title: Functional connectivity and cognitive decline over 3 years in Parkinson disease.
abstract: OBJECTIVE
  To evaluate fMRI whole-brain resting-state functional connectivity changes in relation to cognitive decline in Parkinson disease (PD) over a 3-year period.
  
  
  METHODS
  Resting-state fMRI scans were acquired in 55 patients with PD (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 first performed overall (i.e., 1 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 3-year follow-up period, 36 patients with PD and 12 controls were rescanned to study functional connectivity changes over time and correlate the changes in functional connectivity with deteriorating cognitive and motor function in the PD sample.
  
  
  RESULTS
  In the cross-sectional analysis, we found widespread decreases of resting-state functional connectivity in patients with PD in comparison to controls. Subsequent comparison between the 2 timepoints revealed that patients with PD 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 across time with clinical measures of disease progression, especially cognitive decline.
  
  
  CONCLUSIONS
  In this fMRI study in PD, we demonstrated a progressive loss of resting-state functional connectivity over a period of 3 years for multiple brain regions, especially in posterior parts of the brain. The strong correlation with decreasing cognitive performance supports the pathophysiologic role of reduced functional connectivity in cognitive decline and the development of dementia in PD.
authors.affiliation: From the Departments of Neurology (K.T.E.O.D., H.W.B.), Anatomy and Neurosciences (M.M.S.), Clinical Neuropsychology (J.B.D.), Clinical Epidemiology and Biostatistics (J.W.R.T.), and Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands. kte.oldedubbelink@vumc.nl.
authors.forename: Kim T E
authors.initials: KT
authors.lastname: Olde Dubbelink
authors.affiliation: From the Departments of Neurology (K.T.E.O.D., H.W.B.), Anatomy and Neurosciences (M.M.S.), Clinical Neuropsychology (J.B.D.), Clinical Epidemiology and Biostatistics (J.W.R.T.), and Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Menno M
authors.initials: MM
authors.lastname: Schoonheim
authors.affiliation: From the Departments of Neurology (K.T.E.O.D., H.W.B.), Anatomy and Neurosciences (M.M.S.), Clinical Neuropsychology (J.B.D.), Clinical Epidemiology and Biostatistics (J.W.R.T.), and Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Jan Berend
authors.initials: JB
authors.lastname: Deijen
authors.affiliation: From the Departments of Neurology (K.T.E.O.D., H.W.B.), Anatomy and Neurosciences (M.M.S.), Clinical Neuropsychology (J.B.D.), Clinical Epidemiology and Biostatistics (J.W.R.T.), and Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Jos W R
authors.initials: JW
authors.lastname: Twisk
authors.affiliation: From the Departments of Neurology (K.T.E.O.D., H.W.B.), Anatomy and Neurosciences (M.M.S.), Clinical Neuropsychology (J.B.D.), Clinical Epidemiology and Biostatistics (J.W.R.T.), and Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: From the Departments of Neurology (K.T.E.O.D., H.W.B.), Anatomy and Neurosciences (M.M.S.), Clinical Neuropsychology (J.B.D.), Clinical Epidemiology and Biostatistics (J.W.R.T.), and Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Henk W
authors.initials: HW
authors.lastname: Berendse
mesh_terms: D000368:Aged; D003072:Cognition Disorders / Q000175:diagnosis* / Q000503:physiopathology / Q000523:psychology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000639:trends*; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology* / Q000502:physiology; D010300:Parkinson Disease / Q000175:diagnosis* / Q000503:physiopathology / Q000523:psychology*; D013997:Time Factors