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1.
Cureus ; 15(12): e49851, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38050582

RESUMO

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.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36767575

RESUMO

(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.


Assuntos
COVID-19 , Angústia Psicológica , Feminino , Humanos , COVID-19/psicologia , SARS-CoV-2 , Universidades , Estudos Transversais , Pandemias , Depressão/epidemiologia , Depressão/psicologia , Estresse Psicológico/epidemiologia
3.
Ann Nucl Med ; 37(2): 108-120, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36411357

RESUMO

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.


Assuntos
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/métodos
4.
Health Res Policy Syst ; 20(Suppl 1): 120, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36443753

RESUMO

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.


Assuntos
Demência , Assistência de Longa Duração , Humanos , Idoso , Estudos Prospectivos , Japão , Estudos de Coortes , Cognição
5.
Neuropsychopharmacol Rep ; 42(2): 174-182, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35246952

RESUMO

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.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Esquizofrenia , Doença de Alzheimer/diagnóstico , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Humanos , Testes Neuropsicológicos
6.
BMJ Open ; 11(6): e050948, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145022

RESUMO

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.


Assuntos
Demência , Assistência de Longa Duração , Lista de Checagem , Humanos , Estudos Prospectivos , Inquéritos e Questionários
7.
Psychogeriatrics ; 20(5): 726-736, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32767414

RESUMO

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.


Assuntos
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 , Tiazóis
8.
EJNMMI Res ; 9(1): 91, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31535240

RESUMO

BACKGROUND: Amyloid PET plays a vital role in detecting the accumulation of in vivo amyloid-ß (Aß). The quantification of Aß accumulation has been widely performed using the region of interest (ROI)-based mean cortical standardized uptake value ratio (mcSUVR). However, voxel-based statistical analysis has not been well studied. The purpose of this study was to examine the feasibility of analyzing amyloid PET scans by voxel-based statistical analysis. The results were then compared to those with the ROI-based mcSUVR. In total, 166 subjects who underwent 11C-PiB PET in the J-ADNI multi-center study were analyzed. Additionally, 18 Aß-negative images were collected from other studies to form a normal database. The PET images were spatially normalized to the standard space using an adaptive template method without MRI. The mcSUVR was measured using a pre-defined ROI. Voxel-wise Z-scores within the ROI were calculated using the normal database, after which Z-score maps were generated. A receiver operating characteristic (ROC) analysis was performed to evaluate whether Z-sum (sum of the Z-score) and mcSUVR could be used to classify the scans into positive and negative using the central visual read as the reference standard. PET scans that were equivocal were regarded as positive. RESULTS: Sensitivity and specificity were respectively 90.8% and 100% by Z-sum and 91.8% and 98.5% by mcSUVR. Most of the equivocal scans were subsequently classified by both Z-sum and mcSUVR as false negatives. Z-score maps correctly delineated abnormal Aß accumulation over the same regions as the visual read. CONCLUSIONS: We examined the usefulness of voxel-based statistical analysis for amyloid PET. This method provides objective Z-score maps and Z-sum values, which were observed to be helpful as an adjunct to visual interpretation especially for cases with mild or limited Aß accumulation. This approach could improve the Aß detection sensitivity, reduce inter-reader variability, and allow for detailed monitoring of Aß deposition. TRIAL REGISTRATION: The number of the J-ADNI study is UMIN000001374.

9.
Kaku Igaku ; 56(1): 127-134, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31554771

RESUMO

OBJECTIVE: Obtaining the information on safety and effectiveness of radiopharmaceutical synthesizer NEPTIS plug - 01 and florbetapir (18F) injection solution synthesized by NEPTIS plug - 01 from the post marketing surveillance study. METHODS: Regarding the safety evaluation, failure of device and adverse events were recorded. Regarding the effectiveness evaluation, we assessed the quality of PET images and the impact on the clinical diagnosis. RESULT: During the study period, 12 patients were enrolled. No adverse event was reported from those 12 patients. Two events in 2 patients were reported as a failure of device (In a subsequent investigation, those failures were thought to be caused by inadequacy of procedure manual, which has been revised now). For the quality of PET images, all 12 cases were "good" or "excellent", regardless of the positive or negative of amyloid plaque. The attending physician's diagnosis was changed in 9 patients following the PET imaging. CONCLUSION: NEPTIS plug-01 and florbetapir (18F) were safe and has a favorable effectiveness profile in 12 patients under daily clinical setting.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina/síntese química , Composição de Medicamentos/instrumentação , Etilenoglicóis/síntese química , Vigilância de Produtos Comercializados , Compostos Radiofarmacêuticos/síntese química , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Compostos de Anilina/administração & dosagem , Compostos de Anilina/efeitos adversos , Etilenoglicóis/administração & dosagem , Etilenoglicóis/efeitos adversos , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Placa Amiloide , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Segurança
10.
Psychogeriatrics ; 18(4): 276-282, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30133941

RESUMO

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.


Assuntos
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 Doença
11.
Artigo em Japonês | MEDLINE | ID: mdl-28428473

RESUMO

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.


Assuntos
Demência/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Amiloide/análise , Humanos
12.
Ann Nucl Med ; 31(3): 260-272, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28181118

RESUMO

OBJECTIVE: This Phase 2 study assessed the performance of positron emission tomography (PET) brain images made with Flutemetamol F 18 Injection in detecting ß-amyloid neuritic plaques in Japanese subjects. METHODS: Seventy subjects (25 with probable Alzheimer's disease (pAD), 20 with amnestic mild cognitive impairment (aMCI), and 25 cognitively normal healthy volunteers[HVs]) underwent PET brain imaging after intravenous Flutemetamol F 18 Injection (185 MBq). Images were interpreted as normal or abnormal for neuritic plaque density by each of five non-Japanese and five Japanese readers who were blinded to clinical data. The primary efficacy analysis (based on HV and pAD data) was the agreement of the non-Japanese readers' image interpretations with the clinical diagnosis, resulting in estimates of positive percent agreement (PPA; based on AD subjects; similar to sensitivity) and negative percent agreement (NPA; based on HVs; similar to specificity). Secondary analyses included PPA and NPA for the Japanese readers; inter-reader agreement (IRA); intra-reader reproducibility (IRR); quantitative image interpretations (standardized uptake value ratios [SUVRs]) by diagnostic subgroup; test-retest variability in five pAD subjects; and safety. RESULTS: PPA was 92% for all non-Japanese readers and ranged from 88 to 92% for the Japanese readers. NPA ranged from 96 to 100% for both the non-Japanese readers and the Japanese readers. The majority image interpretations (the interpretations made independently by ≥3 of 5 readers) resulted in PPA values of 92 and 92% and NPA values of 100 and 96% for the non-Japanese and Japanese readers, respectively. IRA and IRR were strong. Composite SUVR values (mean of multiple regional values) allowed clear differentiation between pAD subjects and HVs. Test-retest variability ranged from 1.14 to 2.27%, and test-retest agreement of the blinded visual interpretations was 100% for all readers. Flutemetamol F 18 Injection was generally well tolerated. CONCLUSIONS: The detection of brain neuritic plaques in Japanese subjects using [18F]Flutemetamol PET images gave results highly consistent with clinical diagnosis, with non-Japanese and Japanese readers giving similar results. Inter-reader agreement and intra-reader reproducibility were high for both sets of readers. Visual delineation of abnormal and normal scans was corroborated by quantitative assessment, with low test-retest variability. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT02813070.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Compostos de Anilina/química , Benzotiazóis/química , Encéfalo/efeitos dos fármacos , Disfunção Cognitiva/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Idoso , Idoso de 80 Anos ou mais , Amnésia/diagnóstico por imagem , Encéfalo/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
14.
Nucl Med Biol ; 43(7): 438-44, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27183464

RESUMO

INTRODUCTION: Neuroinflammatory processes play an important role in the pathogenesis of Alzheimer's disease (AD). As a biomarker of neuroinflammatory processes, we designed (11)C-labeled ketoprofen methyl ester ([(11)C]KTP-Me) to increase the blood-brain barrier permeability of ketoprofen (KTP), a selective cyclooxygenase-1 (COX-1) inhibitor. Animal studies indicated that [(11)C]KTP-Me enters the brain and accumulates in activated microglia of inflammatory lesions. In a first-in-human study, we reported that [(11)C]KTP-Me is a safe positron emission tomography (PET) tracer and enters the brain; the radioactivity is washed out from normal cerebral tissue. Here we explored the efficacy of [(11)C]KTP-Me as a diagnostic biomarker of neuroinflammatory processes in AD. METHODS: [(11)C]KTP-Me was synthesized by rapid C-[(11)C]methylation of [(11)C]CH3I and the corresponding arylacetate precursor. Nine subjects (four healthy subjects, two Pittsburgh compound-B (PiB)-positive patients with mild cognitive impairment (MCI), and three PiB-positive AD patients) underwent a dynamic brain PET scan for 70min after injection. We evaluated differences in cortical retention and washout rate in the brain between healthy subjects and MCI/AD patients. RESULTS: A brain distribution pattern reflecting blood flow in the early-phase image was seen in both healthy subjects and MCI/AD patients. Cortical activity gradually cleared in all groups. However, we observed no obvious difference in the washout rate between healthy subjects and MCI/AD patients or between MCI and AD patients. CONCLUSIONS: [(11)C]KTP-Me cannot be useful as a potential diagnostic biomarker for MCI/AD. Further improvements in binding affinity and specificity, etc., are needed to be a diagnostic biomarker of neuroinflammation in AD. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: [(11)C]KTP-Me is a new tracer that targets COX-1. [(11)C]KTP-Me is expected to be a diagnostic biomarker of neuroinflammation in AD in the future. The effectiveness was limited in a small number of AD patients. Therefore, further studies are needed to clarify the usefulness of [(11)C]KTP-Me.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Radioisótopos de Carbono , Cetoprofeno/análogos & derivados , Tomografia por Emissão de Pósitrons/métodos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Feminino , Humanos , Cetoprofeno/metabolismo , Masculino , Pessoa de Meia-Idade
15.
Ann Nucl Med ; 29(5): 391-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25874747

RESUMO

AIM: The aim of the study presented was to investigate the brain uptake properties of the amyloid PET agent [(18)F]flutemetamol in Japanese healthy controls and clinically probable Alzheimer's disease (AD) patients, and to make a comparison with the results of a previously performed study on Caucasian subjects. [(18)F]flutemetamol was recently approved by the American Food and Drug Administration and the European Medicines Agency for visualization of amyloid in vivo. Since the first clinical study of [(18)F]flutemetamol-an (18)F derivative of the PET tracer 11C-Pittsburgh Compound B targeting ß-amyloid--took place, several clinical studies have been performed, but few focusing on a Japanese population. METHODS: In the Step A, three elderly healthy volunteers and three AD subjects underwent dynamic PET scanning 0-30 and 60-150 min after injection of 185 MBq [(18)F]flutemetamol. The brain volume of distribution (VT) was quantified using Logan's linear graphical analysis and as standardized uptake value ratios (SUVR) with a cerebellar reference. The optimal acquisition window was determined from brain time activity curves for Step B. In the Step B, 5 AD and 5 elderly healthy volunteers were scanned from 80 to 140 min after intravenous injection of [(18)F]flutemetamol. The data from the two parts were pooled for estimation of overall efficacy. RESULTS: [(18)F]Flutemetamol injection was shown to be safe-no serious adverse events were reported during this study. A simplified SUVR estimate of the uptake of [(18)F]flutemetamol using a time window of 85-115 min post injection successfully discriminated AD cases from healthy volunteers. AD subjects showed an elevated tracer uptake in prefrontal cortex, the lateral temporal cortex and precuneus amongst other regions. No significant [(18)F]flutemetamol PET differences could be seen between the Japanese AD cases in this study and those from an earlier Caucasian study, or between control subjects in Japanese and Caucasian studies. CONCLUSIONS: This study supports the use of [(18)F]flutemetamol PET in Japanese population as a marker of the presence of fibrillar ß-amyloid. The lack of differences between the Japanese cohort and those from a previous Caucasian cohort supports the extrapolation of results from other Caucasian [(18)F]flutemetamol PET studies to the Japanese population.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Benzotiazóis , Encéfalo/diagnóstico por imagem , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Compostos de Anilina/efeitos adversos , Povo Asiático , Benzotiazóis/efeitos adversos , Encéfalo/metabolismo , Mapeamento Encefálico/métodos , Estudos de Coortes , Feminino , Radioisótopos de Flúor/efeitos adversos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Fatores de Tempo
16.
J Alzheimers Dis ; 45(2): 543-52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25589723

RESUMO

BACKGROUND: 18F-FDG-PET is defined as a biomarker of neuronal injury according to the revised National Institute on Aging­Alzheimer's Association criteria. OBJECTIVE: The objective of this multicenter prospective cohort study was to examine the value of 18F-FDG-PET in predicting the development of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI). METHODS: In total, 114 patients with MCI at 9 participating institutions underwent clinical and neuropsychological examinations, MRI, and 18F-FDG-PET at baseline. The cases were visually classified into predefined dementia patterns by three experts. Anautomated analysis for 18F-FDG-PET was also performed to calculate the PET score. Subjects were followed periodically for 3 years, and progression to dementia was evaluated. RESULTS: In 47% of the patients with MCI, progression of symptoms justified the clinical diagnosis of "probable AD". The PET visual interpretation predicted conversion to AD during 3-year follow-up with an overall diagnostic accuracy of 68%. Overall diagnostic accuracy of the PET score was better than that of PET visual interpretation at all follow-up intervals, and the optimized PET score threshold revealed the best performance at the 2-year follow-up interval with an overall diagnostic accuracy of 83%,a sensitivity of 70%, and a specificity of 90%. Multivariate logistic regression analysis identified the PET score as the most significant predictive factor distinguishing AD converters from non-converters. CONCLUSION: The PET score is the most statistically significant predictive factor for conversion from MCI to AD, and the diagnostic performance of the PET score is more promising for rapid converters over 2 years.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico , Fluordesoxiglucose F18/metabolismo , Tomografia por Emissão de Pósitrons , Idoso , Doença de Alzheimer/complicações , Disfunção Cognitiva/etiologia , Progressão da Doença , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
Nihon Rinsho ; 71(10): 1847-52, 2013 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-24261218

RESUMO

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.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Idoso , Transtornos Globais do Desenvolvimento Infantil/terapia , Humanos
19.
Seishin Shinkeigaku Zasshi ; 115(11): 1127-34, 2013.
Artigo em Japonês | MEDLINE | ID: mdl-24450145

RESUMO

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.


Assuntos
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 Risco
20.
Seishin Shinkeigaku Zasshi ; 114(3): 268-73, 2012.
Artigo em Japonês | MEDLINE | ID: mdl-22568061

RESUMO

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.


Assuntos
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 Saúde
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