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.

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.

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.

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.

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.

Preliminary study of the role of general hospital psychiatric ward for patients with dementia in Japan.

A psychiatric ward in a general hospital might be suitable for people with dementia because of the comprehensive medical care available. The aim was to investigate the characteristics of 86 patients with dementia admitted to psychiatric ward in a general hospital. About 40% of the patients were admitted due to a diagnosis of dementia and the need for treatment of a physical disease. The expected roles of psychiatric ward in a general hospital for patients with dementia include the acute care of physical and psychological problems and a differential diagnosis.

Interaction between memory impairment and depressive symptoms can exacerbate anosognosia: a comparison of Alzheimer's disease with mild cognitive impairment.

OBJECTIVE: To investigate the effects of interactions between memory impairment, depressive symptoms, and anosognosia. METHODS: Anosognosia for memory impairment was assessed in 118 patients with Alzheimer's disease (AD), 47 patients with mild cognitive impairment (MCI), and 17 non-diagnosed controls (NC) using a questionnaire and evaluation of the anosognosia score as the discrepancy between ratings of the patient and a relative. Demographic characteristics, such as the relationship of the patient with the relative and the activities of daily living (ADL) were evaluated. Memory impairment was evaluated with the Rivermead Behavioral Memory Test (RBMT), depressive symptoms were evaluated using the Geriatric Depression Scale (GDS) 15 items version. RESULTS: In the MCI group, a stepwise multiple regression analysis showed an interaction between RBMT and GDS scores, and simple slope analysis indicated that scores for RBMT at low GDS (-1 standard deviation) were positively correlated with self-rated memory impairment. In the AD group, the relationship of the patient with the relative, ADL, and GDS and RBMT scores were associated with the anosognosia score. CONCLUSION: Patients with MCI who have no depressive symptoms may be able to more accurately evaluate their memory impairment than those who have depressive symptoms and patients with AD. The evaluation by relatives, depressive symptoms or ADL of patients may distort evaluation of anosognosia for memory impairment in patients with AD or MCI. It seems necessary to include not only depression scale scores but also results of objective memory tests in the patients' medical information for the correct assessment of anosognosia.

Neural Correlates of Sleep Disturbance in Alzheimer's Disease: Role of the Precuneus in Sleep Disturbance.

BACKGROUND: Sleep disturbance may affect the development of Alzheimer's disease (AD), but the neural correlates of sleep disturbance in AD have not been fully clarified. OBJECTIVE: To examine the factors associated with sleep disturbance in AD. METHODS: A retrospective study was performed in 63 patients with AD. None of the patients had been prescribed antidementia or psychoactive drugs, and all underwent brain magnetic resonance imaging (MRI) before medication. Sleep disturbance was defined as a score of at least 1 point on the sleep disturbance subscale of the Neuropsychiatric Inventory (NPI). Whole brain image analysis was performed using SPM8 and VBM8. A two-sample t-test was used to compare patients with AD with (n = 19) and without (n = 44) sleep disturbance, with age and gender included as covariates. The statistical thresholds were set to an uncorrected p-value of 0.001 at the voxel level and a corrected p-value of 0.05 at the cluster level. In addition, pineal gland volume (PGV) measured using MRI, and white matter hyperintensity (WMH) assessed with the modified Fazekas scale were compared between patients with AD with and without sleep disturbance using independent group t-tests. RESULTS: In whole brain analysis, the precuneus volume in patients with AD with sleep disturbance was significantly smaller than those without sleep disturbance. There were no significant differences in PGV and WMH between the two groups. CONCLUSION: Sleep disturbance in AD was associated with reduction of precuneus volume. This suggests that the precuneus might be an important region in sleep disturbance in AD.

Differences in the neural correlates of frontal lobe tests.

BACKGROUND: The Executive Interview (EXIT25), the executive clock-drawing task (CLOX1), and the Frontal Assessment Battery (FAB) are used to assess executive function at the bedside. These tests assess distinct psychometric properties. The aim of this study was to examine differences in the neural correlates of the EXIT25, CLOX1, and FAB based on magnetic resonance imaging. METHODS: Fifty-eight subjects (30 with Alzheimer's disease, 10 with mild cognitive impairment, and 18 healthy controls) participated in this study. Multiple regression analyses were performed to examine the brain regions correlated with the EXIT25, CLOX1, and FAB scores. Age, gender, and years of education were included as covariates. Statistical thresholds were set to uncorrected P-values of 0.001 at the voxel level and 0.05 at the cluster level. RESULTS: The EXIT25 score correlated inversely with the regional grey matter volume in the left lateral frontal lobe (Brodmann areas 6, 9, 44, and 45). The CLOX1 score correlated positively with the regional grey matter volume in the right orbitofrontal cortex (Brodmann area 11) and the left supramarginal gyrus (Brodmann area 40). The FAB score correlated positively with the regional grey matter volume in the right precentral gyrus (Brodmann area 6). The left lateral frontal lobe (Brodmann area 9) and the right lateral frontal lobe (Brodmann area 46) were identified as common brain regions that showed association with EXIT25, CLOX1, and FAB based only a voxel-level threshold. CONCLUSIONS: The results of this study suggest that the EXIT25, CLOX1, and FAB may be associated with the distinct neural correlates of the frontal cortex.

Reduced Pineal Volume in Alzheimer Disease: A Retrospective Cross-sectional MR Imaging Study.

Purpose To evaluate pineal volume in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and healthy control subjects and to correlate the findings with results of cognitive testing and brain parenchymal volumes. Materials and Methods The ethics committee approved this retrospective study. The participants included 63 patients with AD, 33 patients with MCI, and 24 healthy control subjects. There were 36 men and 84 women, with a mean age (±standard deviation) of 76.7 years ± 7.6. The pineal gland volume and pineal parenchymal volume were measured by using three-dimensional volumetric magnetic resonance imaging (T1-weighted magnetization-prepared rapid gradient-echo sequence; spatial resolution, 0.9 × 0.98 × 0.98 mm). With age and total intracranial volume as covariates, analysis of covariance with the Bonferroni post hoc test was performed to compare the pineal volume among the AD, MCI, and control groups. Multiple regression analyses were used to identify predictor variables associated with pineal volume. Results The mean pineal gland volume in patients with AD (72.3 mm3 ± 5.4; 95% confidence interval [CI]: 61.5 mm3, 83.1 mm3) was significantly smaller than that in control subjects (102.1 mm3 ± 9.0; 95% CI: 84.4 mm3, 119.9 mm3) (P = .019). The mean pineal parenchymal volume in patients with AD (63.8 mm3 ± 4.2; 95% CI: 55.4 mm3, 72.1 mm3) was significantly smaller than that in patients with MCI (81.7 mm3 ± 5.8; 95% CI: 70.3 mm3, 93.1 mm3; P = .044) and control subjects (89.1 mm3 ± 6.9; 95% CI: 75.4 mm3, 102.9 mm3; P = .009). Multiple regression analyses demonstrated that the Mini-Mental State Examination score and total intracranial volume were significant independent predictors of both pineal gland volume and pineal parenchymal volume (P < .001). Conclusion Pineal volume reduction showed correlation with cognitive decline and thus might be useful to predict cognitive decline in patients with AD. © RSNA, 2017.