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BACKGROUND: This study investigated how cognitive function-related simple questions can be used to identify older individuals who are at risk of needing long-term care. METHODS: This cohort study was conducted in Kobe city, Japan. In 2015, the municipal office distributed the Kihon Checklist by post, a 25-item questionnaire including three cognitive function-related questions (questions 18, 19, 20) to citizens aged ≥ 70 years. Need certification is routinely done by Kobe city as part of the national Long-Term Care Insurance Act. The answers to the 2015 questionnaire were merged with need certification data between the questionnaire delivery and the end of December 2019. RESULTS: Of the 77,877 citizens (age: 72.9 ± 2.7 years) who received the questionnaire, 50,154 responded (response rate: 64.4%). During the study period, the cumulative incidence of the need for long-term care was higher in those who did not respond than in those who did (12.5% vs 8.4%; P < 0.001). Among those who responded, the incidence of the need for long-term care was progressively greater as the number of negative answers to cognitive function-related questions increased (5.0%, 8.4%, 15.7% and 30.2% at 4 years' follow-up, for respondents with, respectively, 0, 1, 2 and 3 negative answers). Similarly, when the need certification for long-term care was confined to that accompanied by dementia, the incidence also rose as the number of negative responses to the cognitive function-related questions increased (3.4%, 6.5%, 13.7% and 27.9% for respondents with, respectively, 0, 1, 2 and 3 negative answers). Using multivariate Cox regression analysis, all three cognitive function-related questions were predictive of the need for long-term care, and question 18 (about memory loss) had the highest hazard ratio for predicting the need for long-term care accompanied by dementia. CONCLUSIONS: Use of cognitive function-related simple questions may help identify older adults at risk for needing long-term care, suggesting their potential value for use in administrative and policy approaches aimed at reducing the societal burden of dementia.
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Demência , Assistência de Longa Duração , Humanos , Idoso , Estudos Prospectivos , Japão , Estudos de Coortes , CogniçãoRESUMO
AIM: Many researchers argue that Alzheimer's disease is at least partly caused by deposition of amyloid beta (Aß) in the brain. Ferulic acid (FA) and Angelica archangelica (AA) are candidate agents for reducing Aß and improving cognitive function. Feru-guard 100M is a supplement containing FA and AA extract. Using this supplement, we planned to assess the effect of FA and AA on Aß deposition in the human brain. METHODS: This was an open-label, interventional multi-institutional joint study of Kobe University and the Institute of Biomedical Research and Innovation (Kobe, Japan). Seventeen subjects diagnosed with mild cognitive impairment were divided into two groups: the intervention group (n = 10) and the control group (n = 7). The subjects in the intervention group used Feru-guard 100M every day for 48 weeks, whereas the subjects in the control group did not use the supplement. We assessed the differences between the two groups by examining Aß deposition and brain atrophy at 48 weeks and cognitive function every 24 weeks. We used carbon-11-labelled Pittsburgh compound B (PiB) positron emission tomography to evaluate Aß deposition. RESULTS: There were no significant differences in Aß deposition, brain atrophy, and cognitive function between the two groups. Specifically, differences in Aß deposition change in seven regions of interest examined with PiB positron emission tomography, brain atrophy change in four indicators of voxel-based morphometry, and cognitive impairment measured by five psychological tests were not significantly between the two groups. CONCLUSION: Treatment with Feru-guard 100M, a supplement containing FA and AA extract, for 48 weeks did not reduce cortical PiB retention, which reflects Aß deposition. It also did not suppress the aggravation of brain atrophy or decline in cognitive function.
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Peptídeos beta-Amiloides/efeitos dos fármacos , Angelica archangelica/química , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico , Ácidos Cumáricos/uso terapêutico , Idoso , Doença de Alzheimer/etiologia , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Atrofia , Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono , Disfunção Cognitiva/diagnóstico por imagem , Progressão da Doença , Feminino , Humanos , Japão , Masculino , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , TiazóisRESUMO
BACKGROUND: Confabulations are often observed in patients with Alzheimer's disease (AD) and can increase family caregivers' burdens. Previous studies have focused on the relationship between confabulation and cognitive ability. However, few studies have investigated the association between confabulation and familial factors. Here, we aimed to examine whether confabulation relates to familial factors, such as the level of family caregivers' expressed emotion or the level of functioning of the family. METHODS: Twenty-seven outpatients with AD and their family caregivers participated in this study. We examined confabulations about episodic memory, semantic memory, and future planning using the Modified Confabulation Battery (MCB). We investigated correlations between scores on the MCB and scores on the Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Family Attitude Scale (FAS), and the Family Adaptability and Cohesion Evaluation Scale. Multiple regression analyses were performed using the total scores on the MCB and domain-specific scores on the MCB as dependent variables, and the scores on the MMSE, GDS, and FAS as independent variables. RESULTS: MCB scores were positively related to FAS scores (P < 0.01) and negatively to GDS scores (P < 0.05), but not to MMSE scores. Regarding the three domains the MCB measured, confabulation about episodic memory and future planning showed a positive relationship with FAS scores. CONCLUSIONS: Family attitude was the factor most related to confabulation in our study. Patients with AD may attempt to avoid confronting family caregivers' high emotional expression through confabulation, or confabulation itself might result in high emotional expression among family caregivers. Psychoeducational or therapeutic approaches for family caregivers might reduce confabulation in patients with AD.
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Doença de Alzheimer/psicologia , Cuidadores/psicologia , Família/psicologia , Transtornos da Memória/etiologia , Memória/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Depressão/etiologia , Depressão/psicologia , Feminino , Humanos , Masculino , Transtornos da Memória/psicologia , Rememoração Mental , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Repressão Psicológica , Índice de Gravidade de DoençaRESUMO
Brain imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), can provide essential and objective information for the early and differential diagnosis of dementia. Amyloid PET is especially useful to evaluate the amyloid-ß pathological process as a biomarker of Alzheimer's disease. This article reviews critical points about technical considerations on the scanning and image analysis methods for amyloid PET. Each amyloid PET agent has its own proper administration instructions and recommended uptake time, scan duration, and the method of image display and interpretation. In addition, we have introduced general scanning information, including subject positioning, reconstruction parameters, and quantitative and statistical image analysis. We believe that this article could make amyloid PET a more reliable tool in clinical study and practice.
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Demência/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Amiloide/análise , HumanosRESUMO
Autism spectrum disorders (ASD) have been largely neglected in the field of elderly psychiatry. ASD were characterized by a triad of qualitative impairments in the aspects of social interaction, communication, and restricted patterns of behavior and interests. The prevalence of ASD was not clearly estimated in elderly. In clinical practice, elderly patients with confirmed ASD were not usually diagnosed properly earlier in life for various reasons. However, the understanding of characteristic with ASD is useful for clinicians, because we can arrange a suitable environment for patients with ASD. We tend to make overdiagnoses of ASD because of paying attention to only frontal lobe syndrome. We should exclude neurodegenerative disease, especially frontotemporal lobar degeneration.
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Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Idoso , Transtornos Globais do Desenvolvimento Infantil/terapia , HumanosRESUMO
Depression is a risk factor for dementia in general, including Alzheimer's disease (AD), its premorbid signs are commonly observed, and the morbidity of depression is higher in dementia patients. Dementia with Lewy bodies (DLB) is considered to have an even higher depression prevalence and premorbid depression rate than other dementias such as AD. This led to depression being listed as a supportive feature in the 2005 criteria for the clinical diagnosis of DLB. However, studies investigating the difference in depression between AD and DLB failed to show consistent results. We examined the Geriatric Depression Scale score, which is designed specifically to rate depression in the elderly, for DLB and AD patients. The scores for DLB patients were twice as high as those for AD patients. There was no correlation between the GDS score and age, sex, or Mini-Mental Sate Examination scores. Depression-specific symptoms were more frequent in the DLB group than non-specific symptoms, while less than one third of DLB patients with very high GDS scores were diagnosed with depression or prescribed antidepressants for depressive symptoms. Other researchers reported that depression of DLB was associated with a higher prevalence of psychiatric symptoms other than major depression, and suggested that depression of DLB might be a part of psychiatric syndrome. There has been no systematic study on the validity or risk of pharmacological therapy, as well as the necessity of intervention, for depression or a high GDS score in DLB. Therefore, intervention must rely on the clinical decision of each doctor. In spite of the paucity of current findings, studies on depression of DLB may play a key role in the elucidation of its neuropathology and psychopathology and offer a new view point on understanding depression itself.
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Demência/fisiopatologia , Depressão/fisiopatologia , Doença por Corpos de Lewy/tratamento farmacológico , Doença por Corpos de Lewy/fisiopatologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Demência/complicações , Demência/diagnóstico , Demência/tratamento farmacológico , Depressão/diagnóstico , Depressão/etiologia , Diagnóstico Diferencial , Humanos , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/diagnóstico , Fatores de RiscoRESUMO
(1) Background: The COVID-19 pandemic has distressed many populations worldwide, and since its beginning, many institutes have performed cross-sectional studies to assess mental health. We longitudinally examined psychological distress and depressive symptoms among university staff in Japan from 2019 to 2021, before and during the COVID-19 pandemic.; (2) Methods: Participants were teachers and hospital staff working at institutions related to Kobe University, who completed the Brief Job Stress Questionnaire (BJSQ) from 2019 to 2021. This study used the definition recommended by the guideline to identify high-stress. We analyzed the relationship between those who identified as having high-stress before versus during the COVID-19 pandemic using logistic regression analysis (adjusted for age, sex, and occupation).; (3) Results: Results showed that Stress Reaction scores increased slightly in 2020 and significantly in 2021. Time and other factors had a synergistic effect on mental health. The increase in Stress Reaction was significantly associated with females and nurses over the three years. Those with high-stress in 2019 had approximately twenty-fold odds ratios (OR) of having high-stress in 2020 and 2021.; (4) Conclusions: The long-term COVID-19 pandemic may disturb university staff's mental health. Those who originally experienced high levels of stress were vulnerable to the negative effects of the COVID-19 pandemic.
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COVID-19 , Angústia Psicológica , Feminino , Humanos , COVID-19/psicologia , SARS-CoV-2 , Universidades , Estudos Transversais , Pandemias , Depressão/epidemiologia , Depressão/psicologia , Estresse Psicológico/epidemiologiaRESUMO
OBJECTIVE: A new tau PET tracer [18F]MK-6240 has been developed; however, its dosimetry and pharmacokinetics have been published only for a European population. This study investigated the safety, radiation dosimetry, pharmacokinetics and biodistribution of [18F]MK-6240 in Japanese elderly subjects. Also, the pattern and extent of brain retention of [18F]MK-6240 in Japanese healthy elderly subjects and patients with Alzheimer's disease (AD) were investigated. These Japanese results were compared with previous reports on non-Japanese. METHODS: Three healthy elderly subjects and three AD patients were enrolled. Dynamic whole-body PET scans were acquired for up to 232 min after starting injection of [18F]MK-6240 (370.4 ± 27.0 MBq) for the former, while a dynamic brain scan was performed from 0 to 75 min post injection for the latter. For both groups, brain PET scans were conducted from 90 to 110 min post injection. Sequential venous blood sampling was performed to measure the radioactivity concentration in the whole blood and plasma as well as the percentages of parent [18F]MK-6240 and radioactive metabolites in plasma. Organ doses and effective doses were estimated using the OLINDA Ver.2 software. Standardized uptake value ratios (SUVRs) and distribution volume ratios (DVRs) by Logan reference tissue model (LRTM) were measured in eight brain regions using the cerebellar cortex as the reference. Blood tests, urine analysis, vital signs and electrocardiography were performed for safety assessments. RESULTS: No adverse events were observed. The highest radiation doses were received by the gallbladder (257.7 ± 74.9 µGy/MBq) and the urinary bladder (127.3 ± 11.7 µGy/MBq). The effective dose was 26.8 ± 1.4 µSv/MBq. The parent form ([18F]MK-6240) was metabolized quickly and was less than 15% by 35 min post injection. While no obvious accumulation was found in the brain of healthy subjects, focal accumulation of [18F]MK-6240 was observed in the cerebral cortex of AD patients. Regional SUVRs of the focal lesions in AD patients increased gradually over time, and the difference of SUVRs between healthy subjects and AD patients became large and stable at 90 min after injection. High correlations of SUVR and DVR were observed (p < 0.01). CONCLUSION: The findings supported safety and efficacy of [18F]MK-6240 as a tau PET tracer for Japanese populations. Even though the number of subjects was limited, the radiation dosimetry profiles, pharmacokinetics, and biodistribution of [18F]MK-6240 were consistent with those for non-Japanese populations. TRIAL REGISTRATION: Japan Pharmaceutical Information Center ID, JapicCTI-194972.
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Doença de Alzheimer , Humanos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Distribuição Tecidual , Radiometria , Isoquinolinas/metabolismo , Tomografia por Emissão de Pósitrons/métodosRESUMO
INTRODUCTION: The Kobe project, which utilizes prospective data from the national health insurance system, focuses on early detection and preventive strategies through the Frail Kenshin health check-up program. Previous research has underscored the correlation between tooth loss and the decline in physical and cognitive functions. In this study, using Kobe project data, we examined the link between remaining teeth and long-term care needs in individuals aged 64-65 years, with primary and secondary objectives involving various health parameters and quality of life. METHODS: We analyzed baseline data from a prospective study conducted alongside the Frail Check program for generally healthy individuals aged 64-65 years to examine the relationship between the number of remaining teeth and various health indicators. This study focused on citizens aged 64-65 years to identify those at risk of needing long-term care by the age of 65 years. RESULTS: Data from 1,530 participants were obtained, excluding eight individuals for specific reasons. At the end of the follow-up period, 41 (2.7%) individuals required support and 15 (1.0%) needed long-term care alone. The data revealed a significant association between the number of remaining teeth and the need for long-term care or support, as demonstrated by the Cochran-Armitage trend test (p<0.001). Although trends were noted for nutrition and total Cognitive Functional Instrument Self scores, they did not reach statistical significance. Additionally, a decrease in the number of remaining teeth was significantly associated with worse European Quality of Life Five Dimensions (EQ-5D-5L) visual analog scale scores, mobility, and regular activities (p<0.001). CONCLUSION: Tooth loss indicates the potential long-term care needs of older adults. Monitoring oral health is crucial for addressing care requirements.
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Doença de Alzheimer/patologia , Córtex Cerebral/patologia , Imageamento por Ressonância Magnética , Doenças Neurodegenerativas/patologia , Doenças dos Gânglios da Base/patologia , Proteínas da Membrana Plasmática de Transporte de Dopamina , Dislipidemias , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To assess the attitude of medical care for dementia among the primary care physicians (PCP) in two different areas in Hyogo Prefecture and compare it. METHODS: A 15-item questionnaire related medical care for dementia was developed and sent it by mail to the PCP in December, 2011. RESULTS: One area is an urban area and the other is a rural area. The response rates were 42.9% and 36.7%, respectively. The rate of the PCP in the urban area who was interested to care dementia elderly was higher, compared to the rural area. The integrated medical care net work was well functioning in the urban area. The rate of PCP in the urban area who wanted to have training for dementia care was higher than in the rural area. CONCLUSIONS: Although the rate of elderly in the population in the rural area is higher, the PCP in the rural area seemed not to be interested in dementia care.
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Prestação Integrada de Cuidados de Saúde , Demência/terapia , Coleta de Dados , Prestação Integrada de Cuidados de Saúde/tendências , Humanos , Japão , Médicos de Atenção Primária , Serviços de Saúde Rural , Serviços Urbanos de SaúdeRESUMO
AIM: MATRICS Consensus Cognitive Battery was developed by the National Institute of Mental Health to establish acceptance criteria for measuring cognitive changes in schizophrenia and can be used to assess cognitive functions in other psychiatric disorders. We used a Japanese version of MATRICS Consensus Cognitive Battery to explore the changes in multiple cognitive functions in patients with mild cognitive impairment and mild Alzheimer's disease. METHODS: We administered the Japanese version of MATRICS Consensus Cognitive Battery to 11 patients with mild cognitive impairment (MCI), 11 patients with Alzheimer's disease, and 27 healthy controls. All Japanese versions of MATRICS Consensus Cognitive Battery domain scores were converted to t-scores using sample means and standard deviations and were compared for significant performance differences among healthy control, MCI, and mild Alzheimer's disease groups. RESULTS: Compared with healthy controls, patients with MCI and mild Alzheimer's disease demonstrated the same degree of impairment to processing speed, verbal learning, and visual learning. Reasoning and problem-solving showed significant impairments only in mild Alzheimer's disease. Verbal and visual abilities in working memory showed different performances in the MCI and mild Alzheimer's disease groups, with the Alzheimer's disease group demonstrating significantly more deficits in these domains. No significant difference was found among the groups in attention/vigilance and social cognition. CONCLUSIONS: The Japanese version of MATRICS Consensus Cognitive Battery can be used to elucidate the characteristics of cognitive dysfunction of normal aging, MCI, and mild dementia in clinical practice.
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Doença de Alzheimer , Disfunção Cognitiva , Esquizofrenia , Doença de Alzheimer/diagnóstico , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Humanos , Testes NeuropsicológicosRESUMO
One hundred years has passed since the appearance of the first article on Alzheimer's disease (AD), by Alois Alzheimer. AD is the most common form of dementia, accounting for over 50% of all dementia and affecting more than 26 million people worldwide. Since the 1980s, the pace of research into the nature of AD has greatly accelerated, and investigators currently believe that it will become possible to treat or prevent AD, which is a major socioeconomic concern in all developed countries of the world. Mild cognitive impairment (MCI) is a relatively recent term used to describe people who have some memory problems, but do not actually have dementia. In recent years, some drug treatments that can improve the symptoms of AD have become available. Other treatments that may slow down the progression of AD in the brain are also being developed. It is important that people with AD be identified as early as possible, so that they can benefit from these treatments in the future. Identifying people with MCI is one way to try to achieve this. In Japan, the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) was launched in 2008. It follows the protocols established by US-ADNI, and aims to conduct a longitudinal workup of standardized neuroimaging, biomarker, and clinico-psychological surveys. The Japanese research protocol was designed to maximize compatibility with that of US-ADNI, including structural magnetic resonance imaging (MRI) analysis for the evaluation of brain atrophy, fluorodeoxyglucose (FDG) and amyloid positron emission tomography (PIB-PET), cerebrospinal fluid (CSF) sampling, and APOE genotyping, as well as a set of clinical and psychometric tests that were prepared so as to achieve the greatest compatibility possible with those used in US-ADNI. J-ADNI has recruited approximately 357 participants (142 with amnestic mild cognitive impairment, some 134 elders without impairment, and 72 persons with mild Alzheimer's disease) as of April 15, 2010. Worldwide ADNI activities will allow the establishment of rigorous quantitative descriptions of the natural course of AD in its very early stages. In addition, this project will aid in the clarification and differentiation of MCI and AD. The major goal of this research is the establishment of surrogate markers for AD based on MRI, PET, and CSF data. This data, as well as the methodologies and infrastructure used, will facilitate clinical trials of disease-modifying therapies for AD using surrogate biomarkers, enabling the application of effective therapies with AD/MCI patients, and eventually the prevention of AD. In this symposium, I will speak about MCI and early-stage AD, with a particular focus on the latest clinical neuroimaging data from J-ADNI.
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Transtornos Cognitivos/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: This research project addresses the lack of screening tools for the early detection of high-risk individuals for long-term care, through four individual studies.Study 1 investigates the predictive ability of the 'Kihon Check List', study 2 the 'Cognitive Function instrument' and EuroQol-5 Dimension (EQ-5D) and study 3 the 'Cognitive Function instrument' and EQ-5D as well as the 'Frail Kenshin' health check-up, for incident long-term care certification over a follow-up period of up to 4 years. This is the first large prospective study to evaluate the predictive ability of these tools for the outcome measure long-term care certification. The last subsection of this project study four aims to explore a mixed methods intervention for delaying the need for long-term care. This section is purely exploratory, looking for clues for further studies. METHODS AND ANALYSIS: Baseline data have been collected through local government programs, as well as through postal self-reported questionnaires. The primary outcome variable for all studies is long-term care certification data. Statistical analysis will be carried out using Kaplan-Meier, Multiple Cox regression as well as logistic regression. CONCLUSION: This project hopes to identify tools effective in predicting long-term care need. This will enable identification of citizens that are of higher risk for long-term care in the near future. This subset of high-risk individuals can in the future be addressed for extra support/intervention. ETHICS AND DISSEMINATION: All studies have been approved by respective institutional ethical committees and the WHO ethical committee ERC.0002899. In addition, all studies conform to the provisions of the Declaration of Helsinki and are conducted in accordance with Japan's 'Ethical Guidelines for Medical and Health Research Involving Human Subjects'. All findings will be disseminated at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000023283.
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Demência , Assistência de Longa Duração , Lista de Checagem , Humanos , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
We reported a patient with probable dementia with Lewy bodies (DLB) showing cervical dystonia during treatment with donepezil. A 78-year-old female had been treated with donepezil 5 mg/day for 18 months. The patient admitted to our hospital because of severe antecollis. Antecollis disappeard three weeks after discontinuation of donepezil. Five months later the patient received donepezil 3-5 mg/day for disease progression. The patient showed laterocollis again after a month-treatment with donepezil. Physical examination and labolatory tests were nomal. Magnetic resonance imaging of the neck showed no abnormal finding, but electromyography revealed dystonic changes in the neck muscles. Three weeks after discontinuation of donepezil, laterocollis disappeared. These findings suggest that treatment with donepezil induced cervical dystona in a patient with DLB.
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Indanos/efeitos adversos , Doença por Corpos de Lewy/tratamento farmacológico , Piperidinas/efeitos adversos , Torcicolo/induzido quimicamente , Idoso , Donepezila , Eletromiografia , Feminino , Humanos , Torcicolo/diagnósticoRESUMO
BACKGROUND: Today, Japan is becoming a super-aged society, with senior citizens already constituting over 21% of the population. In this situation, the question of how elderly people can extend their lives and enjoy independent lifestyles is becoming more important. The present study aims to clarify the relationship between the Quality of Life (QOL) of elderly females and their current oral functions and experiences of music and art education in early life. METHODS: We carried out a survey study focusing on elderly females (Takarazuka Revue Company OG group and general female group) by carrying out a questionnaire survey and comparing cognitive function, oral examinations, cerebral atrophy in magnetic resonance imaging, and other characteristics. RESULTS: It was shown that the Takarazuka Revue Company OG group had greater hippocampal volumes and significantly higher cognitive functions than the general female group. In addition, in the general female group, there was a significant correlation between a decrease in the number of remaining teeth and a decrease in activities in daily living, but in the Takarazuka Revue Company OG group, no such correlation was observed. CONCLUSIONS: The results showed that those who have received art education as part of their careers over an extensive period since early life have higher levels of cognitive function, QOL, physical activity, social activity and life satisfaction compared with the general female group; showing that they sense a purpose in life and live with a positive attitude. In contrast, in the general female group, those who have continued to enjoy hobbies have higher levels of cognitive function, QOL, physical activity, social activity and life satisfaction than those who have not, thus showing that they live with a positive attitude.
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Arte , Cognição , Educação , Música , Saúde Bucal , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Atrofia , Encéfalo/patologia , Coleta de Dados , Feminino , Humanos , Japão , Imageamento por Ressonância Magnética , Entrevista Psiquiátrica Padronizada , Comportamento SocialRESUMO
TAC-101, 4-[3,5-bis(trimethylsilyl)benzamido] benzoic acid, is a synthetic ligand for retinoic acid receptor (RAR)-alpha. Here, we demonstrate the contribution of TAC-101-induced AP-1 interference to stabilization of tumor growth. TAC-101 induced transcriptional activation of RAR, resulting in marked elevation of RARbeta, a representative retinoid response marker, and it also significantly repressed the transcriptional activity of AP-1 in JHH-7 cells. In contrast to JHH-7, JHH-6 is another RARalpha-expressing human hepatocellular carcinoma (HCC) cell line with constitutive activation of AP-1, but it is retinoid insensitive and did not respond to the TAC-101-induced RAR signal. TAC-101 did not inhibit AP-1 activity of the JHH-6 cell line, showing that AP-1 interference by TAC-101 must be in parallel with RAR activation. Interleukin-8 (IL-8), one of the AP-1-regulated factors which correlate with a poor prognosis in HCC patients, was found to be overexpressed in JHH-7 cells. TAC-101 reduced IL-8 production without cytotoxicity and inhibited the progression of HCC in the orthotopic mouse model with decreased tumor IL-8 level. These results suggest that downregulation of the extracellular biomarker for AP-1 interference via the induction of retinoid signals will enhance the pharmacological effect of TAC-101 on HCC and it could be useful as a surrogate biomarker of therapeutic efficacy.
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Benzoatos/farmacologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Fator de Transcrição AP-1/metabolismo , Compostos de Trimetilsilil/farmacologia , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Humanos , Interleucina-8/metabolismo , Ligantes , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Receptores do Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico , Fator de Transcrição AP-1/efeitos dos fármacos , Fator de Transcrição AP-1/genéticaRESUMO
OBJECTIVE: To demonstrate the exact nature of the cognitive profile of dementia with Lewy bodies (DLB) on standardized neuropsychological tests including the Wechsler Adult Intelligence Scale--Revised (WAIS-R) and the Wechsler Memory Scale--Revised (WMS-R). DESIGN: We examined the WAIS-R and the WMS-R of 26 patients with probable DLB (based on the Consensus Criteria for the clinical diagnosis of DLB) and of 78 patients with probable Alzheimer's disease (AD) (based on criteria of the National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's disease and Related Disorders Association) who were matched to the patients with DLB 3:1 by Mini-Mental State Examination score. RESULTS: The DLB group scored significantly lower on the Block Design, Object Assembly and Digit Symbol of WAIS-R and significantly higher on the Logical Memory I, Verbal Paired Associates I, Logical Memory II, Visual Paired Associates II, Verbal Paired Associates II and Visual Reproduction II of WMS-R (p < 0.0016 to p < 0.0001). In a comparison between the DLB group and the AD group, a logistic regression analysis revealed that the weighted sum score of the Object Assembly and the Logical Memory II may differentiate DLB from AD with a sensitivity of 0.81 [95% Confidence Intervals (CI) = 0.66-0.96] and a specificity of 0.76 (95% CI = 0.66-0.85). CONCLUSIONS: The WAIS-R and the WMS-R can help to differentiate DLB from AD.
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Doença de Alzheimer/psicologia , Cognição/classificação , Doença por Corpos de Lewy/psicologia , Testes Neuropsicológicos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Corpos de Lewy , Doença por Corpos de Lewy/diagnóstico , Masculino , Memória , Destreza Motora , Análise de Regressão , Percepção VisualRESUMO
Dementia with Lewy bodies (DLB) accounts for 10-25% of all dementia cases in clinical populations and is considered to be the second most common degenerative dementia in elderly people after Alzheimer's disease (AD). Dementia with Lewy bodies is characterized by the presence of cognitive, psychiatric, and motor symptoms. Although the neuropsychological profiles of patients with DLB often differ from those of patients with AD, the diagnostic sensitivity, specificity, and predictive values of these profiles remain largely unknown. The present paper reviews the neuropsychological profiling of DLB and attempts the neuropsychological differentiation of DLB from AD.