Noboru Fujise

Role of Blood Vessels in Producing Pathological Changes in the Brain with Alzheimer's Disease

Abstract: Vascular factors have been shown to be highly involved in the deposition of the amyloid β‐protein (Aβ) in the brain of Alzheimers disease (AD). However, the detailed mechanism remains unknown. Here, we showed that more numerous deposits of Aβ40 and Aβ42 in the brain were found in AD patients than in controls. Together with evidence of no difference in the level of Aβ40 and Aβ42 in sera between sporadic AD and conrols, a certain dysfunction of the blood‐brain barrier could induce an abnormal transport of Aβ from sera to the parenchyma in AD. In addition, vascular Aβ deposits and mature Aβ plaques stained by Congo red in AD brains contained more Aβ40 than Aβ42, whereas Congo red‐negative immature plaques mainly consisted of Aβ42. Our confocal laser scanning microscopy demonstrated an intimate relationship between Aβ40 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 Aβ40 and/or Aβ42 cause Aβ40 deposition in and around blood vessels through unknown but possible mechanisms such as (1) endocytosis of Aβ40, (2) selective transport Aβ40 and Aβ42 into blood vessels and the parenchyma, respectively, and (3) proteolysis of Aβ42 into Aβ40 induced by a putative carboxyl dipeptidase in blood vessels including vascular feet, which is involved in Aβ fibrillation and cognitive deterioration in the patients. Therefore, the accumulation of Aβ40 associated with blood vessels may play a critical role in the development of AD.

Living alone is associated with depression among the elderly in a rural community in Japan

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.

Comparisons of the prevalence of and risk factors for elderly depression between urban and rural populations in Japan

BACKGROUND The aim of the present study was to investigate the differences in the prevalence of and risk factors for elderly depression between urban and rural areas in Japan and to further understanding of the features of elderly depression. METHODS A multistage, random sampling procedure and mailing method were used in urban and rural areas in Kumamoto Prefecture. A total of 2,152 participants aged 65 years and older were evaluated for depression using the Geriatric Depression Scale (GDS). Factors associated with depression were also examined. In order to assess the relationship between risk factors and subjective happiness, the Philadelphia Geriatric Center Morale Scale (PGC-MS) was used. RESULTS Depressive symptoms were associated with living alone, being unemployed, chronic illness, sleep disturbance, suicidal ideation, financial strain, and poor social support; the risk factors for elderly depression were almost the same in the two areas. Although three factors (financial strain, work status, and PGC-MS) were significantly associated with depression in both areas on logistic regression analysis, sleep disturbance was significant only for the urban area, and poor social support was significant only for the rural area. CONCLUSIONS Although factors related to depression did not differ markedly between urban and rural elderly people, some risk factors differed between the two areas. Effective intervention programs for elderly depression should pay more attention to regional differences.

Identification of an aging-related spherical inclusion in the human brain.

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 Alzheimers disease. This inclusion was spherical and 3–20 µm 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.

Mental health among younger and older caregivers of dementia patients

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.

Suicidal ideation and related factors among dementia patients

BACKGROUND 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. METHODS 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. RESULTS 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) (P<0.001). Caregivers of patients with suicidal ideation felt a higher caregiver burden, even after adjusting for BPSD score (P<0.01). LIMITATIONS 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. CONCLUSIONS 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.

Malnutrition in Alzheimer’s Disease, Dementia with Lewy Bodies, and Frontotemporal Lobar Degeneration: Comparison Using Serum Albumin, Total Protein, and Hemoglobin Level

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.

A comparison of Geriatric Depression Scale scores in older Australian and Japanese women.

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 Womens 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.

Comparisons of prevalence and related factors of depression in middle-aged adults between urban and rural populations in Japan.

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.

Effect of lamotrigine in the treatment of bipolar depression with psychotic features: a case report

BackgroundMajor depressive episodes with psychotic features are more common in bipolar disorder than in major depressive disorder; however, there is little information on the optimal treatment for bipolar depression with psychotic features.Case presentationThe patient was a 69-year-old man. At the age of 66, he was admitted to the hospital for the treatment of bipolar depression with psychotic features. He was treated with a combination therapy of antipsychotics and antidepressants during long-term hospitalization. At the age of 69, he relapsed and was admitted to the hospital again. He was initially treated with olanzapine and lithium for the treatment of bipolar depression with psychotic features. He partially responded to the combination therapy, and psychomotor retardation and delusion of guilt disappeared; however, he developed psychomotor agitation and delusion of persecution, which was a mood-incongruent psychotic feature. Finally, he fully recovered with an additional dosage of lamotrigine, and had no experience of relapse after discontinuation of olanzapine.ConclusionsThis case report implicates the utility of lamotrigine for bipolar depression with psychotic features, and further studies are needed to establish the optimal treatment.