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. 2020 Feb 18;94(7):e718-e728.
doi: 10.1212/WNL.0000000000008677. Epub 2019 Dec 18.

Proteinopathy and longitudinal changes in functional connectivity networks in Parkinson disease

Affiliations

Proteinopathy and longitudinal changes in functional connectivity networks in Parkinson disease

Meghan C Campbell et al. Neurology. .

Abstract

Objective: To evaluate resting-state functional connectivity as a potential prognostic biomarker of Parkinson disease (PD) progression. The study examined longitudinal changes in cortical resting-state functional connectivity networks in participants with PD compared to controls as well as in relation to baseline protein measures and longitudinal clinical progression.

Methods: Individuals with PD without dementia (n = 64) and control participants (n = 27) completed longitudinal resting-state MRI scans and clinical assessments including full neuropsychological testing after overnight withdrawal of PD medications ("off"). A total of 55 participants with PD and 20 control participants also completed baseline β-amyloid PET scans and lumbar punctures for CSF protein levels of α-synuclein, β-amyloid, and tau. Longitudinal analyses were conducted with multilevel growth curve modeling, a type of mixed-effects model.

Results: Functional connectivity within the sensorimotor network and the interaction between the dorsal attention network with the frontoparietal control network decreased significantly over time in participants with PD compared to controls. Baseline CSF α-synuclein protein levels predicted decline in the sensorimotor network. The longitudinal decline in the dorsal attention-frontoparietal internetwork strength correlated with the decline in cognitive function.

Conclusions: These results indicate that α-synuclein levels may influence longitudinal declines in motor-related functional connectivity networks. Further, the interaction between cortical association networks declines over time in PD prior to dementia onset and may serve as a prognostic marker for the development of dementia.

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Figures

Figure 1
Figure 1. Resting-state functional connectivity (RSFC) network regions
The expanded seed regions for each RSFC network are displayed as a representative slice for each network. Colors indicate the respective RSFC networks as follows: blue = default mode network (DMN); red = dorsal attention network (DAN); green = frontoparietal control network (FPCN); purple = salience network (SAL); teal = sensorimotor network (SMN). See table e-1 in Campbell et al.9 for a list of seed region coordinates.
Figure 2
Figure 2. Longitudinal network-level resting-state functional connectivity (RSFC) decline in Parkinson disease (PD)
(A) Linear growth curve models reveal a significant group × time interaction for the sensorimotor network (SMN) network, indicating longitudinal decline of SMN RSFC strength for the PD group (blue lines). (B) The interaction, or internetwork RSFC, between dorsal attention network (DAN) and frontoparietal control network (FPCN) declines longitudinally in the PD group (blue lines).
Figure 3
Figure 3. Proteinopathy, longitudinal resting-state functional connectivity (RSFC), and cognitive decline in Parkinson disease (PD)
(A) Within the PD group, sensorimotor network (SMN) RSFC strength declines the most for those with higher levels of CSF α-synuclein (i.e., +1 SD above the mean; blue line), while SMN RSFC strength is already reduced and remains relatively stable for those with lower levels (i.e., −1 SD below the mean; red line) of CSF α-synuclein. (B) Dorsal attention network (DAN)-FPCN internetwork strength declined the most among participants with PD with increased cognitive impairment (i.e., +1 SD above the mean; blue line), as measured by increased Clinical Dementia Rating (CDR) sum of boxes scores.

References

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