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Objective: Olfactory dysfunction is common in patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD). We sought to elucidate brain regions associated with olfactory dysfunction in patients with MCI and early AD by using 123I-IMP-SPECT to detect regional cerebral blood flow (CBF)., Methods: We included 218 patients diagnosed with AD or MCI, who underwent a comprehensive battery of neuropsychiatric and neuropsychological tests, Alzheimer's Disease Assessment Scale-Cognitive Part (ADAS-Cog), and forward- and backward-digit span. Olfactory function was assessed using T&T olfactometry of five odors; patients stated whether they experienced any smell (detection test) and identified the odor (identification test). The association between single-photon emission computerized tomography based regional CBF and olfactory function was examined by voxel-by-voxel multiple regression analysis, considering sex, age, and education as covariate parameters., Results: Of the 218 patients, 78 had mildly impaired olfactory detection and 15 had olfactory detection loss; additionally, 213 had mild olfactory identification impairment. The odor detection score correlated significantly with the ADAS-Cog word recall score (r = 0.193, p = 0.004). The odor identification score correlated significantly with the ADAS memory (r = 0.408, p < 0.001) and ADAS orientation (r = 0.292, p < 0.001) scores. The odor identification score correlated negatively with CBF in the left temporal pole, entorhinal area, and bilateral frontal poles (p < 0.001)., Conclusion: Olfactory identification dysfunction in patients with MCI and AD is attributable to reduced CBF of the left temporal pole, entorhinal area, and bilateral frontal pole., (© 2021 John Wiley & Sons Ltd.)

Background & Aims: We aimed to determine neural correlates of olfactory detection and identification and analyze associations between cognitive function and olfactory identification or detection in very mild amnestic patients., Methods: We recruited 70 patients with chief complaints of memory impairment diagnosed as amnestic mild cognitive impairment (MCI) or Alzheimer's disease (AD) with a clinical dementia rating of 0.5. Olfactory detection and identification were assessed using T&T olfactometry. A voxel-wise correlation analysis of gray matter volume and olfactometry scores was performed. We also analyzed correlations between neuropsychological results and olfactometry scores., Results: A significant negative correlation was observed between detection scores and nucleus accumbens and left parahippocampal gyrus volumes and between identification scores and orbitofrontal, right frontal, and right anterior temporal cortex volumes (p < .001). No significant correlation existed between detection and cognitive assessment scores. Identification score was significantly correlated with the Alzheimer's Disease Assessment Scale-Cognitive Part word recall score (r = 0.305, p = .01)., Conclusions: Olfactory detection and identification dysfunction were attributable to impairments in different regions in MCI and very early AD; the former was attributed to the olfactory circuit, while the latter to neocortices. The dysfunction of identification of olfactory information was associated with episodic memory in those patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Assessing driving aptitude in dementia patients is critically important for both patient and public safety. However, there have been only a few reports on the driving behaviours and accident risk of patients with dementia, especially frontotemporal lobar degeneration (FTLD). Therefore, we compared the characteristics of driving behaviours in patients with FTLD and those with Alzheimer's disease (AD)., Methods: The subjects were 28 FTLD and 67 AD patients who visited the Department of Psychiatry, Kochi Medical School Hospital. We conducted semi-structured interviews with their families and caregivers about traffic accident history and changes in patient driving behaviours after dementia onset and then compared the findings between the two groups., Results: Overall changes in driving behaviours were reported in 89% (25/28) and 76% (51/67) of the FTLD and AD patients, respectively (P = 0.17). In the FTLD group, difficulty in judging inter-vehicle distances, ignoring road signs and traffic signals, and distraction were reported in 50% (14/28), 61% (17/28), and 50% (14/28) of patients, respectively, and 75% (21/28) patients had caused a traffic accident after dementia onset. The risk of causing an accident was higher in the FTLD group than in the AD group (odds ratio = 10.4, 95% confidence interval = 3.7-29.1). In addition, the mean duration between dementia onset and a traffic accident was 1.35 years in the FTLD group compared with 3.0 years in the AD group (P < 0.01)., Conclusions: Patients with FTLD were more likely to show dangerous driving behaviours than those with AD, and the risk of causing a traffic accident may be higher in patients with FTLD from an early disease stage., (© 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.)

Stem cell transplantation therapy is currently in clinical trials for the treatment of ischemic stroke, and several beneficial aspects have been reported. Similarly, in Alzheimer's disease (AD), stem cell therapy is expected to provide an efficient therapeutic approach. Indeed, the intracerebral transplantation of stem cells reduced amyloid-β (Aβ) deposition and rescued memory deficits in AD model mice. Here, we show that intravenous transplantation of bone marrow-derived mononuclear cells (BMMCs) improves cognitive function in two different AD mouse models, DAL and APP mice, and prevents neurodegeneration. GFP-positive BMMCs were isolated from tibiae and femurs of 4-week-old mice and then transplanted intravenously into DAL and APP mice. Transplantation of BMMCs suppressed neuronal loss and restored memory impairment of DAL mice to almost the same level as in wild-type mice. Transplantation of BMMCs to APP mice reduced Aβ deposition in the brain. APP mice treated with BMMCs performed significantly better on behavioral tests than vehicle-injected mice. Moreover, the effects were observed even with transplantation after the onset of cognitive impairment in DAL mice. Together, our results indicate that intravenous transplantation of BMMCs has preventive effects against the cognitive decline in AD model mice and suggest a potential therapeutic effect of BMMC transplantation therapy., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Oxidative stress is known to play a prominent role in the onset and early stage progression of Alzheimer's disease (AD). For example, protein oxidation and lipid peroxidation levels are increased in patients with mild cognitive impairment. Here, we created a double-transgenic mouse model of AD to explore the pathological and behavioral effects of oxidative stress. Double transgenic (APP/DAL) mice were constructed by crossing Tg2576 (APP) mice, which express a mutant form of human amyloid precursor protein (APP), with DAL mice expressing a dominant-negative mutant of mitochondrial aldehyde dehydrogenase 2 (ALDH2), in which oxidative stress is enhanced. Y-maze and object recognition tests were performed at 3 and 6 months of age to evaluate learning and memory. The accumulation of amyloid plaques, deposition of phosphorylated-tau protein, and number of astrocytes in the brain were assessed histopathologically at 3, 6, 9, and 12-15 months of age. The life span of APP/DAL mice was significantly shorter than that of APP or DAL mice. In addition, they showed accelerated amyloid deposition, tau phosphorylation, and gliosis. Furthermore, these mice showed impaired performance on Y-maze and object recognition tests at 3 months of age. These data suggest that oxidative stress accelerates cognitive dysfunction and pathological insults in the brain. APP/DAL mice could be a useful model for exploring new approaches to AD treatment., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Expressed emotion (EE) research has been productive in investigating the influence of the interpersonal environment on a range of disorders. The majority of EE research on the influence of carers has been carried out in the west. This is the first EE study of the carers of people with dementia in Japan. The aim of this study was to investigate the relationships between EE status and aspect of burden through cross-cultural comparison of the two countries, Japan and England, with large cultural and linguistic differences. Comparisons were made between samples of EE of carers of dementia and schizophrenic patients. In total, data on 80 carer/relative-patient dyads were collected and examined: (1) 20 Japanese carers of people with dementia (JD), (2) 20 English carers of patients with Alzheimer's disease (ED), (3) 20 Japanese relatives of patients with schizophrenia (JS), and (4) 20 English relatives of patients with schizophrenia (ES). The Camberwell Family Interview was administered in each country to ascertain levels of EE. Large differences between Japan and England were found in the frequency of critical comments, in which ES>ED>JS>JD. EE correlated significantly with burden in the JD sample alone. With an operational cut-off of 2CC (CC, critical comments), EE correlated significantly with cognitive impairment as well as with clinical severity in the JD sample. There was a tendency for lower expression of both positive and negative emotional reactions towards family members in the Japanese sample. The results of this study indicate that EE is an appropriate measure for use with carers of sufferers of dementia and can be utilized across different cultures. However, flexibility with the cut-offs may be required in Eastern cultures. This needs to be tested on larger samples with sensitivity to illness and cross-cultural differences.

As a result of the growing proportion of drivers aged 65 years and older, it is estimated that the number of elderly drivers with dementia is increasing in Japan. Since June 2002, if a driver is found to be "demented", his/her driving license shall be revoked in Japan. However, there are no consensus guidelines for demented drivers. Between September 1995 and September 2001, we evaluated 30 drivers with dementia (19 males and 11 females, mean age of 69.4 years) in out patients clinic of the Kochi Medical School Hospital and related hospitals. Clinical Diagnosis was Alzheimer's disease in 20, vascular dementia in 3, mixed type dementia in 2, frontotemporal lobar degeneration in 4, other type dementia in 1. We analyzed their driving behavior and family's attitude. Seventy-three point three percent of 30 drivers with dementia continued to drive after diagnosis. In follow-up periods, number of drivers continuing driving was decreased to 13 (43.3%), while six drivers (27.3%) had a traffic accident or violation. Our study suggests that several important medical and social factors should be considered for the management of drivers with dementia. A consensus medical guideline for demented drivers has to be established.