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See detailDissociation between controlled and automatic processes in the behavioral variant of fronto-temporal dementia
Collette, Fabienne ULg; Van der Linden, Martial ULg; Salmon, Eric ULg

in Journal of Alzheimer's Disease [=JAD] (2011), 22(3), 897-907

A decline of cognitive functioning affecting several cognitive domains was frequently reported in patients with frontotemporal dementia. We were interested in determining if these deficits can be ... [more ▼]

A decline of cognitive functioning affecting several cognitive domains was frequently reported in patients with frontotemporal dementia. We were interested in determining if these deficits can be interpreted as reflecting an impairment of controlled cognitive processes by using an assessment tool specifically developed to explore the distinction between automatic and controlled processes, namely the process dissociation procedure (PDP) developed by Jacoby [1]. The PDP was applied to a word stem completion task to determine the contribution of automatic and controlled processes to episodic memory performance and was administered to a group of 12 patients with the behavioural variant of frontotemporal dementia (bv-FTD) and 20 control subjects (CS). Bv-FTD patients obtained a lower performance than CS for the estimates of controlled processes, but no group differences was observed for estimates of automatic processes. The between-groups comparison of the estimates of controlled and automatic processes showed a larger contribution of automatic processes to performance in bv-FTD, while a slightly more important contribution of controlled processes was observed in control subjects. These results are clearly indicative of an alteration of controlled memory processes in bv-FTD. [less ▲]

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See detailIs brain activity during a Stroop inhibitory task modulated by the kind of cognitive control required?
Collette, Fabienne ULg; D'Ostilio, Kevin ULg; D'Argembeau, Arnaud ULg et al

Conference (2011)

Performance on the Stroop task is associated to a large antero-posterior cerebral network involving notably the anterior cingulate and dorsolateral prefrontal cortex. In this study, we used a mixed-BOLD ... [more ▼]

Performance on the Stroop task is associated to a large antero-posterior cerebral network involving notably the anterior cingulate and dorsolateral prefrontal cortex. In this study, we used a mixed-BOLD-fMRI design (N=25) to determine the neural substrates of inhibitory functioning in a Stroop task according to contextual information. Consequently, two task-contexts were created: (1) congruent context with a majority of facilitator items, (2) non-congruent context with mainly interfering items. Based on the dual cognitive control model, we postulated that the non-congruent blocks will involve proactive control, which is anticipatory, sustained, and involved when a large number of interfering items are successively presented. On the contrary, congruent blocks were assumed to involve reactive control, which occurs when few interfering items are presented, and just after the presentation of these items only. On this basis, we hypothesized that the kind of cognitive control modulates cerebral activity associated to inhibitory functioning. For behavioral data, we obtained faster response times for interfering items in the non-congruent vs. congruent condition, indicating proactive control specific to the congruent condition only. Functional neuro-imaging data showed an increased transient activity for interfering vs neutral items in a fronto-parietal network more important in the congruent than in the neutral condition. A similar contrast in the non-congruent condition showed no significant brain activity at the statistical threshold used. These data indicate the existence of a modulation of the cerebral areas associated to inhibitory functioning according to the kind of cognitive control necessary to perform the task. [less ▲]

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See detailThe cerebral metabolic correlates of episodic autobiographical memory in amnestic Mild Cognitive Impairment
Bastin, Christine ULg; Feyers, Dorothée ULg; Jedidi, Haroun ULg et al

in Proceedings of the 5th International Conference on Memory (2011)

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See detailThe neural correlates of cognitive reserve in aging
Bastin, Christine ULg; Bahri, Mohamed Ali ULg; Collette, Fabienne ULg et al

Scientific conference (2011)

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See detailNeural correlates of controlled memory processes in questionable Alzheimer’s disease
Bastin, Christine ULg; Kerrouche, Nacer; LEKEU, Françoise ULg et al

in Ashford, J. Wesson; Rosen, Allyson; Adamson, Maheen (Eds.) et al Advances in Alzheimer's Disease. Volume 2: Handbook of imaging the Alzheimer brain (2011)

Alzheimer’s disease (AD) is characterized by a progressive loss of controlled cognitive processes (processes requiring mental effort and attentional resources), and functional neuroimaging at early stages ... [more ▼]

Alzheimer’s disease (AD) is characterized by a progressive loss of controlled cognitive processes (processes requiring mental effort and attentional resources), and functional neuroimaging at early stages of AD provides an opportunity to tease out the neural correlates of controlled processes. Controlled and automatic memory performance was assessed with the Process Dissociation Procedure in 50 patients diagnosed with questionable Alzheimer’s disease (QAD). The patients’ brain glucose metabolism was measured using FDG-PET. After a follow-up period of 36 months, 27 patients had converted to AD, while 23 remained stable. Both groups showed a similar decrease in controlled memory processes but preserved automatic processes at entry into the study, suggesting that impairment of controlled memory would not be specific for AD. Patients who subsequently converted to Alzheimer type dementia showed significantly decreased brain metabolism at baseline compared to stable QAD in associative cortices known to be involved in AD (the left precuneus, the right inferior parietal lobule and bilateral middle temporal cortex).Voxel-based cognitive and metabolic correlations showed that a decrease in controlled memory processes was preferentially correlated with lower activity in the dorsomedial prefrontal and posterior cingulate cortices in very early AD patients. The dorsomedial prefrontal cortex would play a role in controlled memory processes as they relate to reflective and monitoring processes, while the posterior cingulate cortex is involved in the controlled access to previously encoded episodes. In stable QAD patients, reduced controlled performance in verbal memory correlated with impaired activity in the left anterior hippocampal structure, which would alter the reactivation of associations created at encoding. [less ▲]

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See detailReport of the task force on designing clinical trials in early (predementia) AD
Aisen, P.; Andrieu, S.; Sampaio, C. et al

in Neurology (2011), 76

BACKGROUND: A large number of promising candidate disease-modifying treatments for Alzheimer disease (AD) continue to advance into phase II and phase III testing. However, most completed trials have ... [more ▼]

BACKGROUND: A large number of promising candidate disease-modifying treatments for Alzheimer disease (AD) continue to advance into phase II and phase III testing. However, most completed trials have failed to demonstrate efficacy, and there is growing concern that methodologic difficulties may contribute to these clinical trial failures. The optimal time to intervene with such treatments is probably in the years prior to the onset of dementia, before the neuropathology has progressed to the advanced stage corresponding to clinical dementia. METHOD: An international task force of individuals from academia, industry, nonprofit foundations, and regulatory agencies was convened to discuss optimal trial design in early (predementia) AD. RESULTS: General consensus was reached on key principles involving the scope of the AD diagnosis, the selection of subjects for trials, outcome measures, and analytical methods. CONCLUSION: A consensus has been achieved in support of the testing of candidate treatments in the early (predementia) AD population. [less ▲]

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See detailImpaired Acquisition Of A Mirror-Reading Skill In Alzheimer’s Disease
Merbah, Sarah ULg; Salmon, Eric ULg; Meulemans, Thierry ULg

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2011), 47

Several studies using the mirror-reading paradigm have shown that procedural learning and repetition priming may be preserved in the early stages of Alzheimer's disease (AD) (e.g., Deweer et al., 1994 ... [more ▼]

Several studies using the mirror-reading paradigm have shown that procedural learning and repetition priming may be preserved in the early stages of Alzheimer's disease (AD) (e.g., Deweer et al., 1994). According to the classical interpretation, improved reading time for repeated words is sustained by a repetition priming effect, while procedural learning is demonstrated when this improvement is also observed for new words. Following Masson (1986), the hypothesis tested in the present study was that improved reading of new words could also be due to a repetition priming effect rather than to the acquisition of a mirror-reading skill. Indeed, because the same letters are presented throughout the task, a repetition priming effect for the letters could suffice to explain the improvement in performance. To test this hypothesis, we administered to 30 healthy young and elderly subjects and to 30 AD patients a new mirror-reading task in two phases: an acquisition phase comprising pseudo-words constructed with one part of the alphabet, and a test phase in which both pseudo-words constructed with the same part of the alphabet and pseudo-words constructed with another part of the alphabet were presented. If the new pseudo-words composed with repeated letters were read faster, it would reflect a repetition priming effect; if pseudo-words composed of ‘new’ letters were read faster, it would reflect a procedural learning effect. The results show comparable repetition priming effects in AD patients and in healthy elderly subjects, whereas only healthy subjects showed a procedural learning effect. These results suggest, contrary to previous studies, that the learning of a new perceptual skill may not always be preserved in AD. [less ▲]

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See detailRecollection and familiarity processes in probable Alzheimer's disease: an fMRI study
Genon, Sarah ULg; Collette, Fabienne ULg; Salmon, Eric ULg et al

in Proceedings of the 5th International Conference on Memory (2011)

Cerebral activity associated with recollection and familiarity in 28 patients with Alzheimer’s disease (AD) and 17 healthy controls was directly measured in an event-related fMRI experiment during ... [more ▼]

Cerebral activity associated with recollection and familiarity in 28 patients with Alzheimer’s disease (AD) and 17 healthy controls was directly measured in an event-related fMRI experiment during performance of a recognition memory task with the process dissociation procedure. Brain regions associated to recollection were evidenced by contrasting activations for inclusion and exclusion conditions whereas brain regions related to familiarity were explored with the mean effect of the two conditions (at P < .05 corrected). Twelve patients had null recollection estimates (AD-), whereas 16 patients did experience some recollection although significantly less than controls (AD+). In AD+ and controls, recollection activated the posterior cingulate cortex (PCC). In contrast, familiarity estimates were equivalent in the 3 groups and were associated with brain activations around the intraparietal sulcus (IPS). Thus, in AD, impaired recollection is related to damage of the PCC whereas preserved familiarity is supported by the IPS. [less ▲]

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See detailBrain perfusion patterns in familial frontotemporal lobar degeneration.
Seelaar, H.; Papma, J. M.; Garraux, Gaëtan ULg et al

in Neurology (2011), 77(4), 384-92

OBJECTIVE: Frontotemporal lobar degeneration (FTLD) is a clinically, genetically, and pathologically heterogeneous disorder. The aim of this study was to compare clinical features and perfusion patterns ... [more ▼]

OBJECTIVE: Frontotemporal lobar degeneration (FTLD) is a clinically, genetically, and pathologically heterogeneous disorder. The aim of this study was to compare clinical features and perfusion patterns on SPECT of patients with familial FTLD-TAR DNA binding protein 43 kDa (TDP) and MAPT mutations. METHODS: Patients were included if they had MAPT or GRN mutations, positive family history with pathologically proven FTLD in the patient or first-degree relative, or were part of FTD-MND families. All patients and 10 age- and gender-matched controls underwent measurement of brain perfusion using (99m)Tc-HMPAO SPECT. We used SPM8 to perform image processing and voxel-based group analyses (p < 0.001). Gender and age were included as nuisance variables in the design matrices. RESULTS: Of the 29 patients with familial FTLD, 19 had familial FTLD-TDP (GRN mutations in 6), and 10 had MAPT mutations. At clinical presentation, familial FTLD-TDP patients were older at onset (p = 0.030) and had more memory deficits (p = 0.011), whereas patients with MAPT had more naming deficits (p < 0.001) and obsessive-compulsive behavior (p = 0.001). The between-groups SPECT analyses revealed significantly less perfusion in the right frontal lobe, precuneus, cuneus, and inferior parietal lobule in familial FTLD-TDP, whereas significantly less perfusion was found in the left temporal and inferior frontal gyri in MAPT. Post hoc analysis of familial FTLD-TDP with unknown genetic defect vs MAPT revealed less perfusion in the right frontal and parietal lobe. CONCLUSION: Familial FTLD-TDP shows relatively more posterior hypoperfusion, including the precuneus and inferior parietal lobule, possibly related to significant memory impairment. Patients with MAPT were characterized by impaired perfusion of the temporal regions and naming deficits. [less ▲]

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See detailNeural correlates of cognitive control at the item level in the Stroop task.
Grandjean, Julien ULg; D'Ostilio, Kevin ULg; Fias, Wim et al

Poster (2010, November 15)

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See detailDéficits d’inhibition dans le vieillissement normal et la maladie d’Alzheimer: pas d’atteinte spécifique aux niveaux de traitement perceptif ou moteur
Stawarczyk, David ULg; Grandjean, Julien ULg; Salmon, Eric ULg et al

Poster (2010, September 24)

Introduction. Une diminution des capacités d’inhibition est fréquemment observée dans le vieillissement normal et la maladie d’Alzheimer. Toutefois, peu d’études ont exploré la généralité de ces déficits ... [more ▼]

Introduction. Une diminution des capacités d’inhibition est fréquemment observée dans le vieillissement normal et la maladie d’Alzheimer. Toutefois, peu d’études ont exploré la généralité de ces déficits au sein d’un groupe unique de participants. Objectif. Déterminer si les déficits d’inhibition présents dans le vieillissement normal et la maladie d’Alzheimer sont en accord avec la distinction entre inhibition perceptive et inhibition motrice proposée par Dempster et Corkill (1999). Méthode. Nous avons administré une large batterie d’épreuves d’inhibition à un groupe de participants jeunes, de participants âgés sains et de patients souffrant de maladie d’Alzheimer. L’inhibition perceptive a été évaluée au moyen des épreuves de Stroop et de priming négatif, de la tâche des ailiers et d’une tâche de résolution de conflit perceptif ; l’inhibition motrice a quant à elle été évaluée au moyen de tâches de go/no-go, de stop-signal, d’antisaccade et de résolution de conflit moteur. Résultats. Les résultats obtenus indiquent la présence d’un pattern mixte de déficits, incluant à la fois des épreuves d’inhibition motrice et d’inhibition perceptive, aussi bien chez les sujets âgés sains que chez les patients souffrant de la maladie d’Alzheimer. Des différences qualitatives de performance ont également été observées entre les deux groupes de sujets âgés. Discussion. Nos résultats ne sont pas en la faveur d’une distinction entre inhibition motrice et perceptive. Les déficits d’inhibition observés dans le vieillissement normal peuvent être interprétés dans le sens d’une diminution générale des ressources de traitement tandis que les déficits des patients Alzheimer peuvent être attribués à une capacité réduite de résistance à l’interférence provenant d’informations non pertinentes dans l’environnement externe de la personne. La présence de différences qualitatives de performance entre les deux groupes de sujets âgés semble indiquer que la maladie d’Alzheimer ne consiste pas en une simple accentuation des difficultés déjà observées lors du vieillissement normal. [less ▲]

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See detailIs posterior cerebral hypometabolism always predicitve of dementia in Parkinson's disease?
Deville, Benjamin ULg; Lemaire, Christian ULg; Degueldre, Christian ULg et al

Poster (2010, June 08)

In Parkinson's disease, altered activity in posterior associative cortices has often been associated with dementia. It remains to be determined if this pattern is a reliable marker of a progression toward ... [more ▼]

In Parkinson's disease, altered activity in posterior associative cortices has often been associated with dementia. It remains to be determined if this pattern is a reliable marker of a progression toward dementia in patients without demonstratable dementia. In this retrospective analysis, we used positron emission tomography to study resting-state cerebral fluodeoxyglucose uptake in 8 healthy controls and 8 Parkinson's disease patients who did not have evidence of dementia at the time of assessment. For those patients, clinical follow up was available and we know that they did not meet dementia criteria on average 10,37 years after assessment. The results show that patients had reduced fluodeoxyglucose uptake mostly localised in the right hemisphere and including precuneus, superior temporal, middle temporal and inferior parietal cortices. It also includes right insula. These cerebral activity predominating in posterior cortices is present in non-demened patients but is not always predictive of dementia within the 10,34 years. [less ▲]

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See detailControlled Memory Processes in Questionable Alzheimer's Disease: A View from Neuroimaging Research
Bastin, Christine ULg; Kerrouche N; Lekeu, Françoise ULg et al

in Journal of Alzheimer's Disease [=JAD] (2010), 20(2), 547-560

Alzheimer's disease (AD) is characterized by a progressive loss of controlled cognitive processes, and neuroimaging studies at early stages of AD provide an opportunity to tease out the neural correlates ... [more ▼]

Alzheimer's disease (AD) is characterized by a progressive loss of controlled cognitive processes, and neuroimaging studies at early stages of AD provide an opportunity to tease out the neural correlates of controlled processes. Accordingly, controlled and automatic memory performance was assessed with the Process Dissociation Procedure in 50 patients diagnosed with questionable Alzheimer's disease (QAD). The patients' brain glucose metabolism was measured using FDG-PET. After a follow-up period of 36 months, 27 patients had converted to AD, while 23 remained stable. Both groups showed a similar decrease in controlled memory processes but preserved automatic processes at entry into the study. Voxel-based cognitive and metabolic correlations showed that a decrease in controlled memory processes was preferentially correlated with lower activity in the dorsomedial prefrontal and posterior cingulate cortices in very early AD patients. In stable QAD patients, reduced controlled performance in verbal memory correlated with impaired activity in the left anterior hippocampal structure. The results demonstrated the central role of a medial frontal-posterior cingulate network for controlled processing of episodic memory in the early stages of AD. [less ▲]

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See detailIs Anosognosia in Alzheimer disease also observed for behavioural and personality changes?
Feyers, Dorothée ULg; Bastin, Christine ULg; Jaspar, Mathieu ULg et al

Poster (2010, May 28)

Anosognosia is a frequent manifestation in Alzheimer disease (AD) but its extent is not yet clearly established. While anosognosia for memory deficit has been widely reported, no study has simultaneously ... [more ▼]

Anosognosia is a frequent manifestation in Alzheimer disease (AD) but its extent is not yet clearly established. While anosognosia for memory deficit has been widely reported, no study has simultaneously explored anosognosia for personality and behaviour changes. We have tackled this question with 20 AD patients and 20 matched elderly subjects (ES). Participants (AD and ES) assessed their personality and their reactions in social situation both in current (S1) and past (S1_bef) time period. Assessment of these characteristics was also performed by relatives of the participants (R2 and R2_bef). Mann-Whitney test (p<0.05) were performed between discrepancy scores (calculated by comparing answers of subjects and relatives) obtained for AD and ES. A specific measure of anosognosia was also calculated by comparing S1 and R2. Statistical analyses demonstrated (1) that relatives of AD patients report more personality and behavioural changes across time (S1-S1_bef) than relatives of ES (R2–R2_bef); (2) that self-reported changes were not significantly different between AD patients and ES; (3) that anosognosia (S1-R2) was observed in AD patients for personality changes only. Results obtained support the hypothesis that anosognosia does not affect all domain in AD. Indeed, even if AD patients are no more able to assess their current personality, they perceive adequately their current reactions in social situations. [less ▲]

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