%0 Journal Article %J J Alzheimers Dis %D 2017 %T Quantitative Magnetic Resonance Abnormalities in Creutzfeldt-Jakob Disease and Fatal Insomnia. %A Grau-Rivera, Oriol %A Calvo, Anna %A Bargalló, Nuria %A Monté, Gemma C %A Nos, Carlos %A Lladó, Albert %A Molinuevo, José Luis %A Gelpi, Ellen %A Sánchez-Valle, Raquel %X

BACKGROUND: Quantitative neuroimaging might unveil abnormalities in prion diseases that are not perceivable at visual inspection. On the other hand, scarce studies have quantified volumetric changes in prion diseases.

OBJECTIVES: We aim to characterize volumetric and diffusion tensor imaging (DTI) changes in patients with prion diseases who presented with either Creutzfeldt-Jakob disease (CJD) or fatal insomnia (FI) phenotype.

METHODS: Twenty patients with prion diseases- 15 with CJD and 5 with fatal insomnia (FI)- and 40 healthy controls were examined with a 3-Tesla magnetic resonance imaging scanner. Images were segmented and normalized with SPM12. DTI maps were obtained with FMRIB Software Library. Whole-brain voxel-wise and region-of-interest analyses of volumetric and DTI changes were performed with SPM12. White matter (WM) changes were also analyzed with tract-based spatial statistics. Semiquantitive assessment of neuropathological parameters was compared with DTI metrics in thalamus from 11 patients.

RESULTS: Patients with CJD and FI presented significant atrophy in thalamus and cerebellum. In CJD, mean diffusivity (MD) was decreased in striatum and increased in subcortical WM, while both increased and decreased values were observed across different thalamic nuclei. In FI, MD was increased in thalamus and cerebellum. Spongiform change and PrPSc deposition were more intense in thalamus in CJD than in FI, although no significant correlations arose with MD values in the nuclei studied.

CONCLUSION: Volumetric and DTI abnormalities suggest a central common role of the thalamus in prion diseases. We report, for the first time, quantitative MRI changes in FI, and provide further evidence of WM involvement in prion diseases.

%B J Alzheimers Dis %V 55 %P 431-443 %8 2017 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/27662320?dopt=Abstract %R 10.3233/JAD-160750 %0 Journal Article %J J Alzheimers Dis %D 2016 %T White Matter Abnormalities Track Disease Progression in PSEN1 Autosomal Dominant Alzheimer's Disease. %A Sánchez-Valle, Raquel %A Monté, Gemma C %A Sala-Llonch, Roser %A Bosch, Beatriz %A Fortea, Juan %A Lladó, Albert %A Antonell, Anna %A Balasa, Mircea %A Bargalló, Nuria %A Molinuevo, José Luis %K Adult %K Aging %K Alzheimer Disease %K Brain %K Cohort Studies %K Diffusion Tensor Imaging %K Disease Progression %K Family %K Female %K Heterozygote %K Humans %K Image Processing, Computer-Assisted %K Magnetic Resonance Imaging %K Male %K Mental Status Schedule %K Middle Aged %K Mutation %K Neuropsychological Tests %K Organ Size %K Presenilin-1 %K White Matter %X

PSEN1 mutations are the most frequent cause of autosomal dominant Alzheimer's disease (ADAD), and show nearly full penetrance. There is presently increasing interest in the study of biomarkers that track disease progression in order to test therapeutic interventions in ADAD. We used white mater (WM) volumetric characteristics and diffusion tensor imaging (DTI) metrics to investigate correlations with the normalized time to expected symptoms onset (relative age ratio) and group differences in a cohort of 36 subjects from PSEN1 ADAD families: 22 mutation carriers, 10 symptomatic (SMC) and 12 asymptomatic (AMC), and 14 non-carriers (NC). Subjects underwent a 3T MRI. WM morphometric data and DTI metrics were analyzed. We found that PSEN1 MC showed significant negative correlation between fractional anisotropy (FA) and the relative age ratio in the genus and body of corpus callosum and corona radiate (p <  0.05 Family-wise error correction (FWE) at cluster level) and positive correlation with mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD) in the splenium of corpus callosum. SMC presented WM volume loss, reduced FA and increased MD, AxD, and RD in the anterior and posterior corona radiate, corpus callosum (p <  0.05 FWE) compared with NC. No significant differences were observed between AMC and NC in WM volume or DTI measures. These findings suggest that the integrity of the WM deteriorates linearly in PSEN1 ADAD from the early phases of the disease; thus DTI metrics might be useful to monitor the disease progression. However, the lack of significant alterations at the preclinical stages suggests that these indexes might not be good candidates for early markers of the disease.

%B J Alzheimers Dis %V 51 %P 827-35 %8 2016 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/26923015?dopt=Abstract %R 10.3233/JAD-150899