[show abstract][hide abstract] ABSTRACT: Studies of autobiographical memory in semantic dementia (SD) have yielded either a reversed temporal gradient or spared performances across the entire lifetime. This discrepancy might be owing to the fact that these studies did not take into account disease severity. Our aim was to study patterns of autobiographical memory impairment according to disease severity and to unravel their mechanisms in 14 SD patients, using an autobiographical memory task assessing overall and strictly episodic memories across the entire lifetime. We divided our patients in 2 subgroups of 7 patients each, one mild and one moderate according to their level of disease severity. The results indicated for the mild subgroup selective preserved performances for the most recent time period (last 12 months period) for both autobiographical memory scores. In the moderate subgroup, performances were impaired for both scores whatever the time period. Within-group comparisons across time periods showed a recency effect and a reminiscence bump in the mild subgroup and only a less important recency effect in the moderate subgroup, suggesting that with disease severity, old memories (reminiscence bump) tend to vanish and even recent memories are less well retrieved. A correlation analysis was carried out on the entire group, between the overall autobiographical memory score and performances provided by a general cognitive evaluation (semantic memory, executive functions, working and episodic memory). The results of this analysis reflect that mechanisms of disruption of autobiographical memory in SD predominantly involve a deficit of storage of semantic information in addition to faulty executive retrieval strategies. Finally, our result and those of the literature suggest the existence of 3 distinct autobiographical memory impairment patterns in SD according to disease severity: firstly preserved performances whatever the time period, secondly a reversed temporal gradient with a reminiscence bump and thirdly the appearance of a "step-function".
[show abstract][hide abstract] ABSTRACT: This study aims to map in patients with mild Alzheimer's disease (AD) the correlations between resting-state brain glucose utilization measured by FDG-PET and scores reflecting autonoetic consciousness in an episodic learning and recognition task.
Autonoetic consciousness, that gives a subject the conscious feeling to mentally travelling back in time to relive an event, was assessed using the Remember/Know (R/K) paradigm.
AD patients provided less R responses (reflecting autonoetic consciousness) and more K ones (indicating the involvement of noetic consciousness) than healthy controls. Correct recognitions associated with a R response correlated with the metabolism of frontal areas bilaterally whereas those associated with a K response mainly correlated with the metabolism of left parahippocampal gyrus and lateral temporal cortex.
These data show that recollection is impaired in AD and recognition is more based on a feeling of familiarity than in controls. In addition, the findings of our correlative approach indicate that the impairment of episodic memory is mainly subserved by the dysfunction of frontal areas and of the hippocampal region.
Neurobiology of aging 10/2007; 28(9):1410-20. · 5.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Very few studies have investigated autobiographical memory in the frontal variant of frontotemporal dementia (fv-FTD). The aim of this study was therefore to unravel the mechanisms of autobiographical memory disruption in general and in the anterograde and retrograde components of amnesia in particular, in patients suffering from fv-FTD. An autobiographical memory task assessing overall (AM) and strictly episodic memories (EM) from five lifetime periods covering the entire lifespan revealed the absence of a temporal gradient for both scores, suggesting the existence of a retrieval deficit. An analysis of the correlation between these two scores and a general cognitive assessment of executive function, working, episodic (i.e. new learning ability) and semantic memory, and behavioural changes highlighted the considerable involvement of executive function, semantic memory and, to a lesser degree, episodic memory and behavioural changes. Moreover, step-wise regression analyses performed on the EM score revealed that the executive function was a better predictor of the retrograde component than of the anterograde component, which was linked principally to new episodic learning ability. All these results confirm the impact of executive dysfunction on autobiographical deficits in fv-FTD, and suggest that the mechanisms at the root of autobiographical memory disruption may also involve difficulties in new episodic learning and semantic storage, though this may be due to the fact that we studied an advanced form of fv-FTD.
[show abstract][hide abstract] ABSTRACT: Few studies have investigated autobiographical amnesia in neurodegenerative diseases and yet these pathologies are particularly relevant when addressing the issue of theories of long-term memory consolidation. According to the standard model, the medial temporal lobe (MTL) is involved in the storage and retrieval of episodic and semantic memories during a limited period of years. An alternative model, the multiple trace theory (MTT), suggests that the capacity of the MTL to recollect episodic memories is of a more permanent nature. In order to test these models, we studied three groups of patients with a neurodegenerative disease predominantly affecting different cerebral structures namely the MTL (13 patients in the early stages of Alzheimer's disease) and the neocortex involving either the anterior temporal lobe (10 patients with semantic dementia) or the frontal lobe (15 patients with the frontal variant of frontotemporal dementia, fv-FTD). We compared these groups of patients with control subjects using an original and reliable autobiographical memory task designed specially to assess strictly episodic memory over the entire lifespan. This task, developed on the basis of the most up-to-date definition of episodic memory, takes into account the ability to mentally travel back in time and re-experience the source of acquisition (remembering, i.e. autonoetic consciousness) via the remember/know paradigm. All three groups of patients produced strongly contrasting profiles of autobiographical amnesia (regardless of the nature of the memories), which also differed markedly from that of the control group: temporally graded memory loss in Alzheimer's disease, showing that remote memories are better preserved than recent ones; memory loss with a reversed gradient in semantic dementia; and memory loss without any clear gradient in fv-FTD. Most strictly episodic memories (i.e. unique, specific in time and space, and detailed) were impaired, whatever the time interval considered in the three groups, though the memory loss was ungraded in Alzheimer's disease and fv-FTD, and temporally graded in semantic dementia, sparing the most recent period. A deficit of autonoetic consciousness emerged in Alzheimer's disease and fv-FTD, but not in semantic dementia, though beyond the most recent 12-month period, the latter group could not justify their subjective sense of remembering to the same extent as the controls, in terms of the actual contextual information retrieved-phenomenological, spatial or temporal details. Our results demonstrate that autobiographical amnesia varies according to the nature of the memories under consideration and the locus of cerebral dysfunction. They are discussed in the light of the two competing models of long-term memory consolidation and recent conceptions of autobiographical recollection: new insights based on current concepts of episodic memories challenge the standard model and tend to support the MTT instead.
[show abstract][hide abstract] ABSTRACT: The present study aims to unravel, in the same study, both morphological and functional specific substrates of encoding versus retrieval deficits in patients with amnestic mild cognitive impairment (MCI). For this purpose, 21 highly screened MCI patients with isolated memory impairment, who attended a memory clinic and fulfilled operational criteria for MCI, underwent (i) two episodic memory subtests designed to assess preferentially either incidental encoding or retrieval capacity; (ii) a high-resolution T1-weighted volume MRI scan; and (iii) a resting state [18F]fluoro-2-deoxy-D-glucose PET study. Using statistical parametric mapping, positive correlations between memory scores on one hand, and grey matter density and normalized partial volume effect-corrected brain glucose utilization (ncCMRglc) on the other hand, were computed. Deficits in both encoding and retrieval were correlated with declines in hippocampal region grey matter density. The encoding subtest also correlated with hippocampal ncCMRglc, whereas the retrieval subtest correlated with the posterior cingulate area ncCMRglc only. The present findings highlight a distinction in the neural substrates of encoding and retrieval deficits in MCI. Furthermore, they unravel a partial dissociation between metabolic and structural correlates, suggesting distinct interpretations. Hippocampal atrophy was related to both encoding and retrieval deficits, possibly reflecting a direct effect on hippocampal functioning, as well as an indirect effect, through remote functional disruption, on posterior cingulate region synaptic function, respectively.
[show abstract][hide abstract] ABSTRACT: This study was designed to map in Alzheimer's disease patients the correlations between resting-state brain glucose utilization measured by PET and the number of intrusions obtained by means of a specially designed episodic memory test separately in free recall and in cued recall. SPM revealed significant negative correlations between the number of intrusions in free recall and the metabolism of the right superior frontal gyrus. For the intrusions in cued recall, the negative correlations concerned the left rhinal cortex. Our findings suggest that intrusions in free recall reflect perturbations in strategic processes and that intrusions in cued recall are triggered by the cue in a relatively automatic manner. Frontal dysfunction would be responsible for the former and rhinal dysfunction for the latter.
[show abstract][hide abstract] ABSTRACT: The nature of semantic memory deficit in Alzheimer's disease is still a matter of controversy. To clarify this issue, we examined the evolution of semantic memory impairment in 24 Alzheimer's disease patients by means of a longitudinal study. We used two semantic tasks, one explicit and the other implicit, to evaluate the integrity of the same concepts. The explicit task was a semantic knowledge task composed of naming and questions, involving superordinate and attribute knowledge of concepts. The implicit task, a lexical decision task, assessed semantic priming and allowed a very pure measurement of semantic memory. In this task, related pairs of words had coordinate (e.g. "tiger-lion") or attribute ("tiger-stripe") relationships. In the coordinate relation between two words, the semantic priming performances were at first paradoxical: they increased abnormally (hyperpriming) before falling down, whereas in the attribute condition, the priming effects were first normal and then started to decrease in the final sessions (hypopriming). Compared with the semantic knowledge performance, these apparently disconcerting results reflect a coherent pattern of semantic memory degradation in Alzheimer's disease that is a progressive deterioration starting with specific attribute information. The data reveal in an astonishing yet striking manner the dynamic semantic memory degradation in Alzheimer's disease through the apparently paradoxical semantic priming effects.
[show abstract][hide abstract] ABSTRACT: In a previous investigation, we raised the hypothesis that in Alzheimer's disease the cerebral structures implicated in episodic memory deficits may differ according to the severity of cognitive impairment. To test this hypothesis, Story Recall test scores and PET measurements of resting cerebral glucose utilization, a measure of synaptic integrity, were obtained in 40 patients. Using SPM96 (statistical parametric mapping 1996), positive correlations between the two sets of data were calculated on a voxel basis, first in the whole patient sample and then separately in the two subgroups of 20 patients differing in Mini-Mental State Examination score, i.e. those with least impaired and those with most impaired performance ('less severe' and 'more severe' subgroups, respectively). In the whole sample, significant correlations (P < 0.05, corrected for multiple tests) involved bilaterally not only several limbic structures (the hippocampal/rhinal cortex regions, posterior cingulate gyrus and retrosplenial cortex) but also, and less expectedly, some temporo-occipital association areas. However, the subgroup analysis disclosed that, in the less severe subgroup, all significant correlations (P < 0.005, uncorrected) were restricted to the parahippocampal gyrus and retrosplenial cortex, in accordance with both the distribution of changes in tau in early Alzheimer's disease and the known involvement of this network in normal and impaired memory function, while in the more severe subgroup they mainly involved the left temporal neocortex, which is known to be implicated in semantic memory. These findings suggest that, when episodic memory is mildly impaired, limbic functions are still sufficient to subserve the remaining performance, whereas with more severe memory deficit resulting from accumulated pathology the neocortical areas that are normally involved in semantic memory are recruited, perhaps as a form of (inadequate) compensatory mechanism.
[show abstract][hide abstract] 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.
[show abstract][hide abstract] 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.
[show abstract][hide abstract] 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.