Association depressive symptoms with memory function and social capital before and during COVID-19 in community-dwelling older adults in rural Japan: A retrospective study with a longitudinal data.

OBJECTIVES: This study aimed to investigate the impact of memory function and social capital on depressive symptoms during the COVID-19 pandemic among older adults in rural Japan. METHODS: A retrospective study with longitudinal data was conducted during COVID-19 from May 2021 to November 2021 (T2) in Kurogawa, Japan. The candidate population for this study was 145 with the following requirements: (1) older individuals aged 65 years or above who were registered in the Kurogawa study, and (2) those with previous data (from November 2016 to February 2020; T1 as pre-pandemic). Memory function was assessed using the Wechsler Memory Scale-Revised Logical Memory II delayed recall part A (LM II-DR). Depressive symptoms were assessed using the Japanese version of the 15-item Geriatric Depression Scale (GDS-15). Social capital was evaluated through civic participation, social cohesion, and reciprocity. Fear of the COVID-19 infection (FCV-19S) was evaluated. RESULTS: The final analysis included 96 participants (mean age = 81.0 years, SD = 4.8) Multivariate analysis for GDS-15 score by Mixed Model Repeated Measures (MMRM) revealed significant associations between LM II-DR (ß = -0.13, 95% CI: -0.21-0.05, p = 0.002) and FCV-19S during COVID-19 (ß = 0.08, 95% CI: 0.01-0.15, p = 0.02) with GDS-15 score. However, civic participation, social cohesion and reciprocity were not associated with GDS-15 score. CONCLUSIONS: Among older adults in rural Japan, memory function and fear of the COVID-19 infection were significantly associated with depressive symptoms in MMRM analysis. However, social capital was not associated with depressive symptoms. This highlights the need to address memory function and fear of the COVID-19 infection in interventions for older adults during crises like the COVID-19 pandemic.

Salivary 3-methoxy-4-hydroxyphenylglycol and MRI-based volume change of the precuneus in community-dwelling elderly people.

BACKGROUND: The noradrenergic systems in the brain maintain cognitive functions including attention/concentration and establishment of long-term memory. In addition, hypofunction of noradrenergic systems is supposed to be involved in the pathophysiology of Alzheimer's disease. In this study, we tried to examine the possible associations of concentrations of basal salivary 3-methoxy-4-hydroxyphenylglycol (sMHPG), a major metabolite of noradrenaline, and brain volume changes during 4 years in elderly people living in a rural community. METHODS: The survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 226 residents. Measurements of sMHPG and brain MRIs were collected at Time 1 (2005-2007). Follow-up brain MRIs were taken at Time 2 (2009-2011). A total of 70 participants (18 men, mean age 71.9 ± 4.8 years; 52 women, mean age 72.0 ± 4.3 years) completed this survey. Concentrations of sMHPG at baseline were divided into two groups using the mean value (12.83 ng/ml). We compared the brain volumes between groups with higher and lower sMHPG concentrations over time using voxel-based morphometry implemented with statistical parametric mapping. RESULTS: In participants with higher sMHPG concentrations at baseline, brain volumes including right precuneus were significantly larger 4 years after baseline than those with lower sMHPG concentrations at baseline. No interaction between sMHPG concentration and MRI acquisition interval was found. CONCLUSION: Our results suggest that higher sMHPG concentrations in elderly people might be associated with maintenance of brain volume, especially in brain regions closely related to cognitive function.

Association between cortisol and aging-related hippocampus volume changes in community-dwelling older adults: a 7-year follow-up study.

BACKGROUND: Identifying peripheral biomarkers related to modifiable risk factors to prevent dementia at an early stage will be extremely beneficial. We have been studying how older adults can maintain their mental health and continue to live in a familiar community. The aim of this study is to investigate the association between serum cortisol levels and brain volume among older adults in rural Japan. METHODS: This was a longitudinal study conducted in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and above, as reported previously. We conducted a survey twice. The first survey was conducted from October 2009 to March 2011 (Timepoint 1) and the second was conducted from November 2016 to September 2017 (Timepoint 2). Blood samples for serum cortisol levels analysis were collected from participants at Timepoint 1. Serum cortisol levels were measured using the enzyme-linked immunosorbent assay. The participants underwent brain MRI examinations, and Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) for cognitive function assessment at Timepoint 1 and Timepoint 2. We obtained 70 participants (16 men, mean age 72.69 ± 3.18 years; 54 women, mean age 72.69 ± 4.60 years, at Timepoint 1) for analysis. Correlation analysis was performed between serum cortisol levels at baseline (Timepoint 1) and brain volume (Timepoint 1, Timepoint 2, and Timepoint 1-Timepoint 2 difference) using voxel-based morphometry method. RESULTS: There was no significant difference in serum cortisol levels between men (72.32 ± 17.30 ng/ml) and women (76.60 ± 21.12 ng/ml) at baseline. Additionally, no effect of blood collection time on cortisol levels was observed in these participants. Small volume correction analysis at the cluster level by applying multiple comparison corrections (family-wise error; P < 0.05) showed a negative correlation between serum cortisol levels (Timepoint 1) and brain volume (Timepoint 2) within the region containing the left hippocampus. CONCLUSIONS: Serum cortisol levels may serve as a peripheral biomarker of age-related volume changes involving the hippocampus in older adults aged 65 years and above.

Serum Oxytocin Levels and Logical Memory in Older People in Rural Japan.

OBJECTIVE: The present study aimed to investigate the relationship between serum oxytocin (OT) and logical memory among older people in rural Japan. METHODS: This was a cross-sectional study using a survey conducted from October 2009 through March 2011. Most of the study was conducted as part of a national prevalence survey of dementia in Japan. The final sample comprised 385 community-dwelling people aged 65 years or older living in rural Japan. The mean age and standard deviation were 75.7 ± 6.76 years (144 men, mean age 75.0 ± 6.48 years; 241 women, mean age 76.2 ± 6.91 years). The participants underwent screening examinations for a prevalence survey of dementia. The screening examinations were the Mini-Mental State Examination, Clinical Dementia Rating, and "logical memory A" from the Wechsler Memory Scale-Revised (WMSR). We used the WMSR Logical Memory II delayed recall score (LM II-DR) to assess logical memory. Levels of serum OT were obtained using the enzyme immunoassay method. RESULTS: Serum OT levels were significantly higher among women than men. The present study revealed that serum OT levels were positively associated with LM II-DR in older women living in rural Japan in multiple linear regression analyses. CONCLUSIONS: The present results suggested a positive correlation between OT and logical memory in older women living in rural Japan.

No association of both serum pro-brain-derived neurotrophic factor (proBDNF) and BDNF concentrations with depressive state in community-dwelling elderly people.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is involved in emotional and cognitive function. Low-BDNF levels occur in patients with depression, while proBDNF, a precursor of BDNF with the opposite physiological function, increases in major depression. However, it is unclear whether BDNF and proBDNF are associated with depression in the elderly. The present study aimed to investigate whether serum proBDNF and BDNF are associated with depressive state in community-dwelling elderly people. METHODS: This was a cross-sectional study conducted in Kurogawa-cho Imari, Saga Prefecture, Japan, in people aged ≥65 years. Depressive state was assessed using the Geriatric Depression Scale-Short Form (Japanese version) (GDS). Of the 274 patients who undertook the GDS, those with a medical history affecting cognitive function were excluded, as were those with Mini-Mental State Examination score ≥ 24 or a Clinical Dementia Rating < 0.5. Further, we used delayed recall of 'logical memory A' from the Wechsler Memory Scale-Revised (LMII-DR) for memory assessment. RESULTS: The final sample consisted of 155 individuals (mean age 75.4 ± 6.8 years; 55 men, mean age 74.8 ± 5.9 years; 100 women, mean age 76.3 ± 7.1 years). In the GDS, 139 participants showed a normal score (0-4) and 16 showed depressive tendencies or depression (score: ≥ 5). After examining confounders of the GDS, logistic regression using categorical covariates showed a negative significant difference between depressive state and serum BDNF in the low-BDNF group only, with a positive correlation in the trend test. None of the analyses showed any association between GDS and proBDNF levels. CONCLUSION: ProBDNF and BDNF levels seemed not to be associated with depressive state in community-dwelling elderly people.

Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia.

BACKGROUND: Microglia are resident innate immune cells which release many factors including proinflammatory cytokines or nitric oxide (NO) when they are activated in response to immunological stimuli. Pathophysiology of Alzheimer's disease (AD) is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling is important for microglial functions such as release of NO and cytokines. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of AD, while it remains unclear how donepezil, an acetylcholinesterase inhibitor, affects intracellular Ca2+ mobilization in microglial cells. METHODS: We examined whether pretreatment with donepezil affects the intracellular Ca2+ mobilization using fura-2 imaging and tested the effects of donepezil on phagocytic activity by phagocytosis assay in rodent microglial cells. RESULTS: In this study, we observed that pretreatment with donepezil suppressed the TNFα-induced sustained intracellular Ca2+ elevation in both rat HAPI and mouse primary microglial cells. On the other hand, pretreatment with donepezil did not suppress the mRNA expression of both TNFR1 and TNFR2 in rodent microglia we used. Pretreatment with acetylcholine but not donepezil suppressed the TNFα-induced intracellular Ca2+ elevation through the nicotinic α7 receptors. In addition, sigma 1 receptors were not involved in the donepezil-induced suppression of the TNFα-mediated intracellular Ca2+ elevation. Pretreatment with donepezil suppressed the TNFα-induced intracellular Ca2+ elevation through the PI3K pathway in rodent microglial cells. Using DAF-2 imaging, we also found that pretreatment with donepezil suppressed the production of NO induced by TNFα treatment and the PI3K pathway could be important for the donepezil-induced suppression of NO production in rodent microglial cells. Finally, phagocytosis assay showed that pretreatment with donepezil promoted phagocytic activity of rodent microglial cells through the PI3K but not MAPK/ERK pathway. CONCLUSIONS: These suggest that donepezil could directly modulate the microglial function through the PI3K pathway in the rodent brain, which might be important to understand the effect of donepezil in the brain.

An association between belief in life after death and serum oxytocin in older people in rural Japan.

OBJECTIVE: Previous research suggests that spirituality/religiosity has benefits for both mental and physical health, measured using biological indices such as cortisol and IL-6. However, there have been few studies concerning the association of religious beliefs with oxytocin, a neuropeptide hormone secreted by the pituitary. Levels of peripheral oxytocin are thought to reflect the strength of bonding and stress regulation in social relationships. As such, the oxytocin system may underpin the biological mechanisms by which belief in life after death is associated with good mental and physical health. Here, we examine associations between oxytocin and belief in life after death. METHODS: We recruited 317 community-dwelling people, aged 65 or older, without cognitive or mental deficits, and living in rural Japan. We recorded demographics, belief in life after death, and logical memory using the Wechsler Memory Scale. Levels of serum oxytocin were obtained using an enzyme immunoassay method. RESULTS: Serum oxytocin levels were higher among women than men and were negatively associated with strength of belief in life after death. CONCLUSIONS: Our findings could be interpreted differently depending on whether the anxiogenic or anxiolytic function of the oxytocin system is considered. Greater endorsement of afterlife beliefs may reduce secure attachment. Alternatively, based on the literature suggesting that basal levels of oxytocin are lower in those with reduced relational distress or anxiety, afterlife beliefs may play a role in these reductions. Copyright © 2016 John Wiley & Sons, Ltd.

Belief in life after death, salivary 3-methoxy-4-hydroxyphenylglycol, and well-being among older people without cognitive impairment dwelling in rural Japan.

OBJECTIVES: Research has found that spirituality/religiosity has a salutary association with mental/physical health. However, the association of belief in life after death with well-being has rarely been studied, and the same is true of its association with biological indices, such as monoamine transmitters. Therefore, we examined the associations between well-being and religiosity, salivary 3-methoxy-4-hydroxyphenylglycol (sMHPG), and demographic characteristics. METHODS: The participants were 346 community-dwelling people, aged 65 years or older, without cognitive or mental deficits, in rural Japan. Measures of religiosity consisted of belief in life after death, attachment to life, and experiences related to death and religion. The measures were assessed by scales specifically suited for Japanese religious orientations. Participants' well-being was assessed by a life satisfaction scale containing two subscales. We also measured sMHPG, a major metabolite of noradrenaline that is thought to reflect certain psychological states, such as psychomotor retardation and effortful attention. RESULTS: One subscale of life satisfaction was positively associated with belief in life after death and sMHPG, and the other life satisfaction subscale was positively associated with education and death/religion-related experiences (e.g., visiting family graves or loss of a friend). Gender differences were found in afterlife beliefs and each life satisfaction subscale. CONCLUSIONS: These results suggest that religiosity, including belief in life after death and death/religion-related experiences, is salubriously associated with mental health among older people, especially women, living in rural Japan. The basal level of sMHPG was positively associated with life satisfaction, but not with belief in life after death.

Association between sTREM2, an immune biomarker of microglial activation, and frontal lobe function in community-dwelling older adults: a cross-sectional study.

Objective: Identifying the peripheral biomarkers related to the prevention or modification of unhealthy mental conditions in older adults is extremely beneficial. This study aimed to evaluate the serum levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble form of an innate immune receptor expressed on microglia, in older adults living in a rural community, and their association with cognitive function. Materials and Methods: This survey was conducted between November 2016 and September 2017 in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged ≥65 years. Blood samples were collected from the participants for serum sTREM2 level analysis using a peptide enzyme immunoassay. The participants underwent cognitive function assessments, including the Mini-Mental State Examination, Clinical Dementia Rating, and Frontal Assessment Battery. Therefore, we examined the association between serum sTREM2 levels and cognitive function. Results: Of the 95 participants, 25 were men and 70 were women with a mean age 78.24 ± 3.85 years and 77.96 ± 5.52 years, respectively. Serum sTREM2 levels were negatively associated with Frontal Assessment Battery scores, even after adjusting for age, sex, years of education, and serum high-sensitivity C-reactive protein levels. Conclusion: Serum sTREM2 levels may be associated with frontal lobe function in adults aged ≥65 years.

Relationship between serum cortisol levels, stereotypies, and the presence of autism spectrum disorder in patients with severe intellectual disability.

Stereotypies are one of the diagnostic criteria for autism spectrum disorder (ASD) and are common to both ASD and intellectual disability (ID). Previous studies have been inconclusive, with some showing a positive correlation between stereotypies and cortisol, while others have shown a negative correlation. We hypothesised and investigated the presence of ASD as one of the variables involved in this discrepancy. We tested the following hypotheses on serum cortisol in a total of 84 hospitalised patients with severe ID and ASD with severe ID. Hypothesis (1) Higher levels of stereotypies are associated with higher levels of serum cortisol. Hypothesis (2) The presence of ASD will moderate the association between stereotypies and high serum cortisol levels. The results of the analysis supported hypotheses (1) and (2). We also found that in the population with ID, serum cortisol levels were significantly lower in the ASD group compared to the non-ASD group. The present findings that the association between stereotypies and serum cortisol levels in people with severe ID is moderated by the presence of ASD suggest that the stress response system may function differently in people with ID and ASD than in the general population.

Negative association between basal oxytocin and oxytocin changes after repetitive transcranial magnetic stimulation in patients with treatment-resistant depression.

Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulator effective for treating depressive symptoms in patients with treatment-resistant depression (TRD). One of the multiple mechanisms for its antidepressant effects proposed is related to the hypothalamus. Oxytocin is a neuropeptide synthesized in the hypothalamus that affects human behavior and psychology, including social and affiliative behaviors, stress regulation, and fear and emotion processing. There have been no reports on the relationship between rTMS and oxytocin for the treatment of TRD. Therefore, we aimed to investigate changes in salivary oxytocin concentrations in patients with TRD before and after 6 weeks of rTMS treatment. A total of 28 patients with TRD who received rTMS at Saga University Hospital between August 2013 and August 2020 were included. Although rTMS treatment significantly improved 24-item Hamilton Depression Rating Scale scores, rTMS treatment did not change mean salivary oxytocin after 6 weeks of treatment in patients with TRD. Multiple regression analysis revealed that the change in salivary oxytocin levels after rTMS treatment was negatively associated with basal oxytocin levels before rTMS treatment, suggesting that rTMS treatment tends to decrease oxytocin levels in patients with depression with high basal oxytocin levels while increasing them in those with low basal levels. These findings suggest that rTMS treatment improved depressive symptoms through mechanisms other than the modulatory effect on oxytocin levels in patients with TRD, while there is room for further studies to confirm these findings using a larger patient sample size and/or a sham rTMS procedure.

Saliva levels of 3-methoxy-4-hydroxyphenylglycol and clinical efficacy of mirtazapine or selective serotonin reuptake inhibitors in patients with major depression.

OBJECTIVE: This study compared saliva levels of 3-methoxy-4-hydroxyphenylglycol (sMHPG) in patients with major depressive disorder (MDD) to levels in healthy controls and explored whether sMHPG levels in patients with MDD were a predictive marker for antidepressant efficacy. METHODS: sMHPG levels were compared in 53 patients with MDD and 275 age-matched healthy controls. Patients' depressive symptoms were assessed by the 17-item Hamilton Rating Scale for Depression at baseline and 4 weeks after treatment with selective serotonin reuptake inhibitors (SSRIs, n = 23) or mirtazapine (n = 30), followed by saliva sampling. The mirtazapine group included nine patients who had been treated with an SSRI for more than 4 weeks without any improvement. sMHPG levels were measured by gas chromatography-mass spectrometry. RESULTS: sMHPG levels in MDD patients were significantly higher than in controls. The responder rate to drug treatment at 4 weeks was 62% for mirtazapine (13/21), 57% for SSRIs (13/23), and 89% (8/9) for SSRI plus mirtazapine. sMHPG at baseline in 13 responders treated with SSRIs, but not mirtazapine, was significantly higher than that in non-responder group and showed consequent reduction 4 weeks after treatment. The area under the receiver operating characteristic (ROC) curves of sMHPG for discrimination of SSRI responders and non-responders was 0.86 ± 0.10 (95% confidence interval: 0.64-1.0, p = 0.005). In contrast, the ROC curve of sMHPG levels for discrimination of mirtazapine responders and non-responders was not significant. Adjunctive treatment with mirtazapine to SSRI non-responders was effective, regardless of baseline sMHPG levels. CONCLUSION: sMHPG in patients with MDD was higher than in healthy controls. High baseline sMHPG levels in patients with MDD maybe a predictive marker for SSRI response.

Association between serum oxytocin levels and depressive state in community-dwelling older adults: A cross-sectional study.

Aim: Identifying peripheral biomarkers related to the prevention or modification of unhealthy mental conditions in older adults would be extremely beneficial. This study aimed to evaluate serum oxytocin levels in older adults living in a rural community and their association with cognitive function, anxiety, depressive state, and well-being. Methods: This survey was conducted between November 2016 and September 2017 in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged ≥65 years. Blood samples were collected from the participants for serum oxytocin level analysis, which was performed using peptide enzyme immunoassay. Participants underwent neuropsychological assessments, including the Mini-Mental State Examination, Clinical Dementia Rating, Frontal Assessment Battery, State-Trait Anxiety Inventory, 15-item Geriatric Depression Scale, and 17-item Philadelphia Geriatric Center Morale Scale. We examined the association between serum oxytocin levels and neuropsychological assessment results. Results: Out of 94 participants, 25 were men and 69 were women, with mean ages of 78.24 ± 3.85 years and 78.10 ± 5.43 years, respectively. Serum oxytocin levels were negatively associated with 15-item Geriatric Depression Scale scores. Additionally, nondepressive state/depressive state was classified by the 15-item Geriatric Depression Scale (cut-off 5/6). Logistic regression analysis showed that higher serum oxytocin levels tended to be associated with a less depressive state at that time. Conclusions: Serum oxytocin levels may be associated with depressive state in adults aged ≥65 years.

Serum oxytocin correlated with later logical memory in older Japanese women: A 7-year follow-up study.

Objectives: This study aimed to investigate the longitudinal relationship between serum oxytocin and logical memory among older adults in rural Japan and clarify sex differences in this relationship. Measurements: The first survey was conducted from October 2009 to March 2011 (Time 1) and the second from November 2016 to September 2017 (Time 2). The final analysis for Time 1 included 385 participants (median age 75 years, interquartile range [IQR] 70-81 years) and that for Time 2 included 76 participants (median age 80 years, IQR 76-83 years). We assessed cognition, logical memory, and living conditions, and measured serum oxytocin levels. Logical memory was evaluated using the Wechsler Memory Scale-Revised Logical Memory II delayed recall part A (LM II-DR). Serum oxytocin was measured using the enzyme immunoassay method. Results: The median (IQR) oxytocin level among men (n = 20) was 34 (16-78) pg/mL at Time 1 and 53 (28-140) pg/mL at Time 2. The median (IQR) oxytocin level among women (n = 56) was 117 (35-412) pg/mL at Time 1 and 76 (32-145) pg/mL at Time 2. The median oxytocin level among women at Time 2 was significantly lower than that at Time 1 (p = 0.004). The multivariate analysis showed that for women, LM II-DR score at Time 2 was positively associated with oxytocin level at Time 1 (p = 0.042) and negatively associated with age (p = 0.02). Conclusions: Our study suggests that maintaining high oxytocin levels in older women may prevent age-related decline in logical memory.

Serum soluble triggering receptor expressed on myeloid cells-2 was not altered by rTMS in patients with treatment-resistant depression.

AIM: Repetitive transcranial magnetic stimulation (rTMS) is one of the most effective and minimally invasive treatments for treatment-resistant depression (TRD). However, the mechanism underlying the therapeutic effects of rTMS in patients with TRD remains unclear. In recent years, the pathogenesis of depression has been closely associated with chronic inflammation and microglia are believed to play an important role in chronic inflammation. Triggering receptor expressed on myeloid cells-2 (TREM2) plays an important role in microglial neuroinflammatory regulation. In this study, we investigated the changes in peripheral soluble TREM2 (sTREM2) before and after rTMS treatment in patients with TRD. METHODS: Twenty-six patients with TRD were enrolled in this frequency (10 Hz) rTMS study. Depressive symptoms, cognitive function, and serum sTREM2 concentrations were measured at baseline and the end of the 6-week rTMS treatment. RESULTS: This study showed that rTMS ameliorated depressive symptoms and partially improved cognitive dysfunction in TRD. However, rTMS treatment did not alter serum sTREM2 levels. CONCLUSIONS: This is the first sTREM2 study in patients with TRD who underwent rTMS treatment. These results suggest that serum sTREM2 may not be relevant for the mechanism underlying the therapeutic effect of rTMS in patients with TRD. Future studies should confirm the present findings using a larger patient sample and a sham rTMS procedure, as well as CSF sTREM2. Furthermore, a longitudinal study should be conducted to clarify the effects of rTMS on sTREM2 levels.

Association of saliva 3-methoxy-4-hydroxyphenylglycol levels and a later depressive state in older subjects living in a rural community: 3-year follow-up study.

OBJECTIVE: The aim of the study was to examine the association of saliva levels of 3-methoxy-4-hydroxyphenylglycol (sMHPG) with a later depressive state in older people living in a rural community. METHODS: Baseline sMHPG levels were measured in 214 older subjects followed by completion of the Beck Depression Inventory (BDI) from 2004 to 2006 (time A). The same cohort underwent BDI again from 2007 to 2009 (time B). RESULTS: One hundred forty-four subjects (44 men, 100 women) were reassessed by the BDI. Baseline sMHPG levels in men with a BDI score of ≤9 at time A and a BDI score of ≥10 at time B were significantly higher than those in men with a BDI score of ≤9 at times A and B. In men, there was a significant correlation between baseline sMHPG levels and BDI score at time B (r = 0.40, p = 0.007) but not at time A (r = 0.29, p = 0.06). This association was not significant in women. CONCLUSION: These data indicate that high sMHPG levels at time A could be associated with a later depressive state in older men living in a community.

Baseline saliva level of 3-methoxy-4-hydroxyphenylglycole (MHPG) associates with a consequent cognitive decline in non-demented elderly subjects: three-years follow-up study.

The aim of the study was to explore the relation between saliva level of 3-methoxy-4-hydroxy-phenylglycol (MHPG) and a later cognitive decline in non-demented elderly subjects. We have reported that sMHPG in 214 elderly subjects living in the community (age 74.5±5.9years) was associated with scores on the Mini-Mental State Examination (MMSE) and the Frontal Assessment Battery (FAB) in 2004 to 2006 (Time A). The same cohort underwent these cognitive tests again from 2007 to 2009 (Time B). The cognitive function of the 147 of 214 subjects could be reassessed by the same cognitive tests. The score on the FAB, but not the MMSE, was significantly reduced at Time B (14.6±2.6) compared with that of Time A (15.2±1.9). There was a significant negative correlation between the baseline sMHPG and the changes in the FAB score subtracted from Time B to Time A or the scores on the FAB at Time B in men, but not at Time A. These correlations were not found in women. These data indicate that high sMHPG might be associated with subsequent cognitive decline assessed by the FAB in non-demented elderly men living in the community.

Changes in the metabolites of cerebrospinal fluid induced by rTMS in treatment-resistant depression: A pilot study.

Repetitive transcranial magnetic stimulation (rTMS) improves depressive symptoms in treatment-resistant depression (TRD). This study aimed to analyze changes in cerebrospinal fluid (CSF) metabolites in patients with TRD after rTMS. Five patients with TRD were enrolled in a high frequency (10-Hz) rTMS study. The concentration of 72 CSF metabolites were measured at baseline and at the end of the 6-week rTMS treatment. rTMS significantly increased CSF niacinamide, kynurenine, and creatinine levels and significantly decreased CSF cystine levels, but not the levels of the other 68 CSF metabolites. This is the first CSF metabolomics study on patients with TRD who underwent rTMS.

Association Between sTREM2, an Immune Biomarker of Microglial Activation, and Aging-Related Brain Volume Changes in Community-Dwelling Older Adults: A 7-Year Follow-Up Study.

BACKGROUND: This study aimed to investigate the association between serum levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble form of an innate immune receptor expressed on the microglia, and brain volume in older adults. METHODS: The survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 596 residents. Serum sTREM2 level measurements, brain MRI, Mini-Mental State Examination (MMSE), and clinical dementia rating (CDR) were performed at Time 1 (2009-2011). Follow-up brain MRI, MMSE, and CDR were performed at Time 2 (2016-2017). The interval between Time 1 and Time 2 was approximately 7 years. Sixty-nine participants (16 men, mean age 72.69 ± 3.18 years; 53 women, mean age 72.68 ± 4.64 years) completed this study. We analyzed the correlation between serum sTREM2 levels (Time 1) and brain volume (Time 1, Time 2, and Time 1-Time 2 difference) using voxel-based morphometry implemented with Statistical Parametric Mapping. RESULTS: Participants in this study had lower MMSE and higher CDR scores 7 years after the baseline evaluation. However, analyses at the cluster level by applying multiple comparison corrections (family wise error; P < 0.05) showed no correlation between serum sTREM2 levels and volume of different brain regions, either cross-sectional or longitudinal. CONCLUSION: Serum sTREM2 level could not serve as an immune biomarker of aging-related volume changes in brain regions closely related to cognitive function in older adults aged 65 years and above.