Biomedical subjects

G Chételat

Publications and source records attributed to G Chételat.

7 recordsLinked to original sources

PubMed2006

[Alzheimer's disease and human memory].

Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to a detailed analysis into the framework of cognitive neuropsychology which aimed at describing the deficits of very specific processes. Beyond their clinical interest, these studies contributed to the modelisation of human memory thanks to the characterization of different memory systems and their relationships. The first part of this paper gives an overview of the memory deficits in Alzheimer's disease and insists on particular cognitive phenomena. Hence, several examples are developed in the domains of semantic memory (such as hyperpriming and hypopriming effects) and autobiographical memory. Recent results highlight the existence of severe autobiographical amnesia observed in all neurodegenerative diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's disease (showing that remote memories are better preserved than recent ones), reverse gradient in semantic dementia and no clear gradient in the frontal variant of frontotemporal dementia. The second part of this article presents advances in cognitive neuroscience searching to disclose the cerebral substrates of these cognitive deficits in Alzheimer's disease. The studies using functional imaging techniques are the most informative regarding this problematic. While showing the dysfunctions of an extended network, they emphasize the selectivity of cerebral damages that are at the root of very specific cognitive dysfunctions, coming close in that way to the conceptions of cognitive neuropsychology. These neuroimaging studies unravel the existence of compensatory mechanisms, which until recently were clearly missing in the literature on neurodegenerative diseases. These different researches lead to a wide conception of human memory, not just limited to simple instrumental processes (encoding, storage, retrieval), but necessarily covering models of identity and continuity of the subject, which interact in a dynamic way with eminently changing memory representations.

Alzheimer Disease↗

PubMed2006

[Brain profile of hypometabolism in early Alzheimer's disease: relationships with cognitive deficits and atrophy].

While accurate and early prediction of patients that will develop Alzheimer's disease (AD) in the near future is urgently needed, the amnestic Mild Cognitive Impairment (MCI) state is of particular interest since it most conveniently represents the pre-dementia stage of AD. Consistently, the profile of brain functional alteration constantly evidenced in resting-state SPECT and PET studies is similar to that observed in mild AD, mainly involving the posterior cingulate and temporo-parietal regions. While the former is a characteristic feature of MCI, since it is present in each patient at this stage, the latter seems specifically associated with the future conversion to AD. Moreover, right temporo-parietal hypometabolism has been found to be the best predictor of subsequent global cognitive decline, over and above neuropsychological and MRI volumetric measurements. This review also presents a discussion on the relationships between the brain profile of hypometabolism on the one hand, and cognitive impairment as well as cerebral structural alterations on the other. Thus, firstly, while functional impairment in the posterior cingulate region seems to be associated with deficits in retrieval of episodic memories in MCI, the relationship between right temporo-parietal hypometabolism and cognitive impairment is still obscure. However, several arguments point to its relation with visuo-spatial deficits, which are often associated with future conversion to AD. Secondly, the discordance between brain areas of major functional changes, and those of highest structural alterations, leads to some relevant questions about the relations between both pathological manifestations and their underlying mechanisms. More specifically, additional hypometabolism-inducing factors could occur in areas of highest hypometabolism compared to atrophy, i.e. mainly in posterior associative cortical regions, leading to genuine functional perturbation in early AD before the development of real atrophy and perhaps of disease as well. By contrast, the hippocampus is the main site of atrophy while its functional alteration is still debated, suggesting that compensation/protective mechanisms probably specifically occur in this structure to maintain a high level of metabolism relative to its structural alteration.

Alzheimer Disease↗

PubMed2005

Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study.

Capturing the dynamics of gray matter (GM) atrophy in relation to the conversion from mild cognitive impairment (MCI) to clinically probable Alzheimer's disease (AD) would be of considerable interest. In this prospective study we have used a novel longitudinal voxel-based method to map the progression of GM loss in MCI patients over time and compared converters to non-converters. Eighteen amnestic MCI patients were followed-up for a predefined fixed period of 18 months and conversion was judged according to NINCDS-ADRDA criteria for probable AD. Each patient underwent a high-resolution T1-weighted volume MRI scan both at entry in the study and 18 months later. We used an optimal VBM protocol to compare baseline imaging data of converters to those of non-converters. Moreover, to map GM loss from baseline to follow-up assessment, we used a modified voxel-based morphometry (VBM) procedure specially designed for longitudinal studies. At the end of the follow-up period, seven patients had converted to probable AD. Areas of lower baseline GM value in converters mainly included the hippocampus, parahippocampal cortex, and lingual and fusiform gyri. Regions of significant GM loss over the 18-month follow-up period common to both converters and non-converters included the temporal neocortex, parahippocampal cortex, orbitofrontal and inferior parietal areas, and the left thalamus. However, there was significantly greater GM loss in converters relative to non-converters in the hippocampal area, inferior and middle temporal gyrus, posterior cingulate, and precuneus. This accelerated atrophy may result from both neurofibrillary tangles accumulation and parallel pathological processes such as functional alteration in the posterior cingulate. The ability to longitudinally assess GM changes in MCI offers new perspectives to better understand the pathological processes underlying AD and to monitor the effects of treatment on brain structure.

Aged↗

PubMed2004

[Brain substrates of episodic memory disorders in Alzheimer's disease].

Resting state PET measurement is useful to unravel brain regions whose dysfunction is responsible for impairment of episodic memory in Alzheimer's disease. First, the consistent hypometabolism of posterior cingulate cortex, temporo-parietal cortex and frontal cortex contrasts with the frequent lack of hippocampal hypometabolism, although it is first to be concerned by neurofibrillary tangles. Several hypotheses are proposed to explain this paradoxical result. Second, the correlative approach (correlations between memory performances and metabolic values on a voxel basis) shows that dysfunction of the hippocampal region is responsible for the earliest deficits of episodic memory, and then suggests the recruitment of neocortical temporal areas normally involved in semantic memory, perhaps as a form of a compensatory mechanism. When applied to the study of Mild Cognitive Impairment, this approach is also very fruitful.

Alzheimer Disease↗

PubMed2004

[At the boundary between normal aging and Alzheimer disease].

Accurately predicting the development of probable Alzheimer's disease (AD) early in the course of the disease would have major implications. Hence, the pre-dementia stage of AD has become a major topic of current research. Amnestic 'mild cognitive impairment' (MCI) has recently emerged as the most convenient avenue to address this Issue, since most of MCI patients will progress to AD, at a rate of 10% to 15% per Year, suggesting that MCI represents the clinical manifestation of incipient AD (Petersen et al., 2001). However, all MCI patients would probably not convert to AD, at least in the near future, so that the Issue of prospective longitudinal studies is to detect specific indices of rapid conversion. In this paper, we focus on longitudinal studies using either neuropsychology, or morphological or functional neuroimaging to find predictive markers allowing to distinguish those MCI patients that rapidly convert to AD from those that do not develop the disease during the follow-up period. Whereas functional neuroimaging, and more specifically FDG-PET, seems particularly accurate to predict AD, the combination of multiple approaches is likely to be a promising avenue.

Aging↗

PubMed2003

Mild cognitive impairment: Can FDG-PET predict who is to rapidly convert to Alzheimer's disease?

Patients with mild cognitive impairment (MCI) were assessed, and a metabolic profile associated with conversion to AD at 18-month follow-up was sought. As compared with nonconverters (n = 10), converters (n = 7) had lower fluorodeoxyglucose uptake in the right temporoparietal cortex (p = 0.02, corrected for cluster size), without individual overlap. Awaiting replication in an independent sample, these findings suggest that among patients with MCI, fluorodeoxyglucose PET may accurately identify rapid converters.

Alzheimer Disease↗

PubMed2001

In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer's disease.

Up till now, the study of regional gray matter atrophy in Alzheimer's disease (AD) has been assessed with regions of interest, but this method is time-consuming, observer dependent, and poorly reproducible (especially in terms of cortical regions boundaries) and in addition is not suited to provide a comprehensive assessment of the brain. In this study, we have mapped gray matter density by means of voxel-based morphometry on T1-weighted MRI volume sets in 19 patients with mild AD and 16 healthy subjects of similar age and gender ratio and report highly significant clusters of gray matter loss with almost symmetrical distribution, affecting mainly and in decreasing order of significance the medial temporal structures, the posterior cingulate gyrus and adjacent precuneus, and the temporoparietal association and perisylvian neocortex, with only little atrophy in the frontal lobe. The findings are discussed in light of previous studies of gray matter atrophy in AD based either on postmortem or neuroimaging data and in relation to PET studies of resting glucose consumption. The limitations of the method are also discussed in some detail, especially with respect to the segmentation and spatial normalization procedures as they apply to pathological brains. Some potential applications of voxel-based morphometry in the study of AD are also mentioned.

Aged↗