Cortical microstructure in primary progressive aphasia: a multicenter study

Cortical mean diffusivity is a novel imaging metric sensitive to early changes in neurodegenerative syndromes. Higher cortical mean diffusivity values reflect microstructural disorganization and have been proposed as a sensitive biomarker that might antedate macroscopic cortical changes. We aimed to test the hypothesis that cortical mean diffusivity is more sensitive than cortical thickness to detect cortical changes in primary progressive aphasia (PPA).In this multicenter, case-control study, we recruited 120 patients with PPA (52 non-fluent, 31 semantic, and 32 logopenic variants; and 5 GRN-related PPA) as well as 89 controls from three centers. The 3-Tesla MRI protocol included structural and diffusion-weighted sequences. Disease severity was assessed with the Clinical Dementia Rating scale. Cortical thickness and cortical mean diffusivity were computed using a surface-based approach.The comparison between each PPA variant and controls revealed cortical mean diffusivity increases and cortical thinning in overlapping regions, reflecting the canonical loci of neurodegeneration of each variant. Importantly, cortical mean diffusivity increases also expanded to other PPA-related areas and correlated with disease severity in all PPA groups. Cortical mean diffusivity was also increased in patients with very mild PPA when only minimal cortical thinning was observed and showed a good correlation with measures of disease severity.Cortical mean diffusivity shows promise as a sensitive biomarker for the study of the neurodegeneration-related microstructural changes in PPA.© 2022. The Author(s)

APOE -by-sex interactions on brain structure and metabolism in healthy elderly controls

Altres ajuts: Marató TV3 (531/U/2014); NIH-NIA grants (AG022374, AG13616, AG12101)The APOE effect on Alzheimer Disease (AD) risk is stronger in women than in men but its mechanisms have not been established. We assessed the APOE -by-sex interaction on core CSF biomarkers, brain metabolism and structure in healthy elderly control individuals (HC). Cross-sectional study. HC from the Alzheimer's Disease Neuroimaging Initiative with available CSF (n = 274) and/or 3T-MRI (n = 168) and/or a FDG-PET analyses (n = 328) were selected. CSF amyloid-β (Aβ), total-tau (t-tau) and phospho-tau (p-tau) levels were measured by Luminex assays. We analyzed the APOE -by-sex interaction on the CSF biomarkers in an analysis of covariance (ANCOVA). FDG uptake was analyzed by SPM8 and cortical thickness (CTh) was measured by FreeSurfer. FDG and CTh difference maps were derived from interaction and group analyses. APOE4 carriers had lower CSF Aβ and higher CSF p-tau values than non-carriers, but there was no APOE -by-sex interaction on CSF biomarkers. The APOE -by-sex interaction on brain metabolism and brain structure was significant. Sex stratification showed that female APOE4 carriers presented widespread brain hypometabolism and cortical thinning compared to female non-carriers whereas male APOE4 carriers showed only a small cluster of hypometabolism and regions of cortical thickening compared to male non-carriers. The impact of APOE4 on brain metabolism and structure is modified by sex. Female APOE4 carriers show greater hypometabolism and atrophy than male carriers. This APOE -by-sex interaction should be considered in clinical trials in preclinical AD where APOE4 status is a selection criterion

APOE-by-sex interactions on brain structure and metabolism in healthy elderly controls

BACKGROUND: The APOE effect on Alzheimer Disease (AD) risk is stronger in women than in men but its mechanisms have not been established. We assessed the APOE-by-sex interaction on core CSF biomarkers, brain metabolism and structure in healthy elderly control individuals (HC). METHODS: Cross-sectional study. HC from the Alzheimer's Disease Neuroimaging Initiative with available CSF (n = 274) and/or 3T-MRI (n = 168) and/or a FDG-PET analyses (n = 328) were selected. CSF amyloid-β1-42 (Aβ1-42), total-tau (t-tau) and phospho-tau (p-tau181p) levels were measured by Luminex assays. We analyzed the APOE-by-sex interaction on the CSF biomarkers in an analysis of covariance (ANCOVA). FDG uptake was analyzed by SPM8 and cortical thickness (CTh) was measured by FreeSurfer. FDG and CTh difference maps were derived from interaction and group analyses. RESULTS: APOE4 carriers had lower CSF Aβ1-42 and higher CSF p-tau181p values than non-carriers, but there was no APOE-by-sex interaction on CSF biomarkers. The APOE-by-sex interaction on brain metabolism and brain structure was significant. Sex stratification showed that female APOE4 carriers presented widespread brain hypometabolism and cortical thinning compared to female non-carriers whereas male APOE4 carriers showed only a small cluster of hypometabolism and regions of cortical thickening compared to male non-carriers. CONCLUSIONS: The impact of APOE4 on brain metabolism and structure is modified by sex. Female APOE4 carriers show greater hypometabolism and atrophy than male carriers. This APOE-by-sex interaction should be considered in clinical trials in preclinical AD where APOE4 status is a selection criterion

PROJET DE SPECTROMETRIE NUCLEAIRE A SATURNE

Le projet de spectrométrie nucléaire à haute énergie défini au D.Ph-N/ME de Saclay est décrit. Une résolution de l'ordre de 100 keV pour l'étude de la diffusion de protons de 1 GeV devrait être obtenue et permettre l'étude de nombreux noyaux.A high energy nuclear spectroscopy project has been designed by the D.Ph-N/ME in Saclay. The energy resolution about 100 keV with 1 GeV protons allows the study of many nuclei

SPECTROSCOPIE DE 206, 207, 208Pb

La diffusion de protons de 24,5 MeV par 206, 207, 208Pb a été analysée magnétiquement avec une résolution comprise entre 18 et 25 keV. Dans le domaine d'énergie d'excitation de 4 à 5 MeV nous avons observé des excitations collectives avec des Δ/ de 2, 4, 6 et 8. Les probabilités de transition réduites correspondant à un Δ/ donné sont égales pour ces trois isotopes.The scattering of 24.5 MeV protons by 206, 207, 208Pb has been magnetically analysed with a resolution in the range of 18 to 25 keV. In the 4 to 5 MeV excitation energy region, we have observed collective excitations with Δ/ equal to 2, 4, 6 and 8. The reduced transition probabilities corresponding to the same Δ are equal for these three isotopes

Excitation du deuxième niveau des 64Zn 66Zn et 68Zn par diffusion inélastique de particules α

A study of the angular distributions of alpha particles exciting the second 2+ state of 64Zn, 66Zn, 68Zn was made, using the 43 MeV alpha particle beam of the Saclay cyclotron. Comparison with the elastic angular distributions shows that in the cases of 64 Zn and 66Zn the transition (0+ → 2 +) is not direct, but should be interpreted as a double excitation process. For 68Zn the two processes (direct and double excitation) compete.Une étude des distributions angulaires des particules α excitant le deuxième niveau 2+ des isotopes 64Zn, 66Zn, 68Zn a été entreprise à l'aide du faisceau de particules α de 43 MeV du cyclotron de Saclay. La comparaison de ces distributions angulaires avec celles des particules α diffusées élastiquement montre que pour 64 Zn et 66Zn la transition (0+ → 2 +) n'est pas directe, mais doit être interprétée comme une double excitation. Pour 68Zn les deux processus (direct et double excitation) sont compétitifs