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.

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.

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.

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.

Diagnostic performance and neural basis of the combination of free- and pre-drawn Clock Drawing Test.

OBJECTIVES: This study aimed to clarify the diagnostic performance and neural basis of the Clock Drawing Test (CDT) combining free- and pre-drawn methods. METHODS: This retrospective study included 165 participants (91 with Alzheimer disease [AD], 52 with amnestic mild cognitive impairment [aMCI], and 22 healthy controls [HC]), who were divided into four groups according to their free- and pre-drawn CDT scores: group 1, could do both; group 2, impaired in both; group 3, impaired in pre-drawn CDT; and group 4, impaired in free-drawn CDT. The diagnostic performances of the free-drawn, pre-drawn, and combination methods were compared using receiver operating characteristics analysis; in voxel-based morphometry analysis, the gray matter (GM) volume of groups 2-4 were compared with that of group 1. RESULTS: The area under the curve of the combination method was greater than that of the free- or pre-drawn method alone when comparing AD with HC or aMCI. Group 2 had a significantly smaller GM volume in the bilateral temporal lobes than group 1. Group 3 had a trend toward smaller GM volumes in the right temporal lobe when a liberal threshold was applied. Group 4 had significantly smaller GM volumes in the left temporal lobe than group 1. CONCLUSIONS: This study suggests that the combination method may be able to screen for a wider range of brain dysfunction. Combined use of free- and pre-drawn CDT may be useful for screening for AD and its early detection and treatment.

Diagnostic error regarding the cause of cytopenia when increasing psychotropic drugs: Two case reports.

Several psychotropic drugs can cause cytopenia, especially after increasing dosages or initiating treatment. However, cytopenia in patients with psychiatric disorders can also be due to other conditions such as leukemia. In this report, we discuss two cases of cytopenia that occurred during the adjustment of psychotropic medications in patients with severe psychiatric illness. The initial diagnosis in each case was drug-induced cytopenia; however, later, the cause of cytopenia was found to be acute promyelocytic leukemia. When cytopenia is observed while increasing the dosage of psychotropic drugs, suspicious drugs should be discontinued, though the possibility that cytopenia could be due to other reasons should be considered. If there are no signs of recovering blood cells or if cytopenia is severe, psychiatrists should consult hematologists promptly.

Decision-Making Support for People With Alzheimer's Disease: A Narrative Review.

The proportion of people with dementia has been increasing yearly, and the decision-making capacity of these people has become a major concern in fields such as the financial industry and in medical settings. In this narrative review, we discuss decision-making in people with Alzheimer's disease (AD), and we propose the support for decision-making in people with AD, especially financial and medical decision-making. We summarize several hypotheses and theories on the decision-making capacity of people with AD. These include the frontal lobe hypothesis, physiological theory, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, and the Person-Task-Fit (PTF) framework. Both internal and external factors can affect decision-making by people with AD. Internal factors are affected by changes in the brain and neurotransmitters, as well as alterations in cognitive ability and emotion. External factors include task characters, task contents, and situation influence. Since feedback has a significant effect on decision-making capacity, a series of suggestions may be helpful to improve this capacity, such as explicit advice, simple options, pleasant rewards, the Talking Mats approach, memory and organizational aid, support by caregivers, cognitive training and feedback. Thus, in providing decision-making support for people with AD, it is important to identify the internal and external factors that impair this process and to deal with these factors.

Effects of Hearing Impairment, Quality of Life and Pain on Depressive Symptoms in Elderly People: A Cross-Sectional Study.

Reduction of the incidence of depression and improvement of quality of life (QOL) of elderly people have become important subjects. Various factors are related to depressive symptoms in elderly people, and sensory impairment is a key to health, QOL, and depressive symptoms. In this cross-sectional study, a visual acuity test and audiometry were used to examine the relationships of visual and hearing impairment and other factors with depressive symptoms in elderly people. A group of 490 community-dwelling people aged over 65 years old underwent vision and hearing tests, the Center for Epidemiologic Studies Depression Scale (CES-D), Mini-Mental State Examination (MMSE), and questionnaires on social isolation, QOL, and physical condition. Logistic regression analysis was used to examine factors affecting CES-D. Multivariate logistic regression analysis indicated that hearing impairment, pain score, and satisfaction with human relationships and activities of daily living (ADL) were independent predictors of CES-D scores. Satisfaction with human relationships and ADL can reduce depressive symptoms in elderly people. Hearing impairment, pain, and social contact are also important. Therefore, improvement of social networks, interpersonal relationships, ADL, and hearing impairment may be effective in improving these symptoms in elderly people.

Depression Relapse during Long-Term Remission due to Media-Amplified Fear during the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has reoriented societies across the world and placed a significant burden on caring for mental health among its population. In this study, we reported two cases where patients experiencing severe depression with delusions of having COVID-19 required inpatient treatment after long-term remission owing to the negative impact of media reports related to the pandemic. Despite the aggravation of their anxiety, the patients were unable to distance themselves from negative information in attempts to remain informed through media to prevent their families and themselves from being infected. Self-protection through improved media literacy is imperative for people to protect themselves from the fearmongering of the media and infodemic in the present-day scenario.

Neural Correlates of Mild Behavioral Impairment: A Functional Brain Connectivity Study Using Resting-State Functional Magnetic Resonance Imaging.

BACKGROUND: Mild behavioral impairment (MBI) is associated with accelerated cognitive decline and greater risk of dementia. However, the neural correlates of MBI have not been completely elucidated. OBJECTIVE: The study aimed to investigate the correlation between cognitively normal participants and participants with amnestic mild cognitive impairment (aMCI) using resting-state functional magnetic resonance imaging. METHODS: The study included 30 cognitively normal participants and 13 participants with aMCI (20 men and 23 women; mean age, 76.9 years). The MBI was assessed using the MBI checklist (MBI-C). Region of interest (ROI)-to-ROI analysis was performed to examine the correlation between MBI-C scores and functional connectivity (FC) of the default mode network, salience network, and frontoparietal control network (FPCN). Age, Mini-Mental State Examination score, sex, and education were used as covariates. A p-value of 0.05, with false discovery rate correction, was considered significant. RESULTS: A negative correlation was observed between the MBI-C total score and FC of the left posterior parietal cortex with the right middle frontal gyrus. A similar result was obtained for the MBI-C affective dysregulation domain score. CONCLUSION: FPCN dysfunction was detected as a neural correlate of MBI, especially in the affective dysregulation domain. This dysfunction may be associated with cognitive impairment in MBI and conversion of MBI to dementia; however, further longitudinal data are needed to examine this relationship.