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ABSTRACT: The aim of this study was to study cognitive procedural learning in early Alzheimer's disease (AD). Methods: Cognitive procedural learning was assessed using the Tower of Hanoi (TH) task. In order to take account of possible interactions between different systems during cognitive procedural learning, we also measured non-verbal intellectual functions, working memory, and declarative memory.
Our results showed an apparent preservation of cognitive procedural learning in AD and a deleterious effect of the disease on verbal intelligence and declarative memory. Correlational analyses revealed a difference between AD patients and control participants in the type of processing they applied to the task.
The non-involvement of declarative memory would appear to be partly responsible for a slowdown in the cognitive procedural dynamics of AD patients. As the AD patients were unable to use their declarative memory, they were still in a problem-solving mode at the end of the learning protocol and had to implement higher order cognitive processes (i.e., compensatory mechanisms) to perform the procedural task.
Journal of Neuropsychology 03/2012; 6(1):31-42. · 1.74 Impact Factor
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G Chételat,
M Fouquet,
G Kalpouzos,
I Denghien, V De la Sayette,
F Viader,
F Mézenge,
B Landeau,
J C Baron,
F Eustache,
B Desgranges
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ABSTRACT: The hippocampus is the brain structure of highest and earliest structural alteration in Alzheimer's disease (AD). New developments in neuroimaging methods recently made it possible to assess the respective involvement of the different hippocampal subfields by mapping atrophy on a 3D hippocampal surface view. In this longitudinal study on patients with mild cognitive impairment (MCI), we used such an approach to map the profile of hippocampal atrophy and its progression over an 18-month follow-up period in rapid converters to AD and "non-converters" compared to age-matched controls. For the sake of comparison, we also assessed the profile of hippocampal atrophy associated with AD and with increasing age in a healthy control population ranging from young adult to elderly. We found major involvement of the lateral part of the superior hippocampus mainly corresponding to the CA1 subfield in MCI and AD while increasing age was mainly associated with subiculum atrophy in the healthy population. Moreover, the CA1 subfield also showed highest atrophy rates during follow-up, in both rapid converters and "non-converters" although increased effects were observed in the former group. This study emphasizes the differences between normal aging and AD processes leading to hippocampal atrophy, pointing to a specific AD-related CA1 involvement while subiculum atrophy would represent a normal aging process. Our findings also suggest that the degree of hippocampal atrophy, more than its spatial localization, predicts rapid conversion to AD in patients with MCI.
Neuropsychologia 02/2008; 46(6):1721-31. · 3.64 Impact Factor
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ABSTRACT: Although the patterns of structural and metabolic brain alterations in Alzheimer's disease are being refined and discrepancies between them are being underlined, the exact relationships between atrophy and hypometabolism are still unclear. In this study, we aimed to provide a direct comparison between grey matter atrophy and hypometabolism in a sample of patients with clinically probable Alzheimer's disease, using a voxel-based method specially designed to statistically compare the two imaging modalities. Eighteen patients with probable Alzheimer's disease of mild severity and 15 healthy aged controls underwent both high-resolution T1 MRI and resting-state (18)FDG-PET. The MRI data sets were handled using optimized VBM. The PET data were coregistered to their corresponding MRI, corrected voxel-wise for partial volume averaging and spatially normalized using the same parameters as those of their corresponding MRI volume. A differential smoothing was applied on the MRI and PET data sets to equalize their effective smoothness and resolution. For each patient, Z-score maps of atrophy and hypometabolism were created by comparing to the controls data set, respectively averaged to provide the profile of hypometabolism and atrophy, and entered in a voxel-by-voxel SPM analysis to assess the statistical differences between hypometabolism and atrophy. The observed patterns of hypometabolism and atrophy were consistent with previous studies. However, the direct comparison revealed marked regional variability in the relationship between hypometabolism and atrophy. Thus, the hypometabolism significantly exceeded atrophy in most altered structures, particularly in the posterior cingulate-precuneus, orbitofrontal, inferior temporo-parietal, parahippocampal, angular and fusiform areas. In contrast, a few hypometabolic structures among which the hippocampus exhibited similar degrees of atrophy and hypometabolism, a profile that significantly differed from the posterior cingulate. Excessive hypometabolism relative to atrophy suggests the intervention of additional hypometabolism-inducing factors, such as disconnection and amyloid deposition, resulting in genuine functional perturbation ahead of actual atrophy and perhaps of pathology as well. Conversely, in the hippocampus, where disconnection processes are also likely to occur, relative synaptic compensatory mechanisms may be taking place, maintaining neuronal activity in the face of structural alterations.
Brain 02/2008; 131(Pt 1):60-71. · 9.46 Impact Factor
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ABSTRACT: Rasmussen's syndrome is a rare inflammatory brain disease characterized by severe intractable epilepsy, and unilateral progressive motor defect associated with controlateral hemispheric atrophy. The disorder usually affects children, although occasional reports of adult-onset Rasmussen's syndrome have been reported. We report her four patients in whom seizures began in adolescence or adulthood with clinical and radiological symptoms suggesting the diagnosis of Rasmussen's syndrome. We compared them with thirty-three cases described in the literature between 1987 and 2004. While adult-onset Rasmussen's syndrome may mimic the early-onset form, symptoms often progress more slowly and the neurological defect is more variable. Occipital lobe involvement appears to be more common than in the childhood form, and some atypical features may be noted such as bilateral hemispheric involvement or a picture of temporal lobe epilepsy or the présence of movement disorders at the beginning of the disease. Surgical hemispheric disconnection that appears the most effective treatment in children to improve seizure control is not indicated in adults for evident functional reasons. Based on recent pathogenic concepts, different medical treatments may be proposed. Large multicentric controlled studies are mandatory to define a clear medical therapeutic strategy in these cases of adult-onset.
Revue Neurologique 06/2007; 163(5):573-80. · 0.49 Impact Factor
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ABSTRACT: Several studies noted persistence of memory impairment following an episode of transient global amnesia (TGA) with standard tests.
To specify long-term memory impairments in a group of patients selected with stringent criteria.
Both retrograde and anterograde memory were investigated in 32 patients 13-67 months after a TGA episode with original tasks encompassing retrograde semantic memory (academic, public and personal knowledge), retrograde episodic memory (autobiographical events) and anterograde episodic memory.
Patients had preserved academic and public knowledge. Pathological scores were obtained in personal verbal fluency for the two most recent periods, and patients produced less autobiographical events than controls. However, when they were provided time to detail, memories were as episodic as in controls regardless of their remoteness. Anterograde episodic tasks revealed a mild but significant impairment of the capacity of re-living the condition of encoding, i.e. the moment at which words were presented.
Patients who have suffered from an episode of TGA manifest deficits of memory focused on the retrieval of both recent semantic information and episodic memories and especially the capacity of re-living. These deficits may not result from a deterioration of memory per se but rather from difficulties in accessing memories.
Acta Neurologica Scandinavica 12/2006; 114(5):329-33. · 2.47 Impact Factor
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ABSTRACT: 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.
NeuroImage 11/2005; 27(4):934-46. · 5.89 Impact Factor
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ABSTRACT: To investigate the dynamic time course of transient global amnesia (TGA)--that is, the process of recovery and the interindividual variability--by testing four patients during the day of TGA itself (on three occasions) and at follow up (on two occasions).
A specially designed protocol focusing on semantic (both conceptual and autobiographical knowledge) and episodic (both anterograde and retrograde components) memory.
Every patient showed marked impairment of both anterograde and retrograde episodic memory during the acute phase, with a relative preservation of personal and conceptual semantic knowledge. During the following phase, the authors observed similarities and differences among the patients' patterns of recovery. In general, retrograde amnesia recovered before the anterograde amnesia and anterograde episodic memory was recovered gradually in every case. In contrast, shrinkage of retrograde amnesia was more heterogeneous. In two of the patients, this shrinkage followed a chronological gradient and the most remote events were recovered first. In the two other patients, it depended more on the strength of the trace, and there was no temporal gradient. For the latter, an executive deficit could account for difficulties in accessing both conceptual knowledge and autobiographical memories.
This profile of recovery suggests a "neocortical to medial temporal" process in every case, and the possibility of an additional frontal dysfunction in some cases. Hence, the acute phase seems to be characterised by a common episodic impairment. This variability between subjects appears in the recovery phase with two different patterns of impairment.
Journal of Neurology Neurosurgery & Psychiatry 12/2004; 75(11):1532-40. · 4.76 Impact Factor
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ABSTRACT: 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.
Revue Neurologique 05/2004; 160(4 Pt 2):S55-63. · 0.49 Impact Factor
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ABSTRACT: 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.
Neurology 05/2003; 60(8):1374-7. · 8.31 Impact Factor
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ABSTRACT: Transient global amnesia (TGA) is characterized by a profound but transient deficit of episodic memory. The study of cerebral blood flow and oxygen metabolism with positron emission tomography (PET) provides relevant pathophysiologic data, but only three patients have been reported so far and in only one was concomitant neuropsychological testing performed. We report here the concomitant neuropsychological and PET assessment of two additional patients. Episodic disturbance was characterized by a storage disturbance for one case and an incapacity to learn episodic associations in the other, illustrating cognitive heterogeneity despite similar neurological presentation. PET findings disclosed mild but significant changes in the amygdala (right or left) and left posterior hippocampus, which could account for both the storage disturbance and the inability to associate episodic components. The PET findings also argued in favor of a vascular disturbance accompanying TGA.
Neuroscience Letters 06/2002; 325(1):62-6. · 2.11 Impact Factor
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ABSTRACT: Transient global amnesia (TGA), characterised by a profound anterograde amnesia, is a model of interest to study the acquisition of novel meanings independent of episodic functioning. Three patients were tested during a TGA attack, two in the early recovery phase and the third during the acute phase of TGA, with a semantic priming task involving a restructuring process of conceptual knowledge. During TGA, all patients demonstrated priming effects. Results obtained the day after the episode with the same task showed that these effects persisted at least one day. Episodic memory seems not to be critical for the formation of novel connections among unrelated semantic representations, in accordance with Tulving's model of memory, i.e. episodic memory is not necessary for the acquisition of semantic information.
Neuroreport 01/2002; 12(17):3865-9. · 1.66 Impact Factor
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ABSTRACT: This study examines disorders which affect the intentional gestural organization in Alzheimer's disease. An original and prospective protocol which assessed both the conceptual and production systems (with reference to the Roy and Square model 1985) was presented to 16 patients with Alzheimer's disease (mild to moderate dementia) and 40 healthy elderly subjects. Our study showed impairment of both systems in the Alzheimer's patients group. Two patients presented reverse performance profiles, which were characterized in one case by preservation of the conceptual system and impairment of the production system and in the other by the reverse dissociation. The findings demonstrated that disorders in the intentional gestural organization in Alzheimer's disease usually affect both the conceptual and production systems. The hypothesis concerning the existence of two functionally distinct systems underlying the organization of intentional body movement was corroborated (1) by a lack of significant correlation between the scores obtained in the assessment of the two systems and (2) by the demonstration of the double dissociation.
European Journal of Neurology 12/2001; 8(6):629-41. · 3.69 Impact Factor
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ABSTRACT: While semantic memory deficits are a common landmark of Alzheimer's disease, the nature of these impairments remains to be clarified. Implicit tasks which assess semantic priming effects are often used to understand semantic deficits in Alzheimer's disease, but they have led to unclear conclusions because of methodological problems such as intervention of attentional mechanisms. To explore the effects of semantic priming in Alzheimer's disease and their relationship with semantic memory deficits, we used two tasks, one implicit and the other explicit. The implicit task was a lexical decision task to assess semantic priming, and in which pairs of words had coordinate (tiger-lion) or attribute relationships (zebra-stripe). The explicit task was a semantic knowledge task composed of namings and questions involving superordinate categories and attribute knowledge of concepts. The two tasks systematically assessed the integrity of the same concepts. This protocol was given to 53 Alzheimer's disease patients with mild to moderate dementia and to 20 controls. The Alzheimer's disease group as a whole obtained significantly greater priming effects (hyperpriming) than controls in the coordinate condition, and equivalent priming in the attribute condition. In the coordinate condition, a subgroup of 26 patients, with attribute knowledge deficits, had larger priming effects than both a subgroup without semantic deficits and the control group. These results show that in Alzheimer's disease the semantic priming effects vary according to the degree of attribute loss, and the presence of hyperpriming would reflect semantic memory deficits. This study unravels the fine-grained structure of semantic memory disturbances in Alzheimer's disease with mild to moderate dementia, affecting initially the attributes of concepts within a hierarchical network in which superordinate concepts remain preserved.
Brain 09/2001; 124(Pt 8):1522-32. · 9.46 Impact Factor
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ABSTRACT: 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.
NeuroImage 09/2001; 14(2):298-309. · 5.89 Impact Factor
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ABSTRACT: In this study, we used voxel-based mapping methods to compare the resting cerebral metabolic rate of glucose (CMRglc) measured with PET in five patients with permanent amnesia (three with chronic Wernicke-Korsakoff and two with postanoxia syndrome) to that of nine healthy age-matched subjects. We assessed (i) a group pattern of relative hypometabolism; and (ii) the consistency of this group pattern, if any, in individual subjects, according to etiology. The results from the group analysis documented that permanent amnesia is associated with hypometabolism in the thalamus, posterior cingulate cortex, and mesial prefrontal cortex (near the anterior cingulate gyrus), bilaterally, as well as in the left supramarginal and middle temporal gyri. The individual analysis showed that this group pattern was found in essentially each patient, regardless of the cause of amnesia. Thus, permanent amnesia is subtended by dysfunction in structures belonging to Papez/limbic circuits as well as in left-hemisphere areas typically concerned with verbal functions, probably through a mechanism of thalamo-cortical disconnection and possibly involved in retrograde amnesia. The use of a voxel-based method allowed us to map a common network of synaptic dysfunction in a neuropsychological syndrome regardless of etiology. Our results indicate that this should be a powerful method in functional neuropsychology.
NeuroImage 07/2001; 13(6 Pt 1):1164-73. · 5.89 Impact Factor
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ABSTRACT: When combined with cognitive investigations, functional neuroimaging methods such as positron emission tomography allow to depict the neural substrates that underlie the neuropsychological alterations in Alzheimer's disease. Capitalising on the variance in both cognitive performances and resting cerebral metabolic rate of glucose (CMRGlc) in Alzheimer's disease, it is possible to correlate these two quantitative variables on a pixel-by-pixel basis and to generate maps showing the significant correlations in stereotaxic space. Some examples using this approach in the domain of memory disorders are presented in this brief review. We notably show that the localisation of the significant correlations differs from one memory system to another, as evaluated by clinical memory tasks. This approach also unravels the compensatory mechanisms that take place with evolution of the disease. Over and above its interest in clinical neuropsychology, this method constitutes a new source of inferences complementary to the classic activation paradigm in normal subjects, as the latter identifies the cerebral structures that are involved with, but not necessarily indispensable for, the normal execution of the task. This approach highlights the interest of combining functional neuroimaging and neuropsychology to better understand the neural substrates of cognitive deficits in both patients with memory disorders and elderly normal subjects.
Revue Neurologique 05/2001; 157(4):377-83. · 0.49 Impact Factor
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ABSTRACT: Voxel-based mapping of the correlations between cognitive scores and resting-state brain glucose utilization measured by PET has recently emerged as a novel way to reveal in living patients with Alzheimer's disease (AD) the neural systems whose disruption underlies particular neuropsychological, especially mnemonic, deficits. We have now applied this approach using a novel cognitive paradigm designed to selectively assess verbal episodic memory, and show that in early AD disruption of the left entorhinal cortex underlies this memory deficit, consistent with post mortem data showing that this brain area is affected earliest and most severely by tau pathology in AD.
Neuroreport 04/2001; 12(4):683-5. · 1.66 Impact Factor
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Neurocase 05/2000; 6(3):205-210. · 1.11 Impact Factor
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ABSTRACT: A case of alcoholic Korsakoff syndrome is reported in a 47 year-old-man. Neuropsychological examination revealed an important both anterograd and retrograd amnesia but procedural and short-term memory were not affected nor was intellectual capacity. Cerebral IRM was normal. Pet scan demonstrated a previously unsuspected fact: the diminution of glucose metabolism in the two hippocampus and in the mamillary bodies.
Bulletin de l'Académie nationale de médecine 02/2000; 184(7):1491-7. · 0.25 Impact Factor
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ABSTRACT: A 36-year-old woman experienced an excruciating right retro-orbital paroxysmal headache after a stroke of the anterior two-thirds of the right hemicord at the C1 level (anterior spinal artery territory) and the dorsal medulla (posterior spinal artery territory). A right vertebral artery dissection was demonstrated. This unusual infarct mimicked a cluster headache attack or paroxysmal hemicrania.
Neurology 09/1999; 53(3):632-4. · 8.31 Impact Factor
