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Patients with early-onset Alzheimer’s disease: high field MRI findings. Fidel Núñez* 1, Daniel Alcolea 2, Esther Granell 1, Manel De Juan 1, Yolanda Vives.

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Presentation on theme: "Patients with early-onset Alzheimer’s disease: high field MRI findings. Fidel Núñez* 1, Daniel Alcolea 2, Esther Granell 1, Manel De Juan 1, Yolanda Vives."— Presentation transcript:

1 Patients with early-onset Alzheimer’s disease: high field MRI findings. Fidel Núñez* 1, Daniel Alcolea 2, Esther Granell 1, Manel De Juan 1, Yolanda Vives 3, Albert Lleó 2, Beatriz Gómez 1. 1 Hospital de la Santa Creu i Sant Pau (Barcelona) Radiology (Neuroradiology Unit). 2 Hospital de la Santa Creu i Sant Pau (Barcelona). Neurology. 3 Port d’Informació Científica (PIC), Universitat Autònoma de Barcelona (UAB). *

2 Introduction Although incidence of Alzheimer’s disease (AD) is greater in advanced age, it can begin earlier in life, even before 65 years of age, which is considered early onset Alzheimer’s disease (EAD). Even when it makes for a small percentage of patients with AD, it is still the most frequent cause for early onset dementia 1. Compared to senile or late onset AD (LAD), EAD has more often a genetic cause involved 2-4. A faster clinical course of the disease and more severe symptoms have also been described. Within the multiplicity and heterogeneity of clinical syndromes in AD, a more severe involvement of executive and visuospatial functions has been traditionally described 5, with memory impairment being prominent in a later stage of the disease 6,7.

3 Introduction Structural magnetic resonance imaging (MRI) has allowed to study volume changes in patients with neurodegenerative diseases. Whereas there is wide evidence 8-10 in structural MRI findings in patients with LAD/ mild cognitive impairment, studies in EAD are more limited. Some previous studies have suggested a different pattern of regional volume loss in EAD versus LAD, using voxel based morphometry (VBM) A relative sparing of medial temporal regions and a more selective volume loss in parietal lobes (focused in precuneus and posterior cingulate) have been described in patients with EAD, according to cognitive differences in these versus LAD patients. Differences in Nuclear Medicine studies have also been found 16,17. There is less extent literature in cortical thickness analysis in EAD at present 14.

4 Materials and methods A total of 30 patients with the diagnosis of AD (18 defined as EAD and 12 as LAD) were recruited in the Memory Disorders Unit of our institution. 12 subjects with no cognitive deficits were also included as controls. Demographics, including age at the onset of symptoms, age at MRI study and evolution time can be seen in the table. GROUPAge at onset (years)Age at MRI (years) Clinical evolution time at MRI study (years) averageSDaverageSDaverageSD LAD EAD CONTROL

5 Materials and methods All the patients were studied with a complete neuropsychological battery. No statistically significant differences were found between EAD and LAD groups. Structural MRI: Studies were performed in a high field scan (3T Philips, Achieva 2.6.3), including a volumetric 3DT1 sequence (TR=6.7 ms, TE 3.1 ms, voxel size acquisition 1.2x0.0889x0889 mm). Data processing: MRI studies were prcessed using Freesurfer (version 5.0), with the Dessikan-Killiany atlas for cortical parcellation 19. Statistical analysis of obtained data was made with QDEC software. The performed comparisons were EAD versus controls, LAD versus controls and EAD versus LAD.

6 Results EAD vs controls: Figure shows areas of cortical thinning (in blue) in EAD patiens versus controls, all of them statistically significant (p<0,01). Top row shows results in right hemisphere (lateral and medial surface), and bottom row shows results for left hemisphere. A pattern of manily parietal (including precuneus and posterior cingulate) involvement can be seen, as well as lateral temporal and, in a lesser extent, dorsolateral prefrontal.

7 Results EAD vs controls: Table shows p values in all the clusters with cortical thinning. RIGHT HEMISPHERE LEFT HEMISPHERE CLUSTERp value CLUSTERp value Inferior parietal Supramarginal Supramarginal Superior parietal Isthmus cingulate Precuneus Rostral middle frontal Caudal middle frontal Caudal middle frontal Post central Inferior temporal Middle temporal Superior frontal Rostral middle frontal Precuneus Inferior parietal Middle temporal Isthmus cingulate Superior parietal Superior frontal Paracentral Rostral anterior cingulate Pars opercularis Lateral occipital0.0091

8 Results LAD vs controls: Figure shows areas of cortical thinning (in blue) in LAD patiens versus controls, all of them statistically significant (p<0,01). Top row shows results in right hemisphere (lateral and medial surface), and bottom row shows results for left hemisphere. A pattern of mainly inferior and medial temporal (including fusiform gyrus) involvement can be seen. There is no selective involvement of precuneus, or dorsolateral prefrontal cortex.

9 Results LAD vs controls: Table shows p values in all the clusters with cortical thinning. RIGHT HEMISPHERE LEFT HEMISPHERE CLUSTER p value CLUSTERp value inferior temporal superior temporal inferior parietal inferior temporal superior temporal middle temporal fusiform superior frontal supramarginal paracentral rostral middle frontal fusiform isthmus cingulate pars opercularis pars orbitalis lateral orbitofrontal middle temporal pars orbitalis pars opercularis superior frontal medial orbito-frontal caudal anterior cingulate0.0083

10 Results EAD vs LAD: Figure shows areas of cortical thinning (in blue) in EAD patients. Areas of cortical thinning in LAD are shown in red. All of them are statistically significant (p<0,01). Top row shows results for right hemisphere (lateral and medial surface), and bottom row shows results for left hemisphere. The most imortant loss of cortical thickness in EAD patients can be seen in precuneus. Opposite, in LAD patients a more selective inferior temporal (fusiform gyrus) and inferior frontal cortical thinning can be seen.

11 Results EAD vs LAD: Table shows p values in all the clusters with cortical thinning in EAD patients versus LAD patients. Table shows p values in all the clusters with cortical thinning in LAD patients versus EAD patients. RIGHT HEMISPHERE LEFT HEMISPHERE CLUSTER p value CLUSTERp value Cuneus Precuneus Supramarginal Inferior parietal Inferior parietal Superior temporal Precuneus Caudal middle-frontal Rostral middle frontal Superior parietal Pericalcarine Supramarginal RIGHT HEMISPHERE LEFT HEMISPHERE CLUSTER p value CLUSTERp value Fusiform Superior temporal Enthorinal Pars triangularis Pars orbitalis Lateral orbitofrontal Insula Enthorinal Superior temporal Post-central Precentral Temporal pole Temporal pole Pars opercularis0.0079

12 Discussion EAD patients show cortical thinning predominating in parietal, temporal lateral and dorsolateral prefrontal regions of both hemispheres, with a pattern which is similar in comparison with LAD patients and controls. Precuneus and posterior cingulate cortex (the latter more evident versus control group) involvement is remarkable, and is in line with volumetry (VBM) studies available, which have also related it to the different clinical features in these patients (more visuospatial and executive impairment). Taking into account the lower ages of EAD group (age was not included as a covariable in analysis) makes results more noticeable. Patients of the LAD group show a different pattern of cortical thinning (being compared to controls of similar age) with involvement of inferior and medial temporal regions (and parietal to a lesser extent). These findings are in line with expected changes in AD patients which have been widely shown in volumetry and cortical thickness studies. The absence of precuneus involvement in this group versus controls is also remarkable.

13 Discussion Neuropsychological tests did not show statistically significant results (especially those focused on executive and visuospatial functions) between groups. The different evolution time of the disease at the time of the study (longer in EAD group) might be an explanation. The clinical differences between EAD and LAD have been described in literature predominantly in early stages of the disease, and a faster clinical course of EAD has been suggested as a cause for normalization of differences in neuropsychological tests in later stages of both EAD and LAD 18.

14 Conclusions EAD patients show a pattern of cortical thinning which is different to LAD patients. EAD patients show selective involvement of medial parietal regions (precuneus, posterior cingulate) compared to LAD patients and controls. These findings are in line with current literature. Studies in earlier stages of the disease and focused in neuropsychological differences might be required.

15 References 1- Epidemiology of early-onset dementia: a review of the literature. Renata Teles Vieira et al. Clinical Practice & Epidemiology in Mental Health, 2013, 9, Age at Onset in Two Common Neurodegenerative Diseases Is Genetically Controlled.Yi-Ju Li, et al. J. Hum. Genet. 70:985–993, Early-Onset Autosomal Dominant Alzheimer Disease: Prevalence, Genetic Heterogeneity, and Mutation Spectrum. Dominique Campion, et al. J. Hum. Genet. 65:664–670, The solved and unsolved mysteries of the genetics of early-onset Alzheimer’s disease. E. Rogaeva. NeuroMolecular Medicine 2002, Volume 2, Issue 1, pp What is ‘early onset dementia’? Koho Miyoshi. Psychogeriatrics 2009; 9: 67–72 6- Neuropsychological and Neuroimaging Markers in Early Versus Late-Onset Alzheimer’s Disease.Natalie C. Kaiser, et al. Am J Alzheimers Dis Other Demen Nov 2012 vol. 27 no Nonamnestic Presentations of Early-Onset Alzheimer’s Disease.Mario F. Mendez et al. Am J Alzheimers Dis Other Demen Sept 2012 vol. 27 no The clinical use of structural MRI in Alzheimer disease. Giovanni B. Frisoni et al Nature Reviews Neurology 6, (February 2010). 9-A comprehensive study of gray matter loss in patients with Alzheimer’s disease using optimized voxel-based morphometry.G.B Karas et al. NeuroImage Volume 18, Issue 4.April 2003, Pages 895–907

16 References 10-Differential effects of aging and Alzheimer's disease on medial temporal lobe cortical thickness and surface area. Bradford C. Dickerson et al. Neurobiology of Aging Volume 30, Issue 3, March 2009, Pages 432– Precuneus atrophy in early-onset Alzheimer’s disease: a morphometric structural MRI study. Giorgos Karas et al. Neuroradiology (2007) 49:967– Four subgroups of Alzheimer’s disease based on patterns of atrophy using VBM and a unique pattern for early onset disease. Akihiko Shiino et al. NeuroImage 33 (2006) 17–26 13-Voxel-Based Morphometric Comparison Between Early- and Late-Onset Mild Alzheimer’s Disease and Assessment of Diagnostic Performance of Z Score Images. Kazunari Ishii et al. AJNR Am J Neuroradiol 26:333–340, February Early-onset Alzheimer disease clinical variants. Multivariate analyses of cortical thickness. Gerard R. Ridgway et al.Neurology 2012;79:80–84 15-Structural correlates of early and late onset Alzheimer’s disease: voxel based morphometric study. G.Frisoni, et al. J Neurol Neurosurg Psychiatry 2005;76: Differences in cerebral metabolic impairment between early and late onset types of Alzheimer's disease. Setsu Sakamotoa et al. Journal of the Neurological Sciences Volume 200, Issues 1–2, 15 August 2002, Pages 27–32 17-Working memory and FDG–PET dissociate early and late onset Alzheimer disease patients. G. Kalpouzoset al. Journal of Neurology May 2005, Volume 252, Issue 5, pp Age at onset of Alzheimer's disease. Relation to pattern of cognitive dysfunction and rate of decline. D. Jacobs et al. Neurology, July 1994 vol. 44 no An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Desikan et al.NeuroImage, 31(3): (2006).


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