Dopaminergic degeneration induces early posterior cortical thinning in Parkinson's disease

Background: Cognitive decline in Parkinson's disease (PD) is a highly prevalent condition with no effective treatment. Cortical atrophy is thought to promote its development but to design optimal therapeutic approaches in this clinical setting we need to understand the physiopathological mechanisms leading to this disorder. Objective: To characterize the impact of dopaminergic degeneration on cortical integrity in early PD. Methods: We studied 87 recently-diagnosed PD patients and 38 healthy controls from the Parkinson's Progression Marker Initiative who underwent I123-ioflupane SPECT (DATSCAN) and T1-MRI imaging. Using Freesurfer 6.0, we characterized baseline and longitudinal (one-year) correlations between striatal DAT uptake and cortical thickness. We also addressed the association between these imaging biomarkers and cognitive measures. Results: Reduced DAT uptake in PD patients was associated with cross-sectional and longitudinal cortical thinning in frontal and posterior-cortical brain regions. Imaging parameters correlated with cognitive indicators in multiple domains that extend beyond frontal-executive tasks. Dopaminergic medication attenuated the longitudinal loss of cortical integrity in frontal and a subset of parietal regions, but not in other key regions such as the precuneus. Discussion: To date, posterior cortical alterations in PD, known to play a major role in the development of PD dementia, have mainly been attributed to a cholinergic degeneration occurring in later stages of the disease. Our results suggest that dopamine loss also promotes posterior-cortical atrophy from the very early stages of Parkinson's disease, which may have potential clinical and therapeutic implications.