Cognitive deficits in mild Parkinson's disease are associated with distinct areas of grey matter atrophy

Background and objectives The neuroanatomical substrates underlying cognitive impairment in Parkinson's disease (PD) remain poorly understood. To address this gap, we compared the grey matter atrophy patterns in PD patients with mild cognitive impairment (PD-MCI) with PD patients having no cognitive impairment (PD-NCI), and examined relationships between atrophic regions and cognitive performance in specific domains. Methods 90 non-demented PD patients (64.95 +/- 7.54 years, Hoehn and Yahr = 1.88 +/- 0.39) were classified using formal diagnostic criteria as PD-MCI (n= 23) or PD-NCI (n= 67). Grey matter volume differences were examined using voxel-based morphometry on structural MRI, and multivariate linear regressions were employed to assess the relationships between cognitive performance in specific domains and atrophic regions. Results Patients with PD-MCI had lower global cognition scores compared with PD-NCI (Mini Mental State Examination: 26.9 vs28.4, p= 0.011; Montreal Cognitive Assessment: 24.5 vs 27.0, p<0.001). The PD-MCI group demonstrated significantly poorer performance on executive function, attention, memory and language abilities. Patients with PD-MCI had reductions in grey matter volumes in the left insular, left superior frontal and left middle temporal areas compared to PD-NCI. Multiple regressions controlling for age, education and cardiovascular risk factors revealed significant positive correlations between left insular atrophy and executive-attention dysfunction. Conclusions Domain specific cognitive impairment in mild PD is associated with distinct areas of grey matter atrophy. These regions of atrophy are demonstrable early in the disease course and may serve as a biomarker for dementia in PD.