Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Neurobiol Aging ; 122: 33-44, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36476760

RESUMO

Alzheimer's disease (AD) is associated with alterations in functional connectivity (FC) of the brain. The FC underpinnings of CR, that is, lifelong experiences, are largely unknown. Resting-state FC and structural MRI were performed in 76 CSF amyloid-ß (Aß) negative healthy controls and 152 Aß positive individuals as an AD spectrum cohort (ADS; 55 with subjective cognitive decline, SCD; 52 with mild cognitive impairment; 45 with AD dementia). Following a region-of-interest (ROI) FC analysis, intrinsic network connectivity within the default-mode network (INC-DMN) and anti-correlation in INC between the DMN and dorsal attention network (DMN:DAN) were obtained as composite scores. CR was estimated by education and Lifetime Experiences Questionnaire (LEQ). The association between INC-DMN and MEM was attenuated by higher LEQ scores in the entire ADS group, particularly in SCD. In ROI analyses, higher LEQ scores were associated with higher FC within the DMN in ADS group. INC-DMN remains relatively intact despite memory decline in individuals with higher lifetime activity estimates, supporting a role for functional networks in maintaining cognitive function in AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Reserva Cognitiva , Humanos , Mapeamento Encefálico , Cognição , Encéfalo/diagnóstico por imagem , Peptídeos beta-Amiloides , Imageamento por Ressonância Magnética
2.
J Alzheimers Dis ; 85(3): 1267-1282, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34924387

RESUMO

BACKGROUND: Inflammation has been described as a key pathogenic event in Alzheimer's disease (AD), downstream of amyloid and tau pathology. Preclinical and clinical data suggest that the cholinergic basal forebrain may moderate inflammatory response to different pathologies. OBJECTIVE: To study the association of cholinergic basal forebrain volume and functional connectivity with measures of neuroinflammation in people from the AD spectrum. METHODS: We studied 261 cases from the DELCODE cohort, including people with subjective cognitive decline, mild cognitive impairment, AD dementia, first degree relatives, and healthy controls. Using Bayesian ANCOVA, we tested associations of MRI indices of cholinergic basal forebrain volume and functional connectivity with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglia activation, and serum levels of complement C3. Using Bayesian elastic net regression, we determined associations between basal forebrain measures and a large inflammation marker panel from CSF and serum. RESULTS: We found anecdotal to moderate evidence in favor of the absence of an effect of basal forebrain volume and functional connectivity on CSF sTREM2 and serum C3 levels both in Aß42/ptau-positive and negative cases. Bayesian elastic net regression identified several CSF and serum markers of inflammation that were associated with basal forebrain volume and functional connectivity. The effect sizes were moderate to small. CONCLUSION: Our data-driven analyses generate the hypothesis that cholinergic basal forebrain may be involved in the neuroinflammation response to Aß42 and phospho-tau pathology in people from the AD spectrum. This hypothesis needs to be tested in independent samples.


Assuntos
Doença de Alzheimer/patologia , Prosencéfalo Basal/patologia , Biomarcadores , Colinérgicos , Inflamação/patologia , Idoso , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/patologia , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino
3.
Front Aging Neurosci ; 13: 626974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967736

RESUMO

Background: The hippocampus and its subfields (HippSub) are reported to be diminished in patients with Alzheimer's disease (AD), bipolar disorder (BD), and major depressive disorder (MDD). We examined these groups vs healthy controls (HC) to reveal HippSub alterations between diseases. Methods: We segmented 3T-MRI T2-weighted hippocampal images of 67 HC, 58 BD, and MDD patients from the AFFDIS study and 137 patients from the DELCODE study assessing cognitive decline, including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and AD, via Free Surfer 6.0 to compare volumes across groups. Results: Groups differed significantly in several HippSub volumes, particularly between patients with AD and mood disorders. In comparison to HC, significant lower volumes appear in aMCI and AD groups in specific subfields. Smaller volumes in the left presubiculum are detected in aMCI and AD patients, differing from the BD group. A significant linear regression is seen between left hippocampus volume and duration since the first depressive episode. Conclusions: HippSub volume alterations were observed in AD, but not in early-onset MDD and BD, reinforcing the notion of different neural mechanisms in hippocampal degeneration. Moreover, duration since the first depressive episode was a relevant factor explaining the lower left hippocampal volumes present in groups.

4.
Neuroimage Clin ; 29: 102533, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33360018

RESUMO

BACKGROUND: Cognitive decline has been found to be associated with gray matter atrophy and disruption of functional neural networks in Alzheimer's disease (AD) in structural and functional imaging (fMRI) studies. Most previous studies have used single test scores of cognitive performance among monocentric cohorts. However, cognitive domain composite scores could be more reliable than single test scores due to the reduction of measurement error. Adopting a multicentric resting state fMRI (rs-fMRI) and cognitive domain approach, we provide a comprehensive description of the structural and functional correlates of the key cognitive domains of AD. METHOD: We analyzed MRI, rs-fMRI and cognitive domain score data of 490 participants from an interim baseline release of the multicenter DELCODE study cohort, including 54 people with AD, 86 with Mild Cognitive Impairment (MCI), 175 with Subjective Cognitive Decline (SCD), and 175 Healthy Controls (HC) in the AD-spectrum. Resulting cognitive domain composite scores (executive, visuo-spatial, memory, working memory and language) from the DELCODE neuropsychological battery (DELCODE-NP), were previously derived using confirmatory factor analysis. Statistical analyses examined the differences between diagnostic groups, and the association of composite scores with regional atrophy and network-specific functional connectivity among the patient subgroup of SCD, MCI and AD. RESULT: Cognitive performance, atrophy patterns and functional connectivity significantly differed between diagnostic groups in the AD-spectrum. Regional gray matter atrophy was positively associated with visuospatial and other cognitive impairments among the patient subgroup in the AD-spectrum. Except for the visual network, patterns of network-specific resting-state functional connectivity were positively associated with distinct cognitive impairments among the patient subgroup in the AD-spectrum. CONCLUSION: Consistent associations between cognitive domain scores and both regional atrophy and network-specific functional connectivity (except for the visual network), support the utility of a multicentric and cognitive domain approach towards explicating the relationship between imaging markers and cognition in the AD-spectrum.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Humanos , Imageamento por Ressonância Magnética
5.
Hum Brain Mapp ; 34(8): 1971-81, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22371367

RESUMO

Speech is an important carrier of emotional information. However, little is known about how different vocal emotion expressions are recognized in a receiver's brain. We used multivariate pattern analysis of functional magnetic resonance imaging data to investigate to which degree distinct vocal emotion expressions are represented in the receiver's local brain activity patterns. Specific vocal emotion expressions are encoded in a right fronto-operculo-temporal network involving temporal regions known to subserve suprasegmental acoustic processes and a fronto-opercular region known to support emotional evaluation, and, moreover, in left temporo-cerebellar regions covering sequential processes. The right inferior frontal region, in particular, was found to differentiate distinct emotional expressions. The present analysis reveals vocal emotion to be encoded in a shared cortical network reflected by distinct brain activity patterns. These results shed new light on theoretical and empirical controversies about the perception of distinct vocal emotion expressions at the level of large-scale human brain signals.


Assuntos
Percepção Auditiva/fisiologia , Mapeamento Encefálico , Encéfalo/fisiologia , Emoções/fisiologia , Voz , Adulto , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Fala , Máquina de Vetores de Suporte , Adulto Jovem
6.
Vaccine ; 25(21): 4203-12, 2007 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-17442466

RESUMO

We report the first safety and immunogenicity trial of the Plasmodium falciparum vaccine candidate FMP2.1/AS02A, a recombinant E. coli-expressed protein based upon the apical membrane antigen-1 (AMA-1) of the 3D7 clone formulated with the AS02A adjuvant. We conducted an open-label, staggered-start, dose-escalating Phase I trial in 23 malaria-naïve volunteers who received 8, 20 or 40microg of FMP2.1 in a fixed volume of 0.5mL of AS02A on a 0, 1, and 2 month schedule. Nineteen of 23 volunteers received all three scheduled immunizations. The most frequent solicited local and systemic adverse events associated with immunization were injection site pain (68%) and headache (29%). There were no significant laboratory abnormalities or vaccine-related serious adverse events. All volunteers seroconverted after second immunization as determined by ELISA. Immune sera recognized sporozoites and merozoites by immunofluorescence assay (IFA), and exhibited both growth inhibition and processing inhibition activity against homologous (3D7) asexual stage parasites. Post-immunization, peripheral blood mononuculear cells exhibited FMP2.1-specific lymphoproliferation and IFN-gamma and IL-5 ELISPOT assay responses. This is the first PfAMA-1-based vaccine shown to elicit both potent humoral and cellular immunity in humans. Encouraged by the potential of FMP1/AS02A to target host immunity against PfAMA-1 that is known to be expressed by sporozoite, hepatic and erythrocytic stages, we have initiated field trials of FMP2.1/AS02A in an endemic population in the Republic of Mali.


Assuntos
Antígenos de Protozoários/imunologia , Lipídeo A/análogos & derivados , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/imunologia , Proteínas de Membrana/imunologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Saponinas/imunologia , Adjuvantes Imunológicos , Adolescente , Adulto , Animais , Anticorpos Antiprotozoários/sangue , Linhagem Celular , Proliferação de Células , Células Cultivadas , Cricetinae , Combinação de Medicamentos , Ensaio de Imunoadsorção Enzimática , Escherichia coli/genética , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Cefaleia , Humanos , Imunização Secundária , Interferon gama/biossíntese , Interleucina-5/biossíntese , Leucócitos Mononucleares/imunologia , Lipídeo A/imunologia , Vacinas Antimaláricas/administração & dosagem , Masculino , Merozoítos/imunologia , Mesocricetus , Pessoa de Meia-Idade , Dor , Plasmodium falciparum/crescimento & desenvolvimento , Esporozoítos/imunologia , Vacinas Sintéticas/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA