Cognition and Other Predictors of Functional Disability Among Veterans With Mild Traumatic Brain Injury and Posttraumatic Stress Disorder.

BACKGROUND: Limitations in everyday functioning are frequently reported by veterans with a history of mild traumatic brain injury (mTBI) and/or posttraumatic stress disorder (PTSD). Multiple factors are associated with functional disability among veterans, including depression, poor social support, cognition, and substance use. However, the degree to which these factors, particularly cognitive capacities, contribute to functional limitations remains unclear. METHODS: We evaluated performance on tests of processing speed, executive functioning, attention, and memory as predictors of functioning on the World Health Organization Disability Assessment Scale (WHODAS) 2.0 in 288 veterans. Participants were placed in one of the following groups: PTSD-only, mTBI-only, mTBI + PTSD, and neither PTSD nor mTBI (deployed control group). Cognitive test performances were evaluated as predictors of WHODAS 2.0 functional ratings in regression models that included demographic variables and a range of mood, behavioral health, and postconcussive symptom ratings. RESULTS: Multiple cognitive test performances predicted WHODAS 2.0 scores in the deployed control group, but they generally did not predict functioning in the clinical groups when accounting for demographics, mood, behavioral health, and postconcussive symptoms. CONCLUSIONS: In veterans with mTBI and/or PTSD, cognitive test performances are less associated with everyday functioning than mood and postconcussive symptoms.

COVID-19 and clinical neuropsychology: A review of neuropsychological literature on acute and chronic pulmonary disease.

Objective: The illness resulting from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), better known as COVID-19, has quickly escalated to a worldwide pandemic. Although understanding of the short and long-term manifestations of COVID-19 remains incomplete, there is a preponderance of respiratory pathology in COVID-19 and potential for chronic loss of pulmonary function in recovered patients, raising concerns for associated cognitive impacts.Method: We conducted a narrative review of the existing literature on neuropsychological variables in acute/severe respiratory disease and various forms of chronic pulmonary disease to inform expectations about potential cognitive manifestations of COVID-19.Results: Cognitive dysfunction is common but not inevitable in acute and chronic pulmonary disease, although unique predictors and symptom trajectories appear to be associated with each.Conclusions: Although the full scope of neuropathophysiology associated with COVID-19 remains to be established, pulmonary insults associated with the disease are likely to produce cognitive dysfunction in a substantial percentage of patients.

Polyunsaturated fatty acid modulation of voltage-gated ion channels.

Arachidonic acid (AA) was found to inhibit the function of whole-cell voltage-gated (VG) calcium currents nearly 16 years ago. There are now numerous examples demonstrating that AA and other polyunsaturated fatty acids (PUFAs) modulate the function of VG ion channels, primarily in neurons and muscle cells. We will review and extract some common features about the modulation by PUFAs of VG calcium, sodium, and potassium channels and discuss the impact of this modulation on the excitability of neurons and cardiac myocytes. We will describe the fatty acid nature of the membrane, how fatty acids become available to function as modulators of VG channels, and the physiologic importance of this type of modulation. We will review the evidence for molecular mechanisms and assess our current understanding of the structural basis for modulation. With guidance from research on the structure of fatty acid binding proteins, the role of lipids in gating mechanosensitive (MS) channels, and the impact of membrane lipid composition on membrane-embedded proteins, we will highlight some avenues for future investigations.

Inhibitory effects of polyunsaturated fatty acids on Kv4/KChIP potassium channels.

Kv4/K channel interacting protein (KChIP) potassium channels are a major class of rapidly inactivating K(+) channels in neurons and cardiac muscle. Modulation of Kv4/KChIP channels by polyunsaturated fatty acids (PUFAs) is important in the regulation of cellular excitability and the induction of activity-dependent synaptic plasticity. Using the Xenopus laevis oocyte expression system, we studied the inhibition by PUFAs of the peak outward K(+) current and the accompanying increase in the rate of current inactivation of rKv4.2/rKChIP1b. Inhibitory effects do not depend on KChIP coexpression since Kv4.2 channels lacking an NH(2)-terminal KChIP association region were substantially inhibited by PUFAs and showed strong kinetic modulation. PUFAs accelerated both the fast and slow time constants that describe the kinetics of Kv4/KChIP inactivation. The time course of entry into closed inactivated states was facilitated by PUFAs, but steady-state inactivation and recovery from inactivation were unaltered. PUFA inhibition of Kv4/KChIP current was not use dependent. The concentration-response relationship for arachidonic acid (AA) inhibition of Kv4/KChIP channels mimicked that for activation of TRAAK channels. Internal serum albumin largely prevents the inhibitory effects of externally applied AA, and the membrane-impermeant AA-CoA is inactive when applied externally. Overall, our data suggest that PUFAs inhibit Kv4/KChIP channels by facilitating inactivation from open and closed gating states and that access of the fatty acid to the internal leaflet of the membrane is important. These results improve our understanding of the mechanisms for the inhibitory effects of PUFAs on Kv4/KChIP channel function.