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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]

INTRODUCTION: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention. METHODS: Patients with MCI and age‐matched controls (CN) were administered cognitive tasks during functional near‐infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small‐particle flow cytometry. RESULTS: Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left‐dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification. DISCUSSION: NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology. Highlights: Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI).Functional connectivity (FC) compensation mechanism is lost in MCI.Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI.CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI.NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors. [ABSTRACT FROM AUTHOR]

Impaired cerebrovascular function contributes to the genesis of age‐related cognitive decline. In this study, the hypothesis is tested that impairments in neurovascular coupling (NVC) responses and brain network function predict cognitive dysfunction in older adults. Cerebromicrovascular and working memory function of healthy young (n = 21, 33.2±7.0 years) and aged (n = 30, 75.9±6.9 years) participants are assessed. To determine NVC responses and functional connectivity (FC) during a working memory (n‐back) paradigm, oxy‐ and deoxyhemoglobin concentration changes from the frontal cortex using functional near‐infrared spectroscopy are recorded. NVC responses are significantly impaired during the 2‐back task in aged participants, while the frontal networks are characterized by higher local and global connection strength, and dynamic FC (p < 0.05). Both impaired NVC and increased FC correlate with age‐related decline in accuracy during the 2‐back task. These findings suggest that task‐related brain states in older adults require stronger functional connections to compensate for the attenuated NVC responses associated with working memory load. [ABSTRACT FROM AUTHOR]

Most clinical research has focused on intensity differences of facial expressions between the right and left hemi-face to explore lateralization of emotions in the brain. Observations by social psychologists, however, suggest that control of facial expression is organized predominantly across the upper-lower facial axis because of the phenomena of facial blends: simultaneous display of different emotions on the upper and lower face. Facial blends are related to social emotions and development of display rules that allow individuals to sculpt facial expressions for social and manipulative purposes. We have demonstrated that facial blends of emotion are more easily and accurately posed on the upper-lower than right-left hemiface, and that upper facial emotions are processed preferentially by the right hemisphere whereas lower facial emotions are processed preferentially by the left hemisphere. Based on these results, recent anatomical studies showing separate cortical areas for motor control of upper and lower face and the neurology of posed and spontaneous expressions of emotion, a functional-anatomic model of how the forebrain modulates facial expressions, is presented. The unique human ability to produce facial blends of emotion is, most likely, an adaptive modification linked to the evolution of speech and language. NEUROSCIENTIST 13(5):433-446, 2007. DOI: 10.1177/1073858407305618 KEY WORDS Facial expressions, Emotions, Neuroanatomy, Neurobiology, Sociobiology, Modulation of facial expressions in humans is an adaptation that facilitates emotional and intentional communication between sentient creatures (Panksepp 1998). Although human language has been traditionally viewed as a dominant [...]

Clinical research has concentrated on differences in intensity of expression between the right and left hemiface as a means to assess hemispheric differences in motor control. However, observations by social psychologists suggest that control of facial expression may be organized predominantly across the upper-lower hemiface because during social interactions individuals may produce brief facial blends of emotions, in which the upper and lower face display a different emotion. Full facial versus upper/lower and right/left facial blends of emotion were posed by 20 subjects, 10 men and 10 women ranging in age from 20 to 37 years. The subjects rated the difficulty of each pose on a 5-point Likert scale. Digital photographs of the poses were taken and the full and half-facial poses were shown in random order to four judges who indicated what pose was being performed. The results were very robust and confirmed that facial blends of emotion are more easily and accurately posed on the upper-lower than on the right-left hemiface. Our results are consistent with recent anatomical studies showing separate cortical areas for motor control of the upper versus lower face in primates. Based on recent research exploring hemispheric differences in perceiving facial blends of emotion, the left hemisphere may be more involved with modulating lower facial expressions and the right hemisphere more involved with modulating upper facial expressions.