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Aim The amyloid cascade hypothesis posits that the accumulation of amyloid β (Aβ) is the triggering factor for Alzheimer's disease, which consecutively induces aggregation of tau, synaptic loss, and cell death. Most experimental and clinical evidence supports this model, but the available data are largely qualitative. Here, we tested the amyloid cascade hypothesis by using in vivo evaluation of positron emission tomography and magnetic resonance imaging. Methods Path analysis was used to estimate the relationships among Aβ accumulation (PiB standardized uptake value ratio (SUVR)), tau aggregation and its related neuroinflammation (THK5351 SUVR), grey matter atrophy in the medial temporal region, and memory function in Aβ-positive subjects. We also performed additional regression analyses to evaluate the effect of Aβ on the toxicity of tau aggregation/neuroinflammation. Results Path analysis supported our hypothesized model: Aβ accumulation affected tau aggregation/neuroinflammation in the medial temporal region, and these pathological changes caused of the grey matter atrophy and memory dysfunction. In separate regression analyses, THK5351 SUVR had a significant effect on grey matter atrophy only in PiB-positive subjects. The analysis of the interaction effect showed that the effects of THK5351 SUVR on grey matter atrophy were significantly different between PiB-positive and PiB-negative groups. When we included the effect of being an apolipoprotein E e4 carrier as a covariate, the interaction effect remained significant. Conclusion Our in vivo evaluation of positron emission tomographic and magnetic resonance imaging data supported the amyloid cascade hypothesis. In addition, it indicated that Aβ not only accelerates tau aggregation/neuroinflammation but promotes its toxicity. Our findings showed the importance of understanding the role and therapeutic potential of the interaction between amyloid and tau aggregation/neuroinflammation in Alzheimer's disease.

Aim Educational attainment, occupation, and socioeconomic status have been regarded as major factors influencing cognitive reserve (CR). This study aimed to investigate the interaction effect of amyloid-β/tau burden and education/occupation/socioeconomic status as a proxy for CR on cognitive performance. Methods We analyzed the datasets of the Alzheimer's Disease Neuroimaging Initiative. We included clinically normal subjects and patients with mild cognitive impairment or Alzheimer's disease who had undergone a florbetapir scan within 1 year of a flortaucipir (AV-1451) scan (n = 127). Partial correlation analysis between the standardized uptake value ratio of florbetapir/AV-1451 and the proxy for CR was performed with the 13-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) score as a covariate. Stepwise multiple linear regression analysis was performed to determine the predictors of ADAS-cog performance based on the interaction between the imaging biomarkers and the proxy for CR. Results We found a significant positive partial correlation between educational level and tau pathology in Braak stage 1/2 areas, and we observed significantly higher tau accumulation among participants with higher education when ADAS-cog score was used as a covariate. The interaction between tau and education was a good predictor of cognitive function, with higher tau accumulation showing a greater association with higher ADAS-cog score among participants with less education than among those with more education. Conclusion Our findings indicate the protective effect of education against cognitive dysfunction in early-stage Alzheimer's disease pathology and suggest that education may exert a beneficial effect by reducing the adverse cognitive consequences of tau aggregation.

A community is the totality of human relationships, in which individuals live with and for others. This article discusses promoting dementia-friendly community from the perspective of human relationships within a community. Improving the social well-being of aging people is important; it is especially important for people with dementia, as dementia is a life-changing syndrome that affects all aspects of one's life, including human relationships. Dementia-friendly community requires support from the community in improving the social adaptation of people with dementia, as they experience greater difficulties in social interaction as a result of cognitive decline, especially deterioration of social cognition. They need to be empowered to stay motivated for the opportunity to maintain an active and meaningful life, despite dementia. Flexible provisions of such tailored support can be effective to improve the support network in the community to meet the individual's needs. As social and human resources are limited, it is also necessary to discuss how to share socioeconomic burdens to meet both social sustainability demands and the welfare of aging adults. More discussions that include people with dementia and their family members are required to achieve the purpose of dementia-friendly community. This is important to enhance the well-being of individuals with and without dementia, as well as the society as a whole, through dementia support and dementia prevention activities. Geriatr Gerontol Int 2020; ••: ••-••.

Objective The objectives of the present study were to investigate (1) whether trinary visual interpretation of amyloid positron emission tomography (PET) imaging (negative/equivocal/positive) reflects quantitative amyloid measurements and the time course of 11C-Pittsburgh compound B (PiB) amyloid accumulation, and (2) whether visually equivocal scans represent an early stage of the Alzheimer’s disease (AD) continuum in terms of an intermediate state of quantitative amyloid measurements and the changes in amyloid accumulation over time. Methods From the National Bioscience Database Center Human Database of the Japanese Alzheimer’s Disease Neuroimaging Initiative, we selected 133 individuals for this study including 33 with Alzheimer’s disease dementia (ADD), 52 with late mild cognitive impairment (LMCI), and 48 cognitively normal (CN) subjects who underwent clinical assessment, PiB PET, and structural magnetic resonance imaging (MRI) with 2 or 3-years of follow-up. Sixty-eight of the 133 individuals underwent cerebrospinal fluid amyloid-β1-42 (CSF-Ab42) analysis at baseline. The standard uptake value ratio (SUVR) of PiB PET was calculated with a method using MRI at each visit. The cross-sectional values, longitudinal changes in SUVR, and baseline CSF-Ab42 were compared among groups, which were categorized based on trinary visual reads of amyloid PET (negative/equivocal/positive). Results From the trinary visual interpretation of the PiB PET images, 55 subjects were negative, 8 were equivocal, and 70 were positive. Negative interpretation was most frequent in the CN group (70.8/10.4/18.8%: negative/equivocal/positive), and positive was most frequent in the LMCI group (34.6/1.9/63.5%) and in the ADD group (9.1/6.1/84.8%). The baseline SUVRs were 1.08 ± 0.06 in the negative group, 1.23 ± 0.15 in the equivocal group, and 1.86 ± 0.31 in the positive group (F = 174.9, p 42 level was 463 ± 112 pg/mL in the negative group, 383 ± 125 pg/mL in the equivocal group, and 264 ± 69 pg/mL in the positive group (F = 37, p F = 8.4, p Conclusions Trinary visual interpretation (negative/equivocal/positive) of amyloid PET imaging reflects quantitative amyloid measurements evaluated with PET and the CSF amyloid test as well as the amyloid accumulation over time evaluated with PET over 3 years. Subjects in the early stage of the AD continuum could be identified with an equivocal scan, because they showed intermediate quantitative amyloid PET, CSF measurements, and the amyloid accumulation over time.

Purpose This study aimed to clarify the utility of the Life-trouble Scale-based care planning tool for elderly patients with dementia (Life-trouble Scale, viewpoints, and care points of the elderly with dementia suffering from life troubles) in order to develop an appropriate care plan and practices in a long-term care health facility. Method Participants were elderly patients with dementia who were evaluated by care staff using the abovementioned scale at baseline and after intervention (one month later) from September to December 2017. The patients were divided into an intervention group, which received care based on the Life-Trouble Inclusion Scale, and the control group, which received the usual care. The outcomes of these two groups were compared. Results The intervention and control groups comprised 14 and 12 elderly patients with dementia, respectively. More than 60% of the care staff worked with both groups. Scores on the agitation sub-scale of the NPI [please define abbreviation] and "life-trouble associated with irritation and confusion" sub-scale of the Life-Trouble Scale improved significantly in the intervention group. Among the care staff, self-efficacy related to caring for elderly patients with dementia and scores on the Emotional Exhaustion and Depersonalization sub-scales of the Japanese version of the Maslach Burnout Inventory improved significantly. Conclusion The present findings suggest that care intervention using the Life-trouble Scale-based care planning tool was beneficial for both elderly patients with dementia and their care staff.

Background Overadaptation, the behavior of individuals who follow the expectations of others as perfectly as possible, is often observed and related to maladjustment, school refusal, and physical symptoms; however, no method has been proposed yet to assess the overadaptive tendency. This study evaluated the efficacy of the draw-a-man test as a projective measure of overadaptation in community children. Methods Eighty children (36 boys, 44 girls) aged 6-8 years were assessed for their ability to draw a man using the Goodenough Draw-A-Man Test (DAM test). Class teachers were asked to assess whether the child was overadapting. The total and subscale DAM scores and pass rates were compared between children with a teacher-assessed tendency for overadaptation and control children, separately for girls and boys. Results The mean total DAM score was significantly higher for girls versus boys for both the overadapting children and controls. For boys, no significant differences on the total and subscale DAM scores were noted between the overadapting boys and controls. Conversely, for girls, total and three subscale DAM scores (Mouth/Nose/Ears, Hairs, Fingers) were significantly higher in the overadapting girls versus controls. Moreover, for girls, the DAM pass rates on five items (ratio of head; ears present; position and shape of nose; depiction of hair, not to see the scalp; details of fingers) were higher in the overadapting girls versus controls. Conclusions The DAM test could extract the overadaptive tendencies of girls aged 6-8 years.

Background This study aims to reconsider diagnostic approaches to dementia where pharmacological approaches are not available to reverse the pathological changes caused by dementia. Methods A questionnaire survey was conducted with 524 physicians specialising in dementia management in Aichi, Japan, with 163 (31.1%) valid responses. The survey gathered information on the perceived merits and demerits of the early diagnosis of dementia and the priorities in treating those with mild cognitive impairment (MCI), mild dementia, and moderate or advanced dementia. In the interview survey, 27 outpatients with mild Alzheimer's disease (76.2 ± 7.6 years old; Mini-Mental State Examination score 23.3 ± 2.7 points; 21 women, six men) and 24 family members (12 spouses, 12 children) were asked about their priorities in treatment. Results A total of 61.3% of physicians answered that persons with dementia having more time to accept the diagnosis is a merit of early diagnosis, while 61.3% answered that the possibility of causing anxiety was a demerit. Around 45% of the physicians chose the option 'maintaining cognitive function' as the first priority in cases of MCI and mild dementia, while 39.3% considered it the last priority in moderate or advanced cases. About 22.2% of persons with dementia and 37.5% of their families assigned the highest priority to 'maintaining cognitive function', whereas 37.0% of persons with dementia prioritised 'maintaining quality of life for them and their families'. Conclusions Although it is important to build therapeutic alliances among persons with dementia, their families, and physicians by sharing a common perspective for better treatment of dementia, this study suggested that the three parties do not always share the same vision. Future research is needed to determine how to build therapeutic alliances for better approaches to dementia, especially to ensure that timely diagnosis is beneficial for persons with dementia and their families.

Objectives To investigate the relationship between amyloid-β- and tau-based Alzheimer's disease (AD) pathologies assessed using positron emission tomography imaging and neuropsychiatric symptoms (NPS) in a sample of AD continuum including clinically normal subjects and patients with mild cognitive impairment or AD. Methods We analyzed datasets of the Alzheimer's disease Neuroimaging Initiative and included amyloid-positive subjects who underwent an AV-45 scan within 1 year of an AV-1451 scan (n = 99). Correlation between standardized uptake value ratio (SUVR) of AV-45 and AV-1451 and the Neuropsychiatric Inventory (NPI) score (and its four domain subscores for hyperactivity, psychosis, affective, and apathy) was evaluated. Stepwise logistic regression analysis was used to examine the influence of SUVRs on the presence of NPS. SUVRs were also tested for their ability to discriminate the group with NPS using receiver operating characteristic (ROC) curve analyses. Results Significant positive relationships were found between the total NPI score and affective symptoms and Braak 1&2 (transentorhinal region) AV-1451 SUVR. Stepwise logistic regression analysis identified tau accumulation in the area of Braak 1&2 as a significant covariate discriminating the presence of affective symptoms. The area under the ROC curve analysis showed that subjects with affective symptoms were discriminated by AV-1451 SUVR with an accuracy of 77.7%. Conclusions Tau aggregation in the transentorhinal region, where neurodegeneration affected by tau pathology was seen in the early stage of AD, correlated with more severe NPS, especially affective symptoms. Therefore, tau pathology in the transentorhinal cortex might be associated with affective symptoms in the early stage of AD.

AIM: Most patients with dementia frequently encounter various problems in their daily lives. Those troubles embarrass both the patients and their families, and cause problems for society. However, there have been few scientific reports on the difficulties in the daily life of patients with dementia. Therefore, we tried to clarify the frequency and characteristics of troubles experienced by patients with dementia. METHODS: Seven medical centers treating dementia patients in Okayama Prefecture, Japan, participated in this survey. A total of 737 patients were placed in one of the three groups: a dementia group (n = 478), a mild cognitive impairment group (n = 199) and a control group (n = 60). The frequency of 13 difficulties was scored for each patient. RESULTS: Among normal participants, no person caused these problems once a year or more frequently. "Massive, recurrent buying" and "acts that risk causing a fire" were reported once a year or more for >10% of mild cognitive impairment patients. "Troubles with wealth management" and "troubles with money management" were the most frequent problems of dementia patients. CONCLUSIONS: Several problems are already sometimes encountered in patients with mild cognitive impairment. It would be useful to know which social difficulties are often seen in dementia patients in order to protect the safety of the patients. It is always difficult to balance respecting the autonomy of dementia patients and ensuring their safely.

AIM: Most patients with dementia frequently encounter various problems in their daily lives. Those troubles embarrass both the patients and their families, and cause problems for society. However, there have been few scientific reports on the difficulties in the daily life of patients with dementia. Therefore, we tried to clarify the frequency and characteristics of troubles experienced by patients with dementia. METHODS: Seven medical centers treating dementia patients in Okayama Prefecture, Japan, participated in this survey. A total of 737 patients were placed in one of the three groups: a dementia group (n = 478), a mild cognitive impairment group (n = 199) and a control group (n = 60). The frequency of 13 difficulties was scored for each patient. RESULTS: Among normal participants, no person caused these problems once a year or more frequently. "Massive, recurrent buying" and "acts that risk causing a fire" were reported once a year or more for >10% of mild cognitive impairment patients. "Troubles with wealth management" and "troubles with money management" were the most frequent problems of dementia patients. CONCLUSIONS: Several problems are already sometimes encountered in patients with mild cognitive impairment. It would be useful to know which social difficulties are often seen in dementia patients in order to protect the safety of the patients. It is always difficult to balance respecting the autonomy of dementia patients and ensuring their safely.

Background The cingulate island score (CIScore), which indicates the Z-score ratio of the posterior cingulate gyri to the medial occipital area, has been shown to be useful for differentiating dementia with Lewy bodies from Alzheimer's disease (AD). Our aim was to investigate associations between the clinical symptoms of AD and the CIScore as an index of the relative decrease in perfusion of the posterior cingulate gyri that occurs in the early stages of AD. Methods Seventeen patients with early-stage AD and 13 patients with amnesic mild cognitive impairment were examined. Z-score maps of technetium-99m ethyl cysteinate dimer single-photon emission computed tomography images acquired from the patients were converted, and the CIScore was determined by using the easy Z-score imaging system. The relationships between the CIScore and clinical symptom scores were tested. Results A significant correlation was identified between the CIScore and the Neuropsychiatric Inventory Questionnaire score. No significant correlations were identified between the CIScore and other measures of cognitive function. Based on a CIScore of 0.39, we correctly differentiated patients with and without behavioural and psychological symptoms of dementia (BPSD), with a sensitivity of 72.2% and specificity of 75.0%. Discussion Using technetium-99m ethyl cysteinate dimer single-photon emission computed tomography, we observed that decreased posterior cingulate gyri perfusion, relative to the medial occipital area, in prodromal and early AD was closely associated with behavioural and psychological symptoms of dementia. Therefore, our findings suggest that CIScore is not only useful for discriminating dementia with Lewy bodies from AD, but it can also be clinically used as a specific indicator of the vulnerability to behavioural and psychological symptoms of dementia in the early stages of AD.

Purpose The purpose of this study was to develop the Life-trouble Scale for elderly people with dementia to concretely determine their life troubles in geriatric facilities. Results The subjects of this study were elderly people living in geriatric health services facilities whose degree of life independence was evaluated as ≥II, who had a diagnosis of dementia, and who agreed to participate in this study.The study population included 191 subjects (male, n=144, 75.4%; female, n=47, 24.6%). The average age was 85.72 (±6.96) years, the mean degree of need for nursing care was 3.73 (±1.22), and the mean MMSE score was 9.11 (±8.80).Based on the factor analysis of the Life-trouble Scale, the first factor was named, "Basic Life Behavior and Life Trouble with Communication." The second factor was named, "Life Trouble Associated with Irritation and Confusion". The third factor was named, "Trouble with Human Relations Associated with Feelings and Changes in Consciousness". The fourth factor was named, "Life Trouble Associated with Changes in Consciousness and Repeated Behavior". The Cronbach's α of the 4 factors was 0.884, and the NPI and Crichton rating scales were significantly correlated with the 4 factors. Conclusion The results showed that the Life-trouble Scale had reliability and validity, and that it was useful for solving problems in geriatric health services facilities.

Purpose The purpose of the present study was to clarify how quality of life (QOL) affects the behavioral and psychological symptoms of dementia (BPSDs) among elderly individuals with dementia within long-term care facilities (e.g., long-term healthcare facilities, sanatorium-type medical facilities, and special nursing homes for the elderly). Methods Elderly individuals with dementia were evaluated to determine their activities of daily living (ADL; Katz), Mini-mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), and Quality of life inventory for the elderly with dementia (QOLD) scores. Results The subjects were recruited from intermediate welfare facilities (n = 226, 43.7%), hospitals with supportive care (n=91, 17.6%), and intermediate care facilities (n = 200, 38.7%). The mean age of the subjects was 85.18±7.13 years. The NPI scores revealed that Agitation/Aggression was high among subjects who resided in healthcare health facilities and sanatorium-type medical facilities, while Apathy/Indifference was high in those who resided in special nursing homes. Additionally, a multiple regression analysis found that most of the NPI items, when set as independent variables, displayed a significant association with the same subscale of the QOLD. Conclusion When each item of the NPI was set as a dependent variable in a multiple regression analysis, the scores were significantly related to both subscales of the QOLD. It is suggested that QOL should be maintained or improved in an effort to reduce the incidence of the associated BPSDs in long-term care facilities.

Aim It was recently reported that theory of mind is disturbed in mild Alzheimer's disease dementia (ADD). Some studies have reported reduced scores of ADD patients on false belief tests, even on first-order false belief tests. However, few studies have pursued the neural substrate of false belief tests in patients with ADD in a real-world setting. Methods Sixty-three patients with ADD from outpatient units took the Sally-Anne test and underwent brain single-photon emission computed tomography. Of these patients, 29 answered the Sally-Anne test correctly (successful group) and 34 incorrectly (unsuccessful group). We compared the regional cerebral blood flow between the successful and unsuccessful groups. Results A comparison of the two groups showed a significantly lower uptake in the bilateral posterior cingulate gyrus in the unsuccessful group than in the successful group. Conclusions The posterior cingulate gyrus is known to be particularly activated when individuals remember personal events and infer the mental states of others. We suppose that memory or mentalization in the posterior cingulate gyrus-or both-is essential for patients with ADD to be able to pass the Sally-Anne test.

The aim of this study was to evaluate the safety and efficacy of the early administration haloperidol in preventing the aggravation of postoperative delirium in elderly patients. A total of 201 patients (age ≥75 years) who underwent elective surgery were enrolled. The patients were divided into two groups: the intervention group (n = 101) received prophylactic haloperidol (5 mg); the control group (n = 100) did not. Haloperidol was administered daily during postoperative days 0–5 to the patients who presented with NEECHAM scores of 20–24 when measured at 18:00. The primary endpoint was the incidence of severe postoperative delirium. The incidence of severe postoperative delirium in all patients was 25.1%. The incidence of severe postoperative delirium in the intervention group (18.2%) was significantly lower than that in the control group (32.0%) (p = 0.02). The difference between the two groups was larger when the analysis was limited to the 70 patients who had NEECHAM scores of 20–24 for at least one day during postoperative days 0–5. No adverse effects of the haloperidol were observed. The prophylactic administration of haloperidol at the early stage of delirium significantly reduced the incidence of severe postoperative delirium in elderly patients. Clinical Trial Registration UMIN000007204.

Social cognition has recently been recognized as one of the essential cognitive domains. Some reports suggested that patients with Alzheimer's disease dementia (ADD) presented significant theory of mind deficits even in the mild condition. However, most previous studies included only small numbers of patients with ADD. The present study administered the first-order false belief (Sally-Anne) test to 116 consecutive patients with ADD from the outpatient units of the Memory Clinic and compared the characteristics of the two groups with correct and incorrect answers on the test. Then various clinical characteristics were evaluated. Only 37.1% of patients with ADD correctly answered the Sally-Anne test with the right explanation. Comparison between the two groups of correct and incorrect answers revealed a significant association between the frontal assessment battery score and the result of the Sally-Anne test in the multiple logistic regression analyses. Thus, patients with ADD presented a significant deficit in social cognition even in the mild condition. Frontal dysfunction was thought to be related to the deficits in mild ADD.

Purpose: This study was conducted to clarify the utility of patient-held records as an integrated care approach for patients with dementia in the community. Method: We analyzed the family-held/patient-held records of patients with dementia in the community. The inclusion criteria in the study were as follows: 1) patient-held/family member-held records of patients with dementia in the community; 2) patient-held records designed to share information across different professionals, direct-care staff members, and local government staff; and 3) the continuous participation of psychiatrists in the development and use of the patient-held records. Results: We identified eight sets of family-held/patient-held records in Japanese communities of various sizes, all of which were aimed at integrating information from various services, including information provided by medical and psychiatric professionals to the family and patient. Innovative tools have been available in the areas of the hopes and preferences of the patient, medication and monitoring, sharing information, and the use of information technology. Conclusion and Discussion: Family-held/patient-held records have potential as a tool to enhance the integrated care of people with dementia in the community.

Aim Behavioral and psychological symptoms of dementia are an important source of distress for caregivers. The aim of the present study was to evaluate the effectiveness of educational intervention using printed educational material for reducing distress induced by behavioral and psychological symptoms of dementia among caregivers working at facilities without medical specialists and/or registered nurses. Methods A cluster quasi-randomized, controlled comparative trial was carried out at 17 facilities in Japan. Our intervention was an educational program administered at baseline using printed educational material for the care staff. The primary outcome was evaluated using the Japanese version of the Neuropsychiatric Inventory Questionnaire. The secondary outcome measures were caregiver burnout evaluated using the Japanese version of the Maslach Burnout Inventory and the care dependency of residents measured using the Japanese version of the Care Dependency Scale. Results The total Neuropsychiatric Inventory Questionnaire score decreased significantly in the intervention group (F [1355] = 6.57, P = 0.01), and the difference between the intervention and control groups was also significant (F [1355] = 4.78, P = 0.03). There were no significant changes in the Maslach Burnout Inventory or Care Dependency Scale scores in the intervention group, while the Maslach Burnout Inventory subscale (personal accomplishment) score decreased significantly in the control group. Conclusions Our intervention achieved a significant reduction of distress among caregivers working at care homes without medical specialists and/or registered nurses. The findings of this research show that educational intervention can make a valuable contribution to training programs for care staff. Geriatr Gerontol Int 2017; ••: ••–••.

Background Weight loss is frequently observed in patients with Alzheimer's disease (AD); however, the underlying mechanisms are not well understood. Objects To clarify the associations between nutritional status and AD-related brain changes using Pittsburgh Compound-B (PiB)-PET, fluorodeoxyglucose (FDG)-PET, and structural MRI. Methods The subjects were 34 amyloid-β (Aβ)-positive individuals with mild cognitive impairment or early AD (prodromal/early AD), and 55 Aβ-negative cognitively normal (CN) subjects who attended the Multimodal Neuroimaging for AD Diagnosis (MULNIAD) study. Nutritional status of the subjects was assessed by body mass index and waist to height ratio (waist circumference/height). The associations between nutritional status and brain changes were examined by multiple regression analysis using statistical parametric mapping. Results In the prodromal/early AD group, nutritional status was significantly positively correlated with regional cerebral glucose metabolism (rCGM) in the medial prefrontal cortices, while different topographical associations were seen in the CN group, suggesting these changes were AD-specific. Aβ deposition and gray matter volume were not significantly associated with nutritional status. Sub-analysis in the prodromal/early AD group demonstrated that fat mass index, but not fat-free mass index, was positively correlated with rCGM in the medial prefrontal areas. Conclusion This present study provides preliminary results suggesting that hypometabolism in the medial prefrontal areas is specifically associated with AD-related weight loss, and decrease in fat mass may have a key role.

Biomarkers relevant to the pre-dementia stages of Alzheimer’s disease are needed. Using MEG, PET, and MRI, Nakamura et al. disentangle resting state regional spectral patterns in cognitively normal subjects and individuals with mild cognitive impairment into MEG signatures related to Aβ deposition, disease progression, or changes non-specific to Alzheimer’s disease., Biomarkers useful for the predementia stages of Alzheimer’s disease are needed. Electroencephalography and magnetoencephalography (MEG) are expected to provide potential biomarker candidates for evaluating the predementia stages of Alzheimer’s disease. However, the physiological relevance of EEG/MEG signal changes and their role in pathophysiological processes such as amyloid-β deposition and neurodegeneration need to be elucidated. We evaluated 28 individuals with mild cognitive impairment and 38 cognitively normal individuals, all of whom were further classified into amyloid-β-positive mild cognitive impairment (n = 17, mean age 74.7 ± 5.4 years, nine males), amyloid-β-negative mild cognitive impairment (n = 11, mean age 73.8 ± 8.8 years, eight males), amyloid-β-positive cognitively normal (n = 13, mean age 71.8 ± 4.4 years, seven males), and amyloid-β-negative cognitively normal (n = 25, mean age 72.5 ± 3.4 years, 11 males) individuals using Pittsburgh compound B-PET. We measured resting state MEG for 5 min with the eyes closed, and investigated regional spectral patterns of MEG signals using atlas-based region of interest analysis. Then, the relevance of the regional spectral patterns and their associations with pathophysiological backgrounds were analysed by integrating information from Pittsburgh compound B-PET, fluorodeoxyglucose-PET, structural MRI, and cognitive tests. The results demonstrated that regional spectral patterns of resting state activity could be separated into several types of MEG signatures as follows: (i) the effects of amyloid-β deposition were expressed as the alpha band power augmentation in medial frontal areas; (ii) the delta band power increase in the same region was associated with disease progression within the Alzheimer’s disease continuum and was correlated with entorhinal atrophy and an Alzheimer’s disease-like regional decrease in glucose metabolism; and (iii) the global theta power augmentation, which was previously considered to be an Alzheimer’s disease-related EEG/MEG signature, was associated with general cognitive decline and hippocampal atrophy, but was not specific to Alzheimer’s disease because these changes could be observed in the absence of amyloid-β deposition. The results suggest that these MEG signatures may be useful as unique biomarkers for the predementia stages of Alzheimer’s disease.

Aim In the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), the behavioral variant of major frontotemporal neurocognitive disorder (bvFT-NCD) is subclassified into “probable bvFT-NCD” or “possible bvFT-NCD.” When genetic evidence is unavailable, cases without clinical neuroimaging are subclassified into “possible bvFT-NCD,” whereas cases whose clinical images show the typical characteristics are subclassified into “probable bvFT-NCD.” Thus, the cases that meet the diagnostic criteria of bvFT-NCD based on their symptoms, but lack the neuroimaging characteristics, fall between the two categories of probable and possible bvFT-NCD. These cases herein are defined as “unclassified bvFT-NCD,” and the present study aims at considering an appropriate diagnostic approach to such cases, that is, whether unclassified bvFT-NCD should be included in bvFT-NCD as a third subcategory, or whether it should be classified into diseases other than bvFT-NCD. Methods All patients who presented at the Department of Psychiatry of the National Center for Geriatrics and Gerontology with suspicion of the behavioral variant of frontotemporal dementia between 1 May 2011 and 30 April 2013 were retrospectively rediagnosed based on the DSM-5 criteria. Results A total of 16 cases met the criteria of bvFT-NCD, and among them, eight cases corresponded to unclassified bvFT-NCD. From a cross-sectional and clinical perspective, all eight cases of unclassified bvFT-NCD fulfilled the symptomatic criteria for bvFT-NCD, although the possibilities of Alzheimer's disease and other mental disorders could not be ruled out completely. Conclusions To establish clinical diagnostic criteria for unclassified bvFT-NCD, accumulation of cases and evidence will be required along with longitudinal observation using various diagnostic technologies and post-mortem examination. Geriatr Gerontol Int 2014; 14 (Suppl. 2): 35–44.

Postoperative delirium is the most common postoperative complication in the elderly. The purpose of this study was to evaluate the safety and effectiveness of the preventive administration of low-dose haloperidol on the development of postoperative delirium after abdominal or orthopedic surgery in elderly patients. A total of 119 patients aged 75 years or older who underwent elective surgery for digestive or orthopedic disease were included in this study. Patients were divided into those who did (intervention group, n = 59) and did not (control group, n = 60) receive 2.5 mg of haloperidol at 18:00 daily for 3 days after surgery; a randomized, open-label prospective study was performed on these groups. The primary endpoint was the incidence of postoperative delirium during the first 7 days after the operation. The incidence of postoperative delirium in all patients was 37.8 %. No side effects involving haloperidol were noted; however, the incidences of postoperative delirium were 42.4 and 33.3 % in the intervention and control groups, respectively, which were not significantly different (p = 0.309). No significant effect of the treatment was observed on the severity or persistence of postoperative delirium. The preventive administration of low-dose haloperidol did not induce any adverse events, but also did not significantly decrease the incidence or severity of postoperative delirium or shorten its persistence.

Drug-induced akinesia is a potential cause of pressure ulcers. However, pressure ulcers that are caused by drug-induced akinesia are not considered an adverse drug reaction (ADR). We propose that drug-induced pressure ulcers (DIPU) are pressure ulcers that are caused by an external force that is experienced after drug administration, and we considered resolution of these ulcers after drug discontinuation to be a supportive finding. In this report, we reviewed the medical records of pressure ulcer cases from a 300-bed hospital. Among 148 patients, four patients with pressure ulcers met the criterion for DIPU. In these cases, the suspected DIPU were related to treatment with olanzapine, fluvoxamine, valproic acid, clotiazepam, triazolam and rilmazafone. These drugs were administrated to manage the patients' behavioral and psychological symptoms that accompanied dementia. The DIPU in these patients were categorized as stage IV according to the National Pressure Ulcer Advisory Panel criteria. Discontinuation of the causal drugs led to significant improvements or complete healing of the pressure ulcers, and the patients subsequently recovered their mobility. Therefore, we propose that DIPU are potential ADR that have been overlooked in clinical practice. Thus, recognition of DIPU as an ADR may be important in preventing and appropriately managing pressure ulcers among elderly patients.

On 11 March 2011, a strong earthquake occurred off of Japan's Pacific coast and hit northeastern Japan. The earthquake was followed by huge tsunamis, which destroyed many coastal cities. As a result, the Study Group on Guidelines for the First Steps and Emergency Triage to Manage Elderly Evacuees quickly established guidelines enabling non-medical care providers (e.g. volunteer, helpers, and family members taking care of elderly relatives), public health nurses, or certified social workers to rapidly detect illnesses in elderly evacuees, and 20 000 booklets were distributed to care providers in Iwate, Miyagi, and Fukushima prefectures. The aim of this publication is to reduce susceptibility to disaster-related illnesses (i.e. infectious diseases, exacerbation of underlying illnesses, and mental stress) and deaths in elderly evacuees. Geriatr Gerontol Int 2011; 11: 383–394.

Aim: Art therapy has been reported to have effects on mental symptoms in patients with dementia, and its usefulness is expected. We performed a controlled trial to evaluate the usefulness of art therapy compared with calculation training in patients with mild Alzheimer's disease. Methods: Thirty-nine patients with Alzheimer's disease showing slightly decreased cognitive function allowing treatment on an outpatient basis were randomly allocated to art therapy and control (learning therapy using calculation) groups, and intervention was performed once weekly for 12 weeks. Results: Comparison of the results of evaluation between before and after therapy in each group showed significant improvement in the Apathy Scale in the art therapy group (P = 0.014) and in the Mini-Mental State Examination score (P = 0.015) in the calculation drill group, but no significant differences in the other items between the two groups. Patients showing a 10% or greater improvement were compared between the two groups. Significant improvement in the quality of life (QOL) was observed in the art therapy compared with the calculation training group (P = 0.038, odds ratio, 5.54). anova concerning improvement after each method revealed no significant difference in any item. Conclusion: These results suggested improvement in at least the vitality and the QOL of patients with mild Alzheimer's disease after art therapy compared with calculation, but no marked comprehensive differences between the two methods. In non-pharmacological therapy for dementia, studies attaching importance to the motivation and satisfaction of patients and their family members rather than the superiority of methods may be necessary in the future. Geriatr Gerontol Int 2011; 11: 431–437.

Background: A depressive state with Alzheimer's disease (AD) is difficult to differentiate from major depression (MD) in many cases. The purpose of this study was to identify differences between the two disorders using a battery of clinically available psychological tests. Methods: We evaluated depression and apathy using the Geriatric Depression Scale consisting of 30 items (GDS30) and Apathy Scale in 38 patients with AD and 31 with MD who were diagnosed based on clinical symptoms and radiological findings. In addition, the Cornel Medical Index (CMI) was employed to compare the psychological features of the two disorders. Results: In AD patients, the Apathy Scale score was greater than the GDS30 score, suggesting a strong tendency toward apathy. There was a significant difference in the GDS30/Apathy Scale score ratio between the two groups (P

The most important point for evaluation of the post-operative cognitive dysfunction is that we understand "cognitive function". First we described the definition of the "cognitive function" and second, outlined each function (dysfunction) and introduced the main assessment methods from the view point of neuropsychology. Cognitive function (dysfunction) described in this paper includes consciousness (confusional state, disturbance of consciousness), generalized attention (disorder of generalized attention), memory (amnesia), orientation (disorientation), executive function (dysexecutive syndrome), social cognition (social cognitive impairment), language (aphasia), cognition (agnosia), behavior (apraxia), directed attention (unilateral spatial neglect), and construction (constructional disorder).

Alzheimer disease (AD), the major cause of dementia in the elderly, is characterized by β-amyloid deposition in senile plaques and hyperphosphorylated tau in neurofibrillary tangles. Since albumin, binding and transporting free fatty acids is also the major transporter of β-amyloid, we examined the association between the albumin (ALB) gene and the occurrence of late-onset AD (LOAD). We found that the allele distribution of the intron 4 microsatellite of the ALB gene showed a significant difference (P

Palliative care improves the quality of life of patients and their families facing problems associated with life-threatening illnesses by promoting the prevention and relief of suffering. Palliative care in Japan has been developed mainly for cancer patients. At the National Center for Geriatrics and Gerontology, an end-of-life care team (EOLCT) has been developed to promote palliative care for patients without cancer. In the first 6 months of its operation, 109 requests were received by the team, 40% of which were for patients without cancer or related disease, including dementia, frailty due to advanced age, chronic respiratory failure, chronic heart failure, and intractable neurologic diseases. The main purpose of the EOLCT is to alleviate suffering. The relevant activities of the team include the use of opioids, providing family care, and giving support in decision-making (advance care planning) regarding withholding; enforcement; and withdrawal of mechanical ventilators, gastric feeding tubes, and artificial alimentation. The EOLCT is also involved in ongoing discussions of ethical problems. The team is actively engaged in the activities of the Japanese Geriatric Society and contributes to the development of decision-making guidelines for end-of-life by the Ministry of Health, Labour and Welfare. The EOLCT can be helpful in promoting palliative care for patients with diseases other than cancer. The team offers support during times of difficulty and decision-making.

Quetiapine, which is a new atypical antipsychotic agent, was administered at low doses (25–50 mg/day) for psychotic symptoms in eight elderly patients with physical illnesses. Delirium and hallucination were alleviated by the administration of low doses of quetiapine, and the cause–effect relationship between the administration and alleviation of symptoms was evident, particularly in one patient with delirium, because delirium was alleviated after administration began, was exacerbated after discontinuation of quetiapine, and was alleviated again after administration was resumed. Little improvement was observed in delusions or mood disorders. None of the patients showed exacerbation of physical symptoms or abnormalities in clinical laboratory tests. The results of this study suggest that quetiapine might be effective in reducing delirium and hallucination that often accompany physical illness in elderly people and could be used without adverse effects.

In dementia care, behavioural and psychological symptoms of dementia and physical illness in patients with dementia impose a marked care burden and require medical intervention. Therefore, it is important for patients and their families to select appropriate medical institutions and facilities with nursing units specializing in the care of behavioural and psychological symptoms of dementia, such as geriatric hospitals, which are required to deal with various aspects of dementia. Geriatric hospitals should offer two treatment approaches: a care unit for patients with behavioural and psychological symptoms of dementia or dementia with physical illness, and a multidisciplinary team approach involving physicians, nurses, psychologists, and social workers who provide coping strategies for dementia patients.

Political attention is being increasingly directed to mental health in Japan. Mental disorders are now the fifth priority disease after cancer, stroke, acute myocardial infarction and diabetes for national medical services since April 2013. Each prefecture has to implement strategic mental healthcare plans at the regional level. With the increase in co-morbid mental and physical illnesses, patient information should be shared between psychiatric and non-psychiatric healthcare providers, and coordination is required in the healthcare systems. A better understanding of mental health between patients and medical staffs could contribute to improved access to psychiatric services in the integrated mental health care system. Collaborative care programs focusing on depression screening and management in the Mental Health Care Project for Patients with Physical Illness have been launched among six national specialized care and research centers (cancer, cardiovascular disease, diabetes, child care, geriatric care and neurology and psychiatry) since 2012. These efforts to integrate mental health care into the general health care system would help to improve psychiatric care for elderly patients with physical illnesses.

This study was conducted to assess the effects of antiatherosclerotic treatment with eicosapentaenoic acid (EPA) on the hemodynamics and physical properties of the common carotid artery in elderly patients with atherosclerosis. EPA, found in high levels in fish oil, is an omega-3 polyunsaturated fatty acid that has a variety of pharmacologic effects, including antiplatelet, arterial elasticity-maintaining, and hypolipidemic. EPA has proved to be useful in treating arteriosclerosis obliterans. A total of 18 patients (mean age, 76.2 ± 5.7 years) with atherosclerosis underwent complete Doppler ultrasonic examination of the common carotid artery before and after 16 weeks of treatment with EPA (900 mg or 1800 mg daily). The presence of atherosclerosis was determined by clinical findings, especially according to physical properties of the common carotid artery derived by ultrasound examination. The minimal diameter of the common carotid artery at minimal blood pressure decreased significantly from 7.64 ± 0.93 mm to 7.21 ± 0.97 mm ( P 5 dyne/cm 2 to 8.95 ± 2.78 × 10 5 dyne/cm 2 and from 6.44 ± 2.79 to 5.41 ± 1.79, respectively; P

The care of the aged population living at home is an urgent issue in the developed countries. It is important to investigate the factors in relation to the level of activities of daily life (ADL). It is also important to investigate the death situation in order to protect this population from accidental death. This study was undertaken to investigate whether the pathological change of the brain was one of the decisive factors of ADL and accidental death. Detailed information of ADL was obtained from the family and neighbors of 40 cases that were autopsied medicolegally at the medical examiner office of Osaka prefecture. The information regarding death situation was obtained from the coroner's documents. In each autopsied brain, senile plaques, neurofibrillary tangle (NFT), arteriosclerosis and ischemic changes of the brain were examined. Correlation between the neuropathological change, ADL and the death situation was statistically investigated. The severity and expansion of NFT, which was categorized as Braak's stage, showed significant correlation with ADL. Senile plaques and vascular change showed no significant correlation. Cases that had developed to Braak's isocortical stage showed a tendency to die in the bathroom or toilet. The NFT pathology of the limbic system has been shown to correlate with ADL. The damage of the limbic system might have an influence on the cognitive and behavior function of the brain and may lead to the reduced ADL. In addition, the NFT pathology may be a factor for the autonomic dysfunction and circulatory disorder. Therefore, the NFT pathology is considered to play a role in death during defecation and bathing.

In the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), the behavioral variant of major frontotemporal neurocognitive disorder (bvFT-NCD) is subclassified into "probable bvFT-NCD" or "possible bvFT-NCD." When genetic evidence is unavailable, cases without clinical neuroimaging are subclassified into "possible bvFT-NCD," whereas cases whose clinical images show the typical characteristics are subclassified into "probable bvFT-NCD." Thus, the cases that meet the diagnostic criteria of bvFT-NCD based on their symptoms, but lack the neuroimaging characteristics, fall between the two categories of probable and possible bvFT-NCD. These cases herein are defined as "unclassified bvFT-NCD," and the present study aims at considering an appropriate diagnostic approach to such cases, that is, whether unclassified bvFT-NCD should be included in bvFT-NCD as a third subcategory, or whether it should be classified into diseases other than bvFT-NCD.All patients who presented at the Department of Psychiatry of the National Center for Geriatrics and Gerontology with suspicion of the behavioral variant of frontotemporal dementia between 1 May 2011 and 30 April 2013 were retrospectively rediagnosed based on the DSM-5 criteria.A total of 16 cases met the criteria of bvFT-NCD, and among them, eight cases corresponded to unclassified bvFT-NCD. From a cross-sectional and clinical perspective, all eight cases of unclassified bvFT-NCD fulfilled the symptomatic criteria for bvFT-NCD, although the possibilities of Alzheimer's disease and other mental disorders could not be ruled out completely.To establish clinical diagnostic criteria for unclassified bvFT-NCD, accumulation of cases and evidence will be required along with longitudinal observation using various diagnostic technologies and post-mortem examination.

Behavioral and psychological signs and symptoms of dementia (BPSD) can be interpreted as cognitively impaired patients' responses to external stimuli. The causes of BPSD include physical, psychological, and environmental factors, although combinations of these factors usually contribute to the development of BPSD. Representative conditions that should be distinguished from dementia include delirium, aphasia, and depression. It is important to differentiate depression from apathy associated with dementia. A well-balanced combination of drug therapy and non-pharmacological methods is required for the treatment of BPSD. Non-pharmacological methods should be considered first to address moderate BPSD in particular. It is advisable to carefully provide drug treatment following environmental control and non-drug treatment, and minimize adverse effects taking into consideration the physical characteristics of the elderly. Regarding methods for formulation according to the symptom, hyper- and hypoactivity symptoms should be addressed separately.

Galantamine, rivastigmine, and memantine, for the treatment of Alzheimer-type dementia, became covered by national health insurance last year in Japan. Galantamine and rivastigmine are choline esterase inhibitors, and memantine is a glutamate NMDA receptor antagonist. Galantamine also acts on the nicotinic acetylcholine receptor, in addition to ChEI, and it has an APL action and modulates the receptor function by inducing a structural change of the receptor, as its characteristics. Rivastigmine is used only in patch form, and exhibits an inhibitory effect on butyryl choline esterase. Memantine protects nerve cells by inhibiting excess actions of glutamate. These drugs are also effective for BPSD accompanying dementia. Particularly, memantine exhibits an inhibitory effect on aggressiveness and excitement, as its characteristic. The administration of these 3 drugs for diseases other than Alzheimer-type dementia is not covered by national health insurance. These are expected to be effective for dementia with Lewy bodies, but there has been no evidence reported of an effect on frontotemporal dementia. Dementia manifests diverse symptoms in the course, and consideration of the physical symptoms is indispensable. The thoughtless continuation of anti-dementia and psychiatric agents without consideration of temporary changes and diversity and changes in needs for medical care impair a patient's vital functions and QOL. Those who are involved in the treatment of dementia should always consider the clinical course and changes in needs for psychiatric and physical medical care, and novel anti-dementia drugs should be used based on these.

It is unclear how hospitals should support a patient's decision to return home to die. Thus, we retrospectively examined the usefulness of support from an End-Of-Life Care Team in such difficult decision making. The subjects included non-cancer patients and the elderly. Our results suggest that the burden of making difficult decisions decreases with support from End- Of-Life Care Teams.

We have built active magnetic regenerator (AMR) test apparatuses operated with a gas displacer to transfer the heat from magnetic material unit (AMR bed). Because finding an optimum parameter by experiment is not easy, numerical simulation is necessary to confirm the experimental conditions. As the first step of the project, we developed a 1-dimensional porous media model for hydrogen magnetic refrigerator with a Brayton-likeoperation cycle. This model has been calculated separately for heat exchange fluid and magnetic material. The results using two different magnetic materials have been compared.We confirmed that the simulation results agreed with experimental data of the internal gas displacer system.