A multi-modal study on cerebrovascular dysfunction in cognitive decline of de novo Parkinson's disease

Vascular risk factors are increasingly implicated in Parkinson's disease (PD), but the role of altered cerebrovascular dysfunction in early-stage PD remains unclear. Here, we investigated resting-state cerebrovascular reactivity (RS-CVR), cerebral blood flow (CBF), arterial morphological changes, and corresponding alterations in functional connectivity density (FCD) in de novo PD patients with different cognitive status.

25 de novo PD patients with mild cognitive impairment (PD-MCI), 34 with normal cognition (PD-NC), and 48 healthy controls (HCs) underwent neuropsychological assessments and multimodal MRI. CBF derived from arterial spin labeling, RS-CVR and FCD generated from resting-state functional MRI and the arterial morphology extracted from the magnitude images of multi-echo gradient echo.

RS-CVR significantly decreased in PD patients, particularly in the left occipital gyrus and posterior cerebral artery (PCA) territories. Long-range FCD was reduced in the left inferior occipital gyrus in both PD-NC and PD-MCI compared to HCs (p = 0.005, p < 0.001). In PD-MCI, negative correlations between Stroop Color-Word Test time and RS-CVR in the distal right PCA (r = -0.71, pFDR = 0.030) and middle left PCA (r = -0.66, pFDR = 0.044) were observed. A significant correlation was found between decreased long-range FCD in the left inferior occipital gyrus and poorer Trail Making Test Part B performance (r = -0.63, pFDR = 0.029) in the PD-MCI. No significant differences in CBF, but significant dilation of the left PCA and compensatory CBF increases in the corresponding territory in PD-MCI were found (r = 0.57, pFDR = 0.023).

Microvascular dysfunction, rather than perfusion defects, might underlie early-stage of the de novo PD, especially in the patients with PD-MCI.