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Mild cognitive impairment (MCI) affects nearly 20% of older adults worldwide, with no targetable interventions for prevention. COVID-19 adversely affects cognition, with >70% of older adults with Long COVID presenting with cognitive complaints. Neurovascular coupling (NVC), an essential mechanism of cognitive function, declines with aging and is further attenuated in neurocognitive disorders. The effect of COVID-19 on NVC responses has yet to be addressed in older adults who are vulnerable to dementia progression. Participants with MCI and a history of COVID-19 (COV+, N = 31) and MCI participants with no history of infection (COV− N = 11) participated in this cross-sectional study to determine if COVID-19 affects cerebrocortical NVC responses and vascular function. Functional near-infrared spectroscopy was used to measure cerebrocortical NVC responses, and endothelial function was assessed via insonation of the brachial artery during a flow-mediated dilation protocol. NVC responses were elicited by the working memory n-back paradigm. NVC in the left dorsolateral prefrontal cortex and endothelial function was decreased in the COV+ group compared to the COV− group. These data provide mechanistic insight into how COVID-19 may exacerbate long-term cognitive sequela seen in older adults, highlighting the urgent need for further research and clinical trials to explore novel therapeutic interventions aimed at preserving/restoring NVC. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) is known to be associated with decreased cognitive performance; however, the underlying mechanisms are poorly understood. As interactions between distinct brain regions depend on mental state, functional brain networks established by these connections typically show a reorganization during task. Hence, analysis of functional connectivity (FC) could reveal the task‐related change in the examined frontal brain networks. Our objective was to assess the impact of SD on static FC in the prefrontal and motor cortices and find whether changes in FC correlate with changes in neuropsychological scores. Healthy young male individuals (n = 10, 27.6 ± 3.7 years of age) participated in the study. A battery of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and 48 channel functional near‐infrared spectroscopy (fNIRS) measurements were performed before and after 24 hr of SD. Network metrics were obtained by graph theoretical analysis using the fNIRS records in resting state and during finger‐tapping sessions. During task, SD resulted in a significantly smaller decrease in the number and strength of functional connections (characterizing FC) in the frontal cortex. Changes in the global connection strengths correlated with decreased performance in the paired association learning test. These results indicate a global impact of SD on functional brain networks in the frontal lobes. [ABSTRACT FROM AUTHOR]

Understanding how the brain allocates resources to match the demands of active neurons under physiological conditions is critically important. Increased metabolic demands of active brain regions are matched with hemodynamic responses known as neurovascular coupling (NVC). Several methods that allow noninvasive assessment of brain activity in humans detect NVC and early detection of NVC impairment may serve as an early marker of cognitive impairment. Therefore, non-invasive NVC assessments may serve as a valuable tool to detect early signs of cognitive impairment and dementia. Working memory tasks are routinely employed in the evaluation of cognitive task-evoked NVC responses. However, recent attempts that utilized functional near-infrared spectroscopy (fNIRS) or transcranial Doppler sonography (TCD) while using a similar working memory paradigm did not provide convincing evidence for the correlation of the hemodynamic variables measured by these two methods. In the current study, we aimed to compare fNIRS and TCD in their performance of differentiating NVC responses evoked by different levels of working memory workload during the same working memory task used as cognitive stimulation. Fourteen healthy young individuals were recruited for this study and performed an n-back cognitive test during TCD and fNIRS monitoring. During TCD monitoring, the middle cerebral artery (MCA) flow was bilaterally increased during the task associated with greater cognitive effort. fNIRS also detected significantly increased activation during a more challenging task in the left dorsolateral prefrontal cortex (DLPFC), and in addition, widespread activation of the medial prefrontal cortex (mPFC) was also revealed. Robust changes in prefrontal cortex hemodynamics may explain the profound change in MCA blood flow during the same cognitive task. Overall, our data support our hypothesis that both TCD and fNIRS methods can discriminate NVC evoked by higher demand tasks compared to baseline or lower demand tasks. [ABSTRACT FROM AUTHOR]

Age-related gait dysfunction and balance disorders are a major cause of falls and injury in the elderly population. Epidemiological studies have shown that disturbances in gait coordination which manifest with age are associated with increased morbidity and mortality, impaired cognitive capacity, as well as reduced level of function and loss of independence. In geroscience, mice are the most frequently used model system to test efficiency of antiaging interventions. Despite the clinical importance of age-related gait abnormalities in older adults, the impact of aging on mouse gait coordination is not well documented in the literature. To characterize the effect of aging on mouse gait, we assessed gait function in young (3-month-old) and aged (24-month-old) freely moving C57BL/6 mice using the semiautomated, highly sensitive CatWalk XT system for quantitative assessment of footfall and motor performance. We found that aged mice exhibited significantly decreased cadence and increased stride time variability. Aging also tended to alter footfall patterns. In aged mice, speed, swing speed, stride length, duty cycle, base of support, terminal dual stance, the regularity index, and the gait symmetry index were unaltered. Thus, aging is associated with characteristic alterations in gait function in C57BL/6 mice, which could potentially be assessed as clinically relevant endpoints in geroscience studies testing the effects of antiaging interventions. [ABSTRACT FROM AUTHOR]

Stability of myogenic tone in middle cerebral arteries (MCA) is essential for adequate control over penetration of pressure waves into the distal portion of the cerebral microcirculation. Because the increased pulse pressure observed in advanced aging is associated with cerebromicrovascular injury, the effect of aging on myogenic response of mouse MCAs was determined. Aging did not affect the myogenic constriction in response to static increases in pressure, whereas it significantly impaired pulsatile pressure-induced myogenic tone. Impaired myogenic adaptation of MCAs to pulsatile pressure may allow high pressure to penetrate the distal portion of the cerebral microcirculation, contributing to microvascular damage. [ABSTRACT FROM AUTHOR]

Abstract: Glucose metabolism through the glycolysis and hexosamine pathway has been shown to be altered in type 2 diabetes. However, the fate of glucose through the pentose phosphate pathway (PPP) is currently unclear. In this study, we determined whether the activity of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the PPP, is modulated in the liver of Zucker obese fa/fa rats (9–11 weeks of age). We found that G6PD expression and activity, NADPH levels, and 6-phosphogluconate generation were significantly increased in the liver of fa/fa rats. Inhibition of PI3 kinase and Src kinases decreased (p <0.05) G6PD activity in the fa/fa but not in the lean rat liver, suggesting that G6PD activity is regulated by PI3/Src kinase signaling pathways. G6PD-derived NADPH increased (p <0.05) superoxide anion levels by 70–90% in fa/fa vs lean rat liver, which was inhibited by the NADPH oxidase inhibitor gp91 ds−tat (50 μM) and G6PD inhibitors 6-aminonicotinamide (1 mM) and dehydroepiandrosterone (100 μM), therefore indicating that elevated G6PD activity may be responsible for mediating superoxide generation. Interestingly, we also found a positive correlation between liver hypertrophy/increased G6PD activity (r 2 =0.77; p =0.0009) and liver hypertrophy/superoxide production (r 2 =0.51; p =0.0091) in fa/fa rats. Increased G6PD and NADPH oxidase expression and activity, in young hyperglycemic and hyperinsulinemic rats before the development of diabetes, seems to be a contributing factor in the induction of oxidative stress. Because inhibition of G6PD activity decreases oxidative stress, we conclude that G6PD behaves as a pro-oxidant in the fa/fa rat liver in type 2 diabetes. [Copyright &y& Elsevier]

Age-related gait dysfunction and balance disorders are a major cause of falls and injury in the elderly population. Epidemiological studies have shown that disturbances in gait coordination which manifest with age are associated with increased morbidity and mortality, impaired cognitive capacity, as well as reduced level of function and loss of independence. In geroscience, mice are the most frequently used model system to test efficiency of antiaging interventions. Despite the clinical importance of age-related gait abnormalities in older adults, the impact of aging on mouse gait coordination is not well documented in the literature. To characterize the effect of aging on mouse gait, we assessed gait function in young (3-month-old) and aged (24-month-old) freely moving C57BL/6 mice using the semiautomated, highly sensitive CatWalk XT system for quantitative assessment of footfall and motor performance. We found that aged mice exhibited significantly decreased cadence and increased stride time variability. Aging also tended to alter footfall patterns. In aged mice, speed, swing speed, stride length, duty cycle, base of support, terminal dual stance, the regularity index, and the gait symmetry index were unaltered. Thus, aging is associated with characteristic alterations in gait function in C57BL/6 mice, which could potentially be assessed as clinically relevant endpoints in geroscience studies testing the effects of antiaging interventions. [ABSTRACT FROM AUTHOR]