Objective: To evaluate whether altered cerebrovascular reactivity contributes to midbrain degeneration, perfusion abnormalities, or white matter disease in patients with Parkinson’s disease (PD).

Background: Cerebrovascular dysfunction is believed to play a role in the progression of Parkinson’s disease (PD). Patients with PD exhibit reduced and delayed cerebrovascular reactivity (CVR). However, the implications of altered CVR remain unclear. The current study investigates the relationship between CVR and MRI biomarkers of the substantia nigra degeneration, perfusion and white matter disease in patients with PD and healthy controls (HC).

Method: Patients with PD and age and sex matched HC underwent clinical and neuropsychological assessment and the following MRI imaging: 1) a vasodilatory challenge during functional MRI (fMRI) for the global latency and degree (measured by fit) of CVR, 2) pseudo continuous arterial spin labeling (pCASL) imaging for the arterial transit time (ATT) and global cerebral blood flow (CBF), 3) diffusion tensor imaging (DTI) for white matter damage (peak width of skeletonized mean diffusivity; PSMD), 4) fluid attenuated inversion recovery (FLAIR) for white matter hyperintensity volumes (WMH), and 5) neuromelanin sensitive MRI to quantify substantia nigra pars compacta signal (NM-SNc) for each participant.

Results: 29 PD and 28 HC were included in the analyses. Patients with PD exhibited reduced (F_3,53=6.87, p=0.01) and delayed global CVR (F_3,53=15.74, p<0.001), reduced global CBF (F_3,51=5.42, p=0.024), and reduced NM-SNc (F_3,48=19.73, p<0.001), with no significant differences in WMH and PSMD (though PSMD exhibited a trend: p=0.064).  Longer CVR delays were associated with lower global CBF (r=-0.31; p=0.02) as well as decreased NM-SNc (r=0.28, p=0.04).

Conclusion: Patients with PD exhibited reduced and delayed CVR, global CBF and reduced neuromelanin sensitive signal in the SNc. While effects were small, longer CVR latencies were significantly associated with reduced global CBF and an MRI biomarker of degeneration of the SNc. This suggests that cerebrovascular activity may contribute to perfusion and established disease processes in PD (midbrain degeneration) rather than indicators of cerebrovascular small vessel disease (e.g. PSMD and WMH).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/impact-of-altered-cerebrovascular-reactivity-on-midbrain-degeneration-perfusion-and-white-matter/