White Matter Degeneration Profile in the Cognitive Cortico-Subcortical Tracts in Parkinson’s Disease Alexandru Hanganu, PhD , 1,2 Jean-Christophe Houde, MSc, 3 Vladimir S. Fonov, PhD, 4 Clotilde Degroot, MSc, 5,6 Beatriz Mejia-Constain, PhD, 5 Anne-Louise Lafontaine, MD, 6,7 Val erie Soland, MD, 8 Sylvain Chouinard, MD, 8 Louis D. Collins, PhD, 4 Maxime Descoteaux, PhD, 3 and Oury Monchi, PhD 1,2,5,6,9 * 1 Department of Clinical Neurosciences and Department of Radiology, University of Calgary, Calgary, Alberta, Canada 2 Cumming School of Medicine, Hotchkiss Brain Institute, Calgary, Alberta, Canada 3 Sherbrooke Connectivity Imaging Lab (SCIL), Computer Science Department, Universit e de Sherbrooke, Sherbrooke, Quebec, Canada 4 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montr eal, Quebec, Canada 5 Centre de Recherche, Institut Universitaire de G eriatrie de Montr eal, Montr eal, Quebec, Canada 6 Department of Neurology and Neurosurgery, McGill University, Montr eal, Quebec, Canada 7 Movement Disorders Unit, McGill University Health Center, Montr eal, Quebec, Canada 8 Unit e des Troubles du Mouvement Andr e Barbeau, Centre Hospitalier de l’Universit e de Montr eal, Montr eal, Quebec, Canada 9 Department of Radiology, Faculty of Medicine, University of Montr eal, Montr eal, Quebec, Canada ABSTRACT: Background: In Parkinson’s disease cognitive impairment is an early nonmotor feature, but it is still unclear why some patients are able to maintain their cognitive performance at normal levels, as quanti- fied by neuropsychological tests, whereas others can- not. The objectives of this study were to perform a cross-sectional study and analyze the white matter changes in the cognitive and motor bundles in patients with Parkinson’s disease. Methods: Sixteen Parkinson’s disease patients with normal cognitive performance, 19 with mild cognitive impairment (based on their performance of 1.5 standard deviations below the healthy population mean), and 16 healthy controls were compared with respect to their tractography patterns between the cortical cognitive / motor regions and subcortical structures, using high angular resolution diffusion imaging and constrained spherical deconvolution computation. Results: Motor bundles showed decreased apparent fiber density in both PD groups, associated with a significant increase in diffusivity metrics, number of reconstructed streamlines, and track volumes, compared with healthy controls. By contrast, in the cognitive bundles, decreased fiber density in both Parkinson’s groups was compounded by the absence of changes in diffusivity in patients with normal cognition, whereas patients with cognitive impair- ment had increased diffusivity metrics, lower numbers of reconstructed streamlines, and lower track volumes. Conclusions: Both PD groups showed similar patterns of white matter neurodegeneration in the motor bundles, whereas cognitive bundles showed a distinct pattern: Parkinson’s patients with normal cognition had white matter diffusivity metrics similar to healthy controls, whereas in patients with cognitive impairment white mat- ter showed a neurodegeneration pattern. V C 2018 Interna- tional Parkinson and Movement Disorder Society Key Words: Parkinson’s disease; mild cognitive impairment; white matter; high angular resolution diffu- sion imaging; constrained spherical deconvolution Parkinson’s disease (PD) is a progressive neurodegener- ative disorder characterized by a relatively selective loss of dopaminergic neurons in the substantia nigra and reduction of dopamine nerve terminals in the striatum. 1- 3 Cognitive function is impaired in up to 40% of PD patients in the early stages of the disease, 4,5 and it has been shown that up to 80% of PD patients will eventu- ally develop dementia after more than 8 years of dis- ease. 6 Dorso- and ventrolateral prefrontal cortices (DLPFC, VLPFC) are representative for assessing ------------------------------------------------------------------------------------------------------------------------------ *Correspondence to: Dr. Oury Monchi, PhD, Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada; Oury.Monchi@ucalgary.ca. Relevant conflicts of interest/financial disclosures: All authors have nothing to declare. Received: 14 September 2017; Revised: 22 January 2018; Accepted: 24 January 2018 Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.27364 RESEARCH ARTICLE Movement Disorders, Vol. 00, No. 00, 2018 1