all stages of dementia referred to a memory clinic.

AI-driven robotic chemist for autonomous synthesis of organic molecules.

The automation of organic compound synthesis is pivotal for expediting the development of such compounds. In addition, enhancing development efficiency can be achieved by incorporating autonomous functions alongside automation. To achieve this, we developed an autonomous synthesis robot that harnesses the power of artificial intelligence (AI) and robotic technology to establish optimal synthetic recipes. Given a target molecule, our AI initially plans synthetic pathways and defines reaction conditions. It then iteratively refines these plans using feedback from the experimental robot, gradually optimizing the recipe. The system performance was validated by successfully determining synthetic recipes for three organic compounds, yielding that conversion rates that outperform existing references. Notably, this autonomous system is designed around batch reactors, making it accessible and valuable to chemists in standard laboratory settings, thereby streamlining research endeavors.

Subjective Cognitive Decline and Frailty Trajectories and Influencing Factors in Japanese Community-Dwelling Older Adults: A Longitudinal Study.

We studied frailty and subjective cognitive decline (SCD) trajectories in older Japanese adults and evaluated the influence of various factors on these trajectories. We analyzed data from 1157 non-demented adults aged 70 and above from 2013 to 2019. Frailty was assessed using the self-administered Kihon Checklist (KCL), a Japanese frailty index. SCD was evaluated using the questionnaire of the Subjective Memory Complaints scale. Through group-based joint trajectory models, we discerned three frailty trajectories: non-progressive (n = 775), moderate progressive (n = 312), and rapid progressive (n = 70); and three SCD trajectories: non-progressive (n = 302), moderate progressive (n = 625), and rapid progressive (n = 230). Individuals in the rapid progressive SCD trajectory had a 32.2% probability of also being in the rapid progressive frailty trajectory. In contrast, those in the non-progressive SCD trajectory had zero probability of being in the rapid progressive frailty trajectory. Both the rapid progressive frailty and SCD groups combined had a higher incidence of depressive symptoms and slow gait speed. Our results have found that frailty and SCD share a similar trajectory in Japanese older adults. Additionally, rapid progressive frailty and SCD were associated with the highest risk of depressive symptoms and slow gait speed. Thus, interventions targeting both frailty and cognitive decline should prioritize mental health enhancement and gait speed improvement.

Differential effects of lifestyle activities on disability incidence based on neighborhood amenities.

BACKGROUND: This study examined the effect of neighborhood amenities on disability risk among community-dwelling older adults in Japan, based on lifestyle activities. METHOD: This was an observational prospective cohort study. Participants comprised 13,258 older adults from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. We calculated participants' Walk Score using their home addresses and divided them into three groups: "car-dependent," "somewhat walkable," and "very walkable." We then calculated the average value of lifestyle activities. We divided the neighborhood amenity groups into two groups, "fewer lifestyle activities" and "more lifestyle activities," for a total of six groups. After identifying interactions between neighborhood amenities and lifestyle activities, Cox proportional hazard models to calculate hazard ratios for incident disability risk, based on neighborhood amenities and lifestyle activities. RESULTS: An interaction occurred between neighborhood amenities and lifestyle activities (p < 0.05). Survival probabilities for incident disability based on lifestyle activities were estimated for each neighborhood amenity group: car-dependent, 1.62 (95% CI 1.07 to 2.46); somewhat walkable, 1.08 (95% CI 0.84 to 1.40); and very walkable, 1.05 (95% CI 0.87 to 1.27). Those with fewer lifestyle activities in the car-dependent group exhibited the highest risk of incident disability in the unadjusted and adjusted models. CONCLUSION: Given that the aging population is increasing steadily, considering older adults' neighborhood amenities and lifestyle activities in their day-to-day lives can help clinicians to deliver more older adult-centered care. Incorporating the lifestyle activities and neighborhood amenities of older adults into care planning will lead to the design and development of integrated clinical and community screening programs.

Strategic use of crop residue biochars for removal of hazardous compounds in wastewater.

Crop residues are affordable lignocellulosic waste in the world, and a large portion of the waste has been burned, releasing toxic pollutants into the environment. Since the crop residue is a carbon and ingredient rich material, it can be strategically used as a sorptive material for (in)organic pollutants in the wastewater after thermo-chemical valorization (i.e., biochar production). In this review, applications of crop residue biochars to adsorption of non-degradable synthetic dyes, antibiotics, herbicides, and inorganic heavy metals in wastewater were discussed. Properties (porosity, functional groups, heteroatom, and metal(oxide)s, etc.) and adsorption capacity relationships were comprehensively reviewed. The current challenges of crop residue biochars and guidelines for development of efficient adsorbents were also provided. In the last part, the future research directions for practical applications of the crop residue biochars in wastewater treatment plants have been suggested.

Effects of the APOEɛ4 Allele on the Relationship Between Tau and Amyloid-ß in Early- and Late-Onset Alzheimer's Disease.

BACKGROUND: Little is known regarding the differential effects of the apolipoprotein E (APOE) ɛ4 on the regional topography of amyloid and tau in patients with both early-onset (EOAD) and late-onset Alzheimer's disease (LOAD). OBJECTIVE: To compare the distribution and association of tau, amyloid, and cortical thickness among groups classified by the presence of APOEɛ4 allele and onset age. METHODS: A total of 165 participants including 54 EOAD patients (29 ɛ4-; 25 ɛ4+), 45 LOAD patients (21 ɛ4-; 24 ɛ4+), and 66 age-matched controls underwent 3T MRI, 18F-THK5351 (THK) and 18F-flutemetamol (FLUTE) PET scans, APOE genotyping, and neuropsychological tests. Data for voxel-wise and standardized uptake values from PET scans were analyzed in the context of APOE and age at onset. RESULTS: EOAD ɛ4- patients showed greater THK retention in the association cortices, whereas their EOAD ɛ4+ counterparts had more retention in medial temporal areas. THK topography of LOAD ɛ4+ was similar to EOAD ɛ4 + . THK correlated positively with FLUTE and conversely with mean cortical thickness, being lowest in EOAD ɛ4-, highest in LOAD ɛ4-, and modest in ɛ4+ groups. Even in the APOEɛ4+ groups, THK tended to correlate with FLUTE and mean cortical thickness in the inferior parietal region in EOAD and in the medial temporal region in LOAD. LOAD ɛ4- manifested with prevalent small vessel disease markers and the lowest correlation between THK retention and cognition. CONCLUSION: Our observations suggest the differential effects of the APOEɛ4 on the relationship between tau and amyloid in EOAD and LOAD.

Difference in employment status and onset of disability among Japanese community-dwelling older adults: a prospective cohort study.

OBJECTIVE: This prospective cohort study investigates the relationship between the onset of disability and employment status. METHODS: We investigated 3,741 community-dwelling adults aged 70 or older, who participated in a population-based cohort study in Japan. Their onset of disability was monitored monthly using the long-term care insurance certification registration system, for five years from baseline. Based on an employment status questionnaire, we categorized participants into three groups: (1) employee, (2) self-employed, and (3) not working. Covariates included demographic information, medical history, number of medications, educational level, living alone, social group engagement, smoking status, walking speed, instrumental activities of daily living, global cognitive function, and depressive symptoms. Missing values were managed using multiple imputation. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident disability risk by employment status. RESULTS: The disability incidence rates were 15.3/1,000 (95% CIs: 10.7-22.0) person-years among employees, and 33.0/1000 (95% CIs: 24.4-44.6) and 39.6/1000 (95% CIs: 36.5-43.0) person-years among self-employed and non-working participants, respectively. The adjusted HRs for the onset of disability among non-working and self-employed participants were 1.69 (95% CIs: 1.16-2.46, p = 0.007) and 1.63 (95% CIs: 1.01-2.62, p = 0.044) compared with employees, respectively. Similar results were found among men. Among women, disability onset was not associated with employment status. CONCLUSIONS: Older adults' risk of disability onset differed according to their employment status. Older employees had a lower risk of disability onset than those not working or self-employed.

Truncation or proteolysis of α-synuclein in Parkinsonism.

Posttranslational modifications of α-synuclein, such as truncation or abnormal proteolysis, are implicated in Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). A key focus of this article includes the proteases responsible for inducing truncation, the specific sites susceptible to truncation, and the resultant influence of these truncated species on the seeding and aggregation of endogenous α-synuclein. We also shed light on the unique structural attributes of these truncated species, and how these modifications can lead to distinctive forms of synucleinopathies. In addition, we explore the comparative toxic potentials of various α-synuclein species. An extensive analysis of available evidence of truncated α-synuclein species in human-synucleinopathy brains is also provided. Lastly, we delve into the detrimental impact of truncated species on key cellular structures such as the mitochondria and endoplasmic reticulum. Our article discusses enzymes involved in α-synuclein truncation, including 20 S proteasome, cathepsins, asparagine endopeptidase, caspase-1, calpain-1, neurosin/kallikrein-6, matrix metalloproteinase-1/-3, and plasmin. Truncation patterns impact α-synuclein aggregation - C-terminal truncation accelerates aggregation with larger truncations correlated with shortened aggregation lag times. N-terminal truncation affects aggregation differently based on the truncation location. C-terminally truncated α-synuclein forms compact, shorter fibrils compared to the full-length (FL) protein. N-terminally truncated monomers form fibrils similar in length to FL α-synuclein. Truncated forms show distinct fibril morphologies, increased ß-sheet structures, and greater protease resistance. Misfolded α-synuclein can adopt various conformations, leading to unique aggregates and distinct synucleinopathies. Fibrils, with prion-like transmission, are potentially more toxic than oligomers, though this is still debated. Different α-synuclein variants with N- and C-terminal truncations, namely 5-140, 39-140, 65-140, 66-140, 68-140, 71-140, 1-139, 1-135, 1-133, 1-122, 1-119, 1-115, 1-110, and 1-103 have been found in PD, DLB, and MSA patients' brains. In Parkinsonism, excess misfolded α-synuclein overwhelms the proteasome degradation system, resulting in truncated protein production and accumulation in the mitochondria and endoplasmic reticulum.

Association between COVID-19 emergency declarations and physical activity among community-dwelling older adults enrolled in a physical activity measurement program: Evidence from a retrospective observational study using the regression discontinuity design.

BACKGROUND: The current study examines the negative impact of the coronavirus disease 2019 (COVID-19) emergency declarations on physical activity among the community-dwelling older adults, the participants of a physical activity measurement program, in Japan. METHODS: This retrospective observational study included 1,773 community-dwelling older adults (aged 74.6 ± 6.3 years, 53.9% women) who had participated in the physical activity measurement project from February 2020 to July 2021. We measured physical activity using a tri-axial accelerometer during 547 consecutive days. Three emergency declarations, requesting people to avoid going outside, occurred during the observational period. We multiply-imputed missing values for daily physical activity, such as steps, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) for several patterns of datasets according to the maximum missing rates on a person level. We mainly report the results based on less than 50% of the maximum missing rate (n = 1,056). Other results are reported in the supplemental file. Changes in physical activity before and after the start of each emergency declaration were examined by the regression discontinuity design (RDD) within 14-, 28-, and 56-day bandwidths. RESULTS: For all the participants in the multiply-imputed data with the 14-day bandwidth, steps (coefficients [[Formula: see text]][Formula: see text] 964.3 steps), LPA ([Formula: see text] 5.5 min), and MVPA ([Formula: see text] 4.9 min) increased after the first emergency declaration. However, the effects were attenuated as the RDD bandwidths were widened. No consistent negative impact was observed after the second and third declarations. After the second declaration, steps ([Formula: see text]-609.7 steps), LPA ([Formula: see text]-4.6 min), and MVPA ([Formula: see text]-2.8 min) decreased with the 14-day bandwidth. On the other hand, steps ([Formula: see text] 143.8 steps) and MVPA ([Formula: see text] 1.3 min) increased with the 56-day bandwidth. For the third declaration, LPA consistently decreased with all the bandwidths ([Formula: see text]-2.1, -3.0, -0.8 min for the 14, 28, 56-day bandwidth), whereas steps ([Formula: see text]-529 steps) and MVPA ([Formula: see text]-2.6 min) decreased only with the 28-day bandwidth. CONCLUSIONS: For the community-dwelling older adults who regularly self-monitor their physical activity, the current study concludes that there is no evidence of consistently negative impacts of the emergency declarations by the COVID-19 pandemic.