Effects of Blood Pressure on Cognition and Cerebral Hemodynamics in PD

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and causes disabling non-motor symptoms that include cognitive impairment and low blood pressure (BP) on standing, called orthostatic hypotension (OH). About 30-50% of people with PD have OH; cognitive impairment is also common in PD and has several causes. OH is associated with cognitive impairment in PD, but it is unknown to what extent OH could be a treatable risk factor for cognitive decline. People with PD and OH can experience sudden temporary cognitive dysfunction when upright, suggesting that OH-related drops in BP can transiently reduce blood flow to the brain. In PD, OH also correlates strongly with long-term cognitive decline, predicting a 7-times higher risk of dementia. But it is unclear to what extent episodic cerebral hypoperfusion from OH - even if asymptomatic - contributes to ischemic brain damage that impacts long-term cognitive impairment in PD, which is a critical knowledge gap. This project's objective is to determine how BP affects positional cognitive performance and brain blood flow in PD. We hypothesize that in person with PD patients with OH, but not those without OH, a critical threshold of cerebral hypoperfusion correlates with acute, temporary cognitive deficits when upright compared to supine and contributes to chronic cognitive decline. The proposed experiments will close the existing knowledge gaps by determining the associations between BP and cerebral hemodynamics (brain blood flow) with cognitive performance. Experiments will be performed at baseline and repeated at two years. Sixty non-demented individuals with PD with OH (n=30) and without OH (n=30) will complete a computerized battery of cognitive tests in the supine and upright positions on a tilt table while undergoing simultaneous, non-invasive, continuous monitoring of BP and brain hemodynamics using functional near-infrared spectroscopy (fNIRS). Aim 1 will determine how BP relates to cognitive performance while supine and while upright. Aim 2 will use fNIRS to determine how cerebral hemodynamics (fNIRS) relate to cognitive performance and BP. Aim 3 will repeat the baseline assessments at a two-year follow-up visit to determine which BP and fNIRS measures are most associated with cognitive decline. We will compare these outcomes in participants with and without OH. This study will yield novel data about the short-term and long-term effects of low BP on cognitive performance and brain hemodynamics. Improving understanding of how BP affects cognition in PD will advance knowledge toward developing treatment targets to reverse, prevent, or delay OH-related cognitive impairment.