The Topography of Brain Damage at Different Stages of Parkinson's Disease (S22.006)

Objective: To investigate grey (GM) and white matter (WM) damage in patients at different clinical stages of Parkinson9s disease (PD). Background Pathologic abnormalities in PD extend beyond the nigrostriatal pathways and involve other projection neurons of the brainstem and cortex. Structural and diffusion tensor imaging (DTI) allow to interrogate the in vivo topography of brain tissue damage. Design/Methods: Eighty-nine PD (17 early, 46 mild, 14 moderate, and 12 severe) and 42 healthy subjects underwent structural and DTI. GM atrophy was assessed using voxel-based morphometry, and WM tract damage using tract-based spatial statistics. The correlations between GM and WM damage and the motor and global cognitive status of PD patients were explored. Results: Limbic and neocortical GM atrophy was detected in early PD patients and was found to be more severe in advanced stages. In early PD, the picture of WM damage was dominated by cerebellar involvement. In mild relative to early PD, WM damage involved the brainstem, basal ganglia-thalamo-cortical pathways, olfactory tracts, temporal and frontal WM. The most marked WM damage was found in moderate vs. mild cases, and included interhemispheric, limbic, and cortico-cortical association tracts. In severe PD, limbic tracts and cerebellar WM showed a greater damage than in moderate cases. WM damage correlated with the severity of both motor and cognitive deficits. Conclusions: GM and WM abnormalities beyond the nigrostriatal system accumulate with increasing PD severity. WM damage is likely to contribute to the more severe dysfunction of motor and nonmotor systems occurring in patients at the later-stages. Structural and DTI holds promise to achieve an in vivo PD staging, which should result in an improved understanding of the PD pathological mechanisms, and in the identification of reliable markers to be used in clinical trials. Supported by: Ministry of Science and Technology of the Republic of Serbia (Grant #175090). Disclosure: Dr. Sarro has nothing to disclose. Dr. Agosta received personal compensation for activities with Bayer-Schering AG as a speaker. Dr. Canu has nothing to disclose. Dr. Stojkovic has received personal compensation for activities with Biogen Idec, Bayer Schering Pharma, Teva, Merck, Sanofi, and LFB. Dr. Pievani has nothing to disclose. Dr. Tomic has received personal compensation for activities with PharmaSwiss as a trainer. Dr. Dragasevic has nothing to disclose. Dr. Copetti has nothing to disclose. Dr. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, Bayer Schering, and Biogen Dompe. Dr. Kostic has received personal compensation for activities with Novartis, GlaxoSmithKline, Inc., Boehringer Ingelheim Pharmaceuticals, Inc. and Abbott Laboratories, Inc., Pfizer Inc as a speaker and/or consultant. Dr. Filippi has received personal compensation for activities with ECTRIMS, MSIF, MS Ireland, US NMSS, Bayer-Schering, Biogen-Dompe AG, Genmab, Merck Serono, Pepgen Corporation, Teva, and Sanofi-Aventis. Dr. Filippi has received research support from Teva, Bayer-Schering and Genmab.