Longitudinal Decreases in Functional Connectivity and Cognitive Decline in Parkinson’s Disease

Objective: To longitudinally evaluate fMRI whole-brain resting-state functional connectivity changes in relation to cognitive decline in Parkinson’s disease (PD). Methods: Resting-state fMRI scans were acquired in 55 PD patients (mean age 65.8 years, SD 6.37; average disease duration 9.24 years, SD 3.96) and 15 matched controls (mean age 64.4 years, SD 8.65). We performed overall (i.e. one whole-brain mean) as well as regional (i.e. for all individual regions of interest) functional connectivity analyses, in which we compared subject groups cross-sectionally. After a follow-up period of three years, 36 PD patients and 12 controls were re-scanned to study functional connectivity changes over time, and correlate the changes in functional connectivity with measures of cognitive and motor function in the PD sample. Results: We found widespread decreases in resting-state functional connectivity in PD patients in comparison to controls. Subsequent longitudinal analysis revealed that PD patients displayed further decreases in functional connectivity independent of aging effects. These functional connectivity changes were most prominent for posterior parts of the brain and correlated longitudinally with clinical measures of disease progression, especially cognitive decline. Conclusion: In this longitudinal fMRI study in PD we demonstrated a progressive loss of resting-state functional connectivity for multiple brain regions, especially in posterior parts of the brain. The strong correlation with decreasing cognitive performance supports the pathophysiological role of reduced functional connectivity in cognitive decline and the development of dementia in PD. Kim T.E. Olde Dubbelink1, Menno M. Schoonheim2, Jan Berend Deijen3, Jos W.R. Twisk4, Frederik Barkhof5, Henk W. Berendse1 1Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center 2Department of Anatomy and Neurosciences, VU University Medical Center 3Department of Clinical Neuropsychology, VU University 4Department of Clinical Epidemiology and Biostatistics, VU University Medical Center 5Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands Submitted for publication