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1.
Am J Geriatr Psychiatry ; 27(1): 53-61, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30409550

RESUMO

OBJECTIVES: To test a culturally tailored intervention to improve Alzheimer's disease (AD) literacy among African Americans. DESIGN: A 3-arm randomized comparative effectiveness trial. SETTING: Community sites in Los Angeles, CA. PARTICIPANTS: 193 African American community-dwelling adults, ages 45 to 95 years old. INTERVENTION: All groups attended BrainWorks Live, a culturally tailored, 60-minute talk show and received standard printed educational materials on AD. From there: a) the BrainWorks Live group received no further contact until the post-test; b) one intervention group received a 1-month, culturally tailored, unidirectional, daily text-message program; and c) a second intervention group received daily text messages based on the printed educational materials that the general public would receive. AD literacy was measured at baseline and one month post intervention. MEASUREMENTS: Alzheimer's disease literacy and demographic and health covariates. RESULTS: At one month, participants who received culturally tailored text messages had the highest increase in AD literacy levels, followed by those in the BrainWorks Live arm. Participants who received general text messages had a lower overall increase in AD literacy levels compared to the other arms, but had higher mean AD literacy levels than the BrainWorks Live arm. There was a significantly greater increase in AD literacy levels among participants who received culturally tailored text messages compared with those who attended BrainWorks Live only. There were no other statistically significant differences between arms. CONCLUSIONS: AD literacy among African Americans can be improved after only one month through culturally competent, economically feasible educational formats.


Assuntos
Doença de Alzheimer , Negro ou Afro-Americano , Competência Cultural , Conhecimentos, Atitudes e Prática em Saúde , Letramento em Saúde/métodos , Envio de Mensagens de Texto , Negro ou Afro-Americano/etnologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Humanos , Vida Independente , Los Angeles/etnologia , Masculino , Pessoa de Meia-Idade
2.
J Neurol Neurosurg Psychiatry ; 88(6): 512-519, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28396361

RESUMO

BACKGROUND AND OBJECTIVE: The relationship between repeated concussions and neurodegenerative disease has received significant attention, particularly research in postmortem samples. Our objective was to characterise retired professional ice hockey players' cognitive and psychosocial functioning in relation to concussion exposure and apolipoprotein ε4 status. METHODS: Alumni athletes (N=33, aged 34-71 years) and an age-matched sample of comparison participants (N=18) were administered measures of cognitive function and questionnaires concerning psychosocial and psychiatric functioning. RESULTS: No significant group differences were found on neuropsychological measures of speeded attention, verbal memory or visuospatial functions, nor were significant differences observed on computerised measures of response speed, inhibitory control and visuospatial problem solving. Reliable group differences in cognitive performance were observed on tests of executive and intellectual function; performance on these measures was associated with concussion exposure. Group differences were observed for cognitive, affective and behavioural impairment on psychosocial questionnaires and psychiatric diagnoses. There was no evidence of differential effects associated with age in the alumni athletes. Possession of an apolipoprotein ε4 allele was associated with increased endorsement of psychiatric complaints, but not with objective cognitive performance. CONCLUSIONS: We found only subtle objective cognitive impairment in alumni athletes in the context of high subjective complaints and psychiatric impairment. Apolipoprotein ε4 status related to psychiatric, but not cognitive status. These findings provide benchmarks for the degree of cognitive and behavioural impairment in retired professional athletes and a point of comparison for future neuroimaging and longitudinal studies.


Assuntos
Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/psicologia , Concussão Encefálica/diagnóstico , Concussão Encefálica/psicologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Hóquei/lesões , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Aposentadoria , Transtornos do Comportamento Social/diagnóstico , Transtornos do Comportamento Social/psicologia , Adulto , Idoso , Apolipoproteína E4/análise , Traumatismos em Atletas/epidemiologia , Concussão Encefálica/epidemiologia , Transtornos Cognitivos/epidemiologia , Estudos Transversais , Humanos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Psicometria/estatística & dados numéricos , Valores de Referência , Transtornos do Comportamento Social/epidemiologia , Inquéritos e Questionários
3.
Int J Geriatr Psychiatry ; 31(9): 1064-74, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26807731

RESUMO

BACKGROUND: Pittsburgh compound B ([11C]-PIB) identifies amyloid-ß (Aß) deposition in vivo. Asymptomatic Aß deposition has been reported consistently in some healthy older subjects. Of patients with frontotemporal dementia, those who have later onset have a higher potential for Aß deposition. OBJECTIVE: Comparison of Aß deposition in Alzheimer's disease (AD), healthy older controls, and patients with early- and late-onset semantic dementia (SD), a subtype of frontotemporal dementia. METHODS: Subjects were recruited from tertiary academic care centers specializing in assessment and management of patients with neurodegenerative disease. We used the radiotracer [11C]-PIB in a high-resolution positron emission tomography scanner to evaluate 11 participants with SD (six with onset before age 65 and five with later onset), 9 with probable AD, and 10 controls over age 60. The main outcome measures were frontal, temporal, parietal, and total [11C]-PIB standardized uptake value ratios to establish PIB-positive (PIB+) cutoff. RESULTS: The five patients with late-onset SD were PIB-negative. Two of six with early-onset SD, seven of nine with AD, and 1 of 10 controls were PIB+. The SD participants who were PIB+ did not have memory or visuospatial deficits that are typical in AD. CONCLUSIONS: Aß deposition does not seem to be associated with late-onset SD. Future larger studies might confirm whether a significant minority of early-onset SD patients exhibit Aß deposition. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral/metabolismo , Demência Frontotemporal/metabolismo , Idoso , Compostos de Anilina , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Tiazóis
4.
Neurocase ; 21(4): 429-37, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24837244

RESUMO

Behavioral variant frontotemporal dementia (bvFTD) affects emotional evaluation, but less is known regarding the patients' ability to remember emotional stimuli. Here, bvFTD patients and age-matched controls studied positive, negative, and neutral pictures followed by a recognition memory test. Compared to controls, bvFTD patients showed a reduction in emotional evaluation of negative scenes, but not of positive or neutral scenes. Additionally, the patients showed an overall reduction in recognition memory accuracy, due to impaired recollection in the face of relatively preserved familiarity. These results show that bvFTD reduces the emotional evaluation of negative scenes and impairs overall recognition memory accuracy and recollection.


Assuntos
Emoções , Demência Frontotemporal/psicologia , Reconhecimento Psicológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
5.
Can J Neurol Sci ; 42(6): 389-94, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26329453

RESUMO

OBJECTIVE: To replicate a previous finding that the trajectory of the Neuropsychiatric Inventory (NPI) shifts in the sixth year of behavioural variant frontotemporal dementia (bvFTD). We evaluated longitudinal tracking with both the Frontal Behavioural Inventory (FBI) and NPI, comparing bvFTD against other dementias. METHODS: Chart reviews over two to five years for patients with bvFTD (n=30), primary progressive aphasia (PPA, n=13) and Alzheimer's disease (AD, n=118) at an urban Canadian tertiary clinic specializing in dementia. Linear regressions of the longitudinal data tested predictors of annualized rates of change (ROC) in NPI and FBI total and subscales for apathy and disinhibition among dementia groups. RESULTS: The mode of the overall sample for the most advanced duration of illness observed was 5 years, with the median at 7 years. We did not find a crescendo-decrescendo pattern in scores although, for bvFTD and AD, high initial scores correlated with ensuing downward ROCs on the NPI and FBI. Educational level showed an influence on disinhibition ROCs. The FBI was no more revealing than the NPI for apathy and disinhibition scores in these dementias. CONCLUSIONS: A cognitive reserve effect on behavioural disturbance was supported but it may take longer than our 4 years of observing the clinical sample to record inflection points in the behavioural and psychiatric symptoms seen in bvFTD. The current data only imply that both apathy and disinhibition will diminish over the course of dementia.


Assuntos
Demência/fisiopatologia , Demência/psicologia , Lobo Frontal/fisiopatologia , Testes Neuropsicológicos , Comportamento Problema/psicologia , Adulto , Idoso , Cognição/fisiologia , Demência/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença
6.
Cogn Neuropsychol ; 31(7-8): 565-83, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25358022

RESUMO

Differential patterns of impairment with respect to noun and verb production have been observed in the nonfluent and semantic variants of primary progressive aphasia. However, the factors influencing this discrepancy remain unclear. The present study evaluates verb retrieval in primary progressive aphasia using a naming task and a story completion task. Findings indicate that patients with the semantic variant are influenced by familiarity, frequency, and age of acquisition in both object and action naming, whereas patients with the nonfluent variant are not. Surprisingly, there were no differences in either group between object and action naming, presumably because the lists were well matched on pertinent variables. In the story completion task, greater impairment in semantically heavier than in semantically lighter verbs was observed for the semantic variant, and grammaticality and verb tense agreement was significantly lower in the nonfluent variant. The present findings suggest that lexicosemantic attributes affect verb production in the semantic variant, whereas both lexicosemantic and syntactic attributes affect verb production in the nonfluent variant.


Assuntos
Afasia Primária Progressiva/psicologia , Semântica , Idoso , Afasia Primária Progressiva/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Narração
7.
J Int Neuropsychol Soc ; 20(7): 694-703, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24993774

RESUMO

Mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal dementia. We used a comprehensive neuropsychological battery to investigate whether early cognitive changes could be detected in GRN mutation carriers before dementia onset. Twenty-four at-risk members from six families with known GRN mutations underwent detailed neuropsychological testing. Group differences were investigated by domains of attention, language, visuospatial function, verbal memory, non-verbal memory, working memory and executive function. There was a trend for mutation carriers (n=8) to perform more poorly than non-carriers (n=16) across neuropsychological domains, with significant between group differences for visuospatial function (p<.04; d=0.92) and working memory function (p<.02; d=1.10). Measurable cognitive differences exist before the development of frontotemporal dementia in subjects with GRN mutations. The neuropsychological profile of mutation carriers suggests early asymmetric, right hemisphere brain dysfunction that is consistent with recent functional imaging data from our research group and the broader literature.


Assuntos
Transtornos Cognitivos/etiologia , Demência Frontotemporal/complicações , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação/genética , Adulto , Idoso , Atenção , Análise Mutacional de DNA , Feminino , Demência Frontotemporal/genética , Humanos , Idioma , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Progranulinas , Curva ROC , Estatísticas não Paramétricas , Aprendizagem Verbal
8.
Pharmaceuticals (Basel) ; 17(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38675371

RESUMO

Brain somatic gene recombination (SGR) and the endogenous reverse transcriptases (RTs) that produce it have been implicated in the etiology of Alzheimer's disease (AD), suggesting RT inhibitors as novel prophylactics or therapeutics. This retrospective, proof-of-concept study evaluated the incidence of AD in people with human immunodeficiency virus (HIV) with or without exposure to nucleoside RT inhibitors (NRTIs) using de-identified medical claims data. Eligible participants were aged ≥60 years, without pre-existing AD diagnoses, and pursued medical services in the United States from October 2015 to September 2016. Cohorts 1 (N = 46,218) and 2 (N = 32,923) had HIV. Cohort 1 had prescription claims for at least one NRTI within the exposure period; Cohort 2 did not. Cohort 3 (N = 150,819) had medical claims for the common cold without evidence of HIV or antiretroviral therapy. The cumulative incidence of new AD cases over the ensuing 2.75-year observation period was lowest in patients with NRTI exposure and highest in controls. Age- and sex-adjusted hazard ratios showed a significantly decreased risk for AD in Cohort 1 compared with Cohorts 2 (HR 0.88, p < 0.05) and 3 (HR 0.84, p < 0.05). Sub-grouping identified a decreased AD risk in patients with NRTI exposure but without protease inhibitor (PI) exposure. Prospective clinical trials and the development of next-generation agents targeting brain RTs are warranted.

9.
Hum Brain Mapp ; 34(4): 973-84, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22109837

RESUMO

Semantic (svPPA) and nonfluent (nfPPA) variants of primary progressive aphasia are associated with distinct patterns of cortical atrophy and underlying pathology. Little is known, however, about their contrasting spread of white matter disruption and how this relates to grey matter (GM) loss. We undertook a structural MRI study to investigate this relationship. We used diffusion tensor imaging, tract-based spatial statistics, and voxel-based morphometry to examine fractional anisotropy (FA) and directional diffusivities in nine patients with svPPA and nine patients with nfPPA, and compared them to 16 matched controls after accounting for global GM atrophy. Significant differences in topography of white matter changes were found, with more ventral involvement in svPPA patients and more widespread frontal involvement in nfPPA individuals. However, each group had both ventral and dorsal tract changes, and both showed spread of diffusion abnormalities beyond sites of local atrophy. There was a clear dissociation in sensitivity of diffusion tensor imaging measures between groups. SvPPA patients showed widespread changes in FA and radial diffusivity, whereas changes in axial diffusivity were more restricted and proximal to sites of GM atrophy. NfPPA patients showed isolated changes in FA, but widespread axial and radial diffusivity changes. These findings reveal the extent of white matter disruption in these variants of PPA after accounting for GM loss. Further, they suggest that differences in the relative sensitivity of diffusion metrics may reflect differences in the nature of underlying white matter pathology in these two subtypes.


Assuntos
Afasia Primária Progressiva/patologia , Afasia Primária Progressiva/fisiopatologia , Mapeamento Encefálico , Encéfalo/patologia , Fibras Nervosas Mielinizadas/patologia , Semântica , Idoso , Anisotropia , Imagem de Tensor de Difusão , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
10.
Neurocase ; 19(3): 256-61, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22515731

RESUMO

OBJECTIVE: To study the effect of memantine on apathy, a common symptom of behavioral variant frontotemporal dementia (bvFTD). DESIGN: The patient underwent an off-label trial of memantine with behavioral inventories and [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans performed at baseline, 7 weeks and 6 months. SUBJECT: The patient was a 66-year-old male whose main manifestation of bvFTD was affective, behavioral and cognitive apathy. INTERVENTION: The patient began memantine at an oral dose of 5 mg per morning and titrated up by 5 mg per week to the maintenance dose of 10 mg PO bid. RESULTS: Informants reported reduction of the apathy. The insula and cerebellum, both involved in the salience network, showed improved metabolism. CONCLUSION: Further study to correlate the effects of memantine on apathy and the salience network in bvFTD are warranted.


Assuntos
Apatia/efeitos dos fármacos , Dopaminérgicos/uso terapêutico , Demência Frontotemporal/tratamento farmacológico , Demência Frontotemporal/psicologia , Memantina/uso terapêutico , Idoso , Atrofia/etiologia , Seguimentos , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons
11.
Int J Geriatr Psychiatry ; 28(3): 319-25, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22674572

RESUMO

OBJECTIVES: To follow up on the increases we reported in normalized metabolic activity in salience network hubs from a 2-month open-label study of memantine in frontotemporal dementia (FTD). METHODS: We repeated fluorodeoxyglucose positron emission tomography (FDG-PET) after 6 months of drug use and subjected the data to Statistical Parametrical Mapping (SPM) analysis to reveal clusters of significant change from baseline. We also sought correlations between changes in behavioral disturbances on the Frontal Behavioral Inventory (FBI) and the PET signal. RESULTS: Recruitment of one progressive nonfluent aphasia and one behavioral variant FTD precluded statistical analysis for any FTD subtype other than semantic dementia (SD). The baseline-to-6-month interval showed increased normalized metabolic activity in the left orbitofrontal cortex (p < 0.002) for five participants with SD. The 2-6-month interval revealed a late increase in normalized metabolic activity in the left insula (p < 0.013), right insula (p < 0.009), and left anterior cingulate (p < 0.005). The right anterior cingulate showed both an initial increase and a delayed further increase (2-6 months, p < 0.016). FBI scores worsened by 43.3%. One participant with SD opted not to continue memantine beyond 2 months yet showed similar FDG-PET increases. CONCLUSIONS: Increases in normalized cortical metabolic activity in salience network hubs were sustained in SD over a 6-month period. Because one participant without medication also showed these changes, further investigation is recommended through a double-blind, placebo-controlled study with FDG-PET as an outcome measure.


Assuntos
Antiparkinsonianos/uso terapêutico , Fluordesoxiglucose F18/farmacocinética , Degeneração Lobar Frontotemporal/tratamento farmacológico , Degeneração Lobar Frontotemporal/metabolismo , Memantina/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Degeneração Lobar Frontotemporal/diagnóstico por imagem , Humanos , Projetos Piloto , Fatores de Tempo
12.
Can J Neurol Sci ; 40(1): 21-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23250123

RESUMO

OBJECTIVE: To learn more about the needs and experiences of young carers for patients of frontotemporal dementia (FTD) in order to create a relevant support website for young caregivers to dementia patients. METHODS: Two focus groups were held with a total of fourteen young carers aged 11-18. The data corpus was collected through a semi-structured interview facilitated by a medical journalist who had prior experience as a caregiver to a patient with FTD. The transcripts were narrowed to a dataset for descriptive analysis using a coding scheme to reveal the main themes of their responses. RESULTS: Seven overlapping theme areas were: emotional impact of living with a parent with FTD, caregiving, coping, symptoms, diagnosis, relationships, and support. Based on the participants' responses, a website was launched providing supportive information and counsel for young carers. CONCLUSION: Young carers saw the experience of caring for a parent with early-onset dementia as positive overall, but identified opportunities for professionals to assist them in overcoming stigma and the challenge of balancing childhood and adolescent development within this context.


Assuntos
Cuidadores/psicologia , Demência Frontotemporal/enfermagem , Avaliação das Necessidades , Adaptação Psicológica , Adolescente , Canadá , Criança , Bases de Dados Factuais/estatística & dados numéricos , Emoções/fisiologia , Feminino , Grupos Focais/métodos , Inquéritos Epidemiológicos , Humanos , Entrevistas como Assunto , Masculino , Apoio Social , Estados Unidos
13.
Int Rev Psychiatry ; 25(2): 246-52, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23611354

RESUMO

The effect of early onset frontotemporal dementias (FTD) on spouses and children is profound, requiring different types of support services from pre-existing Alzheimer's disease interventions already in place. This article explores how the needs of families living with FTD resulted in three programme initiatives developed at Baycrest (an academic health sciences centre focused on ageing, in Toronto, Canada) to meet the needs of this population. These included an Internet-based videoconferencing support group for spouses, a website that provides support and counsel for children and their parents, and an adult day programme designed for FTD patients. The strength of these interventions is that services were developed with involvement of stakeholders in FTD care from the start, to deal with gaps in services in a sustainable way.


Assuntos
Serviços Comunitários de Saúde Mental , Demência Frontotemporal/terapia , Adulto , Criança , Serviços Comunitários de Saúde Mental/métodos , Efeitos Psicossociais da Doença , Hospital Dia/métodos , Família/psicologia , Demência Frontotemporal/psicologia , Humanos , Internet , Cônjuges/psicologia , Comunicação por Videoconferência
14.
BMJ Open ; 13(8): e072761, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37536975

RESUMO

OBJECTIVE: This study aims to show the usefulness of incorporating a community-based geographical information system (GIS) in recruiting research participants for the Asian Cohort for Alzheimer's Disease (ACAD) study for using the subgroup of Korean American (KA) older adults. The ACAD study is the first large study in the USA and Canada focusing on the recruitment of Chinese, Korean and Vietnamese older adults to address the issues of under-representation of Asian Americans in clinical research. METHODS: To promote clinical research participation of racial/ethnic minority older adults with and without dementia, we used GIS by collaborating with community members to delineate boundaries for geographical clusters and enclaves of church and senior networks, and KA serving ethnic clinics. In addition, we used socioeconomic data identified as recruitment factors unique to KA older adults which was analysed for developing recruitment strategies. RESULTS: GIS maps show a visualisation of the heterogeneity of the sociodemographic characteristics and the resources of faith-based organisations and KA serving local clinics. We addressed these factors that disproportionately affect participation in clinical research and successfully recruited the intended participants (N=60) in the proposed period. DISCUSSION: Using GIS maps to locate KA provided innovative inroads to successful research outreach efforts for a pilot study that may be expanded to other underserved populations across the USA in the future. We will use this tool subsequently on a large-scale clinical genetic epidemiology study. POLICY IMPLICATION: This approach responds to the call from the National Institute on Aging to develop strategies to improve the health status of older adults in diverse populations. Our study will offer a practical guidance to health researchers and policymakers in identifying understudied and hard-to-reach specific Asian American populations for clinical studies or initiatives. This would further contribute in reducing the health and research disparity gaps among older minority populations.


Assuntos
Doença de Alzheimer , Humanos , Idoso , Asiático , Etnicidade , Sistemas de Informação Geográfica , Grupos Minoritários , Projetos Piloto
15.
Brain ; 134(Pt 9): 2456-77, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21810890

RESUMO

Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.


Assuntos
Comportamento/fisiologia , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/fisiopatologia , Guias como Assunto , Idoso , Feminino , Demência Frontotemporal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
Dement Geriatr Cogn Disord ; 32(2): 150-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21986056

RESUMO

BACKGROUND/AIMS: We review the characteristics of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP) and determine prevalence of behavioral variant of frontotemporal dementia (bvFTD) features in ALSP. METHODS: Clinical and pathological information was abstracted from histopathologically confirmed ALSP cases identified by a systematic literature search. A new case of ALSP presenting as bvFTD was also described. RESULTS: We retrieved 51 ALSP cases. Mean age of onset was 42.2 years. Mean disease duration was 6.2 years, with 24 cases lasting 4 years or fewer. Fourteen cases had 3 or more of the 6 key bvFTD features. White matter hyperintensities on T(2)-weighted MRI, motor symptoms, seizures and amnesia were common. CONCLUSION: ALSP can underlie FTD syndrome, as well as rapidly progressive dementia.


Assuntos
Axônios/patologia , Demência Frontotemporal/diagnóstico , Leucoencefalopatias/diagnóstico , Neuroglia/patologia , Esferoides Celulares/patologia , Diagnóstico Diferencial , Demência Frontotemporal/patologia , Demência Frontotemporal/psicologia , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/patologia , Humanos , Leucoencefalopatias/genética , Leucoencefalopatias/patologia , Leucoencefalopatias/psicologia , Masculino , Pessoa de Meia-Idade , Pigmentação
17.
Int J Geriatr Psychiatry ; 26(12): 1300-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21351153

RESUMO

OBJECTIVE: We explored whether prior findings of reduction in serotonin 2A receptor (5-HT(2A) R) binding with age could be replicated and whether high resolution research tomography (HRRT) for positron emission tomography could compensate for partial volume effects in the presence of age-related brain atrophy, which has been a traditional concern for radioligand PET studies in the elderly. METHODS: We derived 5-HT(2A) R nondisplaceable binding potentials (BP(ND) ) in frontal, temporal, anterior-cingulate, insula, caudate and putamen volumes of interest (VOIs) for 28 healthy subjects (mean ± SD age = 43.9 ± 17.0 years, range: 19-78 years) using HRRT. Partial volume correction (PVC) was performed in the VOI analysis. RESULTS: The 5-HT(2A) R BP(ND) s decreased with age, a relationship best described by an exponential-decay regression. The BP(ND) s were found to be consistent before and after PVC, with an intra-class correlation coefficient of 0.84 and 95% confidence interval = 0.78-0.88. CONCLUSIONS: These new findings update current knowledge, in that the aging process is not always uniform across the life span and suggest that PVC may not be necessary with HRRT in healthy subjects.


Assuntos
Envelhecimento/metabolismo , Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons , Receptor 5-HT2A de Serotonina/metabolismo , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Feminino , Radioisótopos de Flúor , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Pirimidinonas , Radioisótopos , Adulto Jovem
18.
Can J Neurol Sci ; 38(5): 753-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21856580

RESUMO

OBJECTIVE: To guide development of public awareness and caregiver support resources for frontotemporal dementia (FTD) syndromes. METHODS: We used an online survey to explore their needs. The survey was self-administered by self-identified, English-speaking caregivers for patients with FTD in several countries. RESULTS: Of 79 caregiver respondents, approximately half were caring for patients with behavioural variant FTD or semantic dementia. The most common initial symptoms were Changes in Thinking and Judgment. Half of the respondents identified "failure to recognize the early stage of illness as a dementia" as the most troublesome aspect. Accordingly, over 40% of respondents had difficulty obtaining an accurate diagnosis for the patient. Caregivers prioritized family counseling and the public educational message that dementia can affect young people. CONCLUSION: The largest international survey of FTD caregivers to-date showed that support is needed for all family members adapting to the shock of early-onset dementia, and this may be most readily provided online.


Assuntos
Cuidadores/psicologia , Demência Frontotemporal/enfermagem , Avaliação das Necessidades , Adulto , Idoso , Canadá , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Feminino , Demência Frontotemporal/complicações , Demência Frontotemporal/epidemiologia , Inquéritos Epidemiológicos , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades/normas , Testes Neuropsicológicos , Estados Unidos
19.
Neurocase ; 16(1): 15-22, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19866390

RESUMO

UNLABELLED: Neuropathologic change underlying primary progressive aphasia (PPA) most commonly includes one of the frontotemporal lobar degenerations, such as FTLD-tau or FTLD-ubiquitin. The next most frequent etiology of PPA is Alzheimer's disease (AD). We describe 5 subjects with clinical diagnoses of semantic dementia, who underwent longitudinal clinical evaluation and postmortem neuropathology examination of the central nervous system. This case series examines retrospectively which clinical parameters might have pointed to the neuropathological diagnosis of AD. CONCLUSION: family history of late onset dementia, APOEepsilon4 status, combined features of semantic dementia and progressive non-fluent aphasia present early in illness, or generalized seizures, may indicate AD as the underlying pathology of semantic dementia.


Assuntos
Doença de Alzheimer/complicações , Degeneração Lobar Frontotemporal/etiologia , Degeneração Lobar Frontotemporal/patologia , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Mapeamento Encefálico , Degeneração Lobar Frontotemporal/diagnóstico por imagem , Humanos , Imageamento Tridimensional/métodos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Oximas , Mudanças Depois da Morte , Estudos Retrospectivos , Tomografia Computadorizada de Emissão de Fóton Único/métodos
20.
JAMA Neurol ; 77(9): 1099-1109, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32568367

RESUMO

Importance: Insulin modulates aspects of brain function relevant to Alzheimer disease and can be delivered to the brain using intranasal devices. To date, the use of intranasal insulin to treat persons with mild cognitive impairment and Alzheimer's disease dementia remains to be examined in a multi-site trial. Objective: To examine the feasibility, safety, and efficacy of intranasal insulin for the treatment of persons with mild cognitive impairment and Alzheimer disease dementia in a phase 2/3 multisite clinical trial. Design, Setting, and Participants: A randomized (1:1) double-blind clinical trial was conducted between 2014 and 2018. Participants received 40 IU of insulin or placebo for 12 months during the blinded phase, which was followed by a 6-month open-label extension phase. The clinical trial was conducted at 27 sites of the Alzheimer's Therapeutic Research Institute. A total of 432 adults were screened, and 144 adults were excluded. Inclusion criteria included adults aged 55 to 85 years with a diagnosis of amnestic mild cognitive impairment or Alzheimer disease (based on National Institute on Aging-Alzheimer Association criteria), a score of 20 or higher on the Mini-Mental State Examination, a clinical dementia rating of 0.5 or 1.0, and a delayed logical memory score within a specified range. A total of 289 participants were randomized. Among the first 49 participants, the first device (device 1) used to administer intranasal insulin treatment had inconsistent reliability. A new device (device 2) was used for the remaining 240 participants, who were designated the primary intention-to-treat population. Data were analyzed from August 2018 to March 2019. Interventions: Participants received 40 IU of insulin (Humulin-RU-100; Lilly) or placebo (diluent) daily for 12 months (blinded phase) followed by a 6-month open-label extension phase. Insulin was administered with 2 intranasal delivery devices. Main Outcomes and Measures: The primary outcome (mean score change on the Alzheimer Disease Assessment Scale-cognitive subscale 12) was evaluated at 3-month intervals. Secondary clinical outcomes were assessed at 6-month intervals. Cerebrospinal fluid collection and magnetic resonance imaging scans occurred at baseline and 12 months. Results: A total of 289 participants (155 men [54.6%]; mean [SD] age, 70.9 [7.1] years) were randomized. Of those, 260 participants completed the blinded phase, and 240 participants completed the open-label extension phase. For the first 49 participants, the first device used to administer treatment had inconsistent reliability. A second device was used for the remaining 240 participants (123 men [51.3%]; mean [SD] age, 70.8 [7.1] years), who were designated the primary intention-to-treat population. No differences were observed between treatment arms for the primary outcome (mean score change on ADAS-cog-12 from baseline to month 12) in the device 2 ITT cohort (0.0258 points; 95% CI, -1.771 to 1.822 points; P = .98) or for the other clinical or cerebrospinal fluid outcomes in the primary (second device) intention-to-treat analysis. No clinically important adverse events were associated with treatment. Conclusions and Relevance: In this study, no cognitive or functional benefits were observed with intranasal insulin treatment over a 12-month period among the primary intention-to-treat cohort. Trial Registration: ClinicalTrials.gov Identifier: NCT01767909.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Administração Intranasal , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Insulina/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
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