Childhood book availability helps to preserve cognitive function in older adults with low education: Results from the NEIGE study.

OBJECTIVES: It is well-known that low educational attainment is associated with cognitive function decline in older age. Childhood book availability may help to preserve cognitive function in older adults with low education. The study objective was to examine the association between childhood book availability and cognitive function among older adults with low educational attainment, and to investigate the mediating effect of the volume of reading-related brain regions (e.g., superior temporal cortex). METHODS: A cross-sectional study of community-dwelling older Japanese adults aged 65-84 years was conducted (n=474). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Childhood book availability was assessed using a retrospective questionnaire. Brain region volume was measured using magnetic resonance imaging. Multivariate regression modeling and structural equation modeling were used for analysis. RESULTS: Both high educational attainment and childhood book availability were independently associated with high MMSE score. Stratification of educational level showed that childhood book availability was positively associated with MMSE score among participants with low educational attainment (coefficient=1.48, 95% confidence interval (CI): 0.31 to 2.66), but not among those with moderate or high educational attainment (coefficient=-0.01, 95% CI: -1.44 to 1.42 and -1.21, 95% CI: -3.85 to 1.42, respectively). Among participants with low educational attainment, left superior temporal cortex volume mediated the association between childhood book availability and MMSE score. DISCUSSION: The availability of books in childhood helps to preserve cognitive function in older adults with low education via left superior temporal cortex volume. Further research is needed to replicate these findings.

Temporal patterns of sleep latency in central hypersomnia and attention deficit hyperactivity disorder: a cluster analysis exploration using Multiple Sleep Latency Test.

Introduction: Excessive daytime sleepiness (EDS) is a crucial symptom that diminishes the quality of life. The primary causes of EDS are central hypersomnia, including narcolepsy type 1 (NT1), type 2 (NT2), and idiopathic hypersomnia (IH). EDS is often associated with other psychiatric disorders, particularly attention deficit hyperactivity disorder (ADHD). The Multiple Sleep Latency Test (MSLT) is the standard assessment tool for EDS. Although the MSLT yields numerous parameters, most are not employed in clinical practice. In this study, we leveraged novel MSLT parameters to discern central hypersomnia and ADHD presence. Our analysis focused on sleep latency variability and employed cluster analysis to identify unique temporal patterns. Methods: We examined the MSLT data from 333 patients; of these, 200 (aged 14-54, mean: 24.9 ± 8.1, years; 114 females) met the inclusion criteria comprising comprehensive data an Apnea-Hypopnea Index (AHI) below 5, and no prior diagnosis of sleep apnea syndrome. We employed a time-course cluster approach that specifically targeted sleep latency variability during the MSLT. Results: Considering both multiple clustering quality evaluations and the study's objectives, we identified 9 distinct clusters. Clusters 1 and 3 predominantly had MSLT-positive results; Cluster 2 was entirely MSLT-positive; Clusters 4, 5, 6, 8, and 9 were mainly MSLT-negative; and Cluster 7 had mixed results. The diagnosis of hypersomnia varied notably among Clusters 1, 2, 3, and 7, with Cluster 2 demonstrating a pronounced tendency towards NT1 and NT2 diagnoses (p < 0.005). However, no significant correlation was observed between ADHD diagnoses and specific sleep latency patterns in any cluster. Conclusions: Our study highlights the value of time-course clustering in understanding sleep latency patterns of patients with central hypersomnia.

Hippocampal volume mediates the relationship of parental rejection in childhood with social cognition in healthy adults.

Childhood abuse reduces hippocampal and amygdala volumes and impairs social cognition, including the ability to recognize facial expressions. However, these associations have been studied primarily in individuals with a history of severe abuse and psychiatric symptoms; researchers have not determined whether these associations can also be observed in healthy adults. In the present study, we analyzed data from 400 healthy adults (208 men and 192 women) at Tamagawa University. Parental rejection reflecting childhood abuse was assessed using the short form of Egna Minnen Beträffande Uppfostran, while social cognition was assessed using the "Fake Smile Detection Task." Hippocampal and amygdala volumes were extracted from T1-weighted magnetic resonance imaging data using FreeSurfer. We found that greater parental rejection resulted in smaller hippocampal and amygdala volumes and poorer performance in the Fake Smile Detection Task. Structural equation modeling analysis supported the model that hippocampal volume mediates maternal rejection effect on performance on the Fake Smile Detection Task, with involvement of the amygdala. These findings are in line with the structural and functional connectivity found between the hippocampus and amygdala and their joint involvement in social cognition. Therefore, parental rejection may affect hippocampal and amygdala volumes and social cognitive function even in symptom-free adults.

The optimal dose of Ramelteon for the better treatment adherence of delayed sleep-wake phase disorder: a dropout rate study.

Background: Evidence regarding the effectiveness of melatonin receptor agonists in treating delayed sleep-wake phase disorder (DSWPD) remains limited. This study aimed to determine the optimal dose of ramelteon, a melatonin receptor agonist, for the better treatment adherence of DSWPD. Methods: The patients who were diagnosed definitely as having DSWPD by board-certified physicians specialized in sleep medicine and started to receive strategically timed ramelteon medications after the diagnosis were included. Data on the initial ramelteon dose and follow-up duration (up to 24 months) were collected retrospectively. Patients with treatment discontinuation, changes in ramelteon dose, or the addition of other sleep-related medications were considered dropouts. Kaplan-Meier estimates, log-rank tests, and Cox regression analyses were performed. Results: Overall, 373 patients were analyzed. The findings revealed that the 2 mg dose of ramelteon was associated with a lower dropout rate compared to the other doses (8 mg, 4 mg, and 1 mg). The dropout rate for the 2 mg group was estimated to have a hazard ratio (HR) of 0.5762 when compared with the 8 mg dose group. Sex did not reveal a significant HR, whereas older age exhibited a small but significant HR (0.9858). Conclusion: For achieving better adherence, a dosing regimen of strategically timed 2 mg ramelteon may be the best for the treatment of DSWPD. The therapeutic dose window for better adherence seems to center approximately 2 mg of ramelteon. Furthermore, caution should be exercised when treating younger patients to prevent dropouts.

Seizure-related stress and arousal responses mediate a relationship between anxiety trait and state in epilepsy.

BACKGROUND: Epilepsy causes substantial psychological distress and anxiety, primarily due to seizures. However, the impact of stress responses and changes in arousal and their association with anxiety patterns in patients with epilepsy (PWE) remains unclear. This study aimed to investigate the relationships among seizures, stress and arousal characteristics, and trait and state anxiety characteristics in PWE. METHODS: Our sample consisted of 159 outpatients with epilepsy recruited from five institutions in Japan in 2020. Participants completed the State-Trait Anxiety Inventory-Form JYZ (STAI) and the Japanese-Stress Arousal Check List (J-SACL). We analyzed the correlations between inventory scores and clinical information. Using principal component analysis (PCA), we derived epilepsy-specific stress/arousal characteristics, which accounted for high arousal and low-stress levels, termed epilepsy-specific stress or arousal response (ESAR), from the J-SACL scores. We conducted a mediation analysis to assess the mediating role of ESAR in the relationship between traits and state anxiety. RESULTS: We found significant correlations between J-SACL stress and arousal factors (r = -0.845, p < 0.001), ESAR and seizure frequency (r = -0.29, p < 0.001), ESAR and trait anxiety scores on the STAI (r = -0.77, p < 0.0001), and ESAR and state anxiety scores on the STAI (r = -0.60, p < 0.0001). Mediation analysis supported by the Monte Carlo method revealed that ESAR significantly mediated the association between trait and state anxiety. CONCLUSIONS: These findings elucidate the epilepsy-specific stress and arousal characteristics and their roles in mediating traits and state anxiety. These results may reflect the long-term clinical course and unique emotion recognition tendencies in epilepsy.

Increased glutamate and glutamine levels and their relationship to astrocytes and dopaminergic transmissions in the brains of adults with autism.

Increased excitatory neuronal tones have been implicated in autism, but its mechanism remains elusive. The amplified glutamate signals may arise from enhanced glutamatergic circuits, which can be affected by astrocyte activation and suppressive signaling of dopamine neurotransmission. We tested this hypothesis using magnetic resonance spectroscopy and positron emission tomography scan with 11C-SCH23390 for dopamine D1 receptors in the anterior cingulate cortex (ACC). We enrolled 18 male adults with high-functioning autism and 20 typically developed (TD) male subjects. The autism group showed elevated glutamate, glutamine, and myo-inositol (mI) levels compared with the TD group (p = 0.045, p = 0.044, p = 0.030, respectively) and a positive correlation between glutamine and mI levels in the ACC (r = 0.54, p = 0.020). In autism and TD groups, ACC D1 receptor radioligand binding was negatively correlated with ACC glutamine levels (r = - 0.55, p = 0.022; r = - 0.58, p = 0.008, respectively). The enhanced glutamate-glutamine metabolism might be due to astroglial activation and the consequent reinforcement of glutamine synthesis in autistic brains. Glutamine synthesis could underly the physiological inhibitory control of dopaminergic D1 receptor signals. Our findings suggest a high neuron excitation-inhibition ratio with astrocytic activation in the etiology of autism.

Hyperfocus symptom and internet addiction in individuals with attention-deficit/hyperactivity disorder trait.

Background: Hyperfocus symptom is the intense concentration on a certain object. It is a common but often overlooked symptom in those with attention-deficit/hyperactivity disorder (ADHD). Hyperfocus disrupts attention control and results in a focus on inappropriate behaviors. It allows individuals to focus on internet use and make them use internet excessively. This excessive internet use can lead to an addiction. This study investigated the status of IA and hyperfocus, the mediation effect of hyperfocus in relation to IA, and the relationship between ADHD subtypes and hyperfocus in those with ADHD symptoms. Methods: This web-based cross-sectional study included 3,500 Japanese adults who completed internet-based questionnaires, which included the Adult ADHD Self-Report Scale (ASRS), Internet Addiction Test (IAT), and Hyperfocus Scale (HFS) to assess ADHD symptoms, internet dependence, and hyperfocus symptoms, respectively. The mediating role of HFS in the relationship between ASRS and IAT was assessed by mediation analysis. To analyze the relationship between hyperfocus symptoms and ADHD subtypes, we compared the correlation of HFS with the Inattention and Hyperactive Scores of ASRS. Results: ADHD traits were associated with higher IAT scores (p < 0.001) and higher HFS scores (p < 0.001). Mediation analysis and bootstrap testing showed that HFS significantly mediated the association between ASRS and IAT. Analyses of ADHD subtypes demonstrated that HFS was significantly correlated with the Inattention (R = 0.597, p < 0.001) and Hyperactive (R = 0.523, p < 0.001) Scores. The correlation between HFS and the Inattention Score was significantly higher than that between HFS and the Hyperactive Score (p < 0.001). Conclusion: Our findings suggest that hyperfocus may play an important role in addictive behavior in ADHD as a manifestation of attentional control malfunction.

A model for estimating the brainstem volume in normal healthy individuals and its application to diffuse axonal injury patients.

Diffuse axonal injury (DAI) is a subtype of traumatic brain injury that causes acute-phase consciousness disorders and widespread chronic-phase brain atrophy. Considering the importance of brainstem damage in DAI, a valid method for evaluating brainstem volume is required. We obtained volume measurements from 182 healthy adults by analyzing T1-weighted magnetic resonance images, and created an age-/sex-/intracranial volume-based quantitative model to estimate the normal healthy volume of the brainstem and cerebrum. We then applied this model to the volume measurements of 22 DAI patients, most of whom were in the long-term chronic phase and had no gross focal injury, to estimate the percentage difference in volume from the expected normal healthy volume in different brain regions, and investigated its association with the duration of posttraumatic amnesia (which is an early marker of injury severity). The average loss of the whole brainstem was 13.9%. Moreover, the percentage loss of the whole brainstem, and particularly of the pons and midbrain, was significantly negatively correlated with the duration of posttraumatic amnesia. Our findings suggest that injury severity, as denoted by the duration of posttraumatic amnesia, is among the factors affecting the chronic-phase brainstem volume in patients with DAI.

Attention-deficit hyperactivity symptoms and risk of alcohol use relapse.

AIM: Alcohol use disorder (AUD) is frequently accompanied by comorbid attention-deficit hyperactivity disorder (ADHD). Comorbid ADHD has been reported to increase the severity of AUD. We investigated whether ADHD severity also influences AUD relapse risk at baseline and after inpatient treatment. METHODS: In this study, 187 AUD patients admitted to Narimasu Kosei Hospital from October 2019 to March 2021 were included in the analysis. According to the Adult ADHD Self-Report Scale (ASRS), participants were divided into two groups: ASRS+ with ADHD characteristics (n = 43) and ASRS- with low/no ADHD characteristics (n = 144). Groups were compared for AUD relapse risk at the start of treatment (baseline) and before hospital discharge using the multidimensional Alcohol Relapse Risk Scale (ARRS). The change in relapse risk during hospitalization was also compared by assessment of the interaction between groups (ASRS+ vs. ASRS-) and time (at discharge vs. baseline). RESULTS: The total ARRS score and dimension subscores for stimulus-induced vulnerability and emotionality problems were significantly higher in the ASRS+ group at baseline and before discharge compared to the ASRS- group. There was a significant group × time interaction indicating less improvement of stimulus-induced vulnerability during inpatient treatment among the ASRS+ group compared to the ASRS- group. CONCLUSIONS: Our findings suggest that AUD patients with ADHD characteristics have a higher risk of relapse both at baseline and after inpatient treatment. Stimulus-induced vulnerability to relapse is less likely to improve with treatment in patients with ADHD characteristics.

Increase in Cerebral Blood Flow After Catheter Ablation of Atrial Fibrillation.

BACKGROUND: Recent studies have found that atrial fibrillation (AF) is a risk factor for cognitive impairment. Brain hypoperfusion is hypothesized as an underlying mechanism of cognitive decline in AF patients. OBJECTIVES: This study sought to assess changes in cerebral blood flow (CBF) and brain volume after catheter ablation of AF. METHODS: Patients undergoing catheter ablation of AF were enrolled in this prospective study. AF patients being treated with pharmaceuticals alone served as a control group. Brain magnetic resonance imaging was performed before and 6 months after catheter ablation. CBF was assessed by 2-dimensional phase-contrast magnetic resonance angiography. Brain volume and bilateral hippocampal volume were measured using FreeSurfer software. RESULTS: Of the 57 study patients (age 64 ± 11 years; 45 men; paroxysmal AF: n = 22; nonparoxysmal AF: n = 35), 48 patients were freed from tachyarrhythmia recurrence beyond a 3-month blanking period. Changes in CBF and brain perfusion over 6 months were significantly greater in the study patients than control (CBF: 39.26 vs -34.86 mL; P = 0.01, ANCOVA; brain perfusion: 3.78 vs -3.02 mL/100 mL/min; P = 0.009, ANCOVA), while changes in total brain volume and bilateral hippocampal volume were similar between 2 groups (total brain volume: 2.57 vs -2.15 mL; P = 0.32, ANCOVA; bilateral hippocampal volume: 0.03 vs 0.04 mL; P = 0.8, ANCOVA). Nonparoxysmal AF at baseline was an independent predictor of an increase in CBF of >32.6 mL/min. CONCLUSIONS: Catheter ablation of AF has favorable effects on CBF, particularly in nonparoxysmal AF. Our results may partially explain the association between cognitive decline and AF.

Dopamine dysfunction in depression: application of texture analysis to dopamine transporter single-photon emission computed tomography imaging.

Dopamine dysfunction has been associated with depression. However, results of recent neuroimaging studies on dopamine transporter (DAT), which reflect the function of the dopaminergic system, are inconclusive. The aim of this study was to apply texture analysis, a novel method to extract information about the textural properties of images (e.g., coarseness), to single-photon emission computed tomography (SPECT) imaging in depression. We performed SPECT using 123I-ioflupane to measure DAT binding in 150 patients with major depressive disorder (N = 112) and bipolar disorder (N = 38). The texture features of DAT binding in subregions of the striatum were calculated. We evaluated the relationship between the texture feature values (coarseness, contrast, and busyness) and severity of depression, and then examined the effects of medication and diagnosis on such relationship. Furthermore, using the data from 40 healthy subjects, we examined the effects of age and sex on the texture feature values. The degree of busyness of the limbic region in the left striatum linked to the severity of depression (p = 0.0025). The post-hoc analysis revealed that this texture feature value was significantly higher in both the severe and non-severe depression groups than in the remission group (p = 0.001 and p = 0.028, respectively). This finding remained consistent after considering the effect of medication. The effects of age and sex in healthy individuals were not evident in this texture feature value. Our findings imply that the application of texture analysis to DAT-SPECT may provide a state-marker of depression.

Hippocampal calcification and its effects on cognitive function and symptoms in dementia.

BACKGROUND: Hippocampal calcification (HC), highly prevalent in older people, has not attracted attention until recently. Despite its potential effects on cognition and behaviour, and its possible impact on the diagnosis and severity of dementia, it has not been investigated. This study aimed to evaluate the prevalence of HC and its influence on cognition and behavioural symptoms in patients with dementia. METHODS: Data from consecutive patients who visited a medical centre for dementia, for the first time between April 2016 and September 2018, were extracted and analysed. These data included the patients' demographics, the presence of HC and hippocampal thickness as measured on computed tomography, the diagnosis of dementia and its type, cognitive function measured using the Mini-Mental State Examination and the Clock Drawing Test, and the chief complaints or symptoms prompting the visit. RESULTS: A high incidence of HC (85/267 patients) was observed. There was no significant difference in the ages of patients with and without HC. Patients with HC had higher cognitive function than those without HC at their first visit. This result was contrary to our expectations as it was not explained by the chief complaints recorded at the first visit. CONCLUSIONS: Our study showed a high prevalence of HC in older patients with dementia. Patients with HC had better cognitive function than did those without HC during their first hospital visit. This study suggests that HC may not affect the cognitive functions related to dementia. However, further research is needed to evaluate the long-term consequences of dementia with HC.

Association between gratitude, the brain and cognitive function in older adults: Results from the NEIGE study.

OBJECTIVES: Having gratitude is associated with reduced social isolation and depression, which are risk factors for dementia. However, it is unknown whether gratitude is directly associated with cognitive function. This study aimed to determine associations between gratitude and cognitive function and to elucidate the underlying biological mechanism by testing the mediating role of brain regions among healthy older people. METHODS: We used cross-sectional data from the 2017 Neuron to Environmental Impact across Generations (NEIGE) study of community-dwelling older adults aged ≥ 65 years (n = 478). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Levels of gratitude were assessed using the two-items of Gratitude Questionnaire. Volumes of brain regions associated with emotional processing and social interaction were measured by magnetic resonance imaging. Linear regression models and structural equation models were used to examine associations between level of gratitude, brain volume, and cognitive function. RESULTS: The mean gratitude score was 6.3 (SD=0.9) and the mean MMSE score was 27.1 (SD=2.5). Regression analysis showed that higher levels of gratitude were associated with better cognitive function (coefficient=0.25, 95% CI: 0.01, 0.49), adjusting for age, sex, education, marital status, and depressive symptoms. Higher levels of gratitude were associated with larger volumes of right amygdala and left fusiform gyrus. Structural equation model analysis showed that amygdala volumes mediated the association between gratitude and cognitive function. CONCLUSION: Higher levels of gratitude were positively associated with cognitive function, partially mediated through the amygdala, which is involved in processing emotion and memory.

Neighborhood Beauty and the Brain in Older Japanese Adults.

People have a preference for, and feel better in, beautiful natural environments. However, there are no epidemiological studies on the association between neighborhood beauty and neuroimaging measures. We aimed to determine association between neighborhood beauty and regional brain volume. Participants were 476 community-dwelling older adults from the Neuron to Environmental Impact across Generations (NEIGE) study. Subjective neighborhood beauty was assessed through participants' perception of beautiful scenery within 1 km of their home. Objective measures of neighborhood indicators (green spaces, blue spaces, and plant diversity) within 1 km of participants' homes were obtained using a geographic information system. Volumes of brain regions associated with experience of beauty were measured using magnetic resonance imaging. We estimated associations between neighborhood beauty and regional brain volume using linear regression. Of the participants, 42% rated their neighborhoods as very beautiful, and 17% rated them as not at all beautiful. Higher subjective neighborhood beauty was associated with larger bilateral medial orbitofrontal cortex and insula volumes (all p for trend < 0.01). Brain volume was not associated with objective neighborhood measures. Subjective neighborhood beauty was associated with brain regions related to rewards and decision making, suggesting that these brain regions underpin the perception of neighborhood beauty.

Factors associated with anxiety and depression in rheumatoid arthritis patients: a cross-sectional study.

BACKGROUND: The management of anxiety and depression symptoms in rheumatoid arthritis (RA) patients is vital. Previous study findings on this topic are conflicting, and the topic remains to be thoroughly investigated. This study aimed to clarify the association of RA disease activity with anxiety and depression symptoms after controlling for physical disability, pain, and medication. METHODS: We conducted a cross-sectional study of RA patients from the XXX Rheumatoid Arthritis Management Alliance cohort. We assessed patients using the Disease Activity Score (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), and Hospital Anxiety and Depression Scale (HADS). Anxiety and depression symptoms were defined by a HADS score ≥ 8. We analyzed the data using multivariable logistic regression analyses. RESULTS: Of 517 participants, 17.6% had anxiety symptoms and 27.7% had depression symptoms. The multivariable logistic regression analysis demonstrated that DAS28 was not independently associated with anxiety symptoms (odds ratio [OR] [95% confidence interval; CI] 0.93 [0.48-1.78]; p = 0.82) and depression symptoms (OR [95% CI] 1.45 [0.81-2.61]; p = 0.22). However, DAS28 patient global assessment (PtGA) severity was associated with anxiety symptoms (OR [95% CI] 1.15 [1.02-1.29]; p = 0.03) and depression symptoms (OR [95% CI] 1.21 [1.09-1.35]; p < 0.01). Additionally, HAQ-DI scores ≤ 0.5 were associated with anxiety symptoms (OR [95% CI] 3.51 [1.85-6.64]; p < 0.01) and depression symptoms (OR [95% CI] 2.65 [1.56-4.50]; p < 0.01). Patients using steroids were more likely to have depression than those not using steroids (OR [95% CI] 1.66 [1.03-2.67]; p = 0.04). CONCLUSIONS: No association was found between RA disease activity and anxiety and depression symptoms in the multivariable logistic regression analysis. Patients with high PtGA scores or HAQ-DI scores ≤ 0.5 were more likely to experience anxiety and depression symptoms, irrespective of disease activity remission status. Rather than focusing solely on controlling disease activity, treatment should focus on improving or preserving physical function and the patient's overall sense of well-being.

Establishment of induced pluripotent stem cells from schizophrenia discordant fraternal twins.

Schizophrenia (SCZ) is one of the major psychiatric disorders. The genetic factor is certainly influential in the onset of the disease but is not decisive. There is no identified molecular/cellular marker of the disease, and the pathomechanism is still unknown. In this study, we generated human induced pluripotent stem cells (iPSCs) derived from SCZ-discordant fraternal twins, and they could contribute to elucidation of the pathomechanism of SCZ.

Three-Dimensional Convolutional Autoencoder Extracts Features of Structural Brain Images With a "Diagnostic Label-Free" Approach: Application to Schizophrenia Datasets.

There has been increasing interest in performing psychiatric brain imaging studies using deep learning. However, most studies in this field disregard three-dimensional (3D) spatial information and targeted disease discrimination, without considering the genetic and clinical heterogeneity of psychiatric disorders. The purpose of this study was to investigate the efficacy of a 3D convolutional autoencoder (3D-CAE) for extracting features related to psychiatric disorders without diagnostic labels. The network was trained using a Kyoto University dataset including 82 patients with schizophrenia (SZ) and 90 healthy subjects (HS) and was evaluated using Center for Biomedical Research Excellence (COBRE) datasets, including 71 SZ patients and 71 HS. We created 16 3D-CAE models with different channels and convolutions to explore the effective range of hyperparameters for psychiatric brain imaging. The number of blocks containing two convolutional layers and one pooling layer was set, ranging from 1 block to 4 blocks. The number of channels in the extraction layer varied from 1, 4, 16, and 32 channels. The proposed 3D-CAEs were successfully reproduced into 3D structural magnetic resonance imaging (MRI) scans with sufficiently low errors. In addition, the features extracted using 3D-CAE retained the relation to clinical information. We explored the appropriate hyperparameter range of 3D-CAE, and it was suggested that a model with 3 blocks may be related to extracting features for predicting the dose of medication and symptom severity in schizophrenia.