Background:Persons with epilepsy suffer from problems with social adaptation and face numerous social issues, even when the seizures are well-controlled. Facial emotion recognition (FER), one of the key components of social cognition, has been shown to be impaired in persons with mesial temporal lobe epilepsy (MTLE). Objective:To clarify the impairment of neural networks in persons with MTLE, we performed functional magnetic resonance imaging (fMRI) studies of MTLE persons using six dynamic tasks involving FER. Methods:We evaluated brain responses to realistic dynamic facial emotional expressions involving six basic emotions (fear, happiness, anger, sadness, disgust and surprise) in nine persons with left MTLE and ten healthy controls (HCs) using fMRI. Results:We noted brain responses to facial emotions in regions related to FER, such as the anterior insular cortex, medial frontal gyrus, superior frontal gyrus and cerebellum by our moving tasks which involved video tasks used to evaluate FER. Persons with left MTLE showed a reduced response in the right calcarine cortex compared to that of HCs. Conclusions:This is the first study to evaluate task-related fMRI on exposure to six basic emotions involving moving tasks in persons with epilepsy. FER deficit in persons with left MTLE may be partially associated with calcarine activity.

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.

OBJECTIVE:This study evaluated the reliability and validity of the Japanese version of the Somatic Symptom Disorder-B Criteria Scale (J-SSD-12), which assesses psychological features of somatic symptom disorder (SSD) as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Criterion B. METHODS:A total of 1148 Japanese internet panel participants completed the J-SSD-12, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 scale (GAD-7), Patient Health Questionnaire-15 (PHQ-15), and Short Health Anxiety Inventory (SHAI). Confirmatory factor analysis (CFA) examined factorial validity, with a correlated error specified between Items 7 and 10 for their shared negative wording and emphasis on others' evaluations. Reliability was assessed using test-retest correlations, intraclass correlation coefficients (ICCs), and Cronbach's alpha (α). Convergent validity was primarily evaluated through correlations with four additional scales. RESULTS:The mean participant age was 48.8 years (SD = 17.3), and 54.6 % were female. The scree plot and high inter-factor correlations suggested a possible unidimensional structure; however, the one-factor model did not achieve satisfactory fit (Comparative Fit Index [CFI] = 0.94, Root Mean Square Error of Approximation [RMSEA] = 0.107). In contrast, the three-factor structure showed acceptable fit on CFI (0.96) and Tucker-Lewis Index (TLI; 0.95), while RMSEA (0.091) indicated only marginal fit. The J-SSD-12 demonstrated good test-retest reliability (correlation coefficient [r] = 0.72; ICCs = 0.72-0.84) and excellent internal consistency (α = 0.95). Moderate correlations with the PHQ-9, GAD-7, PHQ-15, and SHAI (r = 0.60-0.66) supported convergent validity. CONCLUSION:The J-SSD-12 provides evidence supporting the reliability and validity of assessing SSD-related psychological features in a Japanese sample. Despite certain limitations, this measure appears useful for both research and potential clinical applications.

Metastasis, which is the spread of cancer cells into distant organs, is a critical determinant of prognosis in patients with cancer, and blood vessels are the major route for cancer cells to spread systemically. Extravasation is a critical process for the hematogenous metastasis; however, its underlying molecular mechanisms remain poorly understood. Here, we identified that senescent ECs highly express C-type lectin domain family 1 member B (CLEC-1b), and that endothelial CLEC-1b inhibits the hematogenous metastasis of a certain type of cancer. CLEC-1b expression was enhanced in ECs isolated from aged mice, senescent cultured human ECs, and ECs of aged human. CLEC-1b overexpression in ECs prevented the disruption of endothelial integrity, and inhibited the transendothelial migration of cancer cells expressing podoplanin (PDPN), a ligand for CLEC-1b. Notably, target activation of CLEC-1b in ECs decreased the hematogenous metastasis in the lungs by cancer cells expressing PDPN in mice. Our data reveal the protective role of endothelial CLEC-1b against cancer hematogenous metastasis. Considering the high CLEC-1b expression in senescent ECs, EC senescence may play a beneficial role with respect to the cancer hematogenous metastasis.

BackgroundAtrial 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.MethodsWe 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).ResultsIn 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.ConclusionEstablishing 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.

Autonomic homeostasis is dependent upon several brainstem nuclei, as well as several cortical and subcortical structures. Together, these sites make up, in part, the central autonomic network. Neurogenic orthostatic hypotension (NOH) is a cardinal feature of autonomic failure that occurs due to a failure to increase sympathetic efferent activity in response to postural changes. Therefore, the purpose of the current study was to investigate brainstem functional connectivity in NOH patients with peripheral autonomic lesions resulting in autonomic failure.Fifteen controls (63 ± 13 years) and fifteen Neurogenic Orthostatic Hypotension patients (67 ± 6 years; p = .2) with peripheral autonomic dysfunction completed 5-min of rest and three Valsalva maneuvers during a functional brain scan. Functional connectivity from the brainstem to cortical and subcortical structures were contrasted between patients and controls.At rest controls had significantly greater brainstem connectivity to the anterior cingulate cortex (T-value: 4.29), left anterior insula (T-value:3.31), left putamen (T-value:3.31) and bilateral thalamus (TRIGHT-value: 3.83; TLEFT-value:4.25) (p-FDR < 0.005). During Valsalva, controls showed significantly more connectivity between the brainstem and both the left anterior (cerebellum 4/5) and bilateral posterior cerebellum (cerebellar 9 and left cerebellar 6). Other cerebellar regions included brainstem-to-vermis. Other brainstem-to-cortical and subcortical regions included: bilateral putamen, posterior cingulate cortex (PCC), amygdala and medial prefrontal cortex. There was a significant negative correlation between the brainstem-cerebellar connectivity and severity of autonomic dysfunction (p < .01). During recovery phase of the Valsalva, controls had greater brainstem connectivity to the left thalamus (T-value:4.17); PCC (T-value:3.32); right putamen (T-value:3.28); right paracingulate gyrus (T-value:3.25) and left posterior cerebellum (C9) (T-value:3.21) (p-FDR < 0.05). The effect sizes for each brainstem connectivity during Valsalva and recovery ranged from moderate to strong.Patients with autonomic failure show reduced coupling between the brainstem and regions of the central autonomic network, including the cerebellum, insula, thalamus and cingulate cortices. Connectivity was associated with autonomic impairment. These findings may suggest impaired brainstem connectivity in patients with autonomic failure.

EDITORIAL article Front. Neurosci., 13 January 2023Sec. Autonomic Neuroscience Volume 16 - 2022 | https://doi.org/10.3389/fnins.2022.1130324

Aging is closely associated with the increased morbidity and mortality of ischemic cardiovascular disease, at least partially through impaired angiogenic capacity. Endothelial cells (ECs) play a crucial role in angiogenesis, and their angiogenic capacity declines during aging. Spermidine is a naturally occurring polyamine, and its dietary supplementation has exhibited distinct anti-aging and healthy lifespan-extending effects in various species such as yeast, worms, flies, and mice. Here, we explore the effects of spermidine supplementation on the age-related decline in angiogenesis both in vitro and in vivo. Intracellular polyamine contents were reduced in replicative senescent ECs, which were subsequently recovered by spermidine supplementation. Our findings reveal that spermidine supplementation improved the declined angiogenic capacity of senescent ECs, including migration and tube-formation, without affecting the senescence phenotypes. Mechanistically, spermidine enhanced both autophagy and mitophagy, and improved mitochondrial quality in senescent ECs. Ischemia-induced neovascularization was assessed using the hind-limb ischemia model in mice. Limb blood flow recovery and neovascularization in the ischemic muscle were considerably impaired in aged mice compared to young ones. Of note, dietary spermidine significantly enhanced ischemia-induced angiogenesis, and improved the blood flow recovery in the ischemic limb, especially in aged mice. Our results reveal novel proangiogenic functions of spermidine, suggesting its therapeutic potential against ischemic disease.

The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains to spread worldwide. COVID-19 is characterized by the striking high mortality in elderly; however, its mechanistic insights remain unclear. Systemic thrombosis has been highlighted in the pathogenesis of COVID-19, and lung microangiopathy in association with endothelial cells (ECs) injury has been reported by post-mortem analysis of the lungs. Here, we experimentally investigated the SARS-CoV-2 infection in cultured human ECs, and performed a comparative analysis for post-infection molecular events using early passage and replicative senescent ECs. We found that; (1) SARS-CoV-2 infects ECs but does not replicate and disappears in 72 hours without causing severe cell damage, (2) Senescent ECs are highly susceptible to SARS-CoV-2 infection, (3) SARS-CoV-2 infection alters various genes expression, which could cause EC dysfunctions, (4) More genes expression is affected in senescent ECs by SARS-CoV-2 infection than in early passage ECs, which might causes further exacerbated dysfunction in senescent ECs. These data suggest that sustained EC dysfunctions due to SARS-CoV-2 infection may contribute to the microangiopathy in the lungs, leading to deteriorated inflammation and thrombosis in COVID-19. Our data also suggest a possible causative role of EC senescence in the aggravated disease in elder COVID-19 patients.

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.

Calmodulin-dependent protein kinase II was purified from rabbit brain and its properties were compared with those of calmodulin-dependent protein kinase II from rat brain and calmodulin-dependent glycogen synthase kinase from rabbit skeletal muscle. Rabbit brain calmodulin-dependent protein kinase II was clearly distinguished from rabbit skeletal muscle glycogen synthase kinase with respect to size, behavior on autophosphorylation, immunological cross-reactivity and peptide mapping, but was indistinguishable from rat brain calmodulin-dependent protein kinase II in all respects examined. Thus, differences between calmodulin-dependent protein kinase II and glycogen synthase kinase appear not to reflect a species difference but to reflect a tissue difference.

Introduction: The pandemic of coronavirus disease 2019 (COVID-19), induced by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has posed a global health emergency. COVID-19 vaccines are certainly effective to prevent infection, severe disease, and hospitalization; however, its spreading remains to be uncontrolled worldwide. The striking feature of COVID-19 is the high mortality in the elderly; every 1,000 people infected with SARS-CoV-2, around 116 will die if they are mid-seventies or older, while little will die if they are under the age of 50. Though elderly is more fragile than younger people in general, this substantial difference in mortality strongly suggest a specific factor(s) that aggravate the disease in elder people. Systemic thrombosis has been highlighted in the pathogenesis of COVID-19, and lung microangiopathy in association with endothelial cells (ECs) injury has been reported by post-mortem analysis of the lungs. Hypothesis: Senescent endothelial cells are highly susceptible to SARS-CoV-2 infection. Methods: We experimentally investigated the SARS-CoV-2 infection in ECs, and performed a comparative analysis for post-infection molecular events using young and replicative senescent ECs. Results: We identify that; 1) SARS-CoV-2 infects ECs largely through endocytosis, 2) Senescent ECs are highly susceptible to SARS-CoV-2 infection, possibly through enhanced caveolae-mediated endocytosis, 3) SARS-CoV-2 infection alters various genes expression, which could cause EC dysfunctions, 4) More genes expression is affected in senescent ECs by SARS-CoV-2 infection than in young ECs, which might causes further exacerbated dysfunction in senescent ECs, 5) SARS-CoV-2 infection significantly affected coagulation cascade only in senescent ECs. Conclusions: These data strongly suggest that sustained EC dysfunctions due to SARS-CoV-2 infection may contribute to the microangiopathy in the lungs, leading to deteriorated inflammation and thrombosis in COVID-19. Our data also suggest a possible causative role of EC senescence in the aggravated disease in elder COVID-19 patients.

Research on elderly financial exploitation has mostly focused on financial abuse that occurs in families and other types of trusted relationships. As such, little is known about financial frauds and scams perpetrated by strangers. Financial fraud and scam prevention activities for older adults must be promoted, for which the correlation between the psychological, social, and cognitive characteristics of their vulnerability needs to be determined. The present study aimed to determine whether cognitive decline is a risk factor for scam vulnerability in older adults. Thus, we created a scam vulnerability scale for older adults with cognitive decline and analyzed the data to reveal the correlation between them, including inhibition and executive function. We conducted an interview survey with 50 older adults with cognitive decline (average age: 79.42 years, SD: 5.44) and 51 older adults without cognitive decline (average age: 76.12 years, SD: 5.82). The interview survey included the scam vulnerability scale, psychosocial questionnaires, and neuropsychological tests. The scale included six items with a four-point Likert scale based on a previous study. Hierarchical multiple regression analysis revealed that lower scores on the Japanese version of the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Jcog; indicating higher general cognitive function) correlated with higher scam vulnerability in the cognitive decline group (β = −0.46, p < 0.001). In addition, men were found to be more vulnerable in both groups (cognitive decline group: β = −0.29, p = 0.015, cognitive non-decline group; β = −0.32, p = 0.018). Inhibition and executive function were found not to correlate significantly with scam vulnerability. These results suggest that mild cognitive decline correlates with higher scam vulnerability, whereas moderate to severe cognitive decline correlates with lower vulnerability, possibly because it makes understanding the scam attempt itself difficult. Older adults with mild cognitive decline and their families, particularly those visiting elderly care or outpatient facilities, should be notified of the scam vulnerability of older clients using the ADAS-Jcog score as an index to help them avoid victimization.

To investigate the risk factors associated with cardiovascular diseases and its relation to BMI, body fat mass and plasma leptin level among adolescents in Taitung, Taiwan.A cross-sectional Taitung Children Heart Study for 500 young adolescents between ages 13 and 15 was conducted. Gender-specific regression models were used to determine the associations between BMI, percentage of body fat mass, plasma leptin level and seven CVDs risk factors (systolic and diastolic blood pressure, mean arterial pressure, triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol) before and after adjusting for weight status and age.After adjusting for weight status and age, BMI was positively associated with systolic BP, triglycerides, LDL-cholesterol levels but negatively associated with HDL-cholesterol level in boys while positively associated with systolic and diastolic BP, mean arterial pressure, and LDL-cholesterol level in girls. The percentage of body fat mass was positively associated with triglycerides, total cholesterol, and LDL-cholesterol in boys while positively associated with systolic BP, total cholesterol, and LDL-cholesterol in girls. Plasma leptin was positively associated with triglycerides, total cholesterol and LDL-cholesterol in boys but no statistically significant associations with CVDs risk factors in girls. A strong relationship between the percentage of body fat mass and plasma leptin appeared among all participants (r = 0.59, p < 0.01).BMI, body fat mass and plasma leptin level may be used to identify certain CVDs risk factors among Taitung adolescents. Future researches could consider measuring body fat mass in the relationship of CVDs risk factors instead of plasma leptin among young adolescents.

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.

Food preparation is an instrumental activity of daily living (IADL) affected by even mild cognitive decline. People with cognitive decline may perform some tasks of food preparation if done routinely and with prior proficiency. In Japan, women commonly prepare food owing to the cultural background, but few studies have investigated the impact of dementia in women on food preparation. The aim of the present study was to investigate the relationship between dietary abilities and cognitive and physical decline in the elderly women suspected with dementia.