Exploring the Link Between Pharmacological Management of Orthostatic Hypotension and Cognitive Performance: A Scoping Review.

Abstract

Orthostatic hypotension is recognized as a potential contributor to cognitive impairment in older adults. It is still unknown whether pharmacological treatment of orthostatic hypotension can affect cognition. The aim of this scoping review was to identify whether treatment of orthostatic hypotension with midodrine, droxidopa, and fludrocortisone had any effect on cognitive performance. We searched the databases of Embase and MEDLINE. Key eligibility criteria included observational studies or clinical trials using midodrine, droxidopa, or fludrocortisone to treat adult patients with orthostatic hypotension with cognition assessed. Key search terms used were "orthostatic hypotension," "cognition," "midodrine," "fludrocortisone," and "droxidopa." Quality assessment was performed using the LEGEND (Let Evidence Guide Every New Decision) Evidence Evaluation System. A descriptive synthesis was undertaken because of heterogeneous study designs and assessments, categorizing studies by patient population, with no statistical pooling. Five studies met the criteria for the scoping review. These studies investigated midodrine, droxidopa, and fludrocortisone used individually, or in combination, to treat orthostatic hypotension. Three studies found cognitive improvements with orthostatic hypotension treatment, one found negative cognitive side effects with orthostatic hypotension medications and one study found no significant change. Three patient populations were examined in these studies: patients with dementia, patients with parkinsonism, and patients with spinal cord injury. Included studies were small, observational, and interventional and cognitive outcomes ranged from symptom-based assessments to formal neuropsychological testing. Limited conclusions can be drawn from these five studies because of non-standardized cognitive assessments, small sample sizes, and methodological variability. However, overall, this scoping review provides evidence that treatment of orthostatic hypotension might have a cognitive benefit in certain populations. Further observational studies and clinical trials are warranted to better elucidate whether combinations of midodrine, droxidopa, and fludrocortisone will work in specific patient populations to improve clinical outcomes.