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1.
Cereb Cortex ; 33(8): 4374-4383, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36130116

RESUMO

Time-based prospective memory (TBPM) is defined as the ability to remember to perform intended actions at a specific time in the future. TBPM is impaired in aging, and this decline has been associated with white-matter alterations within the superior fronto-occipital fasciculus. In the present study, we used resting-state functional magnetic resonance imaging from 22 healthy young (26 ± 5.2 years) and 23 older (63 ± 6.1 years) participants to investigate how age-related alterations in resting-state functional connectivity are related to TBPM performance, and whether these alterations are associated with the white-matter disruptions we have previously observed with diffusion tensor imaging. Whole-brain analyses revealed lower resting-state functional connectivity in older participants compared with younger ones, which in turn correlated with TBPM performance. These correlations were mainly located in the salience network and the parietal part of the frontoparietal network. Our findings suggest that resting-state functional connectivity alterations contribute to the age-related decline in TBPM.


Assuntos
Memória Episódica , Substância Branca , Humanos , Idoso , Imagem de Tensor de Difusão , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Substância Branca/patologia , Mapeamento Encefálico , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia
2.
Eur J Neurosci ; 55(2): 624-636, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34978117

RESUMO

Modifications in the processing of information relevant to oneself have been reported in breast cancer (BC) patients. Here, we characterize the longitudinal changes to self-representations in BC patients and how they are related to intrinsic functional brain connectivity. We tested 16 BC patients before (T1) and 1 year after the end of chemotherapy (T2) along with 24 healthy control participants (HC) at similar time points. Participants underwent resting-state fMRI and completed the Questionnaire of Self-Representation (QSR), which evaluates self-assertion and self-esteem. Resting-state functional connectivity (RSFC) was calculated for regions implicated in self-referential processes (dorsomedial prefrontal cortex [dmPFC], posterior cingulate cortex [PCC], and dorsal anterior cingulate cortex [dACC]) and correlated with QSR scores. QSR scores were on average larger in patients compared with HC and did not vary over time. RSFC between the dACC and regions supporting body awareness (precentral/postcentral and supramarginal gyri, superior parietal lobule) decreased more between T1 and T2 in BC patients than in HC. BC patients had lower RSFC than HC between the dmPFC and the PCC, and regions supporting mental imagery (precuneus, lingual gyrus), at each time point, and a greater decrease from T1 and T2. QSR scores negatively correlated with RSFC. Patients described themselves as having greater self-awareness and positive self-image, reflecting a fighting spirit. In parallel, patients presented a decrease in cortical activity related to body awareness and mental imagery of self-representations over time that may be related to the positive self-image patients have and could reflect a temporary adaptive strategy.


Assuntos
Neoplasias da Mama , Encéfalo , Mapeamento Encefálico/métodos , Neoplasias da Mama/tratamento farmacológico , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética
3.
Neuropsychol Rev ; 32(3): 483-505, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34355305

RESUMO

Patients with non-central nervous system (CNS) cancer frequently report cognitive complaints, that are recurrent and affect their quality of life. In order to improve supportive care of these cognitive difficulties, it is important to identify associated factors. Sleep disturbance is a good candidate to study, as patients with non-CNS cancer frequently report sleep disorders, and sleep plays a key role in cognitive functioning. The objective of the present systematic review was to summarize the results of studies evaluating the relationship between cognition and sleep in non-CNS cancer, and to highlight the need for further studies. PubMed [Medline] and Scopus databases were screened from April to November 2020 for studies published in English evaluating the association between cognition and sleep in adults with non-CNS cancer. The characteristics and risk of bias for each of the 30 included studies have been reported. Greater cognitive complaints in patients with non-CNS cancer were related to poorer self-reported sleep quality in almost all studies (n = 22/24). By contrast, around half of the studies reported a significant association between poorer neuropsychological performances and sleep complaints (n = 5/11). The studies were found to have several limitations, such as the lack of a control group, which would have shed the light on the period of occurrence of this association (e.g. after cancer diagnosis or after cancer treatments). Our review also identified factors that may influence the relationship between cognition and sleep. Recommendations are given for improving the methodology of future studies and extending the impact of their results.


Assuntos
Neoplasias , Transtornos do Sono-Vigília , Adulto , Cognição/fisiologia , Humanos , Neoplasias/complicações , Qualidade de Vida , Sono , Transtornos do Sono-Vigília/etiologia
4.
Cereb Cortex ; 31(1): 396-409, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32935836

RESUMO

Time-based prospective memory (TBPM) allows us to remember to perform intended actions at a specific time in the future. TBPM is sensitive to the effects of age, but the neural substrates of this decline are still poorly understood. The aim of the present study was thus to better characterize the brain substrates of the age-related decline in TBPM, focusing on macrostructural gray matter and microstructural white matter integrity. We administered a TBPM task to 22 healthy young (26 ± 5.2 years) and 23 older (63 ± 5.9 years) participants, who also underwent volumetric magnetic resonance imaging and diffusion tensor imaging scans. Neuroimaging analyses revealed lower gray matter volumes in several brain areas in older participants, but these did not correlate with TBPM performance. By contrast, an age-related decline in fractional anisotropy in several white-matter tracts connecting frontal and occipital regions did correlate with TBPM performance, whereas there was no significant correlation in healthy young subjects. According to the literature, these tracts are connected to the anterior prefrontal cortex and the thalamus, 2 structures involved in TBPM. These results confirm the view that a disconnection process occurs in aging and contributes to cognitive decline.


Assuntos
Envelhecimento/fisiologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Disfunção Cognitiva/metabolismo , Adolescente , Adulto , Idoso , Encéfalo/patologia , Disfunção Cognitiva/patologia , Imagem de Tensor de Difusão/métodos , Feminino , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Substância Branca/patologia , Adulto Jovem
5.
Brain ; 143(12): 3850-3864, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33221846

RESUMO

The most recent theories of emotions have postulated that their expression and recognition depend on acquired conceptual knowledge. In other words, the conceptual knowledge derived from prior experiences guide our ability to make sense of such emotions. However, clear evidence is still lacking to contradict more traditional theories, considering emotions as innate, distinct and universal physiological states. In addition, whether valence processing (i.e. recognition of the pleasant/unpleasant character of emotions) also relies on semantic knowledge is yet to be determined. To investigate the contribution of semantic knowledge to facial emotion recognition and valence processing, we conducted a behavioural and neuroimaging study in 20 controls and 16 patients with the semantic variant of primary progressive aphasia, a neurodegenerative disease that is prototypical of semantic memory impairment, and in which an emotion recognition deficit has already been described. We assessed participants' knowledge of emotion concepts and recognition of 10 basic (e.g. anger) or self-conscious (e.g. embarrassment) facial emotional expressions presented both statically (images) and dynamically (videos). All participants also underwent a brain MRI. Group comparisons revealed deficits in both emotion concept knowledge and emotion recognition in patients, independently of type of emotion and presentation. These measures were significantly correlated with each other in patients and with semantic fluency in patients and controls. Neuroimaging analyses showed that both emotion recognition and emotion conceptual knowledge were correlated with reduced grey matter density in similar areas within frontal ventral, temporal, insular and striatal regions, together with white fibre degeneration in tracts connecting frontal regions with each other as well as with temporal regions. We then performed a qualitative analysis of responses made during the facial emotion recognition task, by delineating valence errors (when one emotion was mistaken for another of a different valence), from other errors made during the emotion recognition test. We found that patients made more valence errors. The number of valence errors correlated with emotion conceptual knowledge as well as with reduced grey matter volume in brain regions already retrieved to correlate with this score. Specificity analyses allowed us to conclude that this cognitive relationship and anatomical overlap were not mediated by a general effect of disease severity. Our findings suggest that semantic knowledge guides the recognition of emotions and is also involved in valence processing. Our study supports a constructionist view of emotion recognition and valence processing, and could help to refine current theories on the interweaving of semantic knowledge and emotion processing.


Assuntos
Afasia Primária Progressiva/psicologia , Emoções , Percepção Social , Idoso , Afasia Primária Progressiva/diagnóstico por imagem , Cognição , Imagem de Tensor de Difusão , Expressão Facial , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Conhecimento , Masculino , Pessoa de Meia-Idade , Neuroimagem , Testes Neuropsicológicos , Desempenho Psicomotor , Reconhecimento Psicológico , Semântica
6.
Hum Brain Mapp ; 41(1): 139-149, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31566290

RESUMO

Affective theory of mind (ToM) depends on both the decoding of emotional expressions and the reasoning on emotional mental states from social situations. While previous studies characterized the neural substrates underlying these processes, it remains unclear whether the nature of the emotional state inferred from others can influence the brain activation associated with affective ToM. In the present study, we focused on two types of emotions: basic emotions (BEs) (e.g., anger and surprise), which are innate and universal and self-conscious emotions (e.g., pride and embarrassment), which correspond to a special class of emotions involving the self and including a representation of one's relative reactions to internal and external standards. Specifically, we used an ecological functional MRI paradigm, on 21 healthy young subjects, to compare brain activations during the decoding of and the reasoning on others' self-conscious, basic and neutral mental states. Our results showed that compared to neutral states, the inference of self-conscious and basic emotional states from others elicited more activation in several core regions of affective ToM. Direct comparisons between emotional conditions revealed more activation for self-conscious than BEs in the right temporoparietal junction during the reasoning process and in left middle occipital regions during the decoding process. Further analyses using a localizer task showed that the extrastriate body area was more recruited for decoding others' self-conscious versus BEs, which emphasize the importance of body clues to properly infer these emotions. Using an original task allowing for an ecological assessment of the affective ToM, these results demonstrate that the complexity of the emotion inferred to others can influence the recruitment of ToM network. This study also validates the use of our task as an ecological tool to assess the affective ToM, constituting an avenue for the characterization of ToM impairments in neurological conditions.


Assuntos
Córtex Cerebral/fisiologia , Ego , Emoções/fisiologia , Percepção Social , Teoria da Mente/fisiologia , Percepção Visual/fisiologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Adulto Jovem
7.
Neurocase ; 26(1): 36-41, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31771445

RESUMO

Huntington's disease (HD) is a devastating illness, associated with progressive motor, behavioral and cognitive dysfunctions. However, some studies emphasized that social cognition impairment could occur prior to the onset of these other symptoms. Here, we report the case of a 47 years old patient with early manifest HD, whose complaint was mainly related to the behavioral sphere. He exhibited a significant impairment of Theory of Mind abilities as well as behavioral, and discrete motor symptoms without noticeable cognitive decline. This case study suggests that social cognition impairments and behavioral changes could be in some cases a feature of the disease and may represent a major disability, in early stages of manifest HD.


Assuntos
Sintomas Comportamentais/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Doença de Huntington/fisiopatologia , Cognição Social , Teoria da Mente/fisiologia , Sintomas Comportamentais/etiologia , Disfunção Cognitiva/etiologia , Humanos , Doença de Huntington/complicações , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
8.
Cereb Cortex ; 29(5): 1889-1899, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29668866

RESUMO

Multimodal neuroimaging analyses offer additional information beyond that provided by each neuroimaging modality. Thus, direct comparisons and correlations between neuroimaging modalities allow revealing disease-specific topographic relationships. Here, we compared the topographic discrepancies between atrophy and hypometabolism in two neurodegenerative diseases characterized by distinct pathological processes, namely Alzheimer's disease (AD) versus semantic dementia (SD), to unravel their specific influence on local and global brain structure-function relationships. We found that intermodality topographic discrepancies clearly distinguished the two patient groups: AD showed marked discrepancies between both alterations, with greater hypometabolism than atrophy in large posterior associative neocortical regions, while SD showed more topographic consistency between atrophy and hypometabolism across brain regions. These findings likely reflect the multiple pathologies versus the relatively unitary pathological process underlying AD versus SD respectively. Our results evidence that multimodal neuroimaging-derived indexes can provide clinically relevant information to discriminate the two diseases, and potentially reveal distinct neuropathological processes.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Demência Frontotemporal/metabolismo , Demência Frontotemporal/patologia , Idoso , Doença de Alzheimer/diagnóstico por imagem , Atrofia/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Feminino , Demência Frontotemporal/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons
9.
Brain Cogn ; 136: 103588, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31419764

RESUMO

Although theory of mind (ToM) has been extensively explored in aging, few studies have used the same tool to simultaneously assess and compare its cognitive and affective components. When we administered the Movie for Assessment of Social Cognition, a dynamic sequence of social scenes, to 60 healthy participants (20-75 years), we observed no different age-related decreases in both cognitive and affective ToM. While each component was associated with cognitive measures (i.e., episodic memory and processing speed were predictive of cognitive ToM, and recognition of facial emotion expressions and inhibition were predictive of affective ToM), mediation analyses showed that these measures only mediated the effect of age on affective ToM. Voxelwise regressions with grey-matter volume showed that the components partly rely on the same neural substrates, reflecting either ToM per se or other cognitive processes elicited by this multi-determinant task. We discuss the specific substrates of each ToM component, emphasising the importance of considering the impact of other aspects of cognition, present in more ecological situations, on ToM functioning.


Assuntos
Encéfalo/diagnóstico por imagem , Reconhecimento Facial/fisiologia , Substância Cinzenta/diagnóstico por imagem , Longevidade/fisiologia , Percepção Social , Teoria da Mente/fisiologia , Adulto , Idoso , Emoções/fisiologia , Feminino , Humanos , Inibição Psicológica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto Jovem
10.
BMC Cancer ; 18(1): 866, 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30176833

RESUMO

BACKGROUND: Breast cancer (BC) is the most frequent cancer in women with more than 70% of BC patients being treated with hormonal therapy (HT). Among these patients, some report difficulties in remembering what they are supposed to do at the right moment, referring to prospective memory (PM). PM is essential for autonomy and medical adherence of patients, and requires an ecological assessment. Virtual reality, that recreates naturalistic environment, seems to be a promising method to evaluate PM. Several BC patients also report sleep disturbances. Given the role of sleep on memory consolidation, it is imperative to explore the influence of sleep quality on PM in BC patients treated with HT. The purpose of PROSOM-K study is to assess PM functioning using virtual reality and sleep quality in BC treated or not with HT. METHODS: PROSOM-K is a prospective study including post-menopausal BC patients ≤70 years old treated with radiotherapy (n = 25) or with radiotherapy and HT (n = 25), and healthy post-menopausal women (n = 25) matched for age and education. PM will be assessed using a virtual reality based task. Other cognitive functions and psychosocial factors will be assessed with validated questionnaires and neuropsychological tests. The study is divided in 3 sessions: a session of familiarisation with the virtual environment and the PM task: a day-time session during which participants learn intentions during the morning and recall them in the evening; and a night-time session during which participants learn intentions in the evening and recall them the following morning. Women will be monitored by wrist actigraphy; during the night-time session, objective sleep quality and quantity will be measured by polysomnography. DISCUSSION: This is a novel study aiming to assess PM using virtual reality, coupled with the evaluation of other cognitive functions. Polysomnographic study of sleep will provide further information about architectural sleep disturbances in BC. Association between sleep architecture parameters and PM mechanism in BC women treated with HT will be described in detail. We expect our results will provide knowledge for patients and clinicians and further help to improve patient care and cognitive therapy. TRIAL REGISTRATION: NCT03420105 , registered: January 10, 2018.


Assuntos
Neoplasias da Mama/fisiopatologia , Cognição/fisiologia , Terapia Cognitivo-Comportamental , Transtornos do Sono-Vigília/terapia , Adulto , Idoso , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Estazolam/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Qualidade de Vida , Sono/fisiologia , Transtornos do Sono-Vigília/induzido quimicamente , Transtornos do Sono-Vigília/fisiopatologia , Realidade Virtual
11.
Brain ; 140(12): 3317-3328, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29194503

RESUMO

See Franzmeier and Dyrba (doi:10.1093/brain/awx304) for a scientific commentary on this article. Recent findings suggest that the topography and propagation of lesions in Alzheimer's disease are related to functional connectivity, either showing that regions of high global connectivity are more vulnerable or that lesions propagate neuron-to-neuron from a starting area called the epicentre, thus involving specific connectivity. However, the relative influence of specific and global connectivity and their differential impact on the three main neuroimaging biomarkers of the disease (atrophy, hypometabolism and amyloid-ß deposition) have never been investigated to date. Forty-two healthy elderly subjects and 35 amyloid-ß positive amnestic mild cognitive impairment and Alzheimer's disease patients underwent resting-state functional MRI, anatomical T1-weighted MRI, 18F-fluorodeoxyglucose-PET and florbetapir-PET scans. All patients also underwent follow-up T1-weighted MRI, 18F-fluorodeoxyglucose-PET and florbetapir-PET scans 18 months later to assess the lesion propagation. The epicentre was defined per modality as the most altered region at baseline in patients compared to controls. Maps of global and specific functional connectivity were computed from the resting-state functional MRI data of the healthy elderly subjects. Global connectivity corresponds to the connectivity strength of each grey matter area with the rest of the brain (i.e. all other grey matter areas) while specific connectivity refers to the connectivity of a single specific brain region (the epicentre) with the rest of the brain (i.e. all other brain regions). Maps of baseline alterations and propagation were computed for grey matter atrophy, hypometabolism and amyloid-ß deposition in patients. Regression analyses were performed across the 239 brain regions to assess the links between global or specific functional connectivity in healthy elderly subjects and Alzheimer's disease-related baseline disruptions or alteration propagation. Atrophy at baseline was predicted by specific connectivity and inversely correlated with global connectivity, while hypometabolism and amyloid-ß deposition were positively influenced by both global and specific connectivity. Regarding longitudinal changes, atrophy spread in regions with high specific connectivity while hypometabolism propagated in areas showing high global connectivity. This is the first study to show that global connectivity has an opposite relationship with atrophy versus hypometabolism and amyloid-ß deposition, suggesting that the high level of functional connectivity found in hubs exerts a differential influence on these Alzheimer's disease lesions. These results sustain the hypotheses of higher vulnerability of hubs to hypometabolism and amyloid-ß deposition versus transneuronal propagation of atrophy from the epicentre to connected regions, in Alzheimer's disease. Global and specific connectivity exert a differential influence on, and provide complementary information to predict, the topography of Alzheimer's disease lesions and their propagation.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Imageamento por Ressonância Magnética/normas , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/metabolismo , Tomografia por Emissão de Pósitrons/normas , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos
12.
Hum Brain Mapp ; 38(4): 1791-1800, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27981671

RESUMO

This study aims at further understanding the distinct vulnerability of brain networks in Alzheimer's disease (AD) versus semantic dementia (SD) investigating the white matter injury associated with medial temporal lobe (MTL) atrophy in both conditions. Twenty-six AD patients, twenty-one SD patients, and thirty-nine controls underwent a high-resolution T1-MRI scan allowing to obtain maps of grey matter volume and white matter density. A statistical conjunction approach was used to identify MTL regions showing grey matter atrophy in both patient groups. The relationship between this common grey matter atrophy and white matter density maps was then assessed within each patient group. Patterns of grey matter atrophy were distinct in AD and SD but included a common region in the MTL, encompassing the hippocampus and amygdala. This common atrophy was associated with alterations in different white matter areas in AD versus SD, mainly including the cingulum and corpus callosum in AD, while restricted to the temporal lobe - essentially the uncinate and inferior longitudinal fasciculi - in SD. Complementary analyses revealed that these relationships remained significant when controlling for global atrophy or disease severity. Overall, this study provides the first evidence that atrophy of the same MTL region is related to damage in distinct white matter fibers in AD and SD. These different patterns emphasize the vulnerability of distinct brain networks related to the MTL in these two disorders, which might underlie the discrepancy in their symptoms. These results further suggest differences between AD and SD in the neuropathological processes occurring in the MTL. Hum Brain Mapp 38:1791-1800, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Doença de Alzheimer/complicações , Demência Frontotemporal/complicações , Leucoencefalopatias/etiologia , Lobo Temporal/patologia , Idoso , Doença de Alzheimer/diagnóstico por imagem , Análise de Variância , Atrofia/etiologia , Feminino , Demência Frontotemporal/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Processamento de Imagem Assistida por Computador , Leucoencefalopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estatística como Assunto
13.
J Neurosci ; 35(29): 10402-11, 2015 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-26203136

RESUMO

Neuroimaging biomarkers, namely hippocampal volume loss, temporoparietal hypometabolism, and neocortical ß-amyloid (Aß) deposition, are included in the recent research criteria for preclinical Alzheimer's disease (AD). However, how to use these biomarkers is still being debated, especially regarding their sequence. Our aim was to characterize the cognitive and brain profiles of elders classified as positive or negative for each biomarker to further our understanding of their use in the preclinical diagnosis of AD. Fifty-four cognitively normal individuals (age = 65.8 ± 8.3 years) underwent neuropsychological tests (structural MRI, FDG-PET, and Florbetapir-PET) and were dichotomized into positive or negative independently for each neuroimaging biomarker. Demographic, neuropsychological, and neuroimaging data were compared between positive and negative subgroups. The MRI-positive subgroup had lower executive performances and mixed patterns of lower volume and metabolism in AD-characteristic regions and in the prefrontal cortex. The FDG-positive subgroup showed only hypometabolism, predominantly in AD-sensitive areas extending to the whole neocortex, compared with the FDG-negative subgroup. The amyloid-positive subgroup was older and included more APOE ε4 carriers compared with the amyloid-negative subgroup. When considering MRI and/or FDG biomarkers together (i.e., the neurodegeneration-positive), there was a trend for an inverse relationship with Aß deposition such that those with neurodegeneration tended to show less Aß deposition and the reverse was true as well. Our findings suggest that: (1) MRI and FDG biomarkers provide complementary rather than redundant information and (2) relatively young cognitively normal elders tend to have either neurodegeneration or Aß deposition, but not both, suggesting additive rather than sequential/causative links between AD neuroimaging biomarkers at this age. Significance statement: Neuroimaging biomarkers are included in the recent research criteria for preclinical Alzheimer's disease (AD). However, how to use these biomarkers is still being debated, especially regarding their sequence. Our findings suggest that MRI and FDG-PET biomarkers should be used in combination, offering an additive contribution instead of reflecting the same process of neurodegeneration. Moreover, the present study also challenges the hierarchical use of the neuroimaging biomarkers in preclinical AD because it suggests that the neurodegeneration observed in this population is not due to ß-amyloid deposition. Rather, our results suggest that ß-amyloid- and tau-related pathological processes may interact but not necessarily appear in a systematic sequence.


Assuntos
Doença de Alzheimer/diagnóstico , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico , Imageamento por Ressonância Magnética , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Degeneração Neural/diagnóstico , Neuroimagem/métodos , Testes Neuropsicológicos , Placa Amiloide/diagnóstico
14.
Ann Neurol ; 78(3): 477-86, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26085009

RESUMO

OBJECTIVE: Impaired awareness is a common symptom in many mental disorders including Alzheimer disease (AD). This study aims at improving our understanding of the neural mechanisms underlying anosognosia of memory deficits in AD by combining measures of regional brain metabolism (resting state fluorodeoxyglucose positron emission tomography [FDG-PET]) and intrinsic connectivity (resting state functional magnetic resonance imaging [fMRI]). METHODS: Twenty-three patients diagnosed with probable AD based on clinical and biomarker data and 30 matched healthy control subjects were recruited in this study. An anosognosia index (difference between subjective and objective memory scores) was obtained in each participant. Resting state FDG-PET for glucose metabolism measurement and resting state fMRI for intrinsic connectivity measurement were also performed. AD and control groups were compared on behavioral data, and voxelwise correlations between anosognosia and neuroimaging data were conducted within the AD group. RESULTS: AD patients underestimated their memory deficits. Anosognosia in AD patients correlated with hypometabolism in orbitofrontal (OFC) and posterior cingulate (PCC) cortices. Using OFC and PCC as seed regions, intrinsic connectivity analyses in AD revealed a significant association between anosognosia and reduced intrinsic connectivity between these regions as well as with the medial temporal lobe. INTERPRETATION: Anosognosia in AD is due not only to functional changes within cortical midline structures involved in self-referential processes (OFC, PCC), but also to disconnection between these regions as well as with the medial temporal lobe. These findings suggest that the lack of awareness of memory deficits in AD results from a disruption of the communication within, but also between, the self-related and the memory-related brain networks.


Assuntos
Agnosia/metabolismo , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Transtornos da Memória/metabolismo , Rede Nervosa/metabolismo , Idoso , Idoso de 80 Anos ou mais , Agnosia/diagnóstico , Agnosia/psicologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Encéfalo/patologia , Feminino , Humanos , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Rede Nervosa/patologia
15.
Int Psychogeriatr ; 28(5): 707-17, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26572551

RESUMO

BACKGROUND: Although non-drug interventions are widely used in patients with Alzheimer's disease, few large scale randomized trials involving a long-term intervention and several cognitive-oriented approaches have been carried out. ETNA3 trial compares the effect of cognitive training, reminiscence therapy, and an individualized cognitive rehabilitation program in Alzheimer's disease to usual care. METHODS: This is a multicenter (40 French clinical sites) randomized, parallel-group trial, with a two-year follow-up comparing groups receiving standardized programs of cognitive training (group sessions), reminiscence therapy (group sessions), individualized cognitive rehabilitation program (individual sessions), and usual care (reference group). Six hundred fifty-three outpatients with Alzheimer's disease were recruited. The primary efficacy outcome was the rate of survival without moderately severe to severe dementia at two years. Secondary outcomes were cognitive impairment, functional disability, behavioral disturbance, apathy, quality of life, depression, caregiver's burden, and resource utilization. RESULTS: No impact on the primary efficacy measure was evidenced. For the two group interventions (i.e. cognitive training and reminiscence), none of the secondary outcomes differed from usual care. The larger effect was seen with individualized cognitive rehabilitation in which significantly lower functional disability and a six-month delay in institutionalization at two years were evidenced. CONCLUSIONS: These findings challenge current management practices of Alzheimer's patients. While cognitive-oriented group therapies have gained popularity, this trial does not show improvement for the patients. The individualized cognitive rehabilitation intervention provided clinically significant results. Individual interventions should be considered to delay institutionalization in Alzheimer's disease.


Assuntos
Doença de Alzheimer/reabilitação , Cuidadores/psicologia , Terapia Cognitivo-Comportamental/métodos , Disfunção Cognitiva/epidemiologia , Memória , Psicoterapia de Grupo/métodos , Adaptação Psicológica , Idoso , Idoso de 80 Anos ou mais , Depressão , Feminino , França , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Modelos de Riscos Proporcionais , Escalas de Graduação Psiquiátrica , Qualidade de Vida/psicologia , Resultado do Tratamento
16.
Hum Brain Mapp ; 36(2): 463-74, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25231681

RESUMO

Growing interest has developed in hippocampal subfield volumetry over the past few years and an increasing number of studies use the automatic segmentation algorithm implemented in FreeSurfer. However, this approach has not been validated on standard resolution T1-weighted magnetic resonance (MR) as used in most studies. We aimed at comparing hippocampal subfield segmentation using FreeSurfer on standard T1-weighted images versus manual delineation on dedicated high-resolution hippocampal scans. Hippocampal subfields were segmented in 133 individuals including 98 cognitively normal controls aged 19-84 years, 17 mild cognitive impairment and 18 Alzheimer's disease (AD) patients using both methods. Intraclass correlation coefficients (ICC) and Bland-Altman plots were computed to assess the consistency between both methods, and the effects of age and diagnosis were assessed from both measures. Low to moderate ICC (0.31-0.74) were found for the subiculum and other subfields as well as for the whole hippocampus, and the correlations were very low for cornu ammonis (CA)1 (<0.1). FreeSurfer CA1 volume estimates were found to be much lower than those obtained from manual segmentation, and this bias was proportional to the volume of this structure so that no effect of age or AD could be detected on FreeSurfer CA1 volumes. This study points to the differences in the anatomic definition of the subfields between FreeSurfer and manual delineation, especially for CA1, and provides clue for improvement of this automatic technique for potential clinical application on standard T1-weighted MR.


Assuntos
Envelhecimento/patologia , Doença de Alzheimer/patologia , Disfunção Cognitiva/patologia , Hipocampo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Tamanho do Órgão , Reconhecimento Automatizado de Padrão , Software , Adulto Jovem
17.
Neuropsychol Rev ; 25(3): 326-55, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26319237

RESUMO

Measurement of synaptic activity by Positron Emission Tomography (PET) and its relation to cognitive functions such as episodic memory, working memory and executive functions in healthy humans and patients with neurocognitive disorders have been well documented. In this review, we introduce the concept of PET imaging that allows the observation of a particular biological process in vivo through the use of radio-labelled compounds, its general use to the medical world and its contributions to the understanding of memory systems. We then focus on [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG-PET), the radiotracer that is used to measure local cerebral metabolic rate of glucose that is indicative of synaptic activity in the brain. FDG-PET at rest has been at the forefront of functional neuroimaging over the past 3 decades, contributing to the understanding of cognitive functions in healthy humans and how these functional patterns change with cognitive alterations. We discuss methodological considerations that are important for optimizing FDG-PET imaging data prior to analysis. We then highlight the contribution of FDG-PET to the understanding of the patterns of functional differences in non-degenerative pathologies, normal ageing, and age-related neurodegenerative disorders. Through reasonable temporal and spatial resolution, its ability to measure synaptic activity in the whole brain, independently of any specific network and disease, makes it ideal to observe regional functional changes associated with memory impairment.


Assuntos
Encéfalo/metabolismo , Fluordesoxiglucose F18 , Glucose/metabolismo , Transtornos da Memória/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Envelhecimento/metabolismo , Alcoolismo/complicações , Alcoolismo/diagnóstico por imagem , Alcoolismo/metabolismo , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Atrofia , Encéfalo/diagnóstico por imagem , Feminino , Substância Cinzenta/patologia , Humanos , Processamento de Imagem Assistida por Computador , Transtornos da Memória/complicações , Transtornos da Memória/diagnóstico por imagem , Pessoa de Meia-Idade , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/metabolismo , Processamento de Sinais Assistido por Computador
18.
Neuropsychol Rev ; 25(2): 125-33, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25868986

RESUMO

Transient global amnesia (TGA) is a neurological syndrome that usually occurs in middle-aged or older people. It is characterized by the abrupt onset of profound anterograde amnesia, associated with more variable retrograde amnesia and repetitive questioning. The whole episode lasts no more than 24 h. Almost 60 years after its first descriptions, the etiology of TGA remains unknown. Until now, TGA has been described exclusively as a memory disorder, but there is a growing body of evidence to show that emotional and psychological factors (as anxious and depressive symptoms) are present at different times of TGA. Their role therefore needs to be clarified. First, these factors seem to play a part in triggering TGA, at least for a subgroup of patients, suggesting the existence of an emotional TGA subtype. Second, recent research shows that almost all the TGA patients displayed modifications of their emotional state during the episode, possibly linked to sudden memory loss. The level of depressive and anxious symptoms could even reach a pathological threshold in patients with the so-called "emotional TGA subtype". Third, the persistence of these depressive and anxious symptoms after the end of the episode could account for lasting memory disorders in some patients. Finally, the analysis of these emotional syndrome and emotional factors and the recent data in neuroimaging could allow us to gain a better understanding of the pathophysiological mechanisms behind TGA. The aim of this review was thus to discuss whether the anxious and depressive symptoms are causative, resultant or coincidental of TGA.


Assuntos
Amnésia Global Transitória/fisiopatologia , Amnésia Global Transitória/psicologia , Amnésia Global Transitória/etiologia , Animais , Ansiedade/fisiopatologia , Depressão/fisiopatologia , Humanos
19.
Neuroimage ; 90: 179-88, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24418502

RESUMO

The aim of this study was to explore whether musical practice-related gray matter increases in brain regions are accompanied by modifications in their resting-state functional connectivity. 16 young musically experienced adults and 17 matched nonmusicians underwent an anatomical magnetic resonance imaging (MRI) and a resting-state functional MRI (rsfMRI). A whole-brain two-sample t test run on the T1-weighted structural images revealed four clusters exhibiting significant increases in gray matter (GM) volume in the musician group, located within the right posterior and middle cingulate gyrus, left superior temporal gyrus and right inferior orbitofrontal gyrus. Each cluster was used as a seed region to generate and compare whole-brain resting-state functional connectivity maps. The two clusters within the cingulate gyrus exhibited greater connectivity for musicians with the right prefrontal cortex and left temporal pole, which play a role in autobiographical and semantic memory, respectively. The cluster in the left superior temporal gyrus displayed enhanced connectivity with several language-related areas (e.g., left premotor cortex, bilateral supramarginal gyri). Finally, the cluster in the right inferior frontal gyrus displayed more synchronous activity at rest with claustrum, areas thought to play a role in binding sensory and motor information. We interpreted these findings as the consequence of repeated collaborative use in general networks supporting some of the memory, perceptual-motor and emotional features of musical practice.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Música , Vias Neurais/fisiologia , Plasticidade Neuronal/fisiologia , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Descanso/fisiologia , Adulto Jovem
20.
Hum Brain Mapp ; 35(7): 3066-82, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24214215

RESUMO

Prospective memory (PM) refers to the ability to remember to do something in the future, either in response to an event (event-based) or after a certain amount of time has elapsed (time-based). While the distinction between event- and time-based PM is widely acknowledged in the literature, little is known about the processes they share and those they do not. This is particularly true concerning their brain substrates, as almost all neuroimaging studies so far have focused on event-based PM. We proposed a functional magnetic resonance imaging paradigm assessing both event-based and time-based PM to 20 healthy young individuals. Analyses revealed that event- and time-based PM both induced activation in the posterior frontal and parietal cortices, and deactivation in the medial rostral prefrontal cortex. In addition, activation more specific to each condition, which may underlie differences in strategic monitoring, was highlighted. Thus, occipital areas were more activated during event-based PM, probably reflecting target-checking, while a network comprising the dorsolateral prefrontal cortex, the cuneus/precuneus and, to a lesser extent, the inferior parietal lobule, superior temporal gyrus, and the cerebellum, was more activated in time-based PM, which may reflect the involvement of time-estimation processes. These results confirm the allocation of attentional resources to the maintenance of intention for event-based and time-based PM, as well as the engagement of distinct mechanisms reflecting the monitoring strategies specific to each condition.


Assuntos
Atenção/fisiologia , Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Intenção , Memória Episódica , Tempo de Reação/fisiologia , Adolescente , Adulto , Análise de Variância , Mapeamento Encefálico , Tomada de Decisões Assistida por Computador , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Oxigênio/sangue , Adulto Jovem
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