Vascular mechanisms leading to progression of mild cognitive impairment to dementia after COVID-19: Protocol and methodology of a prospective longitudinal observational study

Abstract

Introduction Mild cognitive impairment (MCI) is a prodromal stage to dementia, affecting up to 20% of the aging population worldwide. Patients with MCI have an annual conversion rate to dementia of 15–20%. Thus, conditions that increase the conversion from MCI to dementia are of the utmost public health concern. The COVID-19 pandemic poses a significant impact on our aging population with cognitive decline as one of the leading complications following recovery from acute infection. Recent findings suggest that COVID-19 increases the conversion rate from MCI to dementia in older adults. Hence, we aim to uncover a mechanism for COVID-19 induced cognitive impairment and progression to dementia to pave the way for future therapeutic targets that may mitigate COVID-19 induced cognitive decline. Methodology A prospective longitudinal study is conducted at the University of Oklahoma Health Sciences Center. Patients are screened in the Department of Neurology and must have a formal diagnosis of MCI, and MRI imaging prior to study enrollment. Patients who meet the inclusion criteria are enrolled and followed-up at 18-months after their first visit. Visit one and 18-month follow-up will include an integrated and cohesive battery of vascular and cognitive measurements, including peripheral endothelial function (flow-mediated dilation, laser speckle contrast imaging), retinal and cerebrovascular hemodynamics (dynamic vessel retinal analysis, functional near-infrared spectroscopy), and fluid and crystalized intelligence (NIH-Toolbox, n-back). Multiple logistic regression will be used for primary longitudinal data analysis to determine whether COVID-19 related impairment in neurovascular coupling and increases in white matter hyperintensity burden contribute to progression to dementia.

Gut Microbiota and Mitochondria: Health and Pathophysiological Aspects of Long COVID

“…Thus, research on the modulation of NAD+ bioavailability may reshape the evolution of immune diseases and hold great future translational potential for new therapies for inflammatory pathologies such as SARS-CoV-2 infection. Meanwhile, dietary precursors such as NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide) can promote NAD+ biosynthesis and increase its intracellular levels, opening avenues for new strategies and future perspectives through their beneficial physiological effects and their interaction with the gut microbiota, which reverse physiological decline and prevent disease through nutrition and food science research [135][136][137][138][139].…”

Neurofilament light chain and glial fibrillary acid protein levels are elevated in post-mild COVID-19 or asymptomatic SARS-CoV-2 cases

“…Research on mild COVID-19 cases indicates a concerning association with cognitive deficits in the general population, regardless of COVID clinical course and severity 12 and with no association with any blood inflammatory marker 13 Particularly, a recent study suggests that even in mild cases COVID-19 infection promote systemic endothelial dysfunction, impair the homeostatic mechanism of neurovascular coupling and promote white matter damage, contributing to the progression of mild cognitive impairment 14 . In another study, post-COVID cognitive dysfunction has been described in 43% of patients and associated with younger age 15 In fact, this cognitive decline is not limited to older adults, as evidenced by another study that documented executive functioning deficits in young and middle-aged adults who were never hospitalized during acute COVID-19 16 .…”