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Abstract
Objective: The purpose of this study was to investigate the relationship between disruption of MRI-measured resting-state functional connectivity (rs-fcMRI) brain networks and CSF levels of potentially pathogenic proteins that reflect brain pathology in Parkinson disease (PD).
Methods: PD participants without dementia (n = 43) and age-matched controls (n = 22) had lumbar punctures to measure CSF protein levels, Pittsburgh compound B (PiB)–PET imaging, and rs-fcMRI while off medication. Imaging analyses focused on 5 major resting-state networks as well as the striatum.
Results: Participants with PD had significantly reduced sensorimotor functional connectivity, which correlated with reduced CSF levels of α-synuclein. The PD group also had significantly stronger default mode network functional connectivity that did not correlate with CSF β-amyloid (Aβ)42 or PiB uptake. In contrast, default mode network functional connectivity in the control group did correlate with CSF Aβ42 levels. Functional connectivity was similar between groups in the dorsal attention, control, and salience networks.
Conclusion: These results suggest that abnormal α-synuclein accumulation, but not Aβ, contributes to the disruption of motor-related functional connectivity in PD. Furthermore, correlating CSF protein measures with the strength of resting-state networks provides a direct link between abnormal α-synuclein metabolism and disrupted brain function in PD.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ANCOVA=
- analysis of covariance;
- BP=
- binding potentials;
- CDR=
- Clinical Dementia Rating;
- DAN=
- dorsal attention network;
- DMN=
- default mode network;
- MCBP=
- mean cortical binding potentials;
- MMSE=
- Mini-Mental State Examination;
- PD=
- Parkinson disease;
- PiB=
- Pittsburgh compound B;
- QA=
- quality assurance;
- ROI=
- region of interest;
- rs-fcMRI=
- resting-state functional connectivity MRI;
- RSN=
- resting-state network;
- SMN=
- sensorimotor network;
- TE=
- echo time;
- TR=
- repetition time;
- UPDRS-III=
- Unified Parkinson's Disease Rating Scale, Part III
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.
Supplemental data at Neurology.org
Editorial, page 2392
- Received October 7, 2014.
- Accepted in final form January 7, 2015.
- © 2015 American Academy of Neurology
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