Electromagnetic signatures of the preclinical and prodromal stages of 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-ß 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-ß-positive mild cognitive impairment (n = 17, mean age 74.7 ± 5.4 years, nine males), amyloid-ß-negative mild cognitive impairment (n = 11, mean age 73.8 ± 8.8 years, eight males), amyloid-ß-positive cognitively normal (n = 13, mean age 71.8 ± 4.4 years, seven males), and amyloid-ß-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-ß 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-ß deposition. The results suggest that these MEG signatures may be useful as unique biomarkers for the predementia stages of Alzheimer's disease.

[A case of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in an elderly woman].

An 84-year-old woman who had diabetes mellitus and atrial fibrillation presented to our hospital with appetite loss and difficulty in standing up. Her cervical, axillary, and mediastinal lymph nodes were swollen. At first, malignant lymphoma was suspected, but positron emission tomography-computed tomography and cervical lymph node biopsy did not support this diagnosis. She was admitted to our hospital 41 days after the first consultation because of appetite loss and fever. We suspected a disorder related to Epstein-Barr virus infection because Epstein-Barr virus-encoded small RNAs were found in the lymph node. She was diagnosed with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) based on the diagnostic criteria of the Japanese Society for Pediatric Infectious Diseases. Her symptoms, including appetite loss and fever, were alleviated after the administration of prednisolone (20 mg per day). She was discharged 90 days after admission. At two weeks after discharge, she was readmitted for respiratory failure, and died five days after readmission.To the best of our knowledge there are no previous reports of EBV-HLH in patients over 80 years of age, and the optimal treatment strategy is unknown. This case suggested that prednisolone may alleviate the symptoms of EBV-HLH. When a patient presents with swollen lymph nodes, clinicians should keep the possibility of EBV-HLH in mind.

[A homebound status is related to a reduction of meal intake in older outpatients, independent depressive mood and their physical function].

AIM: We aimed to investigate the relationship between the frequency at which patients went out and the reduction of meal intake among older outpatients who did not require care. METHODS: The subjects were outpatients of ≥65 years of age who visited the department of geriatric medicine in our hospital for the first time. We analyzed 463 subjects (male, n=184; female, n=279), after excluding patients who had dementia, required care, lived in a nursing home, or had an acute disease.The outcome measure was the reduction of meal intake (a moderate or higher decrease in the patient's meal intake in the past 3 months). The independent measure was homebound status (going-out less than once a week). The covariates were sex, age, number of medications, and Kihon Checklist (categories of undernutrition, oral function, physical function, and mood). A logistic regression analysis was performed. RESULTS: The average age was 79.6±5.9 years in men, 79.9±6.1 years in women. Among the participants, 104 (22.5%) had a homebound status. In the logistic regression analyses, a homebound status was significantly associated with a reduction in meal intake, even after adjustment for potential confounding factors, including depressive mood and a low physical function (OR: 2.0; 95% CI: 1.1-3.6). CONCLUSIONS: A homebound status in older outpatients was related to a decline in their meal intake, independent of depressive mood and a low physical function. A reduction in meal intake leads to a lack of energy and results in malnutrition. Our results suggest that assessing the frequency at independently living older outpatients go out is important for the early prevention of malnutrition.

Successful laparoscopic resection for giant mature cystic teratoma of the pancreas: a case report and surgical refinements.

BACKGROUND: Mature cystic teratomas or dermoid cysts of the pancreas complicate surgical approaches because of their anatomical position and ever-growing size. Herein, we report a case of a giant mature cystic teratoma of the pancreas that was successfully resected via complete laparoscopic distal pancreatectomy (LDP). CASE PRESENTATION: A 39-year-old female patient was referred to our hospital for the evaluation of a pancreatic tumor. Three years of follow-up revealed that the tumor had increased in size to 18 cm, with hyperintense solid components on diffusion-weighted magnetic resonance imaging. Considering the possibility of malignancy, we decided to perform an LDP. The capsule appeared solid enough to withstand the retraction of the endoscopic forceps. Tumor size made it difficult to dissect the dorsal side of the tumor from the caudal to the cranial side. Early transection of the pancreas and additional ports facilitated dissection of the dorsal side of the tumor. We completed the LDP without intraoperative cyst rupture. On pathological examination, the tumor was diagnosed as a mature cystic teratoma originating from the pancreatic tail. The patient was discharged on postoperative day 13 with no complications. CONCLUSION: LDP may be an option for surgical procedures in patients with large cystic lesions of the pancreatic body or tail. Intraoperative observation of the tumor and surgical refinement are necessary to complete the laparoscopic procedure without tumor rupture.

[Palliative care in patients without cancer: Impact of the end-of-life care team].

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.

Relationship between atrophy of the medial temporal areas and cognitive functions in elderly adults with mild cognitive impairment.

AIM: The current study sought to determine which types of cognitive function are related to atrophy of the bilateral medial temporal areas including the entorhinal cortex (MTA-ERC) in elderly adults. METHODS: The subjects were 96 elderly adults (mean age 75.3 years) with mild cognitive impairment. Subjects underwent Wechsler Memory Scale-Revised, logical memory I and II (WMS-R, LM I and II), Rey complex figure retention tests after 3 and 30 min (RCF-3 min and RCF-30 min), digit span backword (DSB), digit symbol-coding (DSC), Stroop Color and Word Test-Interference List (SCWT-IL) as well as magnetic resonance imaging (MRI) and were divided into elderly adults without or with mild to moderate MTA-ERC atrophy, and those with severe atrophy. RESULTS: In all subjects, MTA-ERC atrophy showed significant relationships with age (r = 0.43), education (r = -0.25), WMS-R, LM I (r = -0.21), DSC (r = -0.32), and SCWT-IL (r = 0.32). The mild to moderate atrophy group showed significant relationships between MTA-ERC atrophy and age (r = 0.34), DSC (r = -0.28), and SCWT-IL (r = 0.25). In contrast, in the severe atrophy group, MTA-ERC atrophy was correlated significantly with RCF-3 min (r = -0.70) and RCF-30 min (r = -0.74). The linear regression model included demographic variables and cognitive tests; two variables to survive the step-wise analysis were age (ß = 0.374) and SCWT-IL (ß = 0.247) in all subjects. Age (ß = 0.301), and RCF-30 min (ß = -0.521) and age (ß = 0.460) remained as a significant variable in the mild to moderate atrophy and severe atrophy groups, respectively. CONCLUSION: Executive function tests such as SCWT-IL may be useful as a screening tool to identify mild to moderate MTA-ERC atrophy and a decline in the RCF test may suggest severe MTA-ERC atrophy in elderly adults with MCI.

The relationship between atrophy of the medial temporal area and daily activities in older adults with mild cognitive impairment.

BACKGROUND AND AIMS: Many studies have suggested that social network, leisure activity, and physical activity can have protective effects against dementia and Alzheimer's disease. However, previous studies have not examined the relationship between daily activities and brain atrophy in older adults. This study aimed to explore what kind of daily activities were associated with atrophy of the medial temporal area including the entorhinal cortex (MTA-ERC) in older adults. METHODS: In total, 122 older adults (aged 65 and over) with subjective memory complaints or a Clinical Dementia Rating of 0.5 underwent magnetic resonance imaging, and MTA-ERC atrophy was assessed by the voxel- based morphometry method. Based on magnetic resonance imaging data, the subjects were divided into atrophy and non-atrophy groups. Daily activities were assessed using a 20-item questionnaire (e.g., instrumental activities of daily living, social activities), and we compared activity participation between the groups. RESULTS: The atrophy group (n=37) showed significantly lower participation in 4 out of 20 activity items (cleaning, intellectual activity, culture lessons, and using a personal computer) than the non-atrophy group (n=85). Summed scores of these 4 items (range from 0 to 4) were significantly associated with MTA-ERC atrophy even after adjustment for age, sex, education status, and Mini-Mental State Examination score. CONCLUSIONS: In conclusion, MTAERC atrophy was associated with cognitive activities or household-related activities requiring planning.

[Usefulness of support from end-of-life care teams in difficult decision-making].

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.

Laparoscopic repair and total gastrectomy for delayed traumatic diaphragmatic hernia complicated by intrathoracic gastric perforation with tension empyema: a case report.

BACKGROUND: Blunt traumatic diaphragmatic hernia (TDH) is a complication of blunt diaphragmatic injury. If missed, it could lead to critical presentations, such as incarceration or strangulation of the herniated intra-abdominal organs, and thus, early surgical repair is required. Methods of the operative approach against delayed TDH remain unclear. Even with the spread of the minimally invasive approach, laparotomy has been predominantly selected for cases with hemodynamic or gastrointestinal complaints. Literature on the use of laparoscopy for repair of such cases is limited, and no study has been conducted for those with intrathoracic gastric perforation. CASE PRESENTATION: A 55-year-old male patient with a history of multiple traumas presented with shock, followed by left hypochondrium pain and vomiting. The patient was admitted to the emergency department of our institution and diagnosed with delayed TDH complicated by intrathoracic gastric perforation, and tension empyema. Emergency surgery using laparoscopic approach was performed, despite unstable hemodynamics, considering orientation, exposure, and operativity compared with laparotomy. Repair of the diaphragm plus total gastrectomy was successfully performed by minimally invasive management. The patient made an uneventful recovery without recurrence after 8 months. CONCLUSION: Unstable hemodynamic conditions and intrathoracic gastric perforation could not be contraindications to laparoscopic repair in treating delayed TDH.

The association between decline in physical functioning and atrophy of medial temporal areas in community-dwelling older adults with amnestic and nonamnestic mild cognitive impairment.

OBJECTIVE: To examine whether declining performance in aspects of physical functioning, including lower extremity muscle strength, 1-legged balance, walking speed, and exercise capacity, is associated with atrophy of medial temporal areas in community-dwelling older adults with mild cognitive impairment (MCI). DESIGN: Cross-sectional study. SETTING: General community in Japan. PARTICIPANTS: Community-dwelling older adults 65 years and older with a Clinical Dementia Rating of 0.5 or memory complaints were enrolled in this study. This study examined 34 participants with amnestic MCI (aMCI) and 58 nonamnestic MCI (non-aMCI) participants. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The following physical performance tests were conducted: muscle strength of knee extension, 1-legged standing time, 5-m walking test, and 6-minute walk test (6MWT). The z scores of the voxel-based specific regional analysis system for Alzheimer's disease were determined to assess the degree of atrophy in the bilateral medial temporal areas including the entorhinal cortex (MTA-ERC). RESULTS: In the aMCI group, 6MWT performance was associated with MTA-ERC atrophy (ß=-.462, P=.014) after controlling for age. In the stepwise multiple regression analyses, 6MWT and body mass index were found to be significant determinants of MTA-ERC atrophy in all participants (R(2)=.275), as well as the aMCI and non-aMCI groups when analyzed separately (R(2)=.418 and R(2)=.216, respectively). CONCLUSIONS: A decline in exercise capacity was found to be more closely associated with atrophy of the MTA-ERC compared with other aspects of physical functioning in older adults with MCI, especially the amnestic type. These findings suggest that it is important for future studies to investigate the effects of increased aerobic activity and improved fitness on brain volume in older adults at risk of developing dementia.

Impact of regional white matter hyperintensities on specific gait function in Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Gait disturbance and musculoskeletal changes are evident in persons living with Alzheimer's disease (AD). Because complex gait control requires the integration of neural networks, cerebral small vessel disease (SVD), which is highly prevalent in persons with AD, might have an additional impact on gait disturbance. This study investigated whether white matter hyperintensities (WMH) are more predominantly associated with gait disturbance in persons with AD than in individuals with mild cognitive impairment (MCI) and normal cognition (NC) and further identified the regional impact of WMH on specific gait changes. METHODS: This study included 396 subjects (aged 65 to 86 years, 63.9% female) diagnosed with AD (n = 187), MCI (n = 118), or NC (n = 91). WMH, lacunes, perivascular spaces, and cerebral microbleeds were assessed as markers of SVD. The volume of WMH was quantified in each brain lobe (frontal, temporal, occipital, and parietal) and sublobar regions in the basal ganglia and thalamus. Gait function was assessed using an electronic walkway. We investigated the association between regional WMH and gait disturbance in individuals with AD, MCI, and NC, adjusted for classical and musculoskeletal confounders. RESULTS: Among markers of SVD, WMH were most associated with gait disturbance. In AD subjects, periventricular WMH in the frontal and parietal lobes were associated with slow gait speed (rs  = -0.21, P = 0.007 and rs  = -0.18, P = 0.019, respectively). These lesions were also associated with changes in stride time, double-leg support time, and walking angle (all rs  > 0.20, P < 0.01). Lesions in the basal ganglia and thalamus were associated with slow gait speed (rs  = -0.16, P = 0.034 and rs  = -0.18, P = 0.023, respectively) and greater gait speed variability (rs  = 0.16, P = 0.034 and rs  = 0.20, P = 0.010, respectively). MCI subjects showed only associations between sublobar lesions and shorter stride length (rs  = -0.24, P = 0.016) and increased walking angle (rs  = 0.32, P = 0.002). NC subjects did not show associations between WMH and gait parameters. MCI and NC subjects were more affected by muscle weakness than WMH for global gait function (rs  = 0.42, P < 0.001 and rs  = 0.23, P = 0.046, respectively). CONCLUSIONS: Persons with AD showed a predominant association between WMH and gait disturbance compared with MCI and NC subjects, and regional WMH had a detrimental effect on specific gait changes.

Association between quality of life of demented patients and professional knowledge of care workers.

Professional knowledge about dementia and care methods is necessary for the appropriate care of demented people. In this study, the quality of life of 91 demented people staying at 12 care institutions was evaluated with the Quality of Life Questionnaire for Dementia (QOL-D). The amount of professional knowledge was evaluated in 140 staff members who took care of the patients using the professional knowledge test (PKT), and the mean PKT score was calculated for each institution (professional knowledge of institution). A positive significant correlation was observed between the QOL-D score and the professional knowledge of institution. The correlation remained significant when age, sex, and severity of dementia of demented patients were partialled out. This result indicated that the quality of life of demented people was better at institutions with staff members having more professional knowledge, indicating the importance of education of staff members and the possibility that such education improves the quality of life of the demented people.

[Care and nursing in remodeling long term care insurance].

Long term care insurance was changed in 2006. The main purpose of remodeling is to support preventive care and to develop community comprehensive care center and community based services. Community based services are composed by group homes, night care services, small multi-function complex care services, day care services for dementia, satellite nursing homes. Preventive care in long term care insurance is composed of muscle training, oral care and improvement of nutrition. Visiting nurse services can provide day care at nurse stations. These arrangements are strongly expected to support care workers and visiting nurses. An assessment for dementia, Center version was developed by the Tokyo Center for Dementia Care Training and Research. It is intended to lead to person-centered care for elderly people with dementia. An act to prevent abuse of the elderly has been started in 2005. This was established to protect the property of the elderly, even if they might have cognitive dysfunction. A support doctor system has been started to educate primary care doctors and to make early diagnosis for dementia. These changes are expected to provide better care for old people.

A comparison of depressive mood of older adults in a community, nursing homes, and a geriatric hospital: factor analysis of Geriatric Depression Scale.

The Geriatric Depression Scale (GDS)-15 was used in 607 adults aged 65+ years living in a community, nursing homes, and a general hospital to explore characteristics of depressive mood in different care settings. Factor analysis of GDS-15 extracted 4 factors labeled unhappiness, apathy and anxiety, loss of hope and morale, and energy loss. The scale scores labeled unhappiness, apathy and anxiety, and loss of hope and morale were negatively correlated with the Barthel Index and the Mini-Mental State Examination scores. The results classified the depressive patterns into 2 types, one fitting the nursing home residents and the other fitting the hospital patients. The dominant factors of the nursing-home type were unhappiness and loss of hope and morale, and the hospital type was highly related with apathy and anxiety. The results indicate an extended utility of the GDS-15 for a deeper understanding of depressive mood in various care settings.

[Role of geriatric physicians in the general hospital].

Geriatricians have a major roles to assess and head elderly patients using a team approach. In this paper, the first question is to ask what a geriatrician is, and the second question is to ask the role of a geriatrician. A geriatrician is a coordinator for elderly patients who have physical and mental disorders. We have to take care of not only diseases, but also the patients' lives after discharge from hospital. Geriatrician should coordinates a team approach and maintain contact with care managers. In general hospitals, discharge planning, which supports short and smooth discharge is an important role of geriatrician. We are frequently asked to see elderly patient by specialists because of difficult problems, such as delirium, cognitive dysfunction and communication disorder.

[Reconstruction of the long term care insurance system in Japan].

The Japanese long term care insurance has started since 2000. After 5 years' experience, it is scheduled to change in 2006, the most important point is preventive care which means to stop the deterioration of ADL or cognitive function. Prevention is thought to be best way to cut the cost of care services. The preventive care system will start in April, 2006, over 1 million people with supportive care needs will receive muscle training or oral care and nutritional support from care workers in the community. New comprehensive community centers will open and these should which make assessments for preventive care, and provide consultations for care givers and families, and comprehensive care management in the community, and protect the dignity of the elderly will newly start. To improve quality of care services is important, and each prefecture has to evaluate all services and to publish the data with internet, so that everybody can see it and select the most appropriate care or company. Also, the government will start a new system of community based services including group homes, small and multifunctional care services, and day care services for people with dementia. These services should have one room available for each individual.

[Comprehensive geriatric assessment for management of the elderly with diabetes mellitus].

In medical care for the elderly patients with diabetes mellitus, there are many cases that are not indicated for active treatment, because of their impairment of activity of daily living (ADL), instrumental ADL and cognitive function, and also the presence of some complications, such as cerebrovascular disorder. On the other hand, poor glycemic control is easy to induce dehydration, bacterial infection, and cognitive disorders in the elderly. Thus, it is necessary to maintain good glycemic control to preserve better ADL. However, compulsion of strict glycemic control might rather decrease QOL of the patient. To solve such a medical dilemma, the comprehensive geriatric assessment (CGA) is useful for the individual diabetic patient.

Pressure ulcers induced by drug administration: A new concept and report of four cases in elderly patients.

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.

Validity of the Kihon Checklist for assessing frailty status.

AIM: The Kihon Checklist is extensively used in Japan to identify elderly persons who are at risk of requiring support/care. We aimed to determine whether or not the Kihon Checklist can estimate frailty status defined by the Cardiovascular Health Study criteria. METHODS: This cross-sectional study evaluated the Kihon Checklist and activities of daily living based on self-records maintained with the assistance of nurses in a convenience sample of 164 elderly outpatients who lived without care or support. Body composition was measured using dual energy X-ray absorptiometry. Physical functions, nutritional status, cognitive function and depressive mood were assessed using standardized evaluations. Frailty status was evaluated using the Cardiovascular Health Study frailty criteria. RESULTS: The total Kihon Checklist score closely correlated with validated assessments of physical functions, nutritional state, cognitive function, depressive mood and the number of frailty phenotypes defined by the Cardiovascular Health Study criteria (ρ = 0.655, P < 0.001). The area under the receiver operating characteristics curves for the evaluation of frailty status was 0.81 for prefrailty and 0.92 for frailty. The sensitivity and the specificity were 70.3% and 78.3% for prefrailty, and 89.5% and 80.7% for frailty at total Kihon Checklist scores of 3/4 and 7/8, respectively. CONCLUSION: The Kihon Checklist is a useful tool for frailty screening. Analyzing the results of this self-reporting questionnaire, together with other more high-tech screening modalities, will cost-effectively improve the quality of life for many elderly individuals in a timely manner. Geriatr Gerontol Int 2015; ●●: ●●-●●.