IC‐P‐067: ADVANCED DIFFUSION WEIGHTING IMAGING (DWI) TRACTOGRAPHY OF THE LIMBIC SYSTEM: NOVEL BIOMARKERS OF NEURODEGENERATIVE CHANGES DURING PROGRESSION/CONVERSION FROM COGNITIVE NORMALITY TO AD DEMENTIA

There is growing evidence that the pathophysiological process of Alzheimer's disease (AD) begins decades before the clinical diagnosis (Aisen et al., 2011). Characterization of biological changes in early AD stages is fundamental to develop early detection and disease modifying therapy (Aisen et al., 2013). Hence, the identification of early Magnetic Resonance Imaging (MRI) markers would be essential for the understanding of the dynamic process that determines the progression/conversion from cognitive normality to mild cognitive impairment to the dementia stage of the AD (Ewers et al., 2011). Memory deficits typical for AD are linked to network disintegration (Bokde et al., 2009) and focused damage of the hippocampocentric division of the limbic system (Markowitsch, 2000) and differences in the clinical presentation may be related to key locations and the extension of the damage. New techniques such as Diffusion Weighting Imaging (DWI) tractography are extremely sensitive to discrete anatomical damage of the white matter (Zappala et al., 2012), which may or may not always leads to observable pathological behavior (Thiebaut de Schotten et al., 2011). Hence the DWI tractography of the hippocampocentric division of the limbic system (Catani and Thiebaut de Schotten, 2012; see figure 1) has the potential to highlight MRI markers in various stages of AD (Bokde et al. 2009). We are using recent neuroimaging methodologies to discover new DWI footprints as an indication of impaired anatomical networks (see figure 1) at various stages of AD, which have the potential to model and predict the conversion from cognitive normality to the symptomatic stages of AD. In particular we predict that pathways supporting the hippocampal-diencephalic network will be impaired in early prodromal patients as compared to healthy controls and non prodromal MCI. Results will be available by July 2014, and if successful this approach will be useful to determine if measures of brain 'structural connectivity' can translate into advances in clinical diagnosis, and/or AD-related outcome prognosis for individuals. Proposed functional-anatomical division of the limbic system into three distinct but partially overlapping networks and corresponding clinical syndromes. The main connections of the hippocampal-diencephalic network are the ventral cingulum, the fornix and the mammillo-thalamic tract (the endstations of this network are indicated in yellow). The main nodes of the temporo-amydgala-orbitofrontal network (indicated in green) are connected by the uncinate fasciculus. The dorsal cingulum is the main connection of the medial default network, whose cortical projections are shown in blue (see Catani and Thiebaut de Schotten, 2012)