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.

Impact of Type 2 Diabetes and Glycated Hemoglobin Levels Within the Recommended Target Range on Mortality in Older Adults With Cognitive Impairment Receiving Care at a Memory Clinic: NCGG-STORIES.

OBJECTIVE: To determine the impact of type 2 diabetes and glycated hemoglobin (HbA1c) levels within the recommended target range according to the Japan Diabetes Society/Japan Geriatrics Society Joint Committee on mortality in older adults with cognitive impairment. RESEARCH DESIGN AND METHODS: This retrospective cohort study included 1,528 and 468 patients aged ≥65 years without and with type 2 diabetes, respectively, who were visiting a memory clinic. The 468 patients with type 2 diabetes were divided into three groups (within, above, and below the target range) based on their HbA1c levels, cognitive function, ability to perform activities of daily living, and medications associated with a high risk of hypoglycemia. The impact of diabetes and HbA1c levels on mortality was evaluated using Cox proportional hazards models. RESULTS: Over a median follow-up period of 3.8 years, 353 patients (17.7%) died. Compared with individuals without type 2 diabetes, HbA1c levels above (hazard ratio [HR] 1.70, 95% CI 1.08-2.69) and below (HR 2.15, 95% CI 1.33-3.48) the target range were associated with a higher risk of death; however, HbA1c levels within the target range were not (HR 1.02, 95% CI 0.77-1.36). CONCLUSIONS: HbA1c levels above and below the target range were associated with a higher risk of mortality, whereas patients with HbA1c levels within the target range did not exhibit a higher risk of mortality than individuals without type 2 diabetes. These results provide empirical support for the current target ranges among older adults with cognitive impairment.

Postural Control Characteristics in Alzheimer's Disease, Dementia With Lewy Bodies, and Vascular Dementia.

BACKGROUND: Dementia often results in postural control impairment, which could signify central nervous system dysfunction. However, no studies have compared postural control characteristics among various types of dementia. This study aimed to compare static postural control in patients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and vascular dementia (VaD). METHODS: Cross-sectional relationship between the clinical diagnoses (AD, DLB, VaD, or normal cognition [NC]) of outpatients at a memory clinic and their upright postural control characteristics were examined. In the postural control test, participants were instructed to maintain a static upright standing on a stabilometer for 60 seconds under the eyes-open and eyes-closed conditions. Forty postural control parameters, including distance, position, and velocity in the anterior-posterior and medio-lateral directions, derived from the trajectory of the center of mass sway, were calculated. The characteristics of each type of dementia were compared to those of NC, and the differences among the 3 types of dementia were evaluated using linear regression models. RESULTS: The study included 1 789 participants (1 206 with AD, 111 with DLB, 49 with VaD, and 423 with NC). Patients with AD exhibited distinct postural control characteristics, particularly in some distance and velocity parameters, only in the eyes-closed condition. Those with DLB exhibited features in the mean position in the anterior-posterior direction. In patients with VaD, significant differences were observed in most parameters, except the power spectrum. CONCLUSIONS: Patients with AD, DLB, and VaD display disease-specific postural control characteristics when compared to cognitively normal individuals.

Association between abdominal adiposity and cognitive decline in older adults: a 10-year community-based study.

OBJECTIVES: This study aimed to investigate the association between abdominal adiposity and change in cognitive function in community-dwelling older adults. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal study included older adults aged ≥60 years without cognitive impairment who participated in the National Institute for Longevity Sciences - Longitudinal Study of Aging. MEASUREMENTS: Cognitive function was evaluated biennially using the Mini-Mental State Examination (MMSE) over 10 years. Waist circumference (WC) was measured at the naval level, and subcutaneous fat area (SFA) and visceral fat area (VFA) were assessed using baseline computed tomography scans. WC, SFA, and VFA areas were stratified into sex-adjusted tertiles. A linear mixed model was applied separately for men and women. RESULTS: This study included 873 older adults. In men, the groups with the highest levels of WC, SFA, and VFA exhibited a greater decline in MMSE score than the groups with the lowest levels (ß [95% confidence interval]: WC, -0.12 [-0.23 to -0.01]; SFA, -0.13 [-0.24 to -0.02]; VFA, -0.11 [-0.22 to -0.01]). In women, the group with the highest level of WC and SFA showed a greater decline in MMSE score than the group with the lowest level (WC, -0.12 [-0.25 to -0.01]; SFA, -0.18 [-0.30 to -0.06]), but VFA was not associated with cognitive decline. CONCLUSION: Higher WC, SFA, and VFA in men and higher WC and SFA in women were identified as risk factors for cognitive decline in later life, suggesting that abdominal adiposity involved in cognitive decline may differ according to sex.

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.

Participatory approaches for developing a practical handbook integrating health information for supporting individuals with mild cognitive impairment and their families.

AIM: This study aimed to develop a patient-centred handbook that integrates information on lifestyle modifications and psychological support strategies for individuals with mild cognitive impairment (MCI). This article provides a comprehensive record of the development process. METHODS: We adopted a participatory research model for the methodology, which comprised five phases and involved an interdisciplinary team specializing in dementia and health literacy. Data were initially collected via interviews conducted among patients with MCI (n = 5) and their families (n = 5). Given the study's preliminary nature, depth and richness of the qualitative data were the key concerns for determining the sample size, rather than broad generalizability. We ensured the inclusion of diverse experiences and perspectives by facilitating the creation of patient questions (PQs) that merged scientific evidence with patient perspectives. To enhance the handbook's accessibility and utility, we continuously evaluated the same using patient interviews, health literacy tool assessments and team discussions. This comprehensive approach harmonized scientific knowledge and patient experience, leading to the development of a personalized MCI management guide. RESULTS: The handbook comprises nine domains, encompassing 38 selected PQs: MCI, lifestyle, lifestyle-related diseases, exercise, nutrition, social participation, cognitive training, psychological care and family support. The health literacy handbook was evaluated based on Clear Communication Index scores. The results revealed that 73.7% of the PQs were deemed difficult prerevision, whereas only 5.3% remained challenging postrevision. The formative evaluation underscored the need for more detailed explanations prerevision, whereas postrevision comments focused primarily on editorial suggestions. CONCLUSION: The inclusion of patients' perspectives right from the outset ensured that the handbook met their specific needs. The final version, which reflects all stakeholders' inputs, is now slated for imminent publication. PATIENT OR PUBLIC CONTRIBUTION: Patients and the public participated extensively throughout the project, from initial interviews to material evaluation and refinement.

Factors associated with changes in psychological resilience of older adults with mild cognitive impairment during the COVID-19 pandemic.

Introduction: Psychological resilience is an indicator of mental health, but there has been no research to date on changes in psychological resilience among older adults with mild cognitive impairment (MCI) during the stress of the coronavirus disease 2019 (COVID-19) pandemic including factors related to those changes. To fill the gap, this study examined the factors and the changes in psychological resilience of older adults with MCI during the COVID-19 pandemic. Methods: One hundred thirty participants completed the 10-item version of the Connor-Davidson Resilience Scale (CD-RISC-10) between December 2020 and June 2021 as a baseline assessment and between December 2021 and February 2022 as a follow-up. Participants also answered questions on sleep quality, depression symptoms, activities in daily living (ADL), instrumental ADL and social participation to explore factors associated with changes. Results: In this cohort, the mean CD-RISC-10 scores were significantly higher than the baseline at follow-up (p < 0.05), indicating the improvement of psychological resilience. In multiple regression analyses, sleep quality was significantly correlated with change in CD-RISC-10 score (coefficient = 3.94, 95% confidence interval = 1.11 to 6.78). Discussion: Psychological resilience could improve even during the stress of the COVID-19 pandemic in older adults with MCI who were at risk of developing dementia. The factor associated with improved psychological resilience was good sleep quality.

Cross-sectional association of metrics derived from continuous glucose monitoring with cognitive performance in older adults with type 2 diabetes.

AIM: To examine the association between continuous glucose monitoring (CGM)-derived metrics and cognitive performance in older adults with type 2 diabetes (T2D). MATERIALS AND METHODS: A total of 100 outpatients with T2D aged 70 years or older were analysed. Participants underwent CGM for 14 days. As CGM-derived metrics, mean sensor glucose (SG), glucose coefficient of variation (CV), time in range (TIR; 70-180 mg/dl), time above range (TAR; > 180 mg/dl) and time below range (TBR; < 70 mg/dl), were calculated. Participants underwent cognitive tests, including the Japanese version of the Montreal Cognitive Assessment (MoCA-J), a delayed word-recall test from the Alzheimer's Disease Assessment Scale-cognitive subscale, a digit symbol substitution test, a letter word fluency test, a trail-making test (TMT) and digit span test (DSP). RESULTS: In multiple regression analyses adjusted for confounders, a higher mean SG was associated with a lower performance in MoCA-J and TMT part B (TMT-B) (P < .05). A higher TAR was associated with a lower performance in TMT-B and DSP-backward (P < .05). By contrast, a higher TIR was associated with better function in TMT-B and DSP-backward (P < .05). Furthermore, CV and TBR were not associated with any cognitive function. CONCLUSION: Hyperglycaemia metrics and TIR derived from CGM are associated with cognitive functions, especially with executive function and working memory, in older adults with T2D.

Time trends (2012-2020) in glycated hemoglobin and adherence to the glycemic targets recommended for elderly patients by the Japan Diabetes Society/Japan Geriatrics Society Joint Committee among memory clinic patients with diabetes mellitus.

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

Longitudinal association between nutritional status and behavioral and psychological symptoms of dementia in older women with mild cognitive impairment and early-stage Alzheimer's disease.

BACKGROUND & AIMS: While cross-sectional studies report associations between behavioral and psychological symptoms of dementia (BPSD) and nutritional status as a modifiable factor, their causal relationship remains unclear. Therefore, this study investigated the impact of nutritional status on BPSD. METHODS: This study included women with mild cognitive impairment (MCI) and early-stage Alzheimer's disease (AD) from Memory Clinic, National Center for Geriatrics and Gerontology. The participants were assessed for nutritional status and BPSD using the Mini Nutritional Assessment Short-Form (MNA-SF) and the Dementia Behavior Disturbance Scale (DBD), respectively. Based on their MNA-SF scores, the subjects were classified as well-nourished, at risk of malnutrition, or malnourished. Nutritional status and change in BPSD was examined for association by univariate and multivariate linear regression analyses. RESULTS: This study analyzed 181 women (79 with MCI and 102 with early-stage AD). The multivariate analysis showed that the malnourished subjects or those at risk of malnutrition (54.1%) were significantly associated with increased DBD scores (ß = 0.255, P = 0.003) during follow-up. In addition, multivariate regression analysis incorporating change in DBD sub-score as a dependent variable showed that the malnourished subjects or those at risk of malnutrition were associated with increased DBD sub-scores for "verbal aggressiveness/emotional disinhibition" (ß = 0.247, P = 0.005). CONCLUSIONS: Poor nutritional status increased BPSD, especially verbal aggressiveness/emotional disinhibition, in those with MCI and early-stage AD during 2.5-year follow-up. Patients with MCI and early-stage AD may need to be assessed for nutritional status from early on, at the onset of mild cognitive decline, and require intervention to prevent worsening of BPSD. Further intervention studies in large prospective cohorts are needed to establish nutritional measures to prevent progression of BPSD in older adults with cognitive impairment.

Factors Associated with Behavioral and Psychological Symptoms of Dementia during COVID-19.

(1) Background: Preventive measures to control the spread of COVID-19 are essential, but they often cause social isolation and diminish the physical and mental health of older adults. In cognitively impaired individuals, the pandemic has worsened behavioral and psychological symptoms of dementia (BPSD). Here, we explored the factors contributing to the worsening of BPSD during the COVID-19 pandemic. (2) Methods: Potential patients were identified at a memory clinic in Japan between June 2017 and June 2021. Eligible patients had a diagnosis of mild cognitive impairment (MCI) or dementia during the study period. The outcome was BPSD, as assessed by using the Dementia Behavioral Disorders Scale. Information on patients' lifestyle habits and use of care services was obtained for use as primary explanatory variables; multiple regression analysis was performed to examine the relationship between BPSD and care services use or lifestyle habits. The model was adjusted for sociodemographic factors, and the interaction terms of the pandemic period with lifestyle and service use were included to evaluate the effects of COVID-19. (3) Results: We identified 977 participants with MCI and 1380 with dementia (MCI group: 69.8% age 75 years or older, 54.2% female; dementia group: 79.8% age 75 years or older, 64.8% female). After adjustment for possible confounders, significantly worse BPSD was demonstrated in those who used daycare services during COVID-19 (both MCI and dementia patients; p = 0.007 and p = 0.025 respectively) and in those with poor nutritional function (dementia patients; p = 0.040). (4) Conclusions and Implications: During COVID-19, poor nutritional status and use of daycare services were associated with BPSD in those with cognitive decline. These findings indicate the need to fully examine the quantity and quality of care services for people with cognitive decline during emergencies and to continue to provide effective services.

Psychological Resilience Among Older Japanese Adults With Mild Cognitive Impairment During the COVID-19 Pandemic.

Psychological resilience refers to the ability to cope with adversities, and deficits in resilience might lead to mental illness. The COVID-19 pandemic has had impact on psychological resilience for older adults, but there are as yet no data on its impacts on the mental health of older adults who were living with mild cognitive impairment (MCI). Therefore, the aim of this study was to investigate the impact of the COVID-19 pandemic on psychological resilience in older adults with MCI and to explore associated physical and psychosocial factors. In this cross-sectional study of 268 older adults aged 65-85, we defined MCI as age- and education-adjusted cognitive decline with a standard deviation of 1.0 or more from the reference threshold. During December 2020 to April 2021, we carried out to all participants the 10-item version of the Connor-Davidson Resilience Scale (CD-RISC-10) to measure psychological resilience. We also conducted a comprehensive geriatric assessment including sleep quality and depressive symptoms (Pittsburgh Sleep Quality Index and 15-item Geriatric Depression Scale, respectively). To identify factors associated with CD-RISC-10 scores (mean: 23.3 ± 0.4), multiple regression analysis revealed that older age [coefficient = 0.23, 95% confidence interval (CI) = 0.06-0.39] was significantly correlated with higher scores, whereas poor sleep quality (coefficient = -2.06, 95% CI = -3.93 to -0.19) and depressive symptoms (coefficient = -2.95, 95% CI = -5.70 to -0.21) were significantly correlated with lower scores. In this study, older adults with MCI showed low psychological resilience during the COVID-19 pandemic, and people with low psychological resilience indicated poor sleep quality and depressive symptoms. Our findings suggest directions for devising interventions to maintain mental health and psychological resilience among the vulnerable population of older adults with MCI living under the socially isolated conditions of COVID-19 pandemic restrictions. Our recommendation includes continuous assessment of this population and appropriate care for poor sleep quality and depressive symptoms.

Prevalence of Behavioral and Psychological Symptoms in Patients With Cognitive Decline Before and During the COVID-19 Pandemic.

Objective: Preventive measures to limit the spread of COVID-19 are essential, but often cause social isolation, affecting the physical and mental health of older adults. Patients with dementia are likely to have worsening behavioral and psychological symptoms of dementia (BPSD) owing to pandemic restrictions. To examine this, we described BPSD before and during the COVID-19 pandemic. Methods: We identified patients at a memory clinic in Japan between October 2018 and December 2019 (15 months before the pandemic began, n = 1,384) and between April 2020 and June 2021 (15 months after the State of Emergency was declared; n = 675 patients). A propensity score was used to match 576 patients from each group. The Mini-Mental State Exam was used to classify cognitive function into mild and moderate/severe. Dementia Behavioral Disturbance Scale was used to evaluate BPSD. The association between BPSD before and during the pandemic was evaluated using binomial logistic regression models. Results: The levels of frequent night waking were higher in individuals before the pandemic than in those evaluated during the pandemic in both the mild group [adjusted odds ratio (AOR) = 1.82, 95% CI 1.02-3.23] and the moderate/severe group (AOR = 1.96, 95% CI 1.19-3.23). During the pandemic, physical attacks were higher in the mild group (AOR = 4.25, 95% CI 1.12-16.07), while night wandering was higher in the moderate/severe group (AOR = 2.22, 95% CI 1.03-4.81). Conclusion: In patients with cognitive impairment, some BPSD were more prevalent during the pandemic, depending on dementia severity. The findings pertaining to the higher frequency of sleep disturbance and aggressiveness during COVID-19 should be used to guide BPSD screening in patients with dementia and to provide evidence-based interventions.

Impact of the COVID-19 pandemic on statistical design and analysis plans for multidomain intervention clinical trials: Experience from World-Wide FINGERS.

INTRODUCTION: The coronavirus disease-19 (COVID-19) pandemic presents challenges to the conduct of randomized clinical trials of lifestyle interventions. METHODS: World-Wide FINGERS is an international network of clinical trials to assess the impact of multidomain lifestyle intervention on cognitive decline in at-risk adults. Individual trials are tailoring successful approaches from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) to local cultures and environments. The network convened a forum for researchers to discuss statistical design and analysis issues they faced during the pandemic. We report on experiences of three trials that, at various stages of conduct, altered designs and analysis plans to navigate these issues. We provide recommendations for future trials to consider as they develop and launch behavioral intervention trials. RESULTS: The pandemic led researchers to change recruitment plans, interrupt timelines for assessments and intervention delivery, and move to remote intervention and assessment protocols. The necessity of these changes add emphasis to the importance, in study design and analysis, of intention to treat approaches, flexibility, within-site stratification, interim power projections, and sensitivity analyses. DISCUSSION: Robust approaches to study design and analysis are critical to negotiate issues related to the intervention. The world-wide network of similarly oriented clinical trials will allow us to evaluate the effectiveness of responses to the pandemic across cultures, local environments, and phases of the pandemic.

Methionine utilization by bifidobacteria: possible existence of a reverse transsulfuration pathway.

Although bifidobacteria are already widely used as beneficial microbes with health-promoting effects, their amino acid utilization and metabolism are not yet fully understood. Knowledge about the metabolism of sulfur-containing amino acids in bifidobacteria is especially limited. In this study, we tested the methionine utilization ability of several bifidobacterial strains when it was the sole available sulfur source. Although bifidobacteria have long been predominantly considered to be cysteine auxotrophs, we showed that this is not necessarily the case.

Brain activity associated with the rubber foot illusion.

The internal representation of the body is constantly updated by sensory information based on interactions with the environment. The internal representation of the hand can be experimentally manipulated with the rubber hand illusion (RHI) paradigm. Brain activity during the RHI provides insight into the neural mechanisms underpinning the reconstruction of the internal representation of the hand. Recently, the RHI paradigm has been employed for the lower limb, revealing that the illusion is also induced in the lower limb (rubber foot illusion; RFI). However, the neural correlates of the RFI remain unknown. We used functional magnetic resonance imaging (fMRI) to examine brain activity during the RFI. Forty-four healthy volunteers participated in the fMRI experiment. Significant increases in activation were observed in the bilateral medial and middle frontal gyri, left supplemental motor area, bilateral inferior parietal lobuli, precunei, calcarine cortices, and cerebellar hemispheres; and in the vermis and bilateral thalami during the right RFI. During the left RFI, significant increases in activation were observed in the bilateral medial, middle, and superior frontal gyri; left inferior frontal gyrus and supplemental motor area, bilateral inferior parietal lobuli and middle temporal gyri, and in the left cerebellar hemisphere, vermis, and bilateral thalami. Conjunction analysis revealed that the prefrontal cortex including the bilateral medial and middle frontal gyri, parietal cortex including the bilateral inferior parietal lobuli, and cerebellum including the bilateral cerebellar hemispheres and vermis were conjointly activated during the right and left RFIs. The distribution of co-activated brain areas during the RFI was similar to the previously reported distribution of brain areas activated during the RHI. Co-activation of these brain areas may be associated with the reconstruction of the internal representation of the body. The fact that these areas are activated both in the RFI and RHI will have implications for the treatment of patients with disturbed internal bodily representation.