Objective: To investigate the cerebrovascular contribution to cognitive decline in Parkinson’s disease (PD).

Background: Cognitive impairment is a major non-motor feature of PD. Accruing evidence associates cognitive impairment in aging and Alzheimer’s disease (AD) with neurovascular disease [1]. Despite this, in PD, where cardiovascular dysautonomia is prevalent in 80% of cases [2], the relevance of neurovascular health to cognitive outcomes is unclear. Based on work in AD [3], we hypothesised that PD was associated with haemodynamic changes within the large cerebral vessels, which would be more severe with worsening cognitive function.

Method: 4D flow MRI enables dynamic visualisation of vascular anatomy and blood flow across time. Following clinical and neuropsychological assessment of controls undergoing normal aging (n = 34) and individuals with PD (n = 81), we used 4D flow MRI to investigate haemodynamic changes across the circle of Willis (coW). Scans were acquired using a prototype sequence on a 3T Siemens Skyra MRI (Erlangen, Germany), employing a 3D phase-contrast acquisition with retrospective cardiac gating (velocity encoding (venc): 100 cm/s, phases/bins per cardiac cycle: 20, field of view: 210 x 171 x 40 mm, centred on the coW, spatial resolution: 1mm³ ). Bayesian multilevel regression models were used to 1) compare flow metrics between groups, 2) investigate the association between flow metrics and cognitive ability, and 3) assess the impact of cardiovascular risk factors on flow metrics.

Results: PD was associated with a 10% total cerebral blood flow (CBF) deficit, and reduced flow velocity, unattributable to local anatomical differences. Lower total CBF corresponded with poorer cognitive ability across all participants. Cognitive impairment was associated with increased vascular stiffening in PD. In addition, hyperlipidemia was identified as a compounding risk factor for CBF volume and velocity deficits in PD.

Conclusion: Metrics derived from 4D flow MRI suggest impaired haemodynamics in the large cerebral vessels in PD. These cerebrovascular changes are associated with poorer cognitive function. Given the association of coW stiffening with lower cognitive ability in PD, we speculate that a breakdown of the autoregulatory relationship between the large and small cerebrovasculature may be occurring. Our results support considering neurocardiac targeted interventions to maintain cognitive health in PD.

References: [1] Dag, A., Lucia, B., Halliday, G. M., Geurtsen, G. J., Ballard, C., Ray, C. K., & Weintraub, D. (2021). Parkinson disease-associated cognitive impairment (primer). Nature Reviews: Disease Primers, 7(1).
[2] Goldstein, D. S. (2014). Dysautonomia in Parkinson’s disease: neurocardiological abnormalities. Comprehensive Physiology, 4(2), 805.
[3] Rivera-Rivera, L. A., Turski, P., Johnson, K. M., Hoffman, C., Berman, S. E., Kilgas, P., … & Wieben, O. (2016). 4D flow MRI for intracranial hemodynamics assessment in Alzheimer’s disease. Journal of Cerebral Blood Flow & Metabolism, 36(10), 1718-1730.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neurovascular-involvement-in-parkinsons-disease-cognitive-impairment-a-4d-flow-study/