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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.
GLOSSARY
- AD=
- Alzheimer disease;
- CAMCOG=
- Cambridge Cognitive Examination;
- DMN=
- default mode network;
- FA=
- flip angle;
- FDR=
- false discovery rate;
- GEE=
- generalized estimated equations;
- GLM=
- general linear model;
- LEDD=
- levodopa equivalent daily dose;
- MEG=
- magnetoencephalography;
- MELODIC=
- Multivariate Exploratory Linear Optimized Decomposition into Independent Components;
- PD=
- Parkinson disease;
- PDD=
- Parkinson disease–related dementia;
- ROI=
- region of interest;
- SL=
- synchronization likelihood;
- TE=
- echo time;
- TI=
- inversion time;
- TR=
- repetition time;
- UPDRS-III=
- Unified Parkinson's Disease Rating Scale motor rating
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 2000
Supplemental data at Neurology.org
- Received December 5, 2013.
- Accepted in final form August 20, 2014.
- © 2014 American Academy of Neurology
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