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32 results on '"Locatelli, Maxime"'

1. Cerebral Metabolic Signature of Chronic Benzodiazepine Use in Nondemented Older Adults: An FDG-PET Study in the MEMENTO Cohort

Author

Gallet, Quentin, Bouteloup, Vincent, Locatelli, Maxime, Habert, Marie-Odile, Chupin, Marie, Campion, Jacques-Yves, Michels, Pierre-Emmanuel, Delrieu, Julien, Lebouvier, Thibaud, Balageas, Anna-Chloé, Surget, Alexandre, Belzung, Catherine, Arlicot, Nicolas, Ribeiro, Maria-Joao Santiago, Gissot, Valérie, El-Hage, Wissam, Camus, Vincent, Gohier, Bénédicte, and Desmidt, Thomas

Published
2024
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2. Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study.

Author

Sakr, Fatemah, Grothe, Michel, Cavedo, Enrica, Jelistratova, Irina, Habert, Marie-Odile, Dyrba, Martin, Gonzalez-Escamilla, Gabriel, Bertin, Hugo, Locatelli, Maxime, Lehericy, Stephane, Teipel, Stefan, Dubois, Bruno, and Hampel, Harald

Subjects
Amyloid PET, In vivo staging, Subjective memory complaint, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Cognition, Cognitive Dysfunction, Cohort Studies, Diagnostic Self Evaluation, Female, Follow-Up Studies, Humans, Male, Memory, Mental Status and Dementia Tests
Abstract

BACKGROUND: Current methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimers disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic estimates and can be used to stage an individuals amyloid burden in vivo. Here, we evaluated the validity of this in vivo amyloid staging model in an independent cohort of older people with subjective memory complaints (SMC). We further examined its potential association with subtle cognitive impairments in this population at elevated risk for Alzheimers disease (AD). METHODS: The monocentric INSIGHT-preAD cohort includes 318 cognitively intact older individuals with SMC. All individuals underwent 18F-florbetapir PET scanning and extensive neuropsychological testing. We projected the regional amyloid uptake signal into the previously proposed hierarchical staging model of in vivo amyloid progression. We determined the adherence to this model across all cases and tested the association between increasing in vivo amyloid stage and cognitive performance using ANCOVA models. RESULTS: In total, 156 participants (49%) showed evidence of regional amyloid deposition, and all but 2 of these (99%) adhered to the hierarchical regional pattern implied by the in vivo amyloid progression model. According to a conventional binary classification based on global signal (SUVRCereb = 1.10), individuals in stages III and IV were classified as amyloid-positive (except one in stage III), but 99% of individuals in stage I and even 28% of individuals in stage II were classified as amyloid-negative. Neither in vivo amyloid stage nor conventional binary amyloid status was significantly associated with cognitive performance in this preclinical cohort. CONCLUSIONS: The proposed hierarchical staging scheme of PET-evidenced amyloid deposition generalizes well to data from an independent cohort of older people at elevated risk for AD. Future studies will determine the prognostic value of the staging approach for predicting longitudinal cognitive decline in older individuals at increased risk for AD.

Published
2019

3. Benzodiazepine use and neuroimaging markers of Alzheimer’s disease in nondemented older individuals: an MRI and 18F Florbetapir PET study in the MEMENTO cohort

Author

Gallet, Quentin, Bouteloup, Vincent, Locatelli, Maxime, Habert, Marie-Odile, Chupin, Marie, Delrieu, Julien, Lebouvier, Thibaud, Robert, Gabriel, David, Renaud, Bulteau, Samuel, Balageas, Anna-Chloé, Surget, Alexandre, Belzung, Catherine, Arlicot, Nicolas, Ribeiro, Maria-Joao, Barantin, Laurent, Andersson, Frédéric, Cottier, Jean-Philippe, Gissot, Valérie, El-Hage, Wissam, Camus, Vincent, Gohier, Bénédicte, and Desmidt, Thomas

Published
2022
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4. Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Author

Grasset, Leslie, Proust-Lima, Cécile, Mangin, Jean-François, Habert, Marie-Odile, Dubois, Bruno, Paquet, Claire, Hanon, Olivier, Gabelle, Audrey, Ceccaldi, Mathieu, Annweiler, Cédric, David, Renaud, Jonveaux, Therese, Belin, Catherine, Julian, Adrien, Rouch-Leroyer, Isabelle, Pariente, Jérémie, Locatelli, Maxime, Chupin, Marie, Chêne, Geneviève, and Dufouil, Carole

Published
2022
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6. Cerebral Metabolic Signature of Chronic Benzodiazepine Use in Nondemented Older Adults: An FDG-PET Study in the MEMENTO Cohort

Author

Gallet, Quentin, primary, Bouteloup, Vincent, additional, Locatelli, Maxime, additional, Habert, Marie-Odile, additional, Chupin, Marie, additional, Campion, Jacques-Yves, additional, Michels, Pierre-Emmanuel, additional, Delrieu, Julien, additional, Lebouvier, Thibaud, additional, Balageas, Anna-Chloé, additional, Surget, Alexandre, additional, Belzung, Catherine, additional, Arlicot, Nicolas, additional, Ribeiro, Maria-Joao Santiago, additional, Gissot, Valérie, additional, El-Hage, Wissam, additional, Camus, Vincent, additional, Gohier, Bénédicte, additional, and Desmidt, Thomas, additional

Published
2023
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7. Brain Metabolic Changes in the Presymptomatic Stage of Frontotemporal Dementia Associated with GRN Mutations (S2.006)

Author

Saracino, Dario, primary, Sellami, Leila, additional, Boniface, Hugo, additional, Locatelli, Maxime, additional, Pelegrini-Issac, Mélanie, additional, Funkiewiez, Aurélie, additional, Houot, Marion, additional, Rinaldi, Daisy, additional, Dorgham, Karim, additional, Pasquier, Florence, additional, Chastan, Mathieu, additional, Hitzel, Anne, additional, Pariente, Jérémie, additional, Pallardy, Amandine, additional, Guedj, Eric, additional, Didic, Mira, additional, Kas, Aurelie, additional, Habert, Marie-Odile, additional, and Le Ber, Isabelle, additional

Published
2022
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8. Additional file 1 of Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Author

Grasset, Leslie, Proust-Lima, Cécile, Mangin, Jean-François, Habert, Marie-Odile, Dubois, Bruno, Paquet, Claire, Hanon, Olivier, Gabelle, Audrey, Ceccaldi, Mathieu, Annweiler, Cédric, David, Renaud, Jonveaux, Therese, Belin, Catherine, Julian, Adrien, Rouch-Leroyer, Isabelle, Pariente, Jérémie, Locatelli, Maxime, Chupin, Marie, Chêne, Geneviève, and Dufouil, Carole

Abstract

Additional file 1: PET measurement additional information

Published
2022
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9. Additional file 8 of Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Author

Grasset, Leslie, Proust-Lima, Cécile, Mangin, Jean-François, Habert, Marie-Odile, Dubois, Bruno, Paquet, Claire, Hanon, Olivier, Gabelle, Audrey, Ceccaldi, Mathieu, Annweiler, Cédric, David, Renaud, Jonveaux, Therese, Belin, Catherine, Julian, Adrien, Rouch-Leroyer, Isabelle, Pariente, Jérémie, Locatelli, Maxime, Chupin, Marie, Chêne, Geneviève, and Dufouil, Carole

Abstract

Additional file 8: Fig. S2. Residual correlations of the structural equation model.

Published
2022
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10. Additional file 4 of Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Author

Grasset, Leslie, Proust-Lima, Cécile, Mangin, Jean-François, Habert, Marie-Odile, Dubois, Bruno, Paquet, Claire, Hanon, Olivier, Gabelle, Audrey, Ceccaldi, Mathieu, Annweiler, Cédric, David, Renaud, Jonveaux, Therese, Belin, Catherine, Julian, Adrien, Rouch-Leroyer, Isabelle, Pariente, Jérémie, Locatelli, Maxime, Chupin, Marie, Chêne, Geneviève, and Dufouil, Carole

Abstract

Additional file 4: Table S2. Estimates of the latent variables’ measurement equations from the structural equation model.

Published
2022
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11. Additional file 3 of Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Author

Grasset, Leslie, Proust-Lima, Cécile, Mangin, Jean-François, Habert, Marie-Odile, Dubois, Bruno, Paquet, Claire, Hanon, Olivier, Gabelle, Audrey, Ceccaldi, Mathieu, Annweiler, Cédric, David, Renaud, Jonveaux, Therese, Belin, Catherine, Julian, Adrien, Rouch-Leroyer, Isabelle, Pariente, Jérémie, Locatelli, Maxime, Chupin, Marie, Chêne, Geneviève, and Dufouil, Carole

Abstract

Additional file 3: Table S1. Description of ADRD biomarkers measures by age group, the Memento study

Published
2022
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12. Additional file 7 of Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Author

Grasset, Leslie, Proust-Lima, Cécile, Mangin, Jean-François, Habert, Marie-Odile, Dubois, Bruno, Paquet, Claire, Hanon, Olivier, Gabelle, Audrey, Ceccaldi, Mathieu, Annweiler, Cédric, David, Renaud, Jonveaux, Therese, Belin, Catherine, Julian, Adrien, Rouch-Leroyer, Isabelle, Pariente, Jérémie, Locatelli, Maxime, Chupin, Marie, Chêne, Geneviève, and Dufouil, Carole

Abstract

Additional file 7: Fig. S1. Detailed latent variables composition.

Published
2022
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13. Additional file 2 of Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Author

Grasset, Leslie, Proust-Lima, Cécile, Mangin, Jean-François, Habert, Marie-Odile, Dubois, Bruno, Paquet, Claire, Hanon, Olivier, Gabelle, Audrey, Ceccaldi, Mathieu, Annweiler, Cédric, David, Renaud, Jonveaux, Therese, Belin, Catherine, Julian, Adrien, Rouch-Leroyer, Isabelle, Pariente, Jérémie, Locatelli, Maxime, Chupin, Marie, Chêne, Geneviève, and Dufouil, Carole

Abstract

Additional file 2: Early to midlife ‘social factors’ and latelife ‘lifestyle factors’ latent measures additional information

Published
2022
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14. Additional file 5 of Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Author

Grasset, Leslie, Proust-Lima, Cécile, Mangin, Jean-François, Habert, Marie-Odile, Dubois, Bruno, Paquet, Claire, Hanon, Olivier, Gabelle, Audrey, Ceccaldi, Mathieu, Annweiler, Cédric, David, Renaud, Jonveaux, Therese, Belin, Catherine, Julian, Adrien, Rouch-Leroyer, Isabelle, Pariente, Jérémie, Locatelli, Maxime, Chupin, Marie, Chêne, Geneviève, and Dufouil, Carole

Abstract

Additional file 5: Table S3. Estimates of the direct and indirect effects of social and lifestyle indicators on ADRD biomarkers and cognitive performance using structural equation models, excluding social network from the lifestyle indicator.

Published
2022
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15. Additional file 6 of Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Author

Grasset, Leslie, Proust-Lima, Cécile, Mangin, Jean-François, Habert, Marie-Odile, Dubois, Bruno, Paquet, Claire, Hanon, Olivier, Gabelle, Audrey, Ceccaldi, Mathieu, Annweiler, Cédric, David, Renaud, Jonveaux, Therese, Belin, Catherine, Julian, Adrien, Rouch-Leroyer, Isabelle, Pariente, Jérémie, Locatelli, Maxime, Chupin, Marie, Chêne, Geneviève, and Dufouil, Carole

Abstract

Additional file 6: Table S4. Estimates of the direct and indirect effects of social and lifestyle indicators on ADRD biomarkers and cognitive performance using structural equation models, excluding physical leisure activities items.

Published
2022
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16. Brain Metabolic Profile in Presymptomatic GRN Carriers Throughout a 5-Year Follow-up.

Author

Saracino, Dario, Sellami, Leila, Boniface, Hugo, Houot, Marion, Pélégrini-Issac, Mélanie, Funkiewiez, Aurélie, Rinaldi, Daisy, Locatelli, Maxime, Azuar, Carole, Causse-Lemercier, Valérie, Jaillard, Alice, Pasquier, Florence, Chastan, Mathieu, Wallon, David, Hitzel, Anne, Pariente, Jérémie, Pallardy, Amandine, Boutoleau-Bretonnière, Claire, Guedj, Eric, and Didic, Mira

Published
2023
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17. Brain Metabolic Profile in Presymptomatic GRNCarriers Throughout a 5-Year Follow-up

Author

Saracino, Dario, Sellami, Leila, Boniface, Hugo, Houot, Marion, Pélégrini-Issac, Mélanie, Funkiewiez, Aurélie, Rinaldi, Daisy, Locatelli, Maxime, Azuar, Carole, Causse-Lemercier, Valérie, Jaillard, Alice, Pasquier, Florence, Chastan, Mathieu, Wallon, David, Hitzel, Anne, Pariente, Jérémie, Pallardy, Amandine, Boutoleau-Bretonnière, Claire, Guedj, Eric, Didic, Mira, Migliaccio, Raffaella, Kas, Aurélie, Habert, Marie-Odile, and Le Ber, Isabelle

Published
2023
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18. Additional file 1: of Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study

Author

Fatemah Sakr, Grothe, Michel, Cavedo, Enrica, Jelistratova, Irina, Marie-Odile Habert, Dyrba, Martin, Gonzalez-Escamilla, Gabriel, Bertin, Hugo, Locatelli, Maxime, Stephane Lehericy, Teipel, Stefan, Dubois, Bruno, and Hampel, Harald

Subjects
Space Science, FOS: Biological sciences, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Hardware_REGISTER-TRANSFER-LEVELIMPLEMENTATION, Molecular Biology, 69999 Biological Sciences not elsewhere classified, Developmental Biology
Abstract

Figure S1. Schematic diagram summarizing the pre-processing pipeline. (PDF 276 kb)

Published
2019

19. Additional file 2: of Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study

Author

Fatemah Sakr, Grothe, Michel, Cavedo, Enrica, Jelistratova, Irina, Marie-Odile Habert, Dyrba, Martin, Gonzalez-Escamilla, Gabriel, Bertin, Hugo, Locatelli, Maxime, Stephane Lehericy, Teipel, Stefan, Dubois, Bruno, and Hampel, Harald

Subjects
111714 Mental Health, Cell Biology, FOS: Health sciences, Molecular Biology, Neuroscience, Developmental Biology, Cancer
Abstract

Figure S2. Regional amyloid positivity cutoff value estimation. The figure shows the linear regression plot of the Global 18F-florbetapir PET SUVRcereb of both non-corrected (X-axis) and PVE-corrected PET (Y-axis) along with the generated equation that was used to transform the regional cutoff value of SUVRcereb = 1.135 to a value of SUVRcereb = 0.98 in the PVE-corrected PET data. (PDF 190 kb)

Published
2019
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20. Additional file 3: of Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study

Author

Fatemah Sakr, Grothe, Michel, Cavedo, Enrica, Jelistratova, Irina, Marie-Odile Habert, Dyrba, Martin, Gonzalez-Escamilla, Gabriel, Bertin, Hugo, Locatelli, Maxime, Stephane Lehericy, Teipel, Stefan, Dubois, Bruno, and Hampel, Harald

Subjects
FOS: Computer and information sciences, FOS: Biological sciences, 111714 Mental Health, Computational Biology, FOS: Health sciences, 80699 Information Systems not elsewhere classified, 69999 Biological Sciences not elsewhere classified, Neuroscience, Developmental Biology
Abstract

Figure S3. Model of the hierarchical in vivo amyloid staging scheme. This figure shows the 52 brain regions merged into four larger anatomical divisions based on equal partitions of frequency range as initially defined in the original model. Then the resulting amyloid progression stage (I-IV) is defined by the involvement of the corresponding anatomical division displayed in red in addition to the affected areas of the previous stage (displayed in blue). The amyloid progression stages are displayed on left, midline sagittal and basal brain views. (PDF 312 kb)

Published
2019

21. Additional file 6: of Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study

Author

Fatemah Sakr, Grothe, Michel, Cavedo, Enrica, Jelistratova, Irina, Marie-Odile Habert, Dyrba, Martin, Gonzalez-Escamilla, Gabriel, Bertin, Hugo, Locatelli, Maxime, Stephane Lehericy, Teipel, Stefan, Dubois, Bruno, and Hampel, Harald

Subjects
FOS: Computer and information sciences, FOS: Biological sciences, Medicine, 111714 Mental Health, FOS: Health sciences, 80699 Information Systems not elsewhere classified, 69999 Biological Sciences not elsewhere classified, Neuroscience
Abstract

Figure S4. Amyloid progression model in the INSIGHT-preAD data. This figure shows the amyloid progression model in the INSIGHT-preAD data as implied by the frequency of involvement of the 52 studied brain regions. The frequencies were displayed on left, midline sagittal and basal brain views. (PDF 252 kb)

Published
2019
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22. Additional file 5: of Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study

Author

Fatemah Sakr, Grothe, Michel, Cavedo, Enrica, Jelistratova, Irina, Marie-Odile Habert, Dyrba, Martin, Gonzalez-Escamilla, Gabriel, Bertin, Hugo, Locatelli, Maxime, Stephane Lehericy, Teipel, Stefan, Dubois, Bruno, and Hampel, Harald

Subjects
Physiology, FOS: Clinical medicine, Immunology, 111714 Mental Health, Cell Biology, FOS: Health sciences, Biochemistry, 39999 Chemical Sciences not elsewhere classified, FOS: Chemical sciences, FOS: Biological sciences, mental disorders, FOS: Mathematics, Medicine, 19999 Mathematical Sciences not elsewhere classified, Neuroscience
Abstract

Table S2. Associations between in vivo amyloid stage and cognitive performance. Analysis of Covariance (ANCOVA) assessing the effect of amyloid stage and conventional binary amyloid status on scores of the main principal components as well as the most representative tests for each of these components. (PDF 240 kb)

Published
2019
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23. Additional file 4: of Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study

Author

Fatemah Sakr, Grothe, Michel, Cavedo, Enrica, Jelistratova, Irina, Marie-Odile Habert, Dyrba, Martin, Gonzalez-Escamilla, Gabriel, Bertin, Hugo, Locatelli, Maxime, Stephane Lehericy, Teipel, Stefan, Dubois, Bruno, and Hampel, Harald

Subjects
Pharmacology, Physiology, FOS: Clinical medicine, Immunology, 111714 Mental Health, Computational Biology, Cell Biology, FOS: Health sciences, 39999 Chemical Sciences not elsewhere classified, FOS: Chemical sciences, FOS: Biological sciences, FOS: Mathematics, Medicine, 19999 Mathematical Sciences not elsewhere classified, Neuroscience, Biotechnology
Abstract

Table S1. Principal component analysis applied on the neurocognitive test scores. The table shows the three main components that could be identified based on the principal component analysis and subsequently the contributing tests in each component. (PDF 97 kb)

Published
2019

24. Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study.

Author

Sakr, Fatemah A, Sakr, Fatemah A, Grothe, Michel J, Cavedo, Enrica, Jelistratova, Irina, Habert, Marie-Odile, Dyrba, Martin, Gonzalez-Escamilla, Gabriel, Bertin, Hugo, Locatelli, Maxime, Lehericy, Stephane, Teipel, Stefan, Dubois, Bruno, Hampel, Harald, INSIGHT-preAD study group, Alzheimer Precision Medicine Initiative (APMI), Sakr, Fatemah A, Sakr, Fatemah A, Grothe, Michel J, Cavedo, Enrica, Jelistratova, Irina, Habert, Marie-Odile, Dyrba, Martin, Gonzalez-Escamilla, Gabriel, Bertin, Hugo, Locatelli, Maxime, Lehericy, Stephane, Teipel, Stefan, Dubois, Bruno, Hampel, Harald, INSIGHT-preAD study group, and Alzheimer Precision Medicine Initiative (APMI)

Abstract

BACKGROUND:Current methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimer's disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic estimates and can be used to stage an individual's amyloid burden in vivo. Here, we evaluated the validity of this in vivo amyloid staging model in an independent cohort of older people with subjective memory complaints (SMC). We further examined its potential association with subtle cognitive impairments in this population at elevated risk for Alzheimer's disease (AD). METHODS:The monocentric INSIGHT-preAD cohort includes 318 cognitively intact older individuals with SMC. All individuals underwent 18F-florbetapir PET scanning and extensive neuropsychological testing. We projected the regional amyloid uptake signal into the previously proposed hierarchical staging model of in vivo amyloid progression. We determined the adherence to this model across all cases and tested the association between increasing in vivo amyloid stage and cognitive performance using ANCOVA models. RESULTS:In total, 156 participants (49%) showed evidence of regional amyloid deposition, and all but 2 of these (99%) adhered to the hierarchical regional pattern implied by the in vivo amyloid progression model. According to a conventional binary classification based on global signal (SUVRCereb = 1.10), individuals in stages III and IV were classified as amyloid-positive (except one in stage III), but 99% of individuals in stage I and even 28% of individuals in stage II were classified as amyloid-negative. Neither in vivo amyloid stage nor conventional binary amyloid status was significantly associated with cognitive performance in this preclinical cohort. CONCLUSIONS:The proposed hierarchical staging scheme of PET-evidenced

Published
2019

25. O4-07-05: NIA-AA RESEARCH FRAMEWORK: APPLICATION TO THE FRENCH POPULATION BY INFERENCE FROM THE MEMENTO COHORT

Author

Bouteloup, Vincent, primary, Dufouil, Carole, additional, Mangin, Jean-Francois, additional, Locatelli, Maxime, additional, Pasquier, Florence, additional, Ousset, Pierre Jean, additional, Dubois, Bruno, additional, Blanc, Frederic, additional, Hanon, Olivier, additional, Paquet, Claire, additional, Tison, François, additional, Gabelle, Audrey, additional, Ceccaldi, Mathieu, additional, Annweiler, Cedric, additional, Salmon, Pierre Krolak, additional, Béjot, Yannick, additional, Belin, Catherine, additional, Wallon, David, additional, Paccalin, Marc, additional, Beaufils, Emilie, additional, Boutoleau-Bretonnière, Claire, additional, Gentric, Armelle, additional, Habert, Marie-Odile, additional, Chupin, Marie, additional, and Chêne, Geneviève, additional

Published
2019
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27. Benzodiazepine use and neuroimaging markers of Alzheimer’s disease in nondemented older individuals: an MRI and 18F Florbetapir PET study in the MEMENTO cohort

Author

Gallet, Quentin, Bouteloup, Vincent, Locatelli, Maxime, Habert, Marie-Odile, Chupin, Marie, Delrieu, Julien, Lebouvier, Thibaud, Robert, Gabriel, David, Renaud, Bulteau, Samuel, Balageas, Anna-Chloé, Surget, Alexandre, Belzung, Catherine, Arlicot, Nicolas, Ribeiro, Maria-Joao, Barantin, Laurent, Andersson, Frédéric, Cottier, Jean-Philippe, Gissot, Valérie, El-Hage, Wissam, Camus, Vincent, Gohier, Bénédicte, and Desmidt, Thomas

Abstract

Recent evidence suggests an association between benzodiazepines (BZDs) use and lower brain amyloid load, a hallmark of AD pathophysiology. Other AD-related markers include hippocampal atrophy, but the effect of BZDs on hippocampal volume remains unclear. We aimed at 1) replicating findings on BZDs use and brain amyloid load and 2) investigating associations between BZDs use and hippocampal volume, in the MEMENTO clinical cohort of nondemented older adults with isolated memory complaint or light cognitive impairment at baseline. Total Standardized Uptake Value Ratio (SUVR) of brain amyloid load and hippocampal volume (HV) were obtained, respectively, from 18F Florbetapir positron emission tomography (PET) and magnetic resonance imaging (MRI), and compared between BZD chronic users and nonusers using multiple linear regressions adjusted for age, sex, educational level, ApoE ε4 genotype, cognitive and neuropsychiatric assessments, history of major depressive episodes and antidepressant intake. BZD users were more likely to manifest symptoms of depression, anxiety and apathy. In the MRI subgroup, BZD users were also more frequently females with low education and greater clinical impairments as assessed with the clinical dementia rating scale. Short- versus long-acting BZDs, Z-drugs versus non-Z-drugs BZDs, as well as dose and duration of BZD use, were also considered in the analyses. Total SUVR and HV were significantly lower and larger, respectively, in BZD users (n= 38 in the PET subgroup and n= 331 in the MRI subgroup) than in nonusers (n= 251 in the PET subgroup and n= 1840 in the MRI subgroup), with a medium (Cohen’s d = −0.43) and low (Cohen’s d = 0.10) effect size, respectively. Short-acting BZDs and Z-drugs were more significantly associated with larger HV. We found no effect of dose and duration of BZD use. Our results support the involvement of the GABAergic system as a potential target for blocking AD-related pathophysiology, possibly via reduction in neuronal activity and neuroinflammation. Future longitudinal studies may confirm the causal effect of BZDs to block amyloid accumulation and hippocampal atrophy.

Published
2021
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29. NIA-AA RESEARCH FRAMEWORK: APPLICATION TO THE FRENCH POPULATION BY INFERENCE FROM THE MEMENTO COHORT

Author

Bouteloup, Vincent, Dufouil, Carole, Mangin, Jean-Francois, Locatelli, Maxime, Pasquier, Florence, Ousset, Pierre Jean, Dubois, Bruno, Blanc, Frederic, Hanon, Olivier, Paquet, Claire, Tison, François, Gabelle, Audrey, Ceccaldi, Mathieu, Annweiler, Cedric, Salmon, Pierre Krolak, Béjot, Yannick, Belin, Catherine, Wallon, David, Paccalin, Marc, Beaufils, Emilie, Boutoleau-Bretonnière, Claire, Gentric, Armelle, Habert, Marie-Odile, Chupin, Marie, and Chêne, Geneviève

Published
2019
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31. Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study

Author

Sakr, Fatemah A, Grothe, Michel J, Teipel, Stefan, Dubois, Bruno, Hampel, Harald, group, INSIGHT-preAD study, Initiative, Alzheimer Precision Medicine, Bakardjian, Hovagim, Benali, Habib, Bertin, Hugo, Bonheur, Joel, Boukadida, Laurie, Cavedo, Enrica, Boukerrou, Nadia, Chiesa, Patrizia, Colliot, Olivier, Dubois, Marion, Epelbaum, Stéphane, Gagliardi, Geoffroy, Genthon, Remy, Habert, Marie-Odile, Jelistratova, Irina, Houot, Marion, Kas, Aurélie, Lamari, Foudil, Levy, Marcel, Lista, Simone, Metzinger, Christiane, Mochel, Fanny, Nyasse, Francis, Poisson, Catherine, Potier, Marie-Claude, Revillon, Marie, Santos, Antonio, Andrade, Katia Santos, Sole, Marine, Surtee, Mohmed, de Schotten, Michel Thiebaud, Vergallo, Andrea, Younsi, Nadjia, Dyrba, Martin, Gonzalez-Escamilla, Gabriel, Locatelli, Maxime, Lehericy, Stephane, University of Rostock, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AXA Research Fund, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université - Faculté de Médecine (SU FM), CATI Multicenter Neuroimaging Platform (CATI), Service de médecine nucléaire [CHU Pitié-Salpétrière], Johannes Gutenberg - Universität Mainz (JGU), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Amyloid, psychology [Alzheimer Disease], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, diagnostic imaging [Cognitive Dysfunction], Cohort Studies, metabolism [Cognitive Dysfunction], Diagnostic Self Evaluation, Cognition, Alzheimer Disease, Memory, mental disorders, Humans, Cognitive Dysfunction, ddc:610, physiology [Memory], metabolism [Amyloid], Aged, Aged, 80 and over, Subjective memory complaint, Research, physiology [Cognition], In vivo staging, Mental Status and Dementia Tests, Amyloid PET, Female, psychology [Cognitive Dysfunction], diagnostic imaging [Alzheimer Disease], metabolism [Alzheimer Disease], Follow-Up Studies
Abstract

Background Current methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimer’s disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic estimates and can be used to stage an individual’s amyloid burden in vivo. Here, we evaluated the validity of this in vivo amyloid staging model in an independent cohort of older people with subjective memory complaints (SMC). We further examined its potential association with subtle cognitive impairments in this population at elevated risk for Alzheimer’s disease (AD). Methods The monocentric INSIGHT-preAD cohort includes 318 cognitively intact older individuals with SMC. All individuals underwent 18F-florbetapir PET scanning and extensive neuropsychological testing. We projected the regional amyloid uptake signal into the previously proposed hierarchical staging model of in vivo amyloid progression. We determined the adherence to this model across all cases and tested the association between increasing in vivo amyloid stage and cognitive performance using ANCOVA models. Results In total, 156 participants (49%) showed evidence of regional amyloid deposition, and all but 2 of these (99%) adhered to the hierarchical regional pattern implied by the in vivo amyloid progression model. According to a conventional binary classification based on global signal (SUVRCereb = 1.10), individuals in stages III and IV were classified as amyloid-positive (except one in stage III), but 99% of individuals in stage I and even 28% of individuals in stage II were classified as amyloid-negative. Neither in vivo amyloid stage nor conventional binary amyloid status was significantly associated with cognitive performance in this preclinical cohort. Conclusions The proposed hierarchical staging scheme of PET-evidenced amyloid deposition generalizes well to data from an independent cohort of older people at elevated risk for AD. Future studies will determine the prognostic value of the staging approach for predicting longitudinal cognitive decline in older individuals at increased risk for AD. Electronic supplementary material The online version of this article (10.1186/s13195-019-0466-3) contains supplementary material, which is available to authorized users.

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32. Trial of Deferiprone in Parkinson’s Disease

Author

Devos, David, Labreuche, Julien, Dušek, Petr, Post, Bart, Bloem, Bastiaan R, Berg, Daniela, Maetzler, Walter, Otto, Markus, Habert, Marie-Odile, Lehericy, Stéphane, Ferreira, Joaquim, Dodel, Richard, Rascol, Olivier, Tranchant, Christine, Eusebio, Alexandre, Thobois, Stéphane, Marques, Ana-Raquel, Meissner, Wassilios G, Ory-Magne, Fabienne, Walter, Uwe, de Bie, Rob M A, Gago, Miguel, Vilas, Dolores, Corvol, Jean-Christophe, Kulisevsky, Jaime, Januario, Cristina, Coelho, Miguel V S, Behnke, Stefanie, Worth, Paul, Seppi, Klaus, Ouk, Thavarak, Potey, Camille, Leclercq, Céline, Viard, Romain, Duhamel, Alain, Kuchcinski, Gregory, Lopes, Renaud, Pruvo, Jean-Pierre, Pigny, Pascal, Garçon, Guillaume, Simonin, Ophélie, Carpentier, Jessica, Rolland, Anne-Sophie, Nyholm, Dag, Scherfler, Christoph, Guyon Delannoy, Pauline, Mangin, Jean-François, Chupin, Marie, Bordet, Régis, Dexter, David T, Fradette, Caroline, Spino, Michael, Tricta, Fernando, Ayton, Scott, Bush, Ashley I, Devedjian, Jean-Christophe, Poewe, Werner, Duce, James A, Cabantchik, Ioav, Defebvre, Luc, Deplanque, Dominique, Moreau, Caroline, Group, FAIRPARK-II Study, Compta, Yaroslau, Pavese, Nicola, Růžička, Evžen, Basenau, Sandra, Beliveau, Vincent, Benchetrit, Eve, Best, Laura, Bloem, Bas, Bonicel, Robin, Boraud, T., Bordet, Regis, Bouca, Raquel, Bourdain, Frédéric, Bouzas, Jimena, Brefel-Courbon, Christine, Bubenheim, Michael, Burn, David, Bush, Ashley I, Cabantchik, Ioav, Calvas, Fabienne, Cámara, Ana, Campolongo, Antonia, Carrière, Nicolas, Chaigneau, Véronique, Matthieu, Collin, Compta, Yaroslau, Connelly, John, Cormier-Dequaire, Florence, Cranston, Amy, Dean, Rory, De Marzi, Roberto, Degos, Bertrand, Demotes, Jacques, Dellapina, Estelle, Deplanque, Dominique, Devedjian, Jean-Christophe, Devos, David, Dexter, David, Dodel, Richard, Dongmo, Carole, Duce, James, Duhamel, Alain, Dupouy, Julia, Dusek, Petr, El Mountassir, Fouzia, Eyvrard, Frédéric, Fernández, Manel, Ferreira, Joaquim, Forni, Gian Luca, Foster, Victoria, Foubert-Samier, Alexandra, Fradette, Caroline, Fréville, Laëtitia, Galitzky, Monique, Gaudebout, Cecile, Gelé, Patrick, Giladi, Nir, Grabli, David, Gleixner, Franck, Grolez, Guillaume, Guyon, Pauline, Habert, Marie-Odile, Harroch, Estelle, Hartmann, Andreas, Hirsch, Denise, Hisbergues, Michael, Hobert, Markus A, Hopfner, Franziska, Jurado, Camille, Kaiser, Andreas, Keen, Gill, Klaus, Seppi, Kouassi, Nadège, Labreuch, Julien, Lacomblez, Lucette, Lagha Boukbiza, Ouhaid, Lanthaler, Barbara, Lechatellier, Gilles, Le Forestier, Nadine, Lehmann, Fred, Lloret, Teresa, Le Naour, J., Le Toullec, Benjamin, Locatelli, Maxime, Löhle, Matthias, Lomeña, F., Longato, Nadine, Lützen, Ulf, McNichol, Ann, Maetzler, Corina, Maetzler, Walter, Mahlknecht, Philipp, Mangone, Graziella, Marín-Lahoz, Juan, Mariani, Louise-Laure, Marques, Ana, Matei, Mihaela, Matthias, Löhle, Maucourt Bacchi, Emilie, Meissner, Wassilios, Michon, Amelie, Moreau, Caroline, Nardocci, Nardo, Nosal, Florence, Nyholm, Dag, Oeckl, Patrick, Oravska, Irena, Ory, Fabienne, Otto, Markus, Ouk, Thavarak, Pagonabarraga, Javier, Pascual-Sedano, Berta, Peball, Marina, Phillips, Clélie, Pineau, Fanny, Planellas, Lluís, Pop-Ilieva, Chiesi, Rabier, Aurélie, Olivier, D., Riedel, Christian, Rodrigues, Maura, Roullet-Solignac, Isabelle, Rose, Christian, Rozova, Anna, Růžička, Evžen, Salis, Alexandra, Schäffer, Eva, Scherfler, Christoph, Schiefermeier, Natalia, Seppi, Klaus, Smagghe, Delphine, Silva, Tânia, Silva, Pedro, Socha, Julie, Souyris, Corinne, Spampinato, Umberto, Spino, Michael, Steel, Alison, Sweta, Bajaj, Thalamas, Claire, Teodor, Danaila, Teresa, Anna, Tison, François, Tolosa, Eduardo, Tricta, Fernando, Trifirò Trifirò, Gianluca, Vidailhet, Marie, Wang, Yi, Werkmann, Mario, Yilmas, Rezzak, You, Hana, Zeuner, Kirsten, Defebvre, Luc, Rascol, Olivier, Tranchant, Christine, Eusebio, Alexandre, Thobois, Stéphane, Corvol, Jean-Christophe, Durif, Franck, Meissner, Wassilos, Yaroslau, Compta, Vilas, Dolores, Kulisevsky, Jaime, Poewe, Werner, Ruzicka, Evzen, Gago, Miguel, Januario, Cristina, Vilhena Soares Coelho, Miguel, Berg, Daniela, Behnke, Stefanie, Walter, Uwe, Worth, Paul, Pavese, Nicola, Post, Bart, de Bie, Rob M A, Abbruzzese, Giovanni, Accart, Bertrand, Allain, Marie-Anne, Anheim, Mathieu, Ardigo, Diego, Aracil-Bolaños, Ignacio, Baba, Paul, Bakker, Martijn, Balzer-Geldsetzer, Monika, Bargalló, Núria, Barone, Paolo, Neurology, ANS - Neurodegeneration, and APH - Aging & Later Life

Subjects
administration & dosage [Deferiprone], Dopamine, Dopamine Agents, Medizin, Administration, Oral, Levodopa, Antiparkinson Agents, therapeutic use [Dopamine Agents], therapeutic use [Deferiprone], Deferiprone, metabolism [Iron], adverse effects [Deferiprone], Geriatrics/Aging, Parkinson Disease, General Medicine, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Hematology/Oncology, chemistry [Substantia Nigra], adverse effects [Dopamine Agents], Disease Progression, administration & dosage [Dopamine Agents], physiopathology [Parkinson Disease], adverse effects [Iron Chelating Agents], Neutropenia, analysis [Iron], administration & dosage [Antiparkinson Agents], Iron, metabolism [Parkinson Disease], Neurology/Neurosurgery, therapeutic use [Levodopa], Iron Chelating Agents, pharmacology [Iron Chelating Agents], Double-Blind Method, adverse effects [Antiparkinson Agents], Genetics, diagnostic imaging [Substantia Nigra], metabolism [Substantia Nigra], Humans, ddc:610, diagnostic imaging [Brain], therapeutic use [Antiparkinson Agents], Brain Chemistry, pharmacology [Antiparkinson Agents], therapeutic use [Iron Chelating Agents], Hematology/Oncology General, chemically induced [Neutropenia], pharmacology [Deferiprone], drug therapy [Parkinson Disease], administration & dosage [Iron Chelating Agents], Geriatrics/Aging General, pharmacology [Dopamine Agents], drug effects [Substantia Nigra], Neuroscience
Abstract

Contains fulltext : 287484.pdf (Publisher’s version ) (Open Access) BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P

Published
2022

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