White matter abnormalities as a marker of Parkinson’s disease cognitive impairment: a diffusion tensor imaging study (P3.017)

Objective: To investigate markers of white matter (WM) microstructural integrity across the Parkinson’s disease (PD) cognitive spectrum using diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) and mean diffusivity (MD). Background: Dementia develops in about 80[percnt] of PD patients in longitudinal studies. Abnormalities in WM may contribute to PD cognitive impairment and can be identified with neuroimaging techniques. Thus, DTI holds promise as a biomarker for PD cognitive decline. Methods: Sixty-three PD patients underwent clinical/neuropsychological evaluations, T1- and diffusion-weighted magnetic resonance imaging brain scans, and cognitive classification by Movement Disorder Society criteria (cognitively normal (PD-NC), n=20; mild cognitive impaired (PD-MCI), n=28; demented (PDD), n=15). DTI data were processed with mrDiffusion, and whole-brain comparisons of the resulting smoothed FA and MD maps, controlling for PD duration, were analyzed in SPM8 (p<0.001, uncorrected, k=10). Results: The groups differed in PD duration (mean [SD]: PD-NC 8.8 [3.6], PD-MCI 9.4 [4.2], PDD 13.4 [5.5] years, p=0.007), but not in gender, age (73.4 [6.2] years) or education (15.3 [3.1] years). The PD-MCI group showed decreased FA in frontal, temporal, parietal, and occipital lobes, including the anterior corona radiata, anterior thalamic radiation, inferior fronto-occipital fasciculus, and uncinate fasciculus, and increased MD in frontal, parietal, and temporal lobes, including the superior longitudinal fasciculus, compared to PD-NCs. The PDD group had decreased FA in similar regions but also the posterior corona radiata, and increased MD in frontal, temporal/parietal, and limbic lobes, including corpus callosum splenium and superior longitudinal fasciculus, compared to PD-NCs. Comparisons of PD-MCI and PDD groups revealed no significant FA/MD differences. Conclusion: WM microstructural abnormalities occur in cognitively impaired PD patients, particularly in regions underlying attention/working memory, executive function, memory, and visuospatial processing. Furthermore, greater disruption of posterior WM pathways may signify PD cognitive decline. Acknowledgments: K23NS060949, Parkinson9s Disease Foundation Disclosure: Dr. Goldman has received personal compensation for activities with the American Academy of Neurology, Movement Disorder Society, and Acadia, Pfizer, and Teva Neuroscience. Dr. Goldman has received support from NIH/NINDS, Michael J. Fox Foundation, and the Dr. Merkitch has nothing to disclose. Dr. Bernard has received research support from the Parkinson9s Disease Foundation. Dr. Stebbins has nothing to disclose.