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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.

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.

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).