Effectiveness of a Virtual Reality Open-Air Bath Program in Reducing Loneliness and Improving Brain Function for Dementia Prevention in Older Adults: Protocol for a Prospective Randomized Crossover Study.

BACKGROUND: Older adults often face loneliness due to chronic illness or loss of close ones, a situation worsened by the COVID-19 pandemic. Increased loneliness heightens the risk of diseases, especially dementia, necessitating urgent action. OBJECTIVE: This study aims to assess the impact of a virtual reality (VR)-based open-air bath program on depression and loneliness in older individuals with subjective cognitive decline/mild cognitive impairment attending the Dementia Medical Center in Kyoto, Japan. We further aim to evaluate the feasibility of the program (participant recruitment and adherence) and to measure program enjoyment and satisfaction. METHODS: The study design is a crossover trial with a 1:1 ratio, wherein 12 participants will be randomly assigned to groups 1 and 2, with group 2 serving as a waitlist control and group 1 receiving the VR program from the onset for 6 months; the VR program will be conducted 6 times (monthly). Program completion for group 1 will be followed by an observation period from months 7 to 12. Group 2 will participate in the VR program from months 7 to 12, with an observation period from months 1 to 6. Cognitive tests, psychiatric assessments, and the University of California, Los Angeles Loneliness Scale will be conducted before the study, at 6 months, and at 12 months. Results will be analyzed using repeated-measures ANOVA. Head magnetic resonance imaging and single-photon emission computed tomography scans will be performed before and after the VR program to evaluate changes and effects on brain regions. RESULTS: Recruitment began in September 2023 and data collection is expected to be completed by March 2025. Complete study results will be published by September 2025. CONCLUSIONS: This study examines the preliminary effects of VR on loneliness in older adults with predementia through open-air bath simulations. VR experiences could benefit this population, particularly those with limited outdoor activities. Quantifying VR's impact will aid in determining the size for a larger clinical trial. Qualitative results will inform participation mechanisms and guide the implementation and design of future trials. TRIAL REGISTRATION: University hospital Medical Information Network UMIN000052667; https://tinyurl.com/3yaccay5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57101.

Loneliness and Resting-State Functional Brain Connectivity Among Older Adults: A Proportional Correlation.

OBJECTIVE: Loneliness reportedly increases the risk of dementia, especially Alzheimer's disease (AD). The authors' previous study demonstrated associations between loneliness and structural abnormalities observed in early-stage AD. The present study examined associations between the brain's functional characteristics and loneliness among older adults with concerns about cognitive decline. METHODS: This single-center study included 43 participants (13 with amnestic mild cognitive impairment and 30 with normal cognition). Participants were assessed with the revised University of California Los Angeles (UCLA) Loneliness Scale and underwent resting-state functional MRI. Functional images were preprocessed with the CONN toolbox. The selected seeds were within brain regions reportedly associated with loneliness. One-sample general linear model analysis was performed to examine regressions of UCLA Loneliness Scale scores and functional connectivity between the seeds and regions of interest. RESULTS: The revised UCLA Loneliness Scale scores were positively correlated with functional connectivity between the right hippocampus and left lateral parietal lobe and were negatively correlated with functional connectivity between the left amygdala and left frontal operculum and between the left amygdala and right supramarginal gyrus. Analyses were adjusted for age, sex, and education and scores on the Mini-Mental State Examination and Clinical Dementia Rating scale. CONCLUSIONS: Loneliness was associated with abnormal function of the hippocampus, parts of the parietal lobe and frontal cortex, and the amygdala. These findings may suggest a possible correlation between loneliness and neurological changes associated with dementia.

Intracranial calcifications associated with factors related and unrelated to atherosclerosis in older people: A community dwelling cohort study.

The cause of intracranial calcification is not fully understood. The aim of the current study was to identify factors associated with intracranial calcification and to determine whether these factors differ in calcification of different sites. A total of 404 community-dwelling people aged 65 or older were included in the study. All subjects underwent brain computed tomography (CT), blood tests, and a Mini-Mental State Examination (MMSE). Intracranial calcifications were scored using CT. Stepwise regression analysis was performed to examine factors associated with intracranial calcification, with each calcification score used as a dependent variable. Independent variables included age, gender, hemoglobin A1c (HbA1c), dyslipidemia, estimated glomerular filtration rate (eGFR), blood pressure, body mass index (BMI), smoking, serum iron, ferritin, and intact parathyroid hormone (PTH). Stepwise regression analysis detected male gender as a predictor of pineal gland calcification and intact PTH as a predictor of basal ganglia calcification. Age and lifestyle diseases were identified as predictors of calcification of the falx cerebri, internal carotid arteries, and vertebral arteries. These results indicate that the mechanisms of calcifications of the pineal gland and basal ganglia might differ from that of artery calcification, and that causes of intracranial calcification might be classified using factors that are and are not related to atherosclerosis.

Validation of Wistar-Kyoto rats kept in solitary housing as an animal model for depression using voxel-based morphometry.

Major depressive disorder is a common psychiatric condition often resistant to medication. The Wistar-Kyoto (WKY) rat has been suggested as an animal model of depression; however, it is still challenging to translate results from animal models into humans. Solitary housing is a mild stress paradigm that can simulate the environment of depressive patients with limited social activity due to symptoms. We used voxel-based morphometry to associate the solitary-housed WKY (sWKY) rat model with data from previous human studies and validated our results with behavioural studies. As a result, atrophy in sWKY rats was detected in the ventral hippocampus, caudate putamen, lateral septum, cerebellar vermis, and cerebellar nuclei (p < 0.05, corrected for family-wise error rate). Locomotor behaviour was negatively correlated with habenula volume and positively correlated with atrophy of the cerebellar vermis. In addition, sWKY rats showed depletion of sucrose consumption not after reward habituation but without reward habituation. Although the application of sWKY rats in a study of anhedonia might be limited, we observed some similarities between the regions of brain atrophy in sWKY rats and humans with depression, supporting the translation of sWKY rat studies to humans.

Relationship between Loneliness and Mild Behavioral Impairment: Validation of the Japanese Version of the MBI Checklist and a Cross-Sectional Study.

Background: Mild behavioral impairment (MBI) and loneliness are associated with cognitive decline and an increased risk of dementia. Objective: Our aim was to examine the validity of the Japanese version of the MBI checklist (MBI-C) and investigate the relationship between loneliness and MBI. Methods: The participants in this cross-sectional study included 5 cognitively normal persons and 75 persons with mild cognitive impairment. MBI-C and the revised University of California at Los Angeles loneliness scale (LS) were used to assess MBI and loneliness, respectively. Diagnostic performance of MBI-C was examined using receiver operating characteristic analysis. The relationship between MBI-C and LS was examined using multiple linear regression in 67 subjects who were assessed with both scales, with MBI-C total or domain score as the dependent variable and LS as the independent variable, adjusted for age, gender, living situation, presence of visual and hearing impairment, and Mini-Mental State Examination score. Results: Per the Youden index, in this mostly MCI sample, the optimal MBI-C cut-off score was 5.5 with sensitivity 0.917 and specificity 0.949. In multiple linear regression analysis, LS score was detected as a significant predictor of MBI-C total scores, and MBI-C decreased motivation, affective dysregulation, and abnormal thought and perception scores. Conclusions: The caregiver-rated Japanese MBI-C has excellent diagnostic performance. Loneliness is associated with a greater MBI burden, especially in the decreased motivation, affective dysregulation, and abnormal thought and perception domains. Interventions for loneliness in older people may have the potential to improve MBI.

Relationship between eating problems and the risk of dementia: A retrospective study.

BACKGROUND: Older adults and individuals with decreased cognition often experience appetite changes and weight loss. As weight loss can result in cognitive decline, change in appetite may be an important contributor to the onset of dementia. However, there is a lack of relevant studies on this topic. This study aimed to determine the relationship between appetite changes, weight loss, and dementia onset. METHODS: A total of 135 patients with normal cognitive function, subjective cognitive impairment, and mild cognitive impairment who were assessed using the Neuropsychiatric Inventory 12 item version (NPI-12) and followed up for at least 1 month were enrolled in the study. All patients underwent a Mini-Mental State Examination (MMSE). Eating problems were assessed using the NPI Eating Problems Score. Appetite and weight loss were assessed at the first visit by caregivers. Kaplan-Meier survival analyses with a log-rank test were used to compare the time to the onset of dementia between the presence or absence of the NPI eating problems, appetite loss, weight loss, or NPI depression scores. Cox proportional hazards regression models using the forced entry method were employed to estimate the hazard ratio (HR) for dementia. RESULTS: Weight loss was significantly related to dementia onset (P = 0.027) in the Kaplan-Meier survival analyses, while eating problems, appetite loss, and depression showed no significant association (P = 0.519, P = 0.326, and P = 0.317, respectively). In the Cox proportional hazards regression models, the MMSE score was found to be a significant factor (P = 0.021, HR = 0.871); moreover, weight loss tended to increase the risk of dementia onset (P = 0.057, HR = 1.694). CONCLUSIONS: Weight loss experienced by older adults could contribute to an increased risk of developing dementia.

Contribution of amyloid and putative Lewy body pathologies in neuropsychiatric symptoms.

OBJECTIVES: Neuropsychiatric symptom could be useful for detecting patients with prodromal dementia. Similarities and differences in the NPSs between preclinical/prodromal Alzheimer's disease (AD) and prodromal Parkinson's disease dementia (PDD)/Dementia with Lewy bodies (DLB) may exist. This study aimed to compare the NPSs between preclinical/prodromal AD and prodromal PDD/DLB. METHODS: One hundred and three participants without dementia aged ≥50 years were included in this study. The mild behavioral impairment (MBI) total score and the MBI scores for each domain were calculated using the neuropsychiatric inventory questionnaire score. Participants were divided into five groups based on the clinical diagnosis by neurologists or psychiatrists in each institution based on the results of the amyloid positron emission tomography and dopamine transporter single photon emission computed tomography (DAT-SPECT): Group 1: amyloid-positive and abnormal DAT-SPECT, Group 2: amyloid-negative and abnormal DAT-SPECT, Group 3: amyloid-positive and normal DAT-SPECT, Group 4: mild cognitive impairment unlikely due to AD with normal DAT-SPECT, and Group 5: cognitively normal with amyloid-negative and normal DAT-SPECT. RESULTS: The MBI abnormal perception or thought content scores were significantly higher in Group 1 than Group 5 (Bonferroni-corrected p = 0.012). The MBI total score (Bonferroni-corrected p = 0.011) and MBI impulse dyscontrol score (Bonferroni-corrected p = 0.033) in Group 4 were significantly higher than those in Group 5. CONCLUSION: The presence of both amyloid and putative Lewy body pathologies may be associated with psychotic symptoms.

Survey of physicians' and patients' understanding, perceptions, and attitudes toward depressive state in atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia among older people and has a significant impact on quality of life. However, it is not always perceived as a serious mental health risk. This study investigated the understanding, perceptions, and attitudes toward the risk of depressive state associated with older patients with AF. METHODS: We conducted a quantitative survey in April-June 2021 among patients with AF aged ≥65 years (n = 156), and physicians or cardiologists attending at least 10 older patients with AF annually (n = 158). RESULTS: In total, 45% of patients considered AF a cause of a depressive state. In contrast, 16% of physicians reported that they considered AF a cause of a depressive state. Fifty-two percent of the patients had experienced a depressive state. Of these, 98% expressed that a depressive state lowered their quality of life. Two of the three patients reported that they would consult their physicians if they felt depressed. By contrast, 30% of physicians responded that even if they perceived their patients as depressed, they prescribe anti-anxiety medication but do not refer the patient to psychiatrists. Of the physicians, 50% stated that they did not regard the association of AF and depressive state as serious, although both physicians and patients understood that negative anxiety, such as fear of AF attacks, strokes, or heart failure, was the most important contributor to a depressive state. CONCLUSION: Establishing mental healthcare involving physicians together with psychiatrists is necessary to improve the mental and physical health outcomes for older patients with AF. Geriatr Gerontol Int 2023; 23: 543-548.

Inter-rater reliability of the Conversational Assessment of Neurocognitive Dysfunction.

BACKGROUND: Cognitive assessment through communication has been the focus of recent studies because the conventional cognitive tests are often considered invasive for older people. Although the Conversational Assessment of Neurocognitive Dysfunction is designed to assess cognitive function non-invasively, inter-rater reliability remains unclear. The current study investigated the Conversational Assessment of Neurocognitive Dysfunction's reliability. METHODS: The Conversational Assessment of Neurocognitive Dysfunction was used by four clinical psychologists, who evaluated 38 older people with and without cognitive dysfunction. One clinical psychologist evaluated the assessment based on face-to-face communication with participants, while the other clinical psychologists evaluated it according to the audio data in the digital voice recorder. All clinical psychologists were blind to the results of other conventional cognitive tests and details surrounding participants' daily living activities. RESULTS: The univariate correlation scores of the Conversational Assessment of Neurocognitive Dysfunction among evaluators ranged from 0.61 to 0.79, all of which were significant (P < 0.001). The intraclass correlation coefficient was 0.64 (P < 0.001, 95% CI: 0.53-0.79 for agreement) and 0.67 (P < 0.001, 95% CI: 0.45-0.77 for consistency). The Conversational Assessment of Neurocognitive Dysfunction score of all evaluators was significantly associated with conventional cognitive tests like the Mini-Mental State Examination (P < 0.001). CONCLUSIONS: The findings suggested that the Conversational Assessment of Neurocognitive Dysfunction has moderate to good inter-rater reliability and high concurrent validity as a cognitive assessment tool, and it would be useful in clinical practice.

Emotional Dysregulation in Mild Behavioral Impairment Is Associated with Reduced Cortical Thickness in the Right Supramarginal Gyrus.

BACKGROUND: Mild behavioral impairment (MBI) has attracted attention as a possible precursor symptom of dementia, but its neural basis has not been fully investigated. OBJECTIVE: We aimed to investigate the relationship between MBI and surface area, cortical thickness, and volume in the temporal and parietal lobes, which are strongly associated with dementia and emotional disorders. METHODS: This retrospective study evaluated 123 participants: 90 with mild cognitive impairment (MCI), 13 with subjective cognitive decline (SCD), and 20 cognitively healthy (CH). Using analysis of covariance (ANCOVA) with sex, age, and MMSE score as covariates, cortical thickness, surface area, and volume in 10 regions were compared between groups with and without MBI. Groups with MBI emotional dysregulation were also compared with groups without MBI. RESULTS: ANCOVA revealed significantly smaller cortical thickness in the MBI group's right parahippocampal (p = 0.01) and supramarginal gyri (p = 0.002). After multiple comparison correction, only the right supramarginal gyrus was significantly smaller (p = 0.02). When considering only MBI emotional dysregulation, the right parahippocampal and supramarginal gyrus' cortical thicknesses were significantly smaller in this MBI group (p = 0.03, 0.01). However, multiple comparison correction identified no significant differences (p = 0.14, 0.11). CONCLUSION: Overall MBI and the emotional dysregulation domains were associated with reduced cortical thickness in the right parahippocampal and supramarginal gyri. Since neurodegeneration in the medial temporal and parietal lobe precedes early Alzheimer's disease (AD), MBI, particularly emotion dysregulation, may predict early AD below the diagnostic threshold.

Neuroimaging of mild behavioral impairment: A systematic review.

There are many neuroimaging studies of mild behavioral impairment (MBI), but the results have been somewhat inconsistent. Moreover, it remains unclear whether MBI is a risk factor or prodromal symptom of dementia. Therefore, a systematic review was conducted to summarize the results of neuroimaging studies of MBI and consider whether MBI is a prodromal symptom of dementia in terms of its neural correlates. A systematic review supported by a JSPS Grant-in-Aid for Scientific Research (C) was conducted using MBI neuroimaging studies identified using PubMed, PsycINFO, CINAHL, and Google Scholar on November 1, 2022. The inclusion criteria were (i) neuroimaging study; (ii) research on human subjects; (iii) papers written in English; and (iv) not a case study, review, book, comments, or abstract only. Joanna Briggs Institute critical appraisal checklists were used to assess the quality of selected studies, and 23 structural and functional imaging studies were ultimately included in the systematic review. The structural studies suggested an association of MBI with atrophy in the hippocampus, parahippocampal gyrus, entorhinal cortex, and temporal lobe, whereas the functional studies indicated involvement of an altered default mode network, frontoparietal control network, and salience network in MBI. A limitation in many studies was the use of region-of-interest analysis. The brain areas detected as neural correlates of MBI are considered to be alterations in the early stage of each dementia. Therefore, MBI may emerge against a background of pathological changes in dementia.

The subjective assessment of work and social adjustment impairments and associated psychopathologies in Japanese adult female patients with anorexia nervosa.

Aim: Patients with anorexia nervosa (AN) sometimes undergo a chronic course, and they hardly maintain social participation. Work and social adjustment impairments are generally significantly associated with the clinical symptoms of eating disorders. Psychopathologies associated with the subjective social difficulties of patients with AN have been unclear. This study examined the association between AN psychopathologies and work and social adjustment impairments in adult female patients with AN. Methods: This study included 36 Japanese adult female patients with AN who completed the Work and Social Adjustment Scale (WSAS) and the Eating Disorder Inventory-2 (EDI-2). Spearman's rank correlation coefficient was used to assess correlations between WSAS and EDI-2 or demographic variables. Results: The mean age was 31.8 years, the mean current body mass index was 13.4 kg/m2, and the median illness duration was 5 years. Patients demonstrated social difficulties, especially in social leisure activities. The total WSAS scores were significantly correlated with EDI-2 "impulse regulation" and "asceticism." WSAS "social leisure" was significantly correlated with EDI-2 "bulimia," "interoceptive awareness," "impulse regulation," and "asceticism." Conclusion: Psychopathologies, such as impulse regulation, asceticism, and interoceptive awareness, may be related factors to social difficulties. Emotion regulation, such as impulse regulation and emotional awareness, could be an important realm of treatment not only for psychopathology but also for social functioning in patients with AN.

Older people with severe loneliness have an atrophied thalamus, hippocampus, and entorhinal cortex.

OBJECTIVES: Loneliness has been shown to increase the risk of dementia. However, it is unclear why greater loneliness is associated with greater susceptibility to dementia. Herein, we aimed to examine the morphological characteristics of the brain associated with loneliness in older people concerned about cognitive dysfunction. METHODS: In this retrospective study, 110 participants (80 with amnestic mild cognitive impairment, and 30 cognitively healthy individuals) were included. Participants were assessed using the revised University of California at Los Angeles (UCLA) loneliness scale and had undergone magnetic resonance imaging. Spearman correlation analysis and Mann-Whitney U tests were used to examine the clinical factors associated with loneliness. Multiple regression was performed to examine the relationship between the revised UCLA loneliness scale score and regional gray matter (GM) volume on voxel-based morphometry. RESULTS: The revised UCLA loneliness scale scores were not significantly correlated with age, sex, or mini-mental state examination (MMSE) scores. Multiple regression using age, sex, MMSE score, and total brain volume as covariates showed negative correlations of the revised UCLA loneliness scale scores with the grey matter volume in regions centered on the bilateral thalamus, left hippocampus and left parahippocampal gyrus, and left entorhinal area. CONCLUSIONS: Subjective loneliness was associated with decreased GM volume in the bilateral thalamus, left hippocampus, and left entorhinal cortex of the brain in the older people, thereby providing a morphological basis for the increased risk of dementia associated with greater loneliness.

Pineal volume reduction as the neural correlate of very late-onset schizophrenia-like psychosis.

This study aimed to examine the relationship between pineal parenchymal volume (PPV) and schizophrenia-like psychosis (SLP) at the onset of ≥ 60 years. Exactly 21 patients with SLP, 50 with Alzheimer's disease (AD) with delusions of theft, and 35 with normal cognition were selected. The PPVs in patients with SLP and patients with AD with delusional theft were significantly lower than those in patients with normal cognition. Moreover, PPVs in nine patients with Very late-onset schizophrenia-like psychosis (VLOSLP) tended to be lower than that in patients with normal cognition. Thus, pineal volume reduction could be a neural correlate of VLOSLP.

Psychosocial characteristics of victims of special fraud among Japanese older adults: A cross-sectional study using scam vulnerability scale.

Despite the police preventing special fraud victimisation of older adults, both the number of cases and the amount of damage have remained high in Japan. 'Special fraud', in Japan, is a crime in which victims are tricked by fraudsters who through phone or postcards impersonate the victims' relatives, employees and other associates, to dupe the victims of their cash or other valuables. The number of recognised cases of special fraud has been turned to increase in 2021. Although police or consumer affairs administrations have been conducting all-encompassing enlightenment or public education for prevention, it is also necessary to reach out to those who are vulnerable to fraud. In this study, we determine the psychosocial characteristics of victims of special fraud in Japanese older adults. We analysed the age, gender, education, residential status, household satisfaction, risk perception and scam vulnerability scale of 56 older adults aged 60 years or older (mean age: 79.34 ± 7.51 years, 49 women) who had been victims of special fraud and 99 older adults aged 60 years or older (mean age: 77.73 ± 5.69 years, 61 women) who had never been victims of special fraud. The study found that the victimised older adults were more likely to be females who live alone and go out less frequently than the non-victimised older adults. The total scores of the scam vulnerability scale were higher among the elderly victims of special fraud compared to those who had never been scammed, suggesting that the psychosocial characteristics of victims of special fraud among older adults are being female, living alone, going out infrequently, having high confidence against fraud victimisation and responding quickly to phone calls and unknown visitors. Therefore, government agencies or family members should take care of older women who meet these characteristics to reduce their contact with fraudsters.

Memory trace imbalance in reinforcement and punishment systems can reinforce implicit choices leading to obsessive-compulsive behavior.

We may view most of our daily activities as rational action selections; however, we sometimes reinforce maladaptive behaviors despite having explicit environmental knowledge. In this study, we model obsessive-compulsive disorder (OCD) symptoms as implicitly learned maladaptive behaviors. Simulations in the reinforcement learning framework show that agents implicitly learn to respond to intrusive thoughts when the memory trace signal for past actions decays differently for positive and negative prediction errors. Moreover, this model extends our understanding of therapeutic effects of behavioral therapy in OCD. Using empirical data, we confirm that patients with OCD show extremely imbalanced traces, which are normalized by serotonin enhancers. We find that healthy participants also vary in their obsessive-compulsive tendencies, consistent with the degree of imbalanced traces. These behavioral characteristics can be generalized to variations in the healthy population beyond the spectrum of clinical phenotypes.

Brain Neural Underpinnings of Interoception and Decision-Making in Alzheimer's Disease: A Narrative Review.

This study reviews recent literature on interoception directing decision-making in Alzheimer's disease (AD). According to the somatic marker hypothesis, signals from the internal body direct decision-making and involve the ventromedial prefrontal cortex (vmPFC). After reviewing relevant studies, we summarize the brain areas related to interoception and decision-making (e.g., vmPFC, hippocampus, amygdala, hypothalamus, anterior cingulate cortex, and insular cortex) and their roles in and relationships with AD pathology. Moreover, we outline the relationship among interoception, the autonomic nervous system, endocrine system, and AD pathology. We discuss that impaired interoception leads to decreased decision-making ability in people with AD from the perspective of brain neural underpinning. Additionally, we emphasize that anosognosia or reduced self-awareness and metacognition in AD are remarkably congruent with the malfunction of the autonomic nervous system regulating the interoceptive network. Furthermore, we propose that impaired interoception may contribute to a loss in the decision-making ability of patients with AD. However, there still exist empirical challenges in confirming this proposal. First, there has been no standardization for measuring or improving interoception to enhance decision-making ability in patients with AD. Future studies are required to better understand how AD pathology induces impairments in interoception and decision-making.