Gael chelat


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webinar presented on AlzForum January 5, 2012.

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Gael chelat

  1. 1. Adding Nuance to Staging Diagrams:Integrated Brain Imaging Emphasizes RegionalDifferences in What Changes When on the Long Descent Into Alzheimer’s Gaël Chételat 1 INSERM, U1077, Caen, France 2 Université de Caen Basse-Normandie, UMR-S1077, Caen, France 3 Ecole Pratique des Hautes Etudes, UMR-S1077, Caen, France 4 Centre Hospitalier Universitaire, U1077, Caen, France
  2. 2. Jack et al., Lancet Neurol 2010 Frisoni, Nat Rev Neurol 2010Petersen et al., Lancet Neurol 2010 Perrin et al., Nature 2009
  3. 3. Neuropathology From Thal et al., Braak & Braak, Duyckaerts et al., Delacourte et al., Price et al. Neurofibrillary tangles Progression
  4. 4. GM Amyloid Hypometabolismatrophy deposition
  5. 5. DIRECT VOXEL-BASED COMPARISON BETWEEN GREY MATTER HYPOMETABOLISM AND ATROPHY IN ALZHEIMER’S DISEASE 0 Mean z-score value -2.5 ATROPHY HYPOMETABOLISM Hippocampus Posterior CingulateHypometabolism > Atrophy R1*R2; Moy. Moindres Carrés Effet courant : F(1, 17)=15,056, p=,00120 Décomposition efficace de lhypothèse Les barres verticales représentent les intervalles de confiance à 0,95 0,0 Significant interaction Region*Modality -0,5 F(1,17)=12.056; p=0.0012 -1,0 Amyloid deposition -1,5 VD_1 -2,0 -2,5 R1 -3,0 1 1 2 R1 MRI Z-score PET Z-score 2 R2 Mintun et al., Neurology, 2006 Chételat et al., Brain, 2008
  6. 6. Whole brain patterns of alteration Amyloid deposition Atrophy Hypometabolism 18F florbetapir (AV45) Δhypo-atro = Zhypo minus Zatro-1 -0.5 0.5 1 Δ value 0 mean age-adjusted Z-score 3 La Joie et al. Submitted
  7. 7. Classification of brain regions Temporal, temporo- Hippocampal parietal, PCC-Precun regions Frontal lobe High degree of atro, hypo Atrophy exceeds Clear prediminance of and amylo, but hypometabolism and amyloid deposition predominance of HYPO amyloid deposition La Joie et al. Submitted
  8. 8. Mechanisms that could explainthese regional discrepancies in thedegree of atrophy, hypometabolism and amyloid deposition
  9. 9. Voxel-to-voxel correlations between modalities in AD aMRI FDG-PET Areas where hypometabolism and atrophy are correlated 0.5 Common underlying mechanisms to atrophy and Pearson’s r hypometabolism but additional mechanisms may occur to amplify or attenuate hypometabolism or atrophy in specific brain regions 1 La Joie et al., Submitted
  10. 10. Hippocampal paradox: early functional compensation? * Extend of Hcp activation ** Dickerson et al., Neurology 2005
  11. 11. MRI-PET relationships: findings in AD Nicolas Villain, PhD studentA GM atrophy B Extraction of mean 2.29 T value 5.26 hippocampal Z-score L R Y =-14 C Correlation between hippocampal Z- score and WM atrophy D Correlation between cingulum Z- Extraction of meanE score and hypometabolism cingulum Z-score L R L R L L R L T values R² values R R 0 0.2 0.4 0.6 0.8 1 Villain et al., J Neurosci, 2008
  12. 12. Hippocampal Cingulum bundle Posterior cingulate atrophy disruption hypometabolism Anterior cingulate cortex(BA32) Uncinate fasciculus Subgenual cortex (BA25) Disconnection processes thus appear as one factor that may explain the regional variability in the expression of the different biomarkers, in amplifying hypometabolism in specific brain regions. Villain et al., Brain, 2010
  13. 13. Voxel-to-voxel correlations between modalities in AD FDG-PET AV45-PET Areas where hypometabolism is correlated to amyloid deposition There is a relationship between hypometabolism and amyloid deposition in the PCC and TP cortex La Joie et al., Submited
  14. 14. Functional compensation or brain reserve tomaintain / increasemetabolism within the frontal cortex despite amyloid deposition at the MCI stageCohen et al., JNeurosci 2009
  15. 15. Voxel-to-voxel correlations between modalities in AD No significant correlation aMRI FDG-PET AV45-PET Areas where hypometabolism and atrophy Areas where hypometabolism is correlated are correlated to amyloid deposition Renaud La Joie, 0.5 Pearson’s r 1 PhD student
  16. 16. Correlations between baseline PiB and baseline atrophy Amyloid and atrophy are related only in earliest stages (SCI) and in D. REGIONAL PiB-SUVR versus REGIONAL GM volume within each clinical group regions of highest amyloid (ACC, PCC, TP) (but not in the Hcp) NSLarger GM volume in High versus Low PiB controls NS NS GM atrophy in High versus Low PiB SCI Controls SCI MCI AD Chételat et al.,Chételatof Neurology, 2010 Annals et al., Brain, 2010
  17. 17. Correlation between Hcp volume and regional PiB (voxelwise)Significant in healthy elderly only Bourgeat et al., Neurology , 2010 Chételat et al., Brain, 2011
  18. 18. Region SET 1 - Excessive hypometabolismHigh degree of could be due to amyloidatro, hypo and deposition and amylo, but disconnection from thepredominance hippocampus of HYPORegion SET 2 - Excessive atrophy could be due to local NFT, distantAtrophy exceeds (lateral temporal) amyloidhypometabolism deposition, and functional and amyloid compensation depositionRegion SET 3 - Disconnection but multiple inputs Clear - Lower sensitivity to amyloid prediminance deposition + brain reserve + of amyloid functional compensation deposition processes
  19. 19. GM atrophy WM atrophy Hypometabolism Amyloid deposition (ATRO) (ATRO) (HYPO) (AMYLO) Perforant path Temporal Neocortex AD ATRO AMYLO MCI SCI HC Uncinate fasciculus Hippocampal ATRO ATRO Memory Hippocampal Deficits Subgenual cortex HYPO (BA25) HYPO Subgenual cortex Cingulum bundle (BA25) ATRO ATRO PCC-Precuneus HYPO Anterior cingulate Temporo-parietal (BA32) HYPO HYPO PCC-Precuneus AMYLO Anterior cingulate Temporo-parietal (BA32) AMYLO AMYLO PCC-Precuneus ATRO Anterior cingulate Temporo-parietal (BA32) ATRO ATRO