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The Committee for Treatment Guidelines of Mood Disorders, Japanese Society of Mood Disorders, published a Japanese guideline for the treatment of late-life depression in 2020. Based on that guideline, the present guideline was developed and revised to incorporate the suggestions of global experts and the latest published evidence. In the diagnosis of late-life depression, it is important to carefully differentiate it from bipolar disorders, depressive states caused by physical and organic brain disease, drug effects, and dementia, and to determine the comorbidity between late-life depression and dementia. It is necessary to fully understand the clinical characteristics and psychosocial background of late-life depression, evaluate the patient's condition, and provide basic interventions based on these factors. Problem-solving therapy, reminiscence therapy/life review therapy, and behavioral activation therapy, and other forms of psychotherapy can reduce depressive symptoms. In terms of pharmacotherapy, newer antidepressants or non-tricyclic antidepressants are recommended for late-life depression, and it is recommended that the efficacy of least the minimal effective dosage should first be determined. Switching antidepressants and aripiprazole augmentation can be used to treatment-resistant therapy. Electroconvulsive therapy and repetitive transcranial magnetic stimulation have demonstrated usefulness for late-life depression. Exercise therapy, high-intensity light therapy, and diet therapy also show some effectiveness and are useful for late-life depression. Continuation therapy should be maintained for at least 1 year after remission.

Aim Caregiver burden in dementia is an important issue, but few studies have examined the mental health of younger and older family caregivers by comparing them with age- and gender-matched community residents. We aimed to compare the mental health of dementia caregivers with that of community residents and to clarify factors related to mental health problems in younger and older caregivers. Methods We studied 104 dementia caregivers; 46 were younger (

Background Findings of urban-rural differences in the prevalence of depression have been controversial, and few reports have directly compared the related factors of depression between urban and rural areas. The present study aimed to investigate differences between urban and rural areas in Japan with regards to the prevalence of and related factors of depression in middle-aged adults, in order to further understanding of the features of depression in this demographic. Methods We used a multistage, random sampling procedure and mailing method. In total, 5000 participants were recruited from urban and rural areas in Kumamoto Prefecture (2500 in each area). Participants were aged from 40 to 64 years. Depression was assessed using the Center for Epidemiologic Studies Depression scale (CES-D). Results The prevalence of middle-aged depression was not different between the urban and rural areas. Logistic regression analysis found that being female, living alone, and having a chronic illness were significantly associated with depression in urban-dwelling middle-aged adults. Younger age, sleep disturbance, and financial strain were significantly associated with depression in both urban and rural areas. Limitations The definition of depression was based on CES-D scores, without corroborating clinical evaluation. Conclusions We found no marked differences in the prevalence of middle-aged depression between the urban and rural areas. Some related factors of depression in middle-aged adults differed between urban and rural areas in Japan. Effective intervention programs for middle-aged adults with depression should consider regional differences.

It is generally thought that people with dementia are not able to attempt suicide because of impaired executive function. Little research is available about suicidal ideation among dementia patients. The present study examines 1) the sociodemographic and clinical features of dementia patients with suicidal ideation and 2) the effect of suicidal ideation on caregiver burden.A total of 634 dementia outpatients and their family caregivers participated in this study. Comparisons of variables were made among three groups: patients with suicidal ideation, patients with depression without suicidal ideation, and patients with neither suicidal ideation nor depression. Data were collected between April 2007 and July 2013.Suicidal ideation was seen in 64 patients (10.1%). Patients with suicidal ideation had a significantly higher rate of behavioural and psychological symptoms of dementia (BPSD) (P0.001). Caregivers of patients with suicidal ideation felt a higher caregiver burden, even after adjusting for BPSD score (P0.01).Suicidal ideation was assessed by interview with caregivers, so we may have overlooked people who had suicidal ideation but did not express it to their caregivers.Suicidal ideation among dementia patients should receive greater attention. Adequate assessment of suicidal ideation and psychological support for both patients with suicidal ideation and their caregivers are needed.

Background For patients starting treatment for depression, current guidelines recommend titrating the antidepressant dosage to the maximum of the licenced range if tolerated. When patients do not achieve remission within several weeks, recommendations include adding or switching to another antidepressant. However, the relative merits of these guideline strategies remain unestablished. Methods This multi-centre, open-label, assessor-blinded, pragmatic trial involved two steps. Step 1 used open-cluster randomisation, allocating clinics into those titrating sertraline up to 50 mg/day or 100 mg/day by week 3. Step 2 used central randomisation to allocate patients who did not remit after 3 weeks of treatment to continue sertraline, to add mirtazapine or to switch to mirtazapine. The primary outcome was depression severity measured with the Patient Health Questionnaire-9 (PHQ-9) (scores between 0 and 27; higher scores, greater depression) at week 9. We applied mixed-model repeated-measures analysis adjusted for key baseline covariates. Results Between December 2010 and March 2015, we recruited 2011 participants with hitherto untreated major depression at 48 clinics in Japan. In step 1, 970 participants were allocated to the 50 mg/day and 1041 to the 100 mg/day arms; 1927 (95.8%) provided primary outcomes. There was no statistically significant difference in the adjusted PHQ-9 score at week 9 between the 50 mg/day arm and the 100 mg/day arm (0.25 point, 95% confidence interval (CI), − 0.58 to 1.07, P = 0.55). Other outcomes proved similar in the two groups. In step 2, 1646 participants not remitted by week 3 were randomised to continue sertraline (n = 551), to add mirtazapine (n = 537) or to switch to mirtazapine (n = 558): 1613 (98.0%) provided primary outcomes. At week 9, adding mirtazapine achieved a reduction in PHQ-9 scores of 0.99 point (0.43 to 1.55, P = 0.0012); switching achieved a reduction of 1.01 points (0.46 to 1.56, P = 0.0012), both relative to continuing sertraline. Combination increased the percentage of remission by 12.4% (6.1 to 19.0%) and switching by 8.4% (2.5 to 14.8%). There were no differences in adverse effects. Conclusions In patients with new onset depression, we found no advantage of titrating sertraline to 100 mg vs 50 mg. Patients unremitted by week 3 gained a small benefit in reduction of depressive symptoms at week 9 by switching sertraline to mirtazapine or by adding mirtazapine. Trial registration ClinicalTrials.gov, NCT01109693. Registered on 23 April 2010. Electronic supplementary material The online version of this article (10.1186/s12916-018-1096-5) contains supplementary material, which is available to authorized users.

Malnutrition among dementia patients is an important issue. However, the biochemical markers of malnutrition have not been well studied in this population. The purpose of this study was to compare biochemical blood markers among patients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). A total of 339 dementia outpatients and their family caregivers participated in this study. Low serum albumin was 7.2 times more prevalent among patients with DLB and 10.1 times more prevalent among those with FTLD than among those with AD, with adjustment for age. Low hemoglobin was 9.1 times more common in female DLB patients than in female AD patients, with adjustment for age. The levels of biochemical markers were not significantly correlated with cognitive function. Family caregivers of patients with low total protein, low albumin, or low hemoglobin were asked if the patients had loss of weight or appetite; 96.4% reported no loss of weight or appetite. In conclusion, nutritional status was worse in patients with DLB and FTLD than in those with AD. A multidimensional approach, including blood testing, is needed to assess malnutrition in patients with dementia.

Aim: This study aimed to investigate factors associated with depression in a sample of elderly Japanese individuals in a rural community and to examine differences among factors associated with individuals living alone or living with others. Methods: Using a population-based sample from rural Japan, we assessed a total of 1552 participants aged 65 years or older by mailing a survey and evaluating responses based on the Geriatric Depression Scale. Factors associated with depression were also examined. Results: We received 964 valid responses. Depressed subjects comprised 20.5% of the sample. Living alone was significantly related to depression. In individuals living alone, depression was associated with loss of appetite, suicidal ideation, financial strain, and worries in life. However, multiple linear regression analyses revealed that the influence of living alone was negated by having a good social support system. Conclusion: These findings confirm that living alone is an important factor in depression among the elderly in a rural part of Japan. Results also confirm what others have found in Western cultures: high levels of social support, awareness of receiving social support, and willingness to receive assistance may reduce the risk of depression.

本研究は、行動化（言葉にできずに自傷や暴力など行動に表現すること）を有する青年にケア提供を行っている家族・看護者のストレス軽減を目的としたグループ・コンサルテーションを実施し、その活動の実態を記述し評価することを目的とした。, The purpose of this study was to describe the outcome of group consultation for caregivers who take care of patients act out at home and in the hospitals.

Caregiver burden in dementia is an important issue, but few studies have examined the mental health of younger and older family caregivers by comparing them with age- and gender-matched community residents. We aimed to compare the mental health of dementia caregivers with that of community residents and to clarify factors related to mental health problems in younger and older caregivers.We studied 104 dementia caregivers; 46 were younger (65 years) and 58 were older (≥65 years). A total of 104 community residents who were matched for age and gender were selected. We compared depression (Center for Epidemiologic Studies Depression Scale for younger participants; Geriatric Depression Scale for older participants), health-related quality of life (QOL) short-form health survey (SF-8), sleep problems, and suicidal ideation between the caregivers and community residents by age. Behavioural and psychological symptoms of dementia, activities of daily living (ADL), and instrumental ADL were assessed among patients with dementia using the Neuropsychiatric Inventory, Physical Self-Maintenance Scale, and Lawton Instrumental ADL Scale, respectively.According to SF-8 results, both younger and older caregivers had significantly worse mental QOL than community residents (younger caregivers: 46.3 vs community residents: 49.7, P = 0.017; older caregivers: 48.2 vs community residents: 51.1, P = 0.024) but were not more depressive. Sleep problems were significantly more frequent in younger caregivers (39.1%) than in community residents (17.0%) (P = 0.017). Multiple regression analysis revealed that caregivers' deteriorated mental QOL was associated with patients' behavioural and psychological symptoms of dementia in younger caregivers and with dementia patients' instrumental ADL and female gender in older caregivers.Dementia caregivers had a lower mental QOL than community residents. To maintain caregivers' mental QOL, it is necessary to provide younger caregivers with skills or professional interventions for dealing with behavioural and psychological symptoms of dementia, and older caregivers must be offered adequate care support.

Inclusions, such as corpora amylacea, axonal spheroids and ubiquitin-positive granular structures, are present in aged brains. We found a phosphorylated tau-positive inclusion in brain tissues obtained from 13 non-demented subjects and five patients with Alzheimer's disease. This inclusion was spherical and 3-20 microm in size. It was most frequently detected in the hippocampal CA1 region and in the prosubiculum but was not present in the white matter. The density of this inclusion increased significantly with aging and decreased after the occurrence of neurofibrillary tangles. The presence of the inclusion was confirmed using immunoelectron microscopy. These findings show a possibility that the inclusion is a novel aging-related structure in the human brain.

Background In responses to self-reported depression screening questionnaires, item non-response, which refers to the absence of answers to specific questions, is problematic. The objective of this study were (1) to clarify the features of respondents with item non-response on a self-reported elderly depression screening questionnaire (15-item geriatric depression scale; GDS-15) as compared to respondents with full responses, and (2) to compare positive depression screening rates calculated using two methods: excluding respondents with item non-response (complete case analysis; CCA) and estimating by multiplying mean scores from valid responses by the total number of GDS-15 items for respondents with item non-response. Methods This was a cross-sectional study conducted from 2010 to 2012. Of 4794 elderly subjects (65 years and older) living in one town in Japan 2836 community-dwelling elderly people (59.2%) were included in the analysis. Results Item non-response was observed in 25.0% of respondents. Respondents with item non-response had a higher rate of depression and mental and physical problems. Respondents with depression (estimated GDS-15 score ≥6) and suicidal ideation both had a 1.6-times higher risk of item non-response on the GDS-15. The positive depression screening rate on GDS-15 by CCA was 16.5%, compared with 18.9% when calculated by the estimated GDS-15 score. Limitations Our survey was conducted in one rural area and targeted only elderly people. Conclusion The incidence of item non-response among community-dwelling elderly people was associated with depression of the respondent. Excluding subjects with item non-response when calculating positive depression screening rates in elderly individuals causes the rate to be underestimated.

Vascular factors have been shown to be highly involved in the deposition of the amyloid beta-protein (A beta) in the brain of Alzheimer's disease (AD). However, the detailed mechanism remains unknown. Here, we showed that more numerous deposits of A beta 40 and A beta 42 in the brain were found in AD patients than in controls. Together with evidence of no difference in the level of A beta 40 and A beta 42 in sera between sporadic AD and controls, a certain dysfunction of the blood-brain barrier could induce an abnormal transport of A beta from sera to the parenchyma in AD. In addition, vascular A beta deposits and mature A beta plaques stained by Congo red in AD brains contained more A beta 40 than A beta 42, whereas Congo red-negative immature plaques mainly consisted of A beta 42. Our confocal laser scanning microscopy demonstrated an intimate relationship between A beta 40 and the vascular network. The amount of mature plaques but not that of immature plaques was reportedly correlated with the severity of dementia in AD patients. These results suggest that serum-derived A beta 40 and/or A beta 42 cause A beta 40 deposition in and around blood vessels through unknown but possible mechanisms such as (1) endocytosis of A beta 40, (2) selective transport A beta 40 and A beta 42 into blood vessels and the parenchyma, respectively, and (3) proteolysis of A beta 42 into A beta 40 induced by a putative carboxyl dipeptidase in blood vessels including vascular feet, which is involved in A beta fibrillation and cognitive deterioration in the patients. Therefore, the accumulation of A beta 40 associated with blood vessels may play a critical role in the development of AD.

Apathy includes aspontaneous, indifferent behavior, with loss of motor and affective drive. Apathy is related to the disruption, at various anatomical sites, of frontosubcortical pathways, such as anterior cingulate and bithalamic lesions. Apathy was frequently reported in patients with Alzheimer's disease, post-stroke, and frontotemporal dementia. It is very important to distinguish apathy from depression by the therapeutic view point.

This study aimed to investigate factors associated with depression in a sample of elderly Japanese individuals in a rural community and to examine differences among factors associated with individuals living alone or living with others.Using a population-based sample from rural Japan, we assessed a total of 1552 participants aged 65 years or older by mailing a survey and evaluating responses based on the Geriatric Depression Scale. Factors associated with depression were also examined.We received 964 valid responses. Depressed subjects comprised 20.5% of the sample. Living alone was significantly related to depression. In individuals living alone, depression was associated with loss of appetite, suicidal ideation, financial strain, and worries in life. However, multiple linear regression analyses revealed that the influence of living alone was negated by having a good social support system.These findings confirm that living alone is an important factor in depression among the elderly in a rural part of Japan. Results also confirm what others have found in Western cultures: high levels of social support, awareness of receiving social support, and willingness to receive assistance may reduce the risk of depression.

A 40-year-old man with an anxiety disorder developed sudden-onset right-hand tremor after a fixation wire for a tibial bone fracture was removed. He manifested a resting and action tremor with an irregular pattern. A coherence entrainment test (CET) revealed that the peak power spectral frequency of the right finger tremor was not entrained by simultaneous voluntary left finger tapping, which indicated a non-psychogenic origin. Deep brain stimulation to the left thalamic ventral intermediate nucleus abolished the tremor. We concluded that CET can determine the surgical indications for an unusual tremor that must be differentiated from that of psychogenic origin.

It has been noted the relationship between depression and dementia in elderly. The prevalence of depression in Alzheimer's disease (AD) was reported 20 to 30% in population-based study. Apathy was more frequently observed than depression among demented outpatients in our study. Whereas the apathy has been considered to be a kind of depression traditionally, it has been found that the apathy is distinct from depression recently. In our clinical practice, we frequently realize the close relationship between depression and dementia. It has been reported that risk of AD was 1.71 (odds ratio) in the history of depression more than 25 years ago, and interval between diagnoses of depression and AD was positively related to increased risk of developing AD, suggesting that rather than a prodrome, depression may be a risk factor for AD. Furthermore, Rotterdam Scan Study reported recently that the risk of AD increased to 3.76 in the history of pre-senile depression, while 2.34 in the history of senile depression. On the other hand, it is interesting but still controversial whether depression is associated with the conversion from mild cognitive impairment (MCI) into dementia. The underlying neuropathological condition that causes MCI or dementia might also cause depressive symptoms.

Previously we showed that large multipolar cells immunoreactive for calretinin and subunits 2 and 3 of amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type glutamate receptors (GluR2/3) clustered in the ventral hilus of the mouse dentate gyrus and revealed that they were mossy cells. Although such large calretinin immunoreactive cells were not seen in the dorsal hilus, our Golgi study revealed the presence of mossy cells in the dorsal hilus. As we observed large intensely GluR2/3 immunoreactive cells in the dorsal hilus, we suggested that these calretinin negative but intensely GluR2/3 positive large cells in the dorsal hilus were also mossy cells. In the present study we confirmed this identification with several methods. The extracellular tracer labeling studies revealed that all of 47 mossy cells identified morphologically were intensely GluR2/3 positive but calretinin negative, whereas none of 22 non-mossy hilar neurons were intensely GluR2/3 positive. Electron microscopically most of intensely GluR2/3 positive somata and dendritic processes showed the characteristic ultrastructural features of mossy cells. Furthermore, the fimbria-fornix-hippocampal commissure transection procedures induced the calretinin expression in some of these dorsal GluR2/3 immunoreactive cells. On the basis of these observations, we concluded that the vast majority of intensely GluR2/3 immunoreactive large cells in the mouse dorsal hilus were mossy cells. Then we evaluated the presumed difference in the distribution of mossy cells along the dorsoventral axis by the disector. The numerical density of mossy cells was about 1.4 times larger at the ventral level than at the dorsal level, indicating that the dorsoventral difference in the distribution of mossy cells in the mouse hilus was far smaller than that previously speculated.

In our previous study we revealed the presence of clustered large calretinin-immunoreactive multipolar cells in the ventral hilus of the mouse dentate gyrus and indicated that they might be mossy cells, the principal neurons in the dentate hilus. In the present study we confirmed this identification with several methods and analysed further in detail. In Golgi-impregnated samples mossy cells were easily identified by their locations and characteristic thorny excrescences on their proximal dendrites. Golgi-impregnated mossy cells were observed not only in the ventral hilus but also in the dorsal hilus, where no calretinin-immunoreactive large multipolar cells were encountered. Interestingly, mossy cells exhibited dorsoventral differences in the size and complexity of thorny excrescences; mossy cells at the dorsal and middle levels had larger and more complex thorny excrescences, which covered dendritic shafts for a longer distance, while ventral mossy cells had smaller, simpler and shorter thorny excrescences. Confocal laser scanning light microscopic observations at a high magnification showed that the vast majority of calretinin-immunoreactive large neurons in the ventral hilus displayed the thorny excrescences characteristic to mossy cells. Mossy cells identified with the intracellular injection of Lucifer Yellow were calretinin-immunoreactive. Electron microscopic observations clearly revealed that calretinin-immunoreactive elements showed structural features of mossy cells such as thorny excrescences receiving typical synapses from mossy fibre terminals. At the supragranular zone, a well-known target zone of mossy cell axons, a dense calretinin-immunoreactive band was seen, where numerous calretinin-immunoreactive punctae and fibres were packed. Electron microscopic observations revealed that these calretinin-immunoreactive axon terminals in the supragranular zone made asymmetrical synapses on presumed granule cell dendritic spines. Tracer injection studies and lesion experiments indicated that the supragranular calretinin-immunoreactive axon terminals mainly originated from the large calretinin-immunoreactive multipolar cells in the ipsilateral ventral hilus. Fluorescent double immunostaining for calretinin and glutamate receptor 2/3 (GluR2/3) revealed that all large calretinin-immunoreactive hilar cells in the ventral level were GluR2/3-immunoreactive and almost all intensely GluR2/3-immunoreactive hilar cells in the ventral level were calretinin-immunoreactive. In addition intensely GluR2/3-immunoreactive but calretinin-negative large cells were encountered in the dentate hilus at the dorsal level. On the basis of these observations, we concluded that large calretinin-immunoreactive cells in the ventral hilus of the mouse dentate gyrus were really mossy cells and that mossy cells at the dorsal level were calretinin negative. The present study revealed that mouse mossy cells show the dorsoventral difference in the calretinin immunoreactivity and thus they are chemically heterogeneous.

Calretinin-containing elements were visualized with immunocytochemistry in the adult mouse dentate gyrus (DG). In the ventral DG calretinin immunoreactive (CR-IR) large multipolar cells were clustered; they extended between two and four thick cylindrical dendrites which further branched into several thinner processes. Characteristic grape-like spiny appendages were occasionally observed on these thick and thinner dendritic processes. On the basis of these structural features these large CR-IR cells were identified as hilar mossy cells. At the supragranular zone a dense CR-IR band was seen, where numerous CR-IR punctae and fibers were packed tightly among putative granule cell dendrites. In the granule cell layer, especially at the dorsal DG, numerous faintly CR-IR cells were located at the interface with the hilus. They were triangular in shape and neither calbindin D28k nor GABA positive, but were immunoreactive for highly polysialylated neural cell adhesion molecule (NCAM-H) and thus considered as newly generated neurons. In the molecular layer CR-IR cells were also scattered; they were mainly located near the pial surface and the hippocampal fissure, small in size, ovoid in shape and usually gave rise to one very thin axon-like and one thin cylindrical dendritic process. These cells were assumed to be Cajal-Retzius cells. Throughout the layers, that is, the molecular layer, the granule cell layer and the hilus, CR-IR multipolar and/or fusiform cells were encountered. They resembled those reported in the rat DG in their structural features and usually extended smooth or varicose or sparsely spiny dendritic processes; some of them were confirmed to be GABA-like immunoreactive and/or glutamic acid decarboxylase immunoreactive. The present study showed that CR immunoreactivity in the mouse DG differed significantly from that in the rat and monkey dentate gyri reported previously.

Aims:The aim of this study was to compare the prevalence of depressive symptoms in Australian and Japanese populations of community-dwelling older women using the Geriatric Depression Scale (GDS-15). In addition, the relationship between lifestyle and health factors and higher ratings of depressive symptoms was also examined to determine if there were culturally consistent risk factors associated with higher depressive symptom scores.Methods:A total of 444 community based women aged between 65 and 77 years completed a depressive symptom measure (GDS-15) and provided information on common lifestyle factors. The Australian sample (n = 222) were drawn from the Women's Healthy Ageing Project and the age-matched, Japanese sample from the Kumamoto Ageing Study of Mental Health (n = 222). The GDS was chosen to; (1) reduce the impact of physical symptoms associated with old age and, (2) reduce the inflation in scores that may result from the Japanese tendency to endorse somatic items more often than Western adults.Results:Mean GDS total scores were significantly higher for the Japanese population 3.97 ± 3.69 compared with 1.73 ± 2.7 for Australian women. The percentages of women scoring in the normal; mild and moderate ranges for depression were 91, 7 and 2% for Australia and 67, 24 and 9% for Japan. Scores remained significantly higher for the Japanese cohort when controlling for lifestyle and health factors associated with depression. The analysis of lifestyle and health characteristics showed that the greatest difference between cohorts was in the area of living status, with more Australian women living with their partner and more than three times as many Japanese women living with their children. When the data for the countries was considered independently employment status affected the likelihood of higher depression scores in the Australian sample while heart disease and poor sleep impacted the risk for the Japanese population.Conclusions:Significantly more Japanese women scored within the mild and moderate ranges on the GDS compared with their Australian peers, even when controlling for possible confounding factors. Of the lifestyle and health factors assessed in this analysis no single variable was a common risk factor for higher depressive scores for both countries. The presence of cultural influences that may impact the risk of experiencing depressive symptoms, and culture specific patterns of item endorsement on depressive symptom measures, needs to be explored in more detail.