LONGITUDINAL DIFFUSION TENSOR IMAGING AS A PREDICTOR OF COGNITIVE DOMAIN DECLINE IN EARLY-STAGE PARKINSON’S DISEASE: ICICLE-PD STUDY

Abstract

The risk of patients with Parkinson's disease developing dementia is five times greater than the general population. As the pathophysiological processes underlying Parkinson's disease (PD) dementia are heterogeneous, monitoring the progression of white matter microstructural changes might help identify its role in mediating cognitive deficits in PD. This study investigated whether white matter microstructural abnormalities are predictors of cognitive domains changes in early Parkinson's disease (PD). A total of 123 patients with early PD were enrolled along with 49 controls. Participants were part of the ICICLE-PD (Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation) study and underwent clinical, cognitive and DTI investigations at baseline and 18 months later with cognitive and diffusion tensor imaging. General cognition was tested using the Mini-Mental State Examination. Attention, memory, language, executive and visuospatial functions were assessed based on a selection of subtests from different batteries. Imaging parameters were analysed using Tract Based Spatial Statistics. The relationships between fractional anisotropy (FA) and mean diffusivity (MD) with cognition were investigated using multiple linear regression. All analyses were controlled for age, sex, education, levodopa dose and visit intervals. At baseline, patients with PD had significantly higher widespread MD then controls. At follow-up, both groups showed a further significant FA decrease and MD increase. Baseline MD was a significant predictor of executive function (β (95%CI) -7.85 (-11.81; -3.88), p<0.001) and general cognitive change (β (95%CI) -9.58 (-16.56; -2.60), p 0.008) among patients with PD. MD represents an important correlate and predictor of cognitive change and in PD: DTI is potentially a useful tool in stratification of patients into clinical trials and to monitor the impact of treatment on cognition.