White matter microstructure deteriorates across cognitive stages in Parkinson disease

Objectives: To characterize different stages of Parkinson disease (PD)-related cognitive decline using diffusion tensor imaging (DTI) and investigate potential relationships between cognition and microstructural integrity of primary white matter tracts. Methods: Movement Disorder Society criteria were used to classify 109 patients with PD as having normal cognition (PD-N, n = 63), mild cognitive impairment (PD-MCI, n = 28), or dementia (PD-D, n = 18), and were compared with 32 matched controls. DTI indices were assessed across groups using tract-based spatial statistics, and multiple regression was used to assess association with cognitive and clinical measures. Results: Relative to controls, PD-N showed some increased mean diffusivity (MD) in corpus callosum, but no significantly decreased fractional anisotropy (FA). Decreased FA and increased MD were identified in PD-MCI and PD-D relative to controls. Only small areas of difference were observed in PD-MCI and PD-D compared with PD-N, while DTI metrics did not differ significantly between PD-MCI and PD-D. Executive function, attention, memory, and a composite measure of global cognition were associated with MD, primarily in anterior white matter tracts; only attention was associated with FA. These differences were independent of white matter hyperintensity load, which was also associated with cognition in PD. Conclusions: PD is associated with spatially restricted loss of microstructural white matter integrity in patients with relatively normal cognition, and these alterations increase with cognitive dysfunction. Functional impairment in executive function, attention, and learning and memory appears associated with microstructural changes, suggesting that tract-based spatial statistics provides an early marker for clinically relevant cognitive impairment in PD.