White Matter Structural Network Dysfunction Mediates the Effect of Hypertension on Cognitive Decline in Parkinson Disease

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Abstract
Objectives: Hypertension (HBP) is a risk factor for the development of motor and cognitive functions in Parkinson disease (PD) patients, but the specific mechanism is unclear. This study investigated white matter structural network abnormalities and their mediation effect of cognitive decline in patients with PD and HBP. Methods: PD patients with HBP and normal blood pressure (HBP and non-HBP) underwent conventional and multi-shell diffusion magnetic resonance imaging (MRI) at baseline. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at baseline and 12-month follow-up. Enlarged perivascular spaces (EPVS) in the basal ganglia and midbrain were assessed at baseline. White matter structural network based on the diffusion MRI was constructed. The mediation effect and correlations of EPVS and the network metrics with cognitive function were analyzed. Results: At 12-month follow-up, the cognitive decline was found in the HBP group. Global connectivity was impaired in the HBP group. The number and maximum diameter of EPVS were higher in the HBP group. The nodal connectivity was impaired in the HBP group and associated with the cognitive function at baseline and follow-up. Both global and nodal network metrics, as well as the counts of EPVS mediated the effect of HBP on the cognitive decline. Conclusions: The PD patients with HBP had worse cognitive function. Hypertensive impairment of white matter connectivity may be the underlying mechanism of cognitive decline in PD patients.

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