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IntroductionAdvanced methods of gait research, including approaches to quantify variability, and orderliness/regularity/predictability, are increasingly used to identify patients at risk for the development of cognitive impairment. Cerebral small vessel disease (CSVD) is highly prevalent in older adults and is known to contribute to the development of vascular cognitive impairment and dementia (VCID). Studies in preclinical models demonstrate that subclinical alterations precede CSVD-related cognitive impairment in gait coordination. In humans, CSVD also associates with gait abnormalities. The present study was designed to test the hypothesis that increased gait variability and gait asymmetry predict a decline in cognitive performance in older adults with CSVD.MethodsTo test this hypothesis, we compared cognitive performance and gait function in patients with CSVD (age: 69.8 ± 5.3 years; n = 11) and age- and sex-matched control participants (age: 70.7 ± 5.8 years; n = 11). Based on imaging findings, patients with CSVD were identified [presence of white matter hyperintensities plus silent brain infarcts and/or microhemorrhages on magnetic resonance imaging (MRI) assessment]. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Gait parameters were measured during the single and dual tasks, during which participants, in addition to the motor task, completed a series of mental arithmetic calculations. Spatial and temporal parameters of gait variability, symmetry, and permutation entropy were determined using a pressure-sensitive gait mat during single and dual cognitive task conditions.ResultsPatients with CSVD exhibited lower performance in a visual learning test (p = 0.030) and in a sustained attention test (p = 0.007). CSVD also affected step time variability (p = 0.009) and step length variability (p = 0.017). Step lengths of CSVD participants were more asymmetric (p = 0.043) than that of controls, while the two groups were statistically similar regarding step time symmetry and entropy of step time and length. Gait variability was inversely associated with sustained attention, especially among CSVD patients, and this relationship was significantly different between the two groups. The association of sustained attention with gait symmetry was also significantly different between the two groups.DiscussionOur findings provide additional evidence in support of the concept that increased gait variability and asymmetry may predict cognitive impairment in older adults with CSVD.

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.

Background: Dementia is the sixth leading cause of death in United States and causes significant disability in the aging population. Therefore, conversion of mild cognitive impairment (MCI) to dementia, and conditions affecting conversion (e.g., hypertension), is of the utmost public health concerns. COVID-19 has had a profound effect on the aging population with increased risk of cognitive dysfunction and cerebrovascular complications following recovery of infection. We have strong preliminary data that suggest COVID-19 increases progression rate from MCI to dementia compared to MCI patients with no COVID-19 history (56% vs 23%, respectively, p=0.011). However, mechanisms contributing to these findings have yet to be elucidated. Normal brain function is reliant on endothelium dependent cerebromicrovascular dilation to provide sufficient oxygen and nutrients to active neurons (neurovascular coupling [NVC]). Thus, due to COVID-19’s deleterious effects on the cerebrovasculature and association with cognitive impairment, it is necessary to investigate vascular mechanisms that may contribute to COVID-19 induced cognitive dysfunction. Our central hypothesis is that COVID-19 induces systemic endothelial dysfunction, impairing NVC responses and contributing to increased progression of MCI to dementia. Methods: We are addressing the central hypothesis through prospective follow-up design, assessing systemic and cerebrovascular function at baseline and 18-month follow-up in MCI patients with and without history of COVID-19 infection. We will collect 200 participants over the course of 3 years and progression to dementia data will be measured by semiannual evaluation in the Department of Neurology at the University of Oklahoma Health Sciences Center. Assessment of endothelial function was measured by laser speckle contrast imaging and flow mediated dilation studies. NVC responses were measured with functional near-infrared spectroscopy during cognitive stimulation with n-back test.Preliminary results: Our preliminary results were collected at baseline from 3 MCI patients with no history of cerebrovascular complications (1 COVID+ patient [77 years old, male]; 2 COVID- patients [55 and 65 years old, female]). COVID+ patient showed significant attenuation of NVC responses and peripheral macro- and microvascular endothelial function compared to COVID- patients. Conclusion: Preliminary data suggest that NVC and peripheral macro- and microvascular endothelium may be impaired in MCI patients with history of COVID-19 diagnosis. Further investigation into the role that COVID-19 has on cerebrovascular function and conversion to dementia will enhance the understanding of predisposing factors that influence progression to dementia. These findings may uncover a mechanism for how COVID-19 affects cognitive function, paving the way for future therapeutic interventions targeting neurovascular uncoupling as a prominent feature in the conversion to dementia. American Heart Association (AHA834339), the National Institute on Aging of National Institutes of Health (R01AG075834), and the NIA-supported Geroscience Training Program in Oklahoma (T32AG052363) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.