Diffusion tensor imaging changes in the corpus callosum and cognitive impairment in Parkinson’s disease (P4.029)

Objective: To evaluate diffusion characteristics of the corpus callosum using Diffusion Tensor Imaging (DTI) in a cohort of participants with Parkinson’s disease (PD) with varying degrees of cognitive impairment. Background: A majority of PD patients develop dementia (PDD), often preceded by a prodrome of mild cognitive impairment (PD-MCI). Prior studies have demonstrated DTI changes in the corpus callosum in PD cognitive impairment, but with limited information regarding the sub-regions of the callosum affected. Design/Methods: 75 PD and 24 healthy control (HC) participants received clinical and neuropsychological evaluation, MRI brain scans including DTI sequences, and cognitive classification by Movement Disorder Society criteria (cognitively normal [PD-NC], n=23; PD-MCI, n=35; demented [PDD], n=17). Z-scores for cognitive domain performance (attention/working memory, executive function, memory, language, visuospatial function) were calculated. DWI volumes were pre-processed using FSL, including calculation of Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AD) scalar values which were non-linearly registered to the IIT Brain Atlas mean-FA map. Scalar values of 5 callosal segments were compared between PD and HC cohorts and among PD cognitive groups using MANCOVA models with age, sex, and PD duration as covariates. Regression analyses were performed on cognitive domain scores and callosal scalar values. Results: PD participants showed increased AD values in the anterior 2/3rds of the corpus callosum. PDD participants had increased AD, MD, and RD values in the anterior 1/2 of the callosum compared to PD-NC participants and the anterior 1/6 th of the callosum compared to PD-MCI participants. DTI scalar values and cognitive domain z-scores showed the strongest associations in the most anterior callosal region. Conclusions: DTI changes of the corpus callosum in PD may suggest chronic microstructural changes in white matter. These changes may contribute to PD cognitive dysfunction due to altered information transfer among connected cortical areas. Study Supported by: NIH K23NS060949, Michael J. Fox Foundation, and Parkinson’s Disease Foundation Disclosure: Dr. Bledsoe has received personal compensation for activities with Unum Insurance as a consultant. Dr. Merkitch has nothing to disclose. Dr. Stebbins has received personal compensation for activities with Acadia, Pharmaceuticals, Adamas Pharmaceuticals, Inc., Ceregene, Inc., CHDI Management, Inc., Ingenix Pharmaceutical Services (i3 Research), Neurocrine Biosciences, Inc., and Pfizer, Inc. Dr. Stebbins has received research support from National Institutes of Health, Michael J. Fox Foundation for Parkinson’s Research, Dystonia Coalition, CHDI, International Parkinson and Movement Disorder Society, and CBD Solutions. Dr. Bernard has received research support from the Parkinson9s Disease Foundation. Dr. Goldman has received personal compensation for activities with Acadia, Biogen, Teva, Pfizer, Pri-Med, MedEdicus as a consultant, advisory board member, and for educational activities. Dr. Goldman has received research support from NIH, Michael J. Fox Foundation, Rush University Medical Center, Parkinson’s Disease Foundation, National Parkinson Foundation, Consolidated Anti-Aging, Acadia, Teva, and Biotie.