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BACKGROUND: Work schedules can make it challenging for professional care workers to participate in long-term training programs on managing behavioural and psychological symptoms of dementia (BPSD). Simultaneously, it is necessary to prevent caregivers' negative responses to BPSD, provide a positive environment for people with dementia, and create a system for new management plans, since the initial one is often unsuccessful. Therefore, we developed a short manual-based training system for functional analysis including positive behaviour support and strategies when management plans do not function well. This study aimed to preliminarily examine the usefulness of this system. METHODS: Thirty-five staff members from 12 care facilities participated in the training. For each facility, off-the-job training was performed in two 120-min sessions held over 2 days. Then, care plans were implemented by staff members for a month, during which on-the-job training was provided. The study included 14 people with dementia and BPSD. This was a single-arm study without a control group. Pre- and post-tests were conducted to examine the effects of the training system using the Neuropsychiatric Inventory-Nursing Home Version. RESULTS: The results of the pre- and post-tests for the total scores on severity and occupational disruptiveness significantly improved, with large effect sizes. Regarding symptom domains, delusions, agitation/aggression, and aberrant motor behaviour significantly improved in both severity and occupational disruptiveness. Depression/dysphoria and anxiety significantly improved in severity; however, there were trends of improvement in occupational disruptiveness. In addition, the effect sizes for severity and occupational disruptiveness of delusions and agitation/aggression were large. CONCLUSIONS: This preliminary study suggests that the training system is promising. A randomised controlled trial with a larger sample size is necessary to confirm the findings.
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Demência , Humanos , Demência/diagnóstico , Casas de Saúde , Pessoal de Saúde , Cuidadores/psicologia , AnsiedadeRESUMO
INTRODUCTION: It is critical to develop accurate and universally available biomarkers for dementia diseases to appropriately deal with the dementia problems under world-wide rapid increasing of patients with dementia. In this sense, electroencephalography (EEG) has been utilized as a promising examination to screen and assist in diagnosing dementia, with advantages of sensitiveness to neural functions, inexpensiveness, and high availability. Moreover, the algorithm-based deep learning can expand EEG applicability, yielding accurate and automatic classification easily applied even in general hospitals without any research specialist. METHODS: We utilized a novel deep neural network, with which high accuracy of discrimination was archived in neurological disorders in the previous study. Based on this network, we analyzed EEG data of healthy volunteers (HVs, N = 55), patients with Alzheimer's disease (AD, N = 101), dementia with Lewy bodies (DLB, N = 75), and idiopathic normal pressure hydrocephalus (iNPH, N = 60) to evaluate the discriminative accuracy of these diseases. RESULTS: High discriminative accuracies were archived between HV and patients with dementia, yielding 81.7% (vs. AD), 93.9% (vs. DLB), 93.1% (vs. iNPH), and 87.7% (vs. AD, DLB, and iNPH). CONCLUSION: This study revealed that the EEG data of patients with dementia were successfully discriminated from HVs based on a novel deep learning algorithm, which could be useful for automatic screening and assisting diagnosis of dementia diseases.
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Doença de Alzheimer , Aprendizado Profundo , Doença por Corpos de Lewy , Humanos , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/diagnóstico , Doença de Alzheimer/diagnóstico , EletroencefalografiaRESUMO
OBJECTIVES: To examine the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and tap test response to elucidate the effects of comorbidity of AD in idiopathic normal-pressure hydrocephalus (iNPH). DESIGN: Case-control study. SETTING: Osaka University Hospital. PARTICIPANTS: Patients with possible iNPH underwent a CSF tap test. MEASUREMENTS: Concentrations of amyloid beta (Aß) 1-40, 1-42, and total tau in CSF were measured. The response of tap test was judged using Timed Up and Go test (TUG), 10-m reciprocation walking test (10MWT), Mini-Mental State Examination (MMSE), and iNPH grading scale. The ratio of Aß1-42 to Aß1-40 (Aß42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients. RESULTS: We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aß42/40 ratio was significantly lower (mean [SD] = 0.063 [0.026] vs. 0.083 [0.036], p = 0.008), and total tau in CSF was significantly higher (mean [SD] = 385.6 [237.2] vs. 293.6 [165.0], p = 0.028) in iNPH-nTT than in iNPH-pTT. Stepwise logistic regression analysis revealed that low Aß42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aß42/40 ratio. The association between Aß42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline. CONCLUSIONS: A low CSF Aß42/40 ratio is associated with a poorer cognitive response, but not gait and urinary response, to a tap test in iNPH. Even if CSF biomarkers suggest AD comorbidity, treatment with iNPH may be effective for gait and urinary dysfunction.
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Doença de Alzheimer , Hidrocefalia de Pressão Normal , Humanos , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/complicações , Estudos de Casos e Controles , Proteínas tau/líquido cefalorraquidiano , Equilíbrio Postural , Estudos de Tempo e Movimento , Doença de Alzheimer/complicações , Biomarcadores/líquido cefalorraquidiano , CogniçãoRESUMO
OBJECTIVE: Olfactory dysfunction is common in patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD). We sought to elucidate brain regions associated with olfactory dysfunction in patients with MCI and early AD by using 123I-IMP-SPECT to detect regional cerebral blood flow (CBF). METHODS: We included 218 patients diagnosed with AD or MCI, who underwent a comprehensive battery of neuropsychiatric and neuropsychological tests, Alzheimer's Disease Assessment Scale-Cognitive Part (ADAS-Cog), and forward- and backward-digit span. Olfactory function was assessed using T&T olfactometry of five odors; patients stated whether they experienced any smell (detection test) and identified the odor (identification test). The association between single-photon emission computerized tomography based regional CBF and olfactory function was examined by voxel-by-voxel multiple regression analysis, considering sex, age, and education as covariate parameters. RESULTS: Of the 218 patients, 78 had mildly impaired olfactory detection and 15 had olfactory detection loss; additionally, 213 had mild olfactory identification impairment. The odor detection score correlated significantly with the ADAS-Cog word recall score (r = 0.193, p = 0.004). The odor identification score correlated significantly with the ADAS memory (r = 0.408, p < 0.001) and ADAS orientation (r = 0.292, p < 0.001) scores. The odor identification score correlated negatively with CBF in the left temporal pole, entorhinal area, and bilateral frontal poles (p < 0.001). CONCLUSION: Olfactory identification dysfunction in patients with MCI and AD is attributable to reduced CBF of the left temporal pole, entorhinal area, and bilateral frontal pole.
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Doença de Alzheimer , Disfunção Cognitiva , Encéfalo , Circulação Cerebrovascular , Humanos , Testes NeuropsicológicosRESUMO
OBJECTIVES: Although sleep disturbances are prevalent among patients with dementia with Lewy bodies (DLB), their neural substrates remain unclear. We aimed to clarify the neural substrates of sleep disturbances in patients with DLB. METHODS: We evaluated sleep disturbances, neuropsychiatric symptoms, and brain glucose metabolism in 22 patients with probable DLB using actigraphy, the Neuropsychiatric Inventory (NPI), and 18 F-fluorodeoxyglucose (FDG) positron emission tomography, respectively. Total sleep time (TST) and average activity count per minute (AAC) during sleep were calculated for seven consecutive days via actigraphy. We investigated associations between FDG uptake and the actigraphy parameters using Statistical Parametric Mapping version 12b. Spearman's rank correlation coefficients were used to investigate associations among TST, AAC, and clinical symptoms. The level of statistical significance was set at P < .05. P values were adjusted using the Benjamini-Hochberg method for multiple comparisons. This study was registered with ClinicalTrials.gov (NCT00776347). RESULTS: TST exhibited a significant positive association with FDG uptake in the bilateral orbitofrontal cortex and left thalamus, while AAC exhibited a significant negative association with FDG uptake in the left thalamus and the left parieto-occipital region. FDG uptake in the left pulvinar was associated with both TST and AAC. In addition, TST exhibited a significant negative association with the NPI hallucinations score (r = -0.66, P = .001), while AAC exhibited significant positive associations with the NPI delusions (r = 0.70, P < .001) and hallucinations (r = 0.63, P = .002) scores. CONCLUSIONS: TST and bodily activity during sleep are associated with dysfunction of the left pulvinar and the severity of hallucinations in patients with DLB.
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Doença por Corpos de Lewy , Pulvinar , Actigrafia , Fluordesoxiglucose F18 , Alucinações/diagnóstico por imagem , Alucinações/etiologia , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Sono , Tálamo/diagnóstico por imagemRESUMO
BACKGROUND: Dementia with Lewy bodies (DLB) is characterized by progressive cognitive decline, fluctuating cognition, visual hallucinations, rapid eye movement sleep behavior disorder, and parkinsonism. DLB is the second most common type of degenerative dementia of all dementia cases. However, DLB, particularly in the early stage, is underdiagnosed and sometimes misdiagnosed with other types of dementia. Thus, it is of great interest investigating neurophysiological markers of DLB. METHOD: We introduced exact low-resolution brain electromagnetic tomography (eLORETA)-independent component analysis (ICA) to assess activities of 5 electroencephalography (EEG) resting-state networks (RSNs) in 41 drug-free DLB patients. RESULTS: Compared to 80 healthy controls, DLB patients had significantly decreased activities in occipital visual and sensorimotor networks, where DLB patients and healthy controls showed no age dependences in all EEG-RSN activities. Also, we found correlations between all EEG-RSN activities and DLB symptoms. Specifically, decreased occipital α activity showed correlations with worse brain functions related to attention/concentration, visuospatial discrimination, and global cognition. Enhanced visual perception network activity correlated with milder levels of depression and anxiety. Enhanced self-referential network activity correlated with milder levels of depression. Enhanced memory perception network activity correlated with better semantic memory, visuospatial discrimination function, and global cognitive function as well as with severer visual hallucination. In addition, decreased sensorimotor network activity correlated with a better semantic memory. CONCLUSION: These results indicate that eLORETA-ICA can detect EEG-RSN activity alterations in DLB related to symptoms. Therefore, eLORETA-ICA with EEG data can be a useful noninvasive tool for sensitive detection of EEG-RSN activity changes characteristic of DLB and for understanding the neurophysiological mechanisms underlying this disease.
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Encéfalo/fisiopatologia , Eletroencefalografia , Doença por Corpos de Lewy/fisiopatologia , Doença por Corpos de Lewy/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atenção/fisiologia , Cognição/fisiologia , Feminino , Alucinações/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Percepção/fisiologia , Descanso , Adulto JovemRESUMO
OBJECTIVE: A direct causal relationship of cerebrovascular risk factors/stroke to amyloid ß (Aß) deposition has yet to be shown. We conducted [11 C] Pittsburgh compound B (PiB)-positron emission tomography (PET) analysis on subacute ischemic stroke patients and healthy controls. We hypothesized that subacute ischemic stroke patients would show focal Aß accumulation in cortical regions, which would increase and extend over time during the chronic phase after stroke onset. METHODS: Patients were recruited 14 to 28 days after acute subcortical ischemic stroke and examined with [11 C]PiB-PET scans. Regional time-activity data were analyzed with the Logan graphical method. Whole brain voxel-based analysis was conducted to compare stroke patients with healthy controls. We also performed longitudinal comparison of patients with successive [11 C]PiB-PET scans 1 year after stroke. RESULTS: Voxel-based analysis revealed a significant increase of [11 C]PiB-BPND of the precuneus/posterior cingulate cortex (PCu/PCC) in stroke patients at the subacute stage. Based on stepwise multiple regression analysis of [11 C]PiB-BP changes during follow-up as the dependent variable, years of education was the best independent correlate. There was a significant negative relationship between changes in [11 C]PiB-BP and years of education. CONCLUSIONS: Our results suggest that processes before and after the onset of ischemic stroke may trigger Aß deposition in the PCu/PCC, whereby amyloid deposition begins at an early stage of Alzheimer's disease (AD). Our findings support the existence of a cooperative association between vascular risk factors/stroke and AD progression. Further, educational achievement had a protective effect against the increase in Aß accumulation.
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Peptídeos beta-Amiloides/metabolismo , Isquemia Encefálica/metabolismo , Escolaridade , Giro do Cíngulo/metabolismo , Acidente Vascular Cerebral/metabolismo , Idoso , Doença de Alzheimer , Encéfalo/metabolismo , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Tomografia por Emissão de Pósitrons/métodos , Análise de Regressão , Fatores de RiscoRESUMO
OBJECTIVES: Apathy is prevalent in patients with idiopathic normal pressure hydrocephalus (iNPH), a treatable disorder resulting from ventricular enlargement. We assessed the relationship between apathy and regional cerebral blood flow (rCBF) in patients with iNPH. METHODS: Before lumbo-peritoneal shunt surgery (LPS), 56 iNPH patients were evaluated on apathy and dysphoria subscales of the Neuropsychiatric inventory (NPI), and were divided into two groups according to NPI apathy score: 15 without apathy (iNPH-APA) and 41 with apathy (iNPH+APA). Among iNPH+APA, 29 patients were evaluated for apathy and dysphoria 3 months after LPS, and were divided into two groups on the basis of the change in NPI apathy score: 13 with improvement (iNPH+ImpAPA) and 16 without improvement in apathy (iNPH-ImpAPA). N-isopropyl-p-iodoamphetamine single photon emission computed tomography using the autoradiography method was performed before and after LPS, and rCBF was calculated in 22 regions of interest in the frontal cortex, basal ganglia, and limbic system. RESULTS: In iNPH+APA, rCBF in the right caudate nuclei before LPS was significantly lower than that in iNPH-APA (P = 0.004; two-sample t test). Between iNPH-ImpAPA and iNPH+ImpAPA, a significant group-by-shunt interaction was observed for rCBF in only the right caudate nuclei (F1, 28 = 11.75, P = 0.002; two-way repeated-measures analysis of variance), with increased rCBF in iNPH+ImpAPA but not in iNPH-ImpAPA. The significant group-by-shunt interaction persisted if change in NPI dysphoria scores was used as a covariate (F1, 27 = 8.33, P = 0.008). CONCLUSIONS: Our findings suggest that right caudate dysfunction might cause apathy in iNPH patients.
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Apatia , Circulação Cerebrovascular , Hidrocefalia de Pressão Normal/fisiopatologia , Hidrocefalia de Pressão Normal/psicologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
BACKGROUND: Specific ventriculomegaly features, including tight high-convexity and medial subarachnoid spaces, are found on magnetic resonance images in patients with idiopathic normal pressure hydrocephalus (iNPH). However, some healthy elderly individuals with no typical triad symptoms of iNPH also exhibit specific magnetic resonance image features of iNPH. Therefore, this study quantitatively clarified the brain morphology of suspected iNPH patients with no objective triad symptoms (iNPH-NOS). METHODS: We recruited patients with suspected iNPH and divided them into two groups based on their iNPH grading scale scores: the iNPH-NOS group and the iNPH with apparent objective triad symptoms (iNPH-AOS) group. Data for normal controls (NC) were taken from the database used in our previous study. We compared the relative volumes of ventricle systems (VS), Sylvian fissures (SF), and sulci at high convexity and the midline (SHM), adjusted by the intracranial volume, of the iNPH-NOS, iNPH-AOS, and NC groups. Additionally, we compared the relative volumes of VS, SF, and SHM in iNPH-NOS patients between their first visit and follow-up 1 year later. RESULTS: Fifteen iNPH-NOS patients and 45 iNPH-AOS patients were recruited, and 24 NCs were found in the database. The relative volumes of VS and SF were significantly smaller than in NCs than in the iNPH-NOS and iNPH-AOS groups, and the relative volume of SHM was significantly larger in NCs. The relative volume of SHM was significantly larger in the iNPH-NOS group than in the iNPH-AOS group, but there were no significant differences in the relative volumes of VS and SF between these groups. In the iNPH-NOS group, the relative volumes of VS and SF were significantly smaller at the first visit than 1 year later, whereas the relative volume of SHM was significantly larger. In 6 of 15 iNPH-NOS patients, objective symptoms appeared during the observation period. CONCLUSIONS: Our results indicate that iNPH-NOS patients were in the transitional stage between normal and iNPH-AOS, both morphologically and clinically.
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Encéfalo/diagnóstico por imagem , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
AIM: Alzheimer's disease (AD) pathology is highly prevalent in patients with idiopathic normal pressure hydrocephalus (iNPH), and the presence of AD pathology may involve regional cerebral blood flow (rCBF). In this study, we examined the relationship between rCBF and AD-related biomarkers in the cerebrospinal fluid of iNPH patients. METHODS: Patients with iNPH (n = 39) were classified into groups with (iNPH/AD+) (n=15) and without (iNPH/AD-) (n=24) high biomarker probability of AD (i.e. combined low amyloid ß 42 and high total tau in the cerebrospinal fluid). rCBF was quantified in 17 regions of interest by N-isopropyl-p-[123 I]iodoamphetamine single-photon emission computed tomography with the autoradiography method. We compared rCBF between the iNPH/AD- and iNPH/AD+ groups at baseline using a t-test and then compared changes in rCBF after shunt surgery between the groups using a paired t-test and two-way repeated measures ANOVA. RESULTS: At baseline, there were no significant differences in rCBF between the groups in most regions apart from the putamen. After shunt surgery, a significant increase in rCBF in the putamen, amygdala, hippocampus, and parahippocampal gyrus was observed in iNPH/AD- patients. In iNPH/AD+ patients, no significant improvement in rCBF was observed in any region. In repeated measures analysis of variance, a significant group × shunt interaction was observed in the parietal lobe, frontal lobe, posterior cingulate cortex, precuneus, lateral temporal lobe, amygdala, hippocampus, parahippocampal gyrus, and putamen. CONCLUSIONS: Improvement in rCBF after shunt surgery in iNPH/AD+ patients may be poorer than that in iNPH AD- patients.
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Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Circulação Cerebrovascular , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/metabolismo , Feminino , Humanos , Hidrocefalia de Pressão Normal/sangue , Hidrocefalia de Pressão Normal/complicações , Hidrocefalia de Pressão Normal/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Proteínas tau/metabolismoRESUMO
BACKGROUND: There are some existing barriers posed by neuropsychological tests that interfere with the assessment of cognitive functioning by staff who work in long-term care facilities. The purpose of this study was to investigate the feasibility of assessing cognitive function through conversation. METHODS: A total of 100 care staff was randomly selected as participants. Each staff member evaluated cognitive function in one to three residents using the Conversational Assessment of Neurocognitive Dysfunction (CANDy), which is a screening test for dementia using conversation. Other scales used were the Mini-Mental State Examination (MMSE), Behavioral Pathology in Alzheimer' s Disease (BEHAVE-AD), and quality-of-life questionnaire for the elderly with dementia (QOL-D). RESULTS: A total of 80 care staff members and 158 residents were analyzed. When the CANDy involved an evaluation based on face-to-face communication, it demonstrated significant correlations with the MMSE, BEHAVE-AD, and several indices of the QOL-D (e.g. negative affect and actions, communication ability, restless, and spontaneity and activity). In contrast, when the CANDy involved an evaluation based on an impression of a typical conversation, it only demonstrated significant relationships with the MMSE and the spontaneity and activity index of the QOL-D. CONCLUSIONS: Conversational assessment is a useful means to assess cognitive functioning and to promote interactions between residents and care staff in long-term care facilities.
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Disfunção Cognitiva/diagnóstico , Comunicação , Assistência de Longa Duração/psicologia , Relações Profissional-Paciente , Idoso , Idoso de 80 Anos ou mais , Cognição/fisiologia , Estudos de Viabilidade , Feminino , Pessoal de Saúde/psicologia , Instituição de Longa Permanência para Idosos , Humanos , Japão , Masculino , Casas de Saúde/estatística & dados numéricos , Escalas de Graduação PsiquiátricaRESUMO
BACKGROUND: It is assumed that care services effectively reduce behavioural and psychological symptoms of dementia (BPSD). However, it is unclear which care services are effective for reducing specific BPSD. The aim of this study was to clarify which care services were recognized by care specialists as being effective for reducing each of 11 BPSD. METHODS: We sent unsigned questionnaires to care specialists in Japan. The questionnaires asked specialists to choose from 12 kinds of care services the most, second-most, and third-most effective service for reducing each of 11 BPSD. The most effective service was scored as 3 points, the second-most was 2 points, and the third-most was 1 point. Specialists were also asked to describe why they chose each service. The 12 kinds of care services were categorized into four categories: (i) home-visit; (ii) outpatient; (iii) short-stay; and (iv) facility. Total scores for each category were analyzed using a two-way anova. The reasons care specialists chose each service were analyzed using morphological analysis, and representative reasons were extracted. RESULTS: A total of 103 questionnaires were returned. Of the four service categories, outpatient services yielded the highest score for reducing apathy (P < 0.001) due to the effectiveness of participating in recreation and receiving stimulation. Facility services yielded the highest score for reducing aberrant motor behaviour (P < 0.001). Short-stay services yielded the lowest score for reducing depression (P < 0.001). For eight other kinds of BPSD, there were no significant differences between home-visit and facility services or between outpatient and facility services. CONCLUSIONS: Care specialists reported that effective care services for reducing BPSD differed among types of BPSD. In-home care services might be effective at reducing many BPSD except for aberrant motor behaviour, suggesting that greater use of in-home care services might enable people with BPSD to live in their homes for longer.
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Sintomas Comportamentais/epidemiologia , Transtornos Cognitivos/epidemiologia , Demência/diagnóstico , Assistência de Longa Duração/estatística & dados numéricos , Casas de Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Sintomas Comportamentais/diagnóstico , Sintomas Comportamentais/psicologia , Transtornos Cognitivos/diagnóstico , Demência/epidemiologia , Demência/psicologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Transtornos Mentais/complicações , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaRESUMO
AIM: It is unclear whether carer-held records (CHR) are useful for patients with dementia. In this study, we evaluated the usefulness of the CHR for patients with dementia at the municipal level. METHODS: Candidates for CHR use in this study were informal caregivers of patients with dementia who lived at home in Kawanishi, Japan. CHR users were those who are involved in the patient's care and treatment, such as informal caregivers, family physicians, dementia specialists, care professionals, and care service coordinators, known as ?care managers' in Japan. Collaborative meetings were held every month mainly to help users, especially care managers, learn how to effectively use CHR. We surveyed informal caregivers before and 1.5 years after the start of CHR use to evaluate whether CHR improved collaboration and information provision. The Zarit Caregiver Burden Interview and Dementia Behaviour Disturbance Scale were also administered. We divided the informal caregivers who continued CHR use for 1.5 years into two subgroups based on whether their care manager attended the collaborative meetings at least twice. In addition, we divided informal caregivers into three subgroups depending on their relationship to the patient: spouse, child, or daughter-in-law. RESULTS: The study initially consisted of 201 informal caregivers. Among them, 74 informal caregivers continued CHR use for 1.5 years. The information provision score significantly improved after CHR use for all informal caregivers. The collaboration score significantly improved after CHR use only for informal caregivers whose care managers attended at least two collaborative meetings. The Zarit Caregiver Burden Interview score significantly improved after CHR use for daughter-in-law caregivers. The Dementia Behaviour Disturbance Scale scores did not significantly improve after CHR use. CONCLUSIONS: CHR were useful for informal caregivers of patients with dementia. However, care managers need to teach informal caregivers how to properly use CHR.
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Cuidadores/psicologia , Demência/enfermagem , Família/psicologia , Idoso , Comportamento Cooperativo , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The electroencephalography (EEG) abnormalities found in patients with dementia with Lewy bodies (DLB) are conflicting. In this study, we used magnetoencephalography, which has higher spatial resolution than electroencephalography, to explore neurophysiological features of DLB that may aid in the differential diagnosis. METHODS: Six patients with DLB, 11 patients with Alzheimer's disease, and 11 age-matched normal subjects were recruited. We investigated alterations in the ratio of event-related synchronization (ERS) in the alpha band after eye-closing. RESULTS: Although the averaged ratio change of alpha ERS after eye-closing appeared predominantly in the posterior brain regions in all study groups, DLB patients had the weakest ratio change of alpha ERS. In particular, DLB patients exhibited a significantly reduced ratio change of alpha ERS in the bilateral inferior temporal gyrus, right occipital pole, and left parieto-occipital cortex compared to Alzheimer's disease patients or normal controls. CONCLUSION: Our findings indicated that a reduced ratio change of alpha ERS in the posterior brain regions elicited by eye-closing is a brain electromagnetic feature of DLB.
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Ritmo alfa/fisiologia , Doença de Alzheimer/diagnóstico , Córtex Cerebral/fisiopatologia , Sincronização Cortical/fisiologia , Doença por Corpos de Lewy/diagnóstico , Magnetoencefalografia/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Piscadela/fisiologia , Feminino , Humanos , Doença por Corpos de Lewy/fisiopatologia , Masculino , Fenômenos Fisiológicos Oculares , Percepção Visual/fisiologiaRESUMO
OBJECTIVE: We hypothesized that cerebral amyloid accumulation is reflected in the periphery in the pre-dementia stage and used flow cytometry to investigate the peripheral lymphocytes as an easily accessible biomarker to observe neuro-inflammation. We aimed to determine whether peripheral lymphocytes are related to the cortical amyloid burden or vice versa in cognitively normal older subjects. METHODS: We applied [11 C] Pittsburgh compound B (PiB)-positron emission tomography to 36 cognitively normal older individuals, and Aß deposition was quantified by cortical binding potential (PiB-BPND ). Blood samples were obtained, and lymphocyte subsets were evaluated. We examined differences between low and high PiB-BPND groups in the percentage of B cells, T cells, helper T cells, cytotoxic T cells, regulatory T cells, and natural killer cells. RESULTS: Subjects with high PiB-BPND showed significantly higher percentage of cytotoxic T cells (%CD3+ ). Correlation analysis revealed a significant relationship between the percentage of cytotoxic T cells and global cortical mean PiB-BPND . Hierarchical regression analyses showed that cytotoxic T cells were significantly related to the value of global cortical mean PiB-BPND and vice versa. CONCLUSIONS: Our results indicated that a specific peripheral immune response, reflected in the increased ratio of cytotoxic T cells, could be regarded as a preclinical sign of AD and could be attributed to the Aß neuropathological mechanism. Copyright © 2017 John Wiley & Sons, Ltd.
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Peptídeos beta-Amiloides/sangue , Córtex Cerebral/citologia , Cognição/fisiologia , Linfócitos/citologia , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/metabolismo , Biomarcadores/sangue , Feminino , Citometria de Fluxo , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Linfócitos T Citotóxicos/citologia , Tiazóis/metabolismoRESUMO
BACKGROUND: Sleep disturbances in Alzheimer disease (AD) may affect behavioral and psychological symptoms of dementia (BPSD). Our aim was to elucidate the associations between sleep disturbances and other BPSD at different stages of AD. METHODS: This investigation was part of a multicenter-retrospective study in Japan (J-BIRD). Eligible for final analyses were 684 AD patients. Global severity of dementia was estimated using the Clinical Dementia Rating (CDR) scale. BPSD were assessed using the Neuropsychiatric Inventory (NPI). We analyzed the relationships between sleep disturbances and BPSD at different stages of AD according to the CDR score. RESULTS: Among the 684 AD patients, 146 (21.3%) had sleep disturbances. Patients with very early AD (CDR 0.5) and sleep disturbances had significantly more BPSD than those without sleep disturbances, as indicated by the higher prevalence of the following four NPI items: anxiety, euphoria, disinhibition, and aberrant motor behavior. In AD at CDR 2, (moderate AD) only one NPI item (irritability) was affected, while none was affected at CDR 1 (mild AD) and 3 (severe AD). Multiple regression analyses were performed in those with AD having various CDR scores. At CDR 0.5, the presence of sleep disturbances was associated with a high total NPI score (ß = 0.32, p < 0.001). However, other factors, including cognitive decline, age, gender, and years of education, were not significantly associated with the NPI score. At CDR 1 and 2, no factor was significantly related to BPSD. CONCLUSION: Sleep disturbances were strongly associated with other BPSD in the very early stage of AD. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Doença de Alzheimer/psicologia , Sintomas Comportamentais/psicologia , Transtornos Mentais/psicologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Ansiedade/psicologia , Sintomas Comportamentais/epidemiologia , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Transtornos Mentais/epidemiologia , Transtornos Motores/psicologia , Testes Neuropsicológicos , Prevalência , Escalas de Graduação Psiquiátrica , Análise de Regressão , Estudos Retrospectivos , Índice de Gravidade de Doença , Distúrbios do Início e da Manutenção do Sono/epidemiologiaRESUMO
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-ß (Aß). The genes that govern this process, however, have remained elusive. To this end, we combined distinct mouse strains with transcriptomics to directly identify disease-relevant genes. We show that AD model mice (APP-Tg) with DBA/2 genetic backgrounds have significantly lower levels of Aß accumulation compared with SJL and C57BL/6 mice. We then applied brain transcriptomics to reveal the genes in DBA/2 that suppress Aß accumulation. To avoid detecting secondarily affected genes by Aß, we used non-Tg mice in the absence of Aß pathology and selected candidate genes differently expressed in DBA/2 mice. Additional transcriptome analysis of APP-Tg mice with mixed genetic backgrounds revealed kinesin light chain-1 (Klc1) as an Aß modifier, indicating a role for intracellular trafficking in Aß accumulation. Aß levels correlated with the expression levels of Klc1 splice variant E and the genotype of Klc1 in these APP-Tg mice. In humans, the expression levels of KLC1 variant E in brain and lymphocyte were significantly higher in AD patients compared with unaffected individuals. Finally, functional analysis using neuroblastoma cells showed that overexpression or knockdown of KLC1 variant E increases or decreases the production of Aß, respectively. The identification of KLC1 variant E suggests that the dysfunction of intracellular trafficking is a causative factor of Aß pathology. This unique combination of distinct mouse strains and model mice with transcriptomics is expected to be useful for the study of genetic mechanisms of other complex diseases.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Isoformas de Proteínas/metabolismo , Doença de Alzheimer/genética , Animais , Encéfalo/metabolismo , Cruzamentos Genéticos , Perfilação da Expressão Gênica , Humanos , Cinesinas , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Isoformas de Proteínas/genética , Especificidade da EspécieRESUMO
BACKGROUND: We showed that ventriculoperitoneal (VP) shunt and lumboperitoneal (LP) shunt surgeries are beneficial for patients with idiopathic normal pressure hydrocephalus (iNPH) in the Study of Idiopathic Normal Pressure Hydrocephalus on Neurological Improvement (SINPHONI; a multicenter prospective cohort study) and in SINPHONI-2 (a multicenter randomized trial). Although therapeutic efficacy is important, cost-effectiveness analysis is equally valuable. METHODS: Using both a set of assumptions and using the data from SINPHONI and SINPHONI-2, we estimated the total cost of treatment for iNPH, which consists of medical expenses (e.g., operation fees) and costs to the long-term care insurance system (LCIS) in Japan. Regarding the natural course of iNPH patients, 10% or 20% of patients on each modified Rankin Scale (mRS) show aggravation (aggravation rate: 10% or 20%) every 3 months if the patients do not undergo shunt surgery, as described in a previous report. We performed cost-effectiveness analyses for the various scenarios, calculating the quality-adjusted life year (QALY) and the incremental cost-effective ratio (ICER). Then, based on the definition provided by a previous report, we assessed the cost-effectiveness of shunt surgery for iNPH. RESULTS: In the first year after shunt surgery, the ICER of VP shunt varies from 29,934 to 40,742 USD (aggravation rate 10% and 20%, respectively) and the ICER of LP shunt varies from 58,346 to 80,392 USD (aggravation rate 10% and 20%, respectively), which indicates that the shunt surgery for iNPH is a cost-effective treatment. In the 2nd postoperative year, the cost to the LCIS will continue to decrease because of the lasting improvement of the symptoms due to the surgery. The total cost for iNPH patients will show a positive return on investment in as soon as 18 months (VP) and 21 months (LP), indicating that shunt surgery for iNPH is a cost-effective treatment. CONCLUSIONS: Because the total cost for iNPH patients will show a positive return on investment within 2 years, shunt surgery for iNPH is a cost-effective treatment and therefore recommended. The SINPHONI-2 study was registered with the University Hospital Medical Information Network Clinical Trials registry: UMIN000002730) SINPHONI was registered with ClinicalTrials.gov, no. NCT00221091.
Assuntos
Análise Custo-Benefício , Hidrocefalia de Pressão Normal/cirurgia , Derivação Ventriculoperitoneal/economia , Ensaios Clínicos como Assunto , Feminino , Humanos , Hidrocefalia de Pressão Normal/economia , Japão , Masculino , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Derivação Ventriculoperitoneal/efeitos adversosRESUMO
OBJECTIVE: Previous studies have reported depressive symptoms in the preclinical stages of Alzheimer's disease (AD). The objective of this study was to determine whether depressive symptoms are associated with cortical amyloid burden. In order to do this, we measured cortical amyloid via (11) C-labeled Pittsburgh Compound B ([(11) C]PIB) uptake using positron emission tomography (PET) in cognitively normal subjects. METHODS: We performed [(11) C]PIB-PET in 29 cognitively normal, older participants. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS). Aß deposition was quantified by binding potential (BPND ), and the association between cortical mean BPND values and GDS scores was evaluated. Analysis of parametric BPND images was performed to examine the relationship between regional BPND and GDS scores. RESULTS: We found a positive correlation between depressive symptoms and mean cortical PIB-BPND in groups of subjects with middle to high PIB-BPND . There was little change in GDS-depression score between subjects with low and middle PIB-BPND levels, while an increase in GDS was shown in the high PIB-BPND group. The main BPND increase was localized to the precuneus/posterior cingulate cortex (PCu/PCC) in subjects with high PIB-BPND , and we found a significant positive relationship between PIB-BPND in this area and depressive symptoms. CONCLUSIONS: Emotional dysregulation because of Aß neuropathology in the PCu/PCC may relate to depressive symptoms. More specifically, we found that older, cognitively normal patients with depressive episodes were more likely to have underlying AD pathology. Thus, depressive symptoms may increase the predictive ability of the identification of future AD cases. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Peptídeos beta-Amiloides/análise , Encéfalo/diagnóstico por imagem , Cognição , Depressão/diagnóstico , Idoso , Doença de Alzheimer/patologia , Compostos de Anilina , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Projetos Piloto , Tomografia por Emissão de Pósitrons , TiazóisRESUMO
BACKGROUND: Patients with Alzheimer's disease (AD) manifest various impairments in eating behavior. However, few previous studies have directly investigated the gustatory function of AD patients, and results have been inconsistent. METHODS: Thirty-two AD patients (Clinical Dementia Rating (CDR) 0.5/1/2, respectively 11/15/6 patients) and 22 normal control participants were examined to measure detection and recognition thresholds of the four elemental tastes (sweet, salty, sour, and bitter), and their ability to discriminate between tastes. Effects of demographic and clinical factors (age, sex, histories of alcohol and tobacco consumption, and CDR grade) on gustatory threshold were examined using ordinal logistic regression analysis. Performance was compared between AD and control groups. RESULTS: Total threshold values (the sum of threshold grades for the four tastes) for detection and recognition of tastes were significantly higher in the AD group. Detection thresholds for sweet, salty, and bitter, and recognition thresholds for sweet and sour, were also significantly higher in the AD group. Ordinal logistic regression analysis revealed that CDR grade was the only factor that significantly affected both total threshold values. Regarding taste discrimination, there were no significant differences between the AD group and control group. CONCLUSIONS: These findings suggest that progression of dementia severity accompanies gustatory decline. Although it seemingly paradoxical, weight loss and preference for sweet tastes are frequently, often simultaneously, observed in AD. Gustatory dysfunction may be partially involved in these symptoms. Thus, the nutritional care of patients with AD could be improved by making the taste of meals stronger, while controlling calorie and mineral intake.