Abstract
Mild cognitive impairment in Parkinson's disease is associated with progression to dementia (Parkinson's disease dementia) in a majority of patients. Determining structural imaging biomarkers associated with prodromal Parkinson's disease dementia may allow for the earlier identification of those at risk, and allow for targeted disease modifying therapies. One hundred and five non-demented subjects with newly diagnosed idiopathic Parkinson's disease and 37 healthy matched controls had serial 3 T structural magnetic resonance imaging scans with clinical and neuropsychological assessments at baseline, which were repeated after 18 months. The Movement Disorder Society Task Force criteria were used to classify the Parkinson's disease subjects into Parkinson's disease with mild cognitive impairment (n = 39) and Parkinson's disease with no cognitive impairment (n = 66). Freesurfer image processing software was used to measure cortical thickness and subcortical volumes at baseline and follow-up. We compared regional percentage change of cortical thinning and subcortical atrophy over 18 months. At baseline, cases with Parkinson's disease with mild cognitive impairment demonstrated widespread cortical thinning relative to controls and atrophy of the nucleus accumbens compared to both controls and subjects with Parkinson's disease with no cognitive impairment. Regional cortical thickness at baseline was correlated with global cognition in the combined Parkinson's disease cohort. Over 18 months, patients with Parkinson's disease with mild cognitive impairment demonstrated more severe cortical thinning in frontal and temporo-parietal cortices, including hippocampal atrophy, relative to those with Parkinson's disease and no cognitive impairment and healthy controls, whereas subjects with Parkinson's disease and no cognitive impairment showed more severe frontal cortical thinning compared to healthy controls. At baseline, Parkinson's disease with no cognitive impairment converters showed bilateral temporal cortex thinning relative to the Parkinson's disease with no cognitive impairment stable subjects. Although loss of both cortical and subcortical volume occurs in non-demented Parkinson's disease, our longitudinal analyses revealed that Parkinson's disease with mild cognitive impairment shows more extensive atrophy and greater percentage of cortical thinning compared to Parkinson's disease with no cognitive impairment. In particular, an extension of cortical thinning in the temporo-parietal regions in addition to frontal atrophy could be a biomarker in therapeutic studies of mild cognitive impairment in Parkinson's disease for progression towards dementia.
Highlights
Parkinson’s disease is a progressive neurodegenerative disorder affecting over 4 million people worldwide above the age of 50, with a prevalence that is expected to double to 9.3 million by 2030 (Dorsey et al, 2007)
Parkinson’s disease eventually developing mild cognitive impairment (PD-MCI) subjects were significantly older than Parkinson’s disease with no cognitive impairment (PD-NC) subjects (P = 0.001), there were no significant differences in age between PD-MCI and healthy controls (P = 0.170) or between PD-NC and healthy controls (P = 0.308)
Compared to PD-NC, levodopa equivalent daily dose intake was significantly higher in PD-MCI (P 5 0.001) at baseline but there were no significant differences in levodopa equivalent daily dose intake at follow-up and changes of dosage over 18 months
Summary
Parkinson’s disease is a progressive neurodegenerative disorder affecting over 4 million people worldwide above the age of 50, with a prevalence that is expected to double to 9.3 million by 2030 (Dorsey et al, 2007). Previous voxel-based morphometric (VBM) studies have found detected atrophy in the temporal, parietal and frontal cortices in PD-MCI compared to Parkinson’s disease with no cognitive impairment (PD-NC) (Song et al, 2011; Melzer et al, 2012). These anatomical changes were mirrored by neurocognitive functional abnormalities (Nombela et al, 2014). A previous VBM study with a large sample of 148 subjects with Parkinson’s disease did not reveal any significant grey matter atrophy in PD-MCI compared with healthy controls (Pereira et al, 2012). Surface-based analyses of cortical thickness may prove to be more sensitive than VBM (Pereira et al, 2012), as there is evidence from corticometry studies showing cortical thinning in temporal and parietal regions in PD-MCI relative to PD-NC (Pagonabarraga et al, 2013; Pereira et al, 2014; Segura et al, 2014)
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