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.

Harmonizing multisite data with the ComBat method for enhanced Parkinson's disease diagnosis via DAT-SPECT.

Background: Dopamine transporter single-photon emission computed tomography (DAT-SPECT) is a crucial tool for evaluating patients with Parkinson's disease (PD). However, its implication is limited by inter-site variability in large multisite clinical trials. To overcome the limitation, a conventional prospective correction method employs linear regression with phantom scanning, which is effective yet available only in a prospective manner. An alternative, although relatively underexplored, involves retrospective modeling using a statistical method known as "combatting batch effects when combining batches of gene expression microarray data" (ComBat). Methods: We analyzed DAT-SPECT-specific binding ratios (SBRs) derived from 72 healthy older adults and 81 patients with PD registered in four clinical sites. We applied both the prospective correction and the retrospective ComBat correction to the original SBRs. Next, we compared the performance of the original and two corrected SBRs to differentiate the PD patients from the healthy controls. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). Results: The original SBRs were 6.13 ± 1.54 (mean ± standard deviation) and 2.03 ± 1.41 in the control and PD groups, respectively. After the prospective correction, the mean SBRs were 6.52 ± 1.06 and 2.40 ± 0.99 in the control and PD groups, respectively. After the retrospective ComBat correction, the SBRs were 5.25 ± 0.89 and 2.01 ± 0.73 in the control and PD groups, respectively, resulting in substantial changes in mean values with fewer variances. The original SBRs demonstrated fair performance in differentiating PD from controls (Hedges's g = 2.76; AUC-ROC = 0.936). Both correction methods improved discrimination performance. The ComBat-corrected SBR demonstrated comparable performance (g = 3.99 and AUC-ROC = 0.987) to the prospectively corrected SBR (g = 4.32 and AUC-ROC = 0.992) for discrimination. Conclusion: Although we confirmed that SBRs fairly discriminated PD from healthy older adults without any correction, the correction methods improved their discrimination performance in a multisite setting. Our results support the utility of harmonization methods with ComBat for consolidating SBR-based diagnosis or stratification of PD in multisite studies. Nonetheless, given the substantial changes in the mean values of ComBat-corrected SBRs, caution is advised when interpreting them.

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.

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.