Multimodal Imaging to Distinguish In Vivo Early Onset Alzheimer's Disease from Behavioral Variant of Frontotemporal Dementia (P4.012)

Objective.To compare early-onset Alzheimer’s disease (EOAD) and behavioural variant of frontotemporal dementia (bvFTD) using a multimodal approach combining structural (cortical thickness [CT] and white matter [WM] microstructural measures) and functional (resting state functional [RS-fMRI] connectivity) MRI. Background.At onset, EOAD and bvFTD can present with similar symptoms and similar pattern of brain atrophy leading to a challenging differential diagnosis. Methods.Sixty-two probable EOAD patients, 27 probable bvFTD patients and 48 controls were studied. Subjects underwent 3DT1-weighted MRI, diffusion tensor (DT)-MRI and RS-fMRI. CT measures and DT metrics from the main interhemispheric and long associative tracts were obtained. RS fMRI data were analyzed using a model free approach. A Random Forest (RF) approach was applied to explore the role of MRI data in classifying the two syndromes. Results.Compared to controls, each patient group showed a widespread pattern of brain alterations. Compared to bvFTD, EOAD patients showed reduced CT in the bilateral posterior cingulate and inferior parietal gyri, WM damage of the splenium of the corpus callosum, and decreased functional connectivity of the posterior cingulum within the default mode network. Compared to EOAD, bvFTD patients showed reduced CT in the orbitofrontal cortices and temporal pole bilaterally, and WM damage of the corpus callosum, cingulum, superior longitudinal and uncinate fasciculi bilaterally. RF analysis revealed that the best predictors of differential diagnosis among MRI measures were the CT values of the inferior/medial parietal cortices and right temporal poles. Conclusions.Multimodal imaging can help understanding differences between early onset dementia phenotypes. The direct comparison among syndromes revealed that EOAD is characterized by a more severe thinning of the posterior brain regions, while WM damage was diffusely greater in bvFTD patients. RF analysis suggests that CT measures may represent a useful tool to distinguish EOAD from bvFTD at individual patient level in clinical practice.   Disclosure: Dr. Canu has nothing to disclose. Dr. Agosta has received personal compensation for activities with Biogen Idec and EXCEMED– Excellence in Medical Education. Dr. Mandic-Stojmenovic has nothing to disclose. Dr. Stojkovic has nothing to disclose. Dr. Stefanova has nothing to disclose. Dr. imperiale has nothing to disclose. Dr. Copetti has nothing to disclose. Dr. Kostic has received personal compensation for activities with Novartis, Boehringer Ingelheim Pharmaceuticals, Merck & Co., Inc., Lundbeck Research USA, Inc., GlaxoSmithKline, Hoffman-La Roche, Alkaloid, and AbbVie as a speaker. Dr. Filippi has received personal compensation for activities for consulting services and/or speaking activities from Biogen Idec, Excemed, Novartis, and Teva Pharmaceutical Industries.