We aimed to psychometrically evaluate and validate a Japanese version of the Social Functioning in Dementia scale (SF-DEM-J) and investigate changes in social function in people with dementia during the coronavirus disease-19 (COVID-19) pandemic.

We interviewed people with mild cognitive impairment (MCI) and mild dementia and their caregivers during June 2020–March 2021 to validate patient- and caregiver-rated SF-DEM-J and compared their scores at baseline (April 2020 to May 2020) and at 6–8 months (January 2021 to March 2021) during a time of tighter COVID-19 restrictions.

The neuropsychology clinic in the Department of Psychiatry at Osaka University Hospital and outpatient clinic in the Department of Psychiatry and Neurology at Daini Osaka Police Hospital, Japan.

103 dyads of patients and caregivers.

SF-DEM-J, Mini-Mental State Examination, Neuropsychiatric Inventory, UCLA Loneliness Scale, and Apathy Evaluation Scale.

The scale’s interrater reliability was excellent and test–retest reliability was substantial. Content validity was confirmed for the caregiver-rated SF-DEM-J, and convergent validity was moderate. Caregiver-rated SF-DEM-J was associated with apathy, irritability, loneliness, and cognitive impairment. The total score of caregiver-rated SF-DEM-J and the score of Section 2, “communication with others,” significantly improved at 6–8 months of follow-up.

The SF-DEM-J is acceptable as a measure of social function in MCI and mild dementia. Our results show that the social functioning of people with dementia, especially communicating with others, improved during the COVID-19 pandemic, probably as a result of adaptation to the restrictive life.

Although the previous studies indicated that impaired cerebrospinal fluid (CSF) dynamics might contribute to the pathophysiology of Alzheimer’s disease (AD), the longitudinal changes of CSF volumes in AD has been still unclear. In this study, using the methodology of quantitative assessment of CSF volumes in idiopathic normal pressure hydrocephalus (iNPH), we assessed longitudinal changes in CSF volumes in AD patients.

The subjects were the patients with mild cognitive impairment and dementia due to AD who visited Osaka University Hospital from November 2009 to October 2018. We excluded the patients with gait disturbances and MRI findings such as Disproportionately enlarged subarachnoid-space hydrocephalus (DESH), which was the suggestive finding of iNPH. For each subject, MRI was performed in the first visit and 1 year later. We quantitatively measured CSF volumes in DESH-related regions, such as ventricle systems (VS), Sylvian fissures (SF), and sulci at high convexity and the midline (SHM)., using an automatic brain volumetric software program (AVSIS) (Ishii et al. 2006, 2013). The ratio of each regional volume to the intracranial volume was calculated and we compared these parameters between two visits.

We enrolled 98 patients with AD (mean (SD) age = 76.0 (5.7)). Wilcoxon signed rank test revealed that, while the ratios of CSF volumes in VS and SF significantly increased during the one-year observation (VS: 4.01 (1.05) % vs 4.14 (1.09) %, p<0.001 ;SF: 1.40 (0.21) % vs 1.42 (0.22) %, p=0.007), those in SHM significantly decreased (4.30 (0.70) % vs 4.23 (0.69) %, p<0.001). The change ratio of relative volumes in VS was correlated with those in SF and SHM (r=0.451, p<0.001; r=-0.350, p<0.001).

In patients with AD, the CSF volumes in VS and SF increased while CSF volumes in SHM decreased. This trend of the longitudinal change was similar to the change in the patients with iNPH. The finding of this study indicates that, in the patients with AD, CSF dynamics may be impaired like the patients with iNPH.

The present study aimed to compare the social function between mild cognitive impairment (MCI), mild Alzheimer’s disease (AD) dementia, and mild dementia with Lewy bodies (DLB) using the Japanese version of Social Functioning in Dementia scale (SF-DEM-J).

We interviewed 103 patients and family caregivers from June 2020 to March 2021: 54 patients with MCI, 34 with mild AD dementia, and 15 with mild DLB. We compared the caregiver-rated SF-DEM-J, Clinical Dementia Rating (CDR), MMSE, age, length of education, Geriatric Depression Scale (GDS), the University of California, Los Angeles Loneliness Scale (UCLA-LS), Neuropsychiatric Inventory (NPI), and informant version of the Apathy Evaluation Scale (AES) between MCI, mild AD dementia, and mild DLB groups using Kruskal-Wallis test with Dunn-Bonferroni correction for post-hoc analyses. We compared sex, living situation, and caregiver demographics between three groups using chi-square test. We performed correlation analysis between the score of each psychological test and the scores of SF-DEM-J within group using Spearman’s rank correlation coefficient.

For SF-DEM-J, the score of section 2 (communicating with others) was significantly worse in mild AD dementia than in mild DLB. The scores of section 1 (spending with others) and section 3 (sensitivity to others) and the total score did not significantly differ between three groups. The score of section 1 was significantly associated with MMSE in MCI, with anxiety and disinhibition of NPI, and AES in mild AD dementia, and with GDS in mild DLB. The score of section 2 was significantly associated with AES in MCI and mild AD dementia, with UCLA-LS in MCI, and with the length of education in mild DLB. The score of section 3 was significantly associated with agitation and irritability of NPI in MCI and mild AD dementia. The total score was associated with UCLA-LS and AES in MCI, and with AES in mild AD dementia.

Factors affecting social functioning differed between MCI, mild AD dementia, and mild DLB. Apathy, agitation and irritability affected social functioning in MCI and mild AD dementia while depressive mood affected social functioning in mild DLB.

Residents who lived near the Fukushima Power Plant accident were forced to change their lifestyle after the 2011 accident. This study aimed to elucidate the association of resident lifestyle and psychological factors with onset of hepatobiliary enzyme abnormalities (HEA) after the accident.

This longitudinal study included 15705 residents who underwent a comprehensive health check, as well as a mental health and lifestyle survey between June 2011 and March 2012. Follow-up surveys were conducted between June, 2012 and March 2018. Risk factors for new HEA onset were evaluated using the Cox proportional hazards model, moreover, population attributable risks for new HEA onset were calculated.

HEA developed in 29.7% of subjects. In addition to metabolic factors such as overweight, hyperglycemia, and hyperlipidemia; there were differences in alcohol intake, evacuation, unemployment, educational background, and psychological distress between subjects with and without HEA onset. After we adjusted for potential confounding factors, an association of being overweight, hypertension, and dyslipidemia, as well as alcohol consumption, evacuation, and psychological distress with increased risk of HEA onset was realized. Among these identified risk factors, evacuation accounted for the greatest share.

Metabolic characteristics and disaster-related lifestyle aspects, including mental status, were risk factors for HAE onset after the Fukushima Power Plant accident.

To examine the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) and tap test response to elucidate the effects of comorbidity of AD in idiopathic normal-pressure hydrocephalus (iNPH).

Case–control study.

Osaka University Hospital.

Patients with possible iNPH underwent a CSF tap test.

Concentrations of amyloid beta (Aβ) 1–40, 1–42, and total tau in CSF were measured. The response of tap test was judged using Timed Up and Go test (TUG), 10-m reciprocation walking test (10MWT), Mini-Mental State Examination (MMSE), and iNPH grading scale. The ratio of Aβ1–42 to Aβ1–40 (Aβ42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients.

We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aβ42/40 ratio was significantly lower (mean [SD] = 0.063 [0.026] vs. 0.083 [0.036], p = 0.008), and total tau in CSF was significantly higher (mean [SD] = 385.6 [237.2] vs. 293.6 [165.0], p = 0.028) in iNPH-nTT than in iNPH-pTT. Stepwise logistic regression analysis revealed that low Aβ42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aβ42/40 ratio. The association between Aβ42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline.

A low CSF Aβ42/40 ratio is associated with a poorer cognitive response, but not gait and urinary response, to a tap test in iNPH. Even if CSF biomarkers suggest AD comorbidity, treatment with iNPH may be effective for gait and urinary dysfunction.

Abnormalities in neurotransmission via N-methyl-d-aspartic acid receptor (NMDAR) play a role in the pathophysiology of neuropsychiatric disorders. The impact of repetitive transcranial magnetic stimulation (rTMS) on NMDAR-related amino acids remains unknown. We aim to investigate the effects of rTMS on NMDAR-related amino acids in serum of post-stroke patients.

Ninety-five consecutive post-stroke patients with upper limb hemiparesis were recruited. In 27 patients, the Beck Depression Inventory (BDI) score was 10 or higher. Twelve depressed patients underwent rehabilitation in combination with rTMS and 15 non-depressed patients underwent rehabilitation only without rTMS for 14 days. 1 Hz rTMS was applied to the primary motor area in the non-lesional hemisphere. BDI was conducted before and after treatment. Serum glutamine, glutamate, glycine, l-serine, and d-serine levels were measured before and after treatment.

There were no differences between depressed patients and non-depressed patients in clinical characteristics, levels of the five amino acids in serum, and the ratio of amino acids. However, in 27 depressed patients, there was a significant correlation between levels of glutamate in serum and BDI (ρ = 0.428, p = 0.026). BDI decreased significantly in depressed patients after treatment with or without rTMS. d-serine decreased in the rehabilitation with rTMS group, but increased in the rehabilitation without rTMS group. l-serine increased in the rehabilitation with rTMS group, but decreased in the rehabilitation without rTMS group.

The results suggest that rTMS can modulate NMDAR-related amino acids in blood, producing beneficial effects.

Although alterations in the dendritic spine density in the brain regions may play a role in the stress-induced depression-like phenotype, the precise mechanisms are unknown. The aim was to investigate the role of spine density in the brain regions after chronic social defeat stress (CSDS).

We examined dendritic spine density in the medial prefrontal cortex (mPFC), CA1, CA3, dentate gyrus (DG) of hippocampus, nucleus accumbens (NAc), and ventral tegmental area (VTA) of susceptible and resilient mice after CSDS.

Spine density in the prelimbic area of mPFC, CA3, and DG in the susceptible group, but not resilient group, was significantly lower than control group. In contrast, spine density in the NAc and VTA in the susceptible group, but not resilient group, was significantly higher than control group.

The results suggest that regional differences in spine density may contribute to resilience versus susceptibility in mice subjected to CSDS.

The product of the G72 gene is an activator of d-amino acid oxidase and has been suggested to play a role in the pathogenesis of schizophrenia. Increased G72 protein levels may be associated with disturbed glutamatergic transmission and increased reactive oxygen species. Only one pilot study by Lin et al. has investigated the potential role of serum G72 protein levels as a biomarker for schizophrenia. In this study, we aimed to compare serum G72 protein levels between patients with schizophrenia and healthy controls, and to retest the results of the previous pilot study.

In total, 107 patients with a diagnosis of schizophrenia according to the inclusion and exclusion criteria and 60 age–sex-matched healthy controls were included in the study. The groups were compared regarding serum G72 protein levels.

The mean serum G72 protein values were 495.90±152.03 pg/ml in the schizophrenia group and 346.10±102.08 pg/ml in the healthy control group. The mean serum G72 protein level was significantly increased in the schizophrenia group compared with the healthy control group (t=−3.89, p<0.001). A receiver operating characteristics analysis was performed to compare the schizophrenia and healthy control groups. It was determined that the cut-off value was 141.51 pg/ml with a sensitivity of 0.991 and a specificity of 0.821.

We suggest that serum G72 protein levels may represent a candidate biomarker for schizophrenia and have confirmed the results of the previous preliminary study. Additional studies with larger sample sizes and the inclusion of first episode schizophrenia patients are required to clarify the reliability and validity of serum G72 protein levels as a biomarker for schizophrenia.

Glutamatergic neurotransmission via the N-methyl-d-aspartate (NMDA) receptor is integral to the pathophysiology of depression. This study was performed to examine whether amino acids related to NMDA receptor neurotransmission are altered in the serum of patients with depression.

We measured the serum levels of d-serine, l-serine, glycine, glutamate and glutamine in patients with depression (n=70), and age-matched healthy subjects (n=78).

Serum levels of d-serine and l-serine in patients with depression were significantly higher than those of healthy controls (p<0.001). In contrast, serum levels of glycine, glutamate and glutamine did not differ between the two groups. Interestingly, the ratio of l-serine to glycine in patients was significantly higher than that of healthy controls (p<0.001).

This study suggests that serine enantiomers may be peripheral biomarkers for depression, and that abnormality in the d-serine-l-serine-glycine cycle plays a role in the pathophysiology of depression.

Treatment-resistant depression is a challenging problem in the clinical setting. Tipepidine has been used as a non-narcotic antitussive in Japan since 1959.

We administered tipepidine to 11 patients with treatment-resistant depression. Tipepidine was given for 8 weeks as an augmentation.

Tipepidine significantly improved depression scores on the Hamilton Rating Scale for depression. Add-on treatment with tipepidine significantly improved scores on the trail making test and Rey auditory verbal learning test. However, no changes were observed in blood concentrations of stress-related hormones (adrenocorticotropic hormone, cortisol, dehydroepiandrosterone sulphate) with tipepidine augmentation.

Tipepidine might be a potential therapeutic drug for treatment-resistant depression.

Accumulating evidences suggest that pro-inflammatory cytokines such as interleukin-6 (IL-6) play a role in the pathophysiology of depression. In the learned helplessness (LH) paradigm, ~35% rats are resilient to inescapable stress.

Levels of IL-6 in the serum and medial prefrontal cortex (mPFC) of LH rats (susceptible) and non-LH rats (resilience) were measured using enzyme-linked immunosorbent assay and western blot analysis, respectively.

Serum levels of IL-6 in the LH rats were significantly higher than those of control and non-LH rats. In contrast, tissue levels of IL-6 in the mPFC were not different among three groups.

The results suggest that peripheral IL-6 may contribute to resilience versus susceptibility to inescapable stress.

A recent clinical study demonstrated that sodium benzoate (SB), a prototype competitive d-amino acid oxidase inhibitor, was effective in the treatment of several symptoms, such as positive and negative symptoms, and cognitive impairment in medicated patients with schizophrenia. The objective of the study was to examine the effects of SB on behavioural abnormalities such as pre-pulse inhibition (PPI) deficits and hyperlocomotion in mice after a single administration of the N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine (PCP).

The effects of SB on behavioural abnormalities (PPI deficits and hyperlocomotion) in mice after PCP administration were examined. Furthermore, effects of SB on tissue levels of amino acids were also examined.

A single oral dose of SB (100, 300, or 1000 mg/kg) attenuated PPI deficits in mice after administration of PCP (3.0 mg/kg, s.c.) in a dose-dependent manner. In contrast, L-701,324 (10 mg/kg), an antagonist at the glycine site of the NMDA receptor, did not affect the effect of SB (1000 mg/kg) on PCP-induced PPI deficits. Furthermore, a single oral dose of SB (1000 mg/kg) significantly attenuated the hyperlocomotion in mice after administration of PCP (3.0 mg/kg, s.c.). However, a single oral dose of SB (1000 mg/kg) caused no changes to d-serine levels in plasma or in the frontal cortex, hippocampus, and striatum of these animals.

This study suggests that SB induced antipsychotic effects in the PCP model of schizophrenia, although it did not increase d-serine levels in the brain.