Cortico-striatal functional connectivity and cerebral small vessel disease: Contribution to mild Parkinsonian signs
James B Hengenius1, Nicolaas I Bohnen2, Andrea Rosso1
1Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Background And Purpose:
Mild Parkinsonian signs (MPS) are common in older adults. We hypothesized that MPS are associated with lower functional connectivity (FC) in dopamine-dependent cortico-striatal networks, and these associations vary with white matter hyperintensity (WMH), a risk factor for MPS.
Methods:
We examined resting-state functional MRI in 266 participants (mean age 83; 57% female; 41% African American) with data on MPS (Unified Parkinson's Disease Rating Scale), demographics, cognition, muscle-skeletal, and cardiometabolic health. FC between cortex and striatum was examined separately for sensorimotor, executive, and limbic functional subregions. Logistic regression tested the association of FC in each network with MPS, adjusted for covariates. Interactions of FC by WMH were tested; and analyses were repeated stratified by WMH above/below the median.
Results:
Compared to those without MPS, those with MPS had lower cortico-striatal FC in the left executive network (adjusted odds ratio [95% confidence interval], p-value: 0.188 [0.043, 0.824], .027). The interaction with WMH was p = .064; left executive FC was inversely associated with MPS for high WMH (0.077 [0.010, 0.599], .014) but not low WMH participants (1.245 [0.128, 12.132], .850).
Conclusions:
MPS appear related to lower executive network FC, robust to adjustment for other risk factors, and stronger for those with higher burden of WMH. Future longitudinal studies should examine the interplay between cerebral small vessel disease and connectivity influencing MPS.
Insights
Mild Parkinsonian signs (MPS) are linked to reduced executive network functional connectivity (FC). This association is stronger in individuals with higher white matter hyperintensity (WMH) burden.
Area of Science:
- Neuroscience
- Gerontology
- Radiology
Background:
- Mild Parkinsonian signs (MPS) are prevalent in aging populations.
- Cerebral small vessel disease, indicated by white matter hyperintensity (WMH), is a known risk factor for MPS.
- Dopamine-dependent cortico-striatal networks are crucial for motor control and cognition.
Purpose of the Study:
- To investigate the association between functional connectivity (FC) in dopamine-dependent cortico-striatal networks and MPS.
- To examine whether white matter hyperintensity (WMH) modifies the relationship between FC and MPS.
Main Methods:
- Resting-state functional MRI was used to assess FC in 266 older adults (mean age 83).
- FC was analyzed in sensorimotor, executive, and limbic cortico-striatal subregions.
- Logistic regression models, adjusted for covariates, tested associations between FC and MPS, including interactions with WMH.
Main Results:
- Individuals with MPS exhibited lower functional connectivity (FC) in the left executive cortico-striatal network compared to those without MPS.
- A significant interaction between FC and WMH was observed (p = .064).
- The inverse association between left executive FC and MPS was significant in participants with high WMH but not in those with low WMH.
Conclusions:
- Mild Parkinsonian signs (MPS) are associated with reduced executive network FC, independent of other risk factors.
- This association is amplified in individuals with a higher burden of white matter hyperintensity (WMH).
- Future research should explore the interplay of cerebral small vessel disease and brain connectivity in the development of MPS.
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