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See detail[18F]UCB-H as a new PET radiotracer for Synaptic vesicle protein 2A: A first clinical trial.
Bahri, Mohamed Ali ULg; Stifkens, M; Bastin, Christine ULg et al

in Tijdschrift voor Nucleaire Geneeskunde (2015, May 09), 37(3), 1457-1458

The synaptic vesicle protein 2A (SV2A) is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is ... [more ▼]

The synaptic vesicle protein 2A (SV2A) is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown, e.g., by the fact that it is a binding site and the primary mechanism of the antiepileptic drug levetiracetam. This drug has recently been suggested to reduce synaptic deficits in a mouse model for Alzheimer’s disease. We here aimed to investigate the cerebral distribution of [18F]UCB-H, which has a high affinity with the SV2A. Dynamic PET data of the head of 4 healthy volunteers were acquired over 100 minutes after injection of 170.4 ± 24.9 MBq of GMP produced [18F]UCB-H. The arterial input function (IF) was obtained by blood sampling but also derived from the dynamic data using the correlation coefficient method. Blood data revealed a consistent amount of [18F]UCB-H in whole blood and plasma indicating a very low degree of binding of the tracer to the red blood cells. The unchanged fraction of [18F]UCB-H in plasma showed a bi-exponential behavioral decrease with a starting fraction of 92% of the injected amount of the tracer, measured at 3 min post injection. This fraction decreased to about 50% at 10 min post injection. The image-derived arterial IFs showed to be very similar to the measured ones with a peak-ratio around 0.91 and an area-under-curve ratio about 0.98. The PET images showed a high and rapid uptake of [18F]UCB-H in the grey matter structures, matching the known ubiquitous distribution of the SV2A in the brain. The kinetics of the tracer in the brain was characterized by an initial high uptake phase followed by rapid washout. For the three standard compartmental models (1-tissue, 2-tissue, and Logan Plot), similar results were obtained with both the measured and image-derived IFs. Nevertheless the two-tissue compartment model fitted the experimental data best and provided a total distribution volume of the [18F]UCB-H in the brain greater than 7 mL/cm3 and a specific distribution volume around 3 mL/cm3. Our results suggest that [18F]UCB-H is a good candidate as radiotracer for brain SV2A proteins and could be used for human studies (dosimetry has already been reported elsewhere). Image-derived IF showed to be useful for quantitative studies without the need to the arterial blood sampling. This new tracer could help to assess SV2A modifications in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailEpisodic memory in Alzheimer’s disease: Investigation of recollection and familiarity processes
Bastin, Christine ULg

Scientific conference (2015, March 12)

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See detail[18F]UCB-H as a new PET radiotracer for Synaptic vesicle protein 2A: A first clinical trial
Bahri, Mohamed Ali ULg; Stifkens, Mathieu; Bastin, Christine ULg et al

Poster (2015, January 27)

SV2A is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown, e.g., by the fact that it is ... [more ▼]

SV2A is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown, e.g., by the fact that it is a binding site and the primary mechanism of levetiracetam. Levetiracetam is an antiepileptic drug which has recently been suggested to reduce synaptic deficits in a mouse model for Alzheimer’s disease. We here aimed to investigate the cerebral distribution of [18F]UCB-H, which has a high affinity with the SV2A. Dynamic PET data of the head of 4 healthy volunteers were acquired over 100 minutes after injection of 170.4 ± 24.9 MBq of GMP produced [18F]UCB-H. The arterial input function (IF) was obtained by blood sampling. The IF was also derived from the dynamic data using the correlation coefficient method. Blood data revealed a consistent amount of [18F]UCB-H in whole blood and plasma indicating a very low degree of binding of the tracer to the red blood cells. The image-derived arterial IFs were showed to be very similar to the measured ones with a peak-ratio around 0.91 and an area-under-curve ratio about 0.98. The [18F]UCB-H PET data showed a high and rapid uptake in the grey matter structures, matching the known ubiquitous distribution of the SV2A in the brain. The kinetics of the tracer in the brain was characterized by an initial high uptake phase followed by rapid washout allowing the standard compartmental modeling (1-tissue, 2-tissue, and Logan Plot). The three models gave similar results with both the measured and image-derived IFs. The total distribution volume of the tracer in the brain was greater than 7 mL/cm3. Our results suggest that [18F]UCB-H is a good candidate as radiotracer for brain SV2A proteins and could be used for human studies. Image-derived IF showed to be useful for quantitative studies without the need to the arterial blood sampling. SV2A modifications may consequently be assessed in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailBridging familiarity-based recognition memory and novelty detection: A matter of timing
Delhaye, Emma ULg; Bastin, Christine ULg; Moulin, Christopher et al

Poster (2015)

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See detailL’impact du trouble cognitif léger et de la maladie d’Alzheimer sur la recollection et la familiarité
Simon, Jessica ULg; Bastin, Christine ULg

in Revue de Neuropsychologie (2015), 7(3), 177-188

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See detailBrain metabolic dysfunction in Capgras delusion during Alzheimer’s disease: a positron emission tomography study
Jedidi, Haroun ULg; Daury, Noémy; Rémi, Capa et al

in American Journal of Alzheimer's Disease & Other Dementias (2015), 30(7), 699-706

Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since ... [more ▼]

Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since little is known regarding the neural correlates of Capgras syndrome, the cerebral metabolic pattern of a patient with probable Alzheimer’s disease (AD) and Capgras syndrome was compared with those of 24 healthy elderly subjects and 26 AD patients without delusional syndrome. Compared to the healthy and AD groups, the patient had significant hypometabolism in frontal and posterior midline structures. In light of current neural models of face perception, our patient’s Capgras syndrome may be related to impaired recognition of a familiar face, subserved by the posterior cingulate/precuneus cortex, and impaired reflection about personally relevant knowledge related to a face, subserved by the dorsomedial prefrontal cortex. [less ▲]

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See detail3D shape perception in posterior cortical atrophy: a visual neuroscience perspective
Gillebert, Céline; Schaeverbeke, J.; Bastin, Christine ULg et al

in Journal of Neuroscience (2015), 35(37), 12673-12692

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See detailPrevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage
Vos; VERHEY, F.; Frölich, L. et al

in Brain : A Journal of Neurology (2015), 138

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See detailRecognition of Personally Familiar Faces and Functional Connectivity in Alzheimer’s Disease
Kurth, Sophie ULg; Moyse, Evelyne ULg; Bahri, Mohamed Ali ULg et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2015), 67

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See detailImpairment of age estimation from faces in Alzheimer’s disease
Moyse, Evelyne ULg; Bastin, Christine ULg; Salmon, Eric ULg et al

in Journal of Alzheimer's Disease [=JAD] (2015), 45

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See detailThe neural basis of temporal order processing in past and future thought
D'Argembeau, Arnaud ULg; Jeunehomme, Olivier ULg; Majerus, Steve ULg et al

in Journal of Cognitive Neuroscience (2015), 27

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See detailMémoire épisodique et vieillissement normal : L'effet de la manipulation de la facilité de traitement perceptif en reconnaissance
Bastin, Christine ULg; Willems, Sylvie ULg

Poster (2014, September 16)

Etant donné que le vieillissement normal s’accompagne d’un déclin de la recollection tandis que la familiarité reste préservée, les tâches mnésiques facilitant l’utilisation de la familiarité ... [more ▼]

Etant donné que le vieillissement normal s’accompagne d’un déclin de la recollection tandis que la familiarité reste préservée, les tâches mnésiques facilitant l’utilisation de la familiarité permettraient de réduire les différences liées à l’âge en mémoire épisodique. Cette étude a évalué deux questions : 1) L’utilisation de la familiarité en reconnaissance peut-elle être favorisée en augmentant la différence de facilité de traitement perceptif (fluence) entre les items étudiés et les nouveaux items ? ; 2) Cette manipulation permet-elle de réduire l’effet de l’âge ? Deux tâches de reconnaissance ont été proposées à 24 participants jeunes et 24 participants âgés. Dans une tâche « sans recouvrement », les mots cibles et les mots nouveaux ne possédaient aucune lettre commune. L’exposition préalable aux mots cibles induisait donc une fluence sur les mots, mais également sur les lettres de sorte que la différence de fluence devenait un indice saillant et fiable pour distinguer cibles et distracteurs. Dans une tâche « avec recouvrement », les mots cibles et les mots nouveaux contenaient des lettres communes. Les résultats ont répliqué l’effet de l’âge sur la recollection (réponses Remember), avec préservation de la familiarité (réponses Know). Par ailleurs, nous observons 1) une amélioration de la discrimination dans la tâche « sans recouvrement », avec un plus grand nombre de reconnaissances correctes et moins de fausses reconnaissances (les deux basés sur la familiarité). De plus, 2) les différences liées à l’âge dans la capacité à discriminer cibles et distracteurs (reconnaissances correctes - fausses reconnaissances) étaient significativement réduites dans la tâche sans recouvrement par rapport à la tâche avec recouvrement. Ces données suggèrent que minimiser la similarité perceptive entre les mots cibles et les mots distracteurs, et donc augmenter la fluence, permet de réduire les différences liées à l’âge en reconnaissance en facilitant l’utilisation de la familiarité. [less ▲]

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