Changes in Functional and Structural Brain Connectome Along the Alzheimer’s Disease Continuum (P3.033)

Objective: To investigate structural and functional brain network architecture in patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI), stratified in converters (c-aMCI) and non-converters (nc-aMCI) to AD; and to assess the relationship between healthy brain network functional connectivity and the topography of brain atrophy in patients along the AD continuum. Background: The study of the effects of the disease on the brain networks along the AD continuum is critical in conceptualizing and predicting networked disease evolution in vivo . Design/Methods: Ninety-four AD patients, 47 aMCI patients (25 c-aMCI within 36 months) and 53 age- and sex-matched healthy underwent 3D T1-weighted MRI, diffusion tensor MRI and resting state functional MRI. Graph analysis and connectomics assessed global and local, structural and functional topological network properties and regional connectivity. Healthy topological features of brain regions were assessed based on their connectivity with the point of maximal atrophy (epicenter) in AD and aMCI patients. Results: Brain network graph analysis properties were severely altered in AD patients. Structural brain network was already altered in c-aMCI patients relative to healthy controls in particular in the temporal and parietal brain regions, while functional connectivity did not change. Structural connectivity alterations distinguished c-aMCI from nc-aMCI cases. In both AD and c-aMCI, the point of maximal atrophy was located in left hippocampus (disease-epicenter). Brain regions most strongly connected with the disease-epicenter in the healthy functional connectome were also the most atrophic in both AD and c-aMCI patients. Conclusions: Progressive degeneration in the AD continuum is associated with an early breakdown of anatomical brain connections and follows the strongest connections with the disease-epicenter. These findings support the hypothesis that the topography of brain connectional architecture can modulate the spread of AD through the brain. Study Supported by: The study was supported by the Italian Ministry of Health (grant number GR-2010-2303035) and Alzheimer’s Drug Discovery Foundation (grant number 20131211). Disclosure: Dr. Agosta has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EXCEMED— Excellence in Medical Education. Dr. Basaia has nothing to disclose. Dr. Canu has nothing to disclose. Dr. imperiale has nothing to disclose. Dr. Magnani has nothing to disclose. Dr. Falautano has nothing to disclose. Dr. Comi has nothing to disclose. Dr. Falini has nothing to disclose. Dr. Filippi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Merk-Serono, Novartis, Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in an editorial capacity for Journal of Neurology. Dr. Filippi has received research support from Biogen Idec, Novartis, Teva Pharmaceutical Industries.