Resting-state fMRI in Parkinson's disease patients with cognitive impairment: A meta-analysis

Background. Cognitive impairment is a common non-motor symptom in Parkinson's disease. So far, the underlying pathophysiology remains unclear. Several alterations in functional network connectivity have been described in Parkinson's disease patients with cognitive impairment which are probably the result of the heterogenous pathophysiology underlying this cognitive decline, including dopaminergic and cholinergic deficits. Accordingly, the reported resting-state connectivity patterns vary greatly among studies. Objective: To evaluate the localization and magnitude of functional connectivity patterns in resting-state brain networks in Parkinson's disease patients with cognitive impairment by pooling data from available studies. Methods: We searched PubMed, the Cochrane Library, MEDLINE, Embase and PsycINFO to identify functional MRI studies in Parkinson's disease patients with cognitive impairment. A voxel-based meta-analysis combined with quality statistics was performed, using the anisotropic effect-size version of the signed differential mapping method. Results: Seventeen studies with cognitively impaired Parkinson's disease patients were included consisting of 222 Parkinson's disease patients with mild cognitive impairment, 68 patients with Parkinson's disease dementia, 289 cognitively unimpaired Parkinson's disease patients and 353 healthy controls. Parkinson's disease patients with cognitive impairment predominantly showed a reduced connectivity in specific brain regions that are part of the default mode network. Conclusion: Cognitive impairment in Parkinson's disease is associated with reduced connectivity in networks relevant to cognition, most prominently the default mode network. Specific alterations in functional connectivity may contribute to cognitive decline in Parkinson patients and may be a promising future biomarker.