Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Suzanne D. Vernon, Sherlyn Funk, Lucinda Bateman, Gregory J. Stoddard, Sarah Hammer 1, Karen Sullivan, Jennifer Bell , Saeed Abbaszadeh, W. Ian Lipkin and Anthony L. Komaroff
Background: Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment (“brain fog”), orthostatic intolerance (OI), and other symptoms (“Long COVID”). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet the criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.
Methods: We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smartphone-based app (DANA).
Results: The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time in DANA worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).
Conclusions: A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of DANA to assess cognition can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.
Gratitude Interventions with Direct Care Workers in a Dementia-Specific Assisted Living: A Pilot Study; 2022.
Stephanie Arcadia, Ian Coffman, Corinna E. Lathan, PhD, Linda Roszak Burton, Tabassum Majid, MAgs, PhD
Background: Reports on a high degree of caregiver burnout, toxic work environments, and a chronically disengaged workforce create significant problems for dementia-specific healthcare organizations. Previous research indicates that gratitude interventions can result in greater employee engagement and decrease the rate of burnout. Limited studies have focused on direct care workers in dementia healthcare organizations. No validated tools have been used to measure direct care workers’ brain health in healthcare organizations.
Methods: Baseline and post-assessment surveys on engagement, workplace meaningfulness, and gratitude were conducted with direct care workers (n=17). In addition to the surveys, a novel neurocognitive assessment tool was administered at baseline, midpoint, and post-intervention with staff. This tool (DANA) consisted of reaction time-based cognitive efficiency measures. Statistical analysis included a paired t-test to test significant difference between scores.
Conclusions: This pilot study indicated that dementia healthcare direct care workers can be engaged with novel technology measures of brain health and wellbeing. In addition, adaptive gratitude intervention may have an impact on workplace engagement. Further research needs to replicate and expand gratitude-based interventions to determine long-term impact, behavioral, and biological mechanism of action for both staff and dementia residents.
Behavioral health characteristics of a technology-enabled sample of Alzheimer’s caregivers with high caregiver burden. mHealth 2017;3:36.
Coffman I, Resnick HE, Lathan CE
Background: Caregivers of persons with dementia/Alzheimer’s disease (AD) experience considerable physical and psychological burdens associated with their caregiving role. Although mobile technologies have the potential to deliver caregiver supports, it is necessary to demonstrate that caregivers in need of these supports are technology-enabled, that they can be identified and accessed, and that they experience the same unfavorable mental health outcomes characteristic of the broader caregiving population. Our objective was to enroll a cohort of technology-enabled caregivers to determine basic demographic characteristics and assess level of caregiver burden, depression, anxiety, and sleep disturbance as part of a larger project to deliver caregiver support.
Methods: Web-based enrollment and data collection measuring caregiver burden with the Zarit Burden Interview (ZBI), anxiety and depression with the M-3, and sleep disturbance with the PROMIS Sleep Disturbance form.
Results: A total of 165 caregivers enrolled via an online portal, all of whom provided care for someone with AD and owned a smart phone. Mean age of this group with 57.9 years, 90.3% was female, 88.5% was White, 51.5% reported providing care for a parent, 9.3% reported providing care for more than 10 years, and 24.8% reported providing more than 100 hours of care each week. Sixty-four percent of caregivers screened positive for both anxiety and depression, and nearly 62% of the sample had moderate or severe caregiver burden. Scores on depression, anxiety, and sleep quality assessments correlated moderately or strongly with caregiver burden.
Conclusions: Dementia caregivers with Internet and smartphone access demonstrate high levels of caregiver burden, depression, and anxiety, and are well-suited to receive caregiver support services delivered via mobile devices that target these issues.
Computerized cognitive testing norms in active-duty military personnel: Potential for contamination by psychologically unhealthy individuals. Applied Neuropsychology: Adult, 1-7.
Coffman, I., Resnick, H. E., Drane, J., & Lathan, C. E. (2017
Normative reference data used for clinical interpretation of neuropsychological testing results are only valid to the extent that the sample they are based on is composed of “normal” individuals. Accordingly, efforts are made to exclude individuals with histories and/or diagnoses that might bias test performance. In this report, we focus on these features in active-duty military personnel because published data on computerized neurocognitive testing norms for this population have not explicitly considered the consequences of neurobehavioral disorders (e.g., PTSD, depression), which are prevalent in this population and known to affect performance on some cognitive assessments. We administered DANA, a mobile, neurocognitive assessment tool, to a large sample of active-duty military personnel and found that scores on self-administered psychological assessments negatively impacted a number of neurocognitive tests. These results suggest that neurobehavioral disorders that are relatively common in this population should be controlled for when establishing normative datasets for neurocognitive outcomes.
Performance on the Defense Automated Neurobehavioral Assessment across controlled environmental conditions. Applied Neuropsychology: Adult, 23(6), 411-417.
Haran, F. J., Dretsch, M. N., & Bleiberg, J. (2016).
Neurocognitive assessment tools (NCAT) are commonly used to screen for changes in cognitive functioning following a mild traumatic brain injury and to assist with a return to duty decision. As such, it is critical to determine if performance on the Defense Automated Neurobehavioral Assessment (DANA) is adversely affected by operationally-relevant field environments. Differences in DANA performance between a thermoneutral environment and three simulated operationally-relevant field environments across the thermal stress continuum were calculated for 16 healthy U.S. Navy service members. Practice effects associated with brief test-retest intervals were calculated within each environmental condition. There were no significant differences between the simulated environmental conditions suggesting that performance on the DANA Brief is not impacted by thermal stress. Additionally, there were no significant differences in performance within each simulated environmental condition associated with repeated administrations.
Defense Automated Neurobehavioral Assessment Accurately Measures Cognition in Patients Undergoing Electroconvulsive Therapy for Major Depressive Disorder. The journal of ECT, 34(1), 14-20.
Hollinger, K. R., Woods, S. R., Adams-Clark, A., Choi, S. Y., Franke, C. L., Susukida, R., … & Kaplin, A. I. (2018).
Objectives The Defense Automated Neurobehavioral Assessment (DANA) is an electronic cognitive test battery. The present study compares DANA to the standard Mini-Mental State Examination (MMSE) in subjects undergoing electroconvulsive therapy for the treatment of major depressive disorder.
Methods Seventeen inpatient subjects in the Johns Hopkins Hospital Department of Psychiatry were administered longitudinal paired DANA and MMSE tests (7.6 ± 4.1 per patient) from January 10, 2014 to September 26, 2014. Regression analyses were conducted (with or without MMSE scores of 30) to study the impact of the MMSE upper limit, and within-subject regression analyses were conducted to compare MMSE and DANA scores over time.
Results Statistically significant relationships were measured between DANA and MMSE scores. Relationships strengthened when MMSE scores of 30 were omitted from analyses, demonstrating a ceiling effect of the MMSE. Within-subject analyses revealed relationships between MMSE and DANA scores over the duration of the inpatient stay.
Conclusions Defense Automated Neurobehavioral Assessment is an electronic, mobile, repeatable, sensitive, and valid method of measuring cognition over time in depressed patients undergoing electroconvulsive therapytreatment. Automation of the DANA allows for more frequent cognitive testing in a busy clinical setting and enhances cognitive assessment sensitivity with a timed component to each test.
Cognition, mood, and purpose in life in neuromyelitis optica spectrum disorder. Journal of the neurological sciences, 362, 85-90.
Hollinger, K. R., Franke, C., Arenivas, A., Woods, S. R., Mealy, M. A., Levy, M., & Kaplin, A. I. (2016).
Background: Neuromyelitis optica (NMO) is a rare inflammatory disease of the central nervous system. Individuals with NMO often experience cognitive impairment and changes in mood.
Methods: Using the computerized defense automated neurobehavioral assessment (DANA) cognitive assessment battery, along with standard purpose in life (PIL) and depression (PHQ-9) tests, we studied the relationship between cognitive function, mood, and PIL in subjects with NMO (n=25) and healthy control (n=20) participants. Results: After controlling for age, gender, highest level of education, PHQ-9 score, and number of hours of sleep the previous night, NMO patients had a 13.8%-17.8% decrease in code substitution (CS) test performance compared to control subjects (p < 0.05). No significant differences were observed between groups in total PHQ-9 scores, but nearly 3x more NMO patients exhibited signs of mild, moderate or severe depression as compared to controls (58% vs 21%, respectively). Mood was not related to cognitive performance in either cohort. Opposing relationships between cognition and PIL were observed in NMO and control groups, with higher PIL associated with better cognition in NMO but worse cognition in controls.
Conclusions: Cognitive impairment is present in NMO, and the computerized DANA CS test is sensitive at detecting impairments. NMO patients with low PIL are more likely to be cognitively impaired than those with high PIL.
“Defense Automated Neurobehavioral Assessment (DANA)-psychometric properties of a new field-deployable neurocognitive assessment tool.” Military medicine 178.4 (2013): 365-371.
Lathan, Corinna, et al.
The Defense Automated Neurobehavioral Assessment (DANA) is a new neurocognitive assessment tool that includes a library of standardized cognitive and psychological assessments, with three versions that range from a brief 5-minute screen to a 45-minute complete assessment. DANA is written using the Android open-source operating system and is suitable for multiple mobile platforms. This article presents testing of DANA by 224 active duty U.S. service members in five operationally relevant environments (desert, jungle, mountain, arctic, and shipboard). DANA was found to be a reliable instrument and compared favorably to other computer-based neurocognitive assessments. Implications for using DANA in far-forward military settings are discussed.
A Pilot to Investigate the Feasibility of Mobile Cognitive Assessment of elderly patients and caregivers in the home. J Geriatrics Palliative Care 2016;4(1): 6.
Lathan CE, Coffman I, Shewbridge R, Lee M, Cirio R, et al.
Background: The number of older adults with Alzheimer’s disease (AD) has been steadily increasing and is likely to triple by 2050. Parallel increases in AD and informal AD caregivers who experience their own physical and cognitive challenges will result in the need for tools that can help both populations track their cognitive health easily, both in the clinic and at home.
Methods: DANA, a tablet-based, FDA-cleared computerized cognitive assessment tool, was used over 90 days among seven caregiver-AD patient dyads in-clinic and at home to assess DANA’s sensitivity in detecting mild cognitive impairment and dementia as well as its feasibility in the home and clinic.
Results: DANA is sensitive to certain differences in cognitive performance between AD patients and caregiver. Most subtests were found to be feasible for in-home use among both patients and caregivers.
Conclusion: DANA shows promise for use both in-clinic and in the home to track cognitive performance of AD patients and their caregivers.
A pilot virtual case-management intervention for caregivers of persons with Alzheimer’s disease. Journal of Hospital Management and Health Policy, 2(4).
Lathan, C. E., Coffman, I., Sidel, S., & Alter, C. (2018).
Background: Caregivers of persons with Alzheimer’s disease (AD) may experience negative physical and mental health outcomes associated with their caregiving role. In this report, we summarize our findings from a pilot study meant to evaluate the feasibility of a novel mHealth platform utilizing a virtual case management platform as a means of AD caregiver support.
Methods: Twenty AD caregivers with mild-to-moderate to severe burden and moderate behavioral health challenges were recruited to take part in a 3-month, single-arm pilot intervention study utilizing a virtual case management platform. Pre- and post-study measures of symptoms related to caregiver burden and mental health were collected in addition to data on qualitative aspects of the intervention.
Results: Thirteen subjects completed the study. Pre/post behavioral measures were consistent with symptom improvement. Engagement metrics and qualitative feedback suggest that the intervention platform was actively and appropriately utilized.
Conclusions: Initial findings suggest that further research into the potential efficacy of the intervention is warranted.
Prospective, Head-to-Head Study of Three Computerized Neurocognitive Assessment Tools Part 2: Utility for Assessment of Mild Traumatic Brain Injury in Emergency Department Patients. Journal of the International Neuropsychological Society, 23(4), 293-303.
Nelson, L. D., Furger, R. E., Gikas, P., Lerner, E. B., Barr, W. B., Hammeke, T. A., … & McCrea, M. A. (2017).
Objectives: The aim of this study was to evaluate the reliability and validity of three computerized neurocognitive assessment tools (CNTs; i.e., ANAM, DANA, and ImPACT) for assessing mild traumatic brain injury (mTBI) in patients recruited through a level I trauma center emergency department (ED).
Methods: mTBI (n=94) and matched trauma control (n=80) subjects recruited from a level I trauma center emergency department completed symptom and neurocognitive assessments within 72 hr of injury and at 15 and 45 days post-injury. Concussion symptoms were also assessed via phone at 8 days post-injury.
Results: CNTs did not differentiate between groups at any time point (e.g., M 72-hr Cohen’s d=−.16, .02, and .00 for ANAM, DANA, and ImPACT, respectively; negative values reflect greater impairment in the mTBI group). Roughly a quarter of stability coefficients were over .70 across measures and test–retest intervals in controls. In contrast, concussion symptom score differentiated mTBI vs. control groups acutely), with this effect size diminished over time (72-hr and day 8, 15, and 45 Cohen’s d=−.78, −.60, −.49, and −.35, respectively).
Conclusions: The CNTs evaluated, developed and widely used to assess sport-related concussion, did not yield significant differences between patients with mTBI versus other injuries. Symptom scores better differentiated groups than CNTs, with effect sizes weaker than those reported in sport-related concussion studies. Nonspecific injury factors, and other characteristics common in ED settings, likely affect CNT performance across trauma patients as a whole and thereby diminish the validity of CNTs for assessing mTBI in this patient population. (JINS, 2017, 23, 293–303)
Performance on the DANA Brief Cognitive Test correlates with MACE Cognitive Score and may be a new tool to diagnose concussion. Frontiers in neurology, 11, 839.
Pryweller, J. R., Baughman, B. C., Frasier, S. D., O’Conor, E. C., Pandhi, A., Wang, J., … & Tsao, J. W. (2020).
Nearly 380,000 U.S. service members between 2000 and 2017 were, and at least 300,000 athletes annually are, diagnosed with concussion. It is imperative to establish a gold-standard diagnostic test to quickly and accurately diagnose concussion. In this non-randomized, prospective study, we examined the reliability and validity of a novel neurocognitive assessment tool, the Defense Automated Neurobehavioral Assessment (DANA), designed to be a more sensitive, yet efficient, measure of concussion symptomatology. In this study, the DANA Brief version was compared to an established measure of concussion screening, the Military Acute Concussion Evaluation (MACE), in a group of non-concussed service members. DANA Brief subtests demonstrated low to moderate reliability, as measured by intra-class correlation coefficient (ICC; values range: 0.28–0.58), which is comparable to other computerized neurocognitive tests that are widely-implemented to diagnose concussion. Statistically significant associations were found between learning and memory components of the DANA Brief and the diagnostic MACE cognitive test score (DANA Brief subtests: CDD: R2 = 0.05, p = 0.023; CDS: R2 = 0.10, p = 0.010). However, a more robust relationship was found between DANA Brief components involving attention and working memory, including immediate memory, and the MACE cognitive test score (DANA Brief subtests: GNG: R2 = 0.08, p = 0.003; PRO: R2 = 0.08, p = 0.002). These results provide evidence that the DANA Rapid version, a 5-min assessment self-administered on a hand-held portable device, based on the DANA Brief version, may serve as a clinically useful and improved neurocognitive concussion screen to minimize the time between injury and diagnosis in settings where professional medical evaluation may be unavailable or delayed. The DANA’s portability, durability, shorter test time and lack of need for a medical professional to diagnose concussion overcome these critical limitations of the MACE.
From battlefield to home: a mobile platform for assessing brain health. mHealth 2016;2:30
Resnick HE, Lathan CE.
Resnick HE, Lathan CE.
Cognitive testing batteries have been used for decades to diagnose deficits associated with conditions such as head injury, age-related cognitive decline, and stroke, and they have also been used extensively for educational evaluation and planning. Cognitive testing is generally office-based, administered by professionals, uses paper and pencil testing modalities, reports results as summary scores, and is a “one shot deal” whose primary objective is to identify the presence and severity of cognitive deficit. This paper explores innovative departures from historical cognitive testing strategies and paradigms. The report explores (I) a shift from disease diagnosis in the office setting to mobile tracking of cognitive health and wellness in any setting; (II) the strength of computer-based cognitive measures and their role in facilitating development of new computational methods; and (III) using cognitive testing to inform on individual-level outcomes over time rather than dichotomous metrics at a single point in time.
“AltitudeOmics: Decreased reaction time after high altitude cognitive testing is a sensitive metric of hypoxic impairment.”NeuroReport 25.11 (2014): 814.
Roach, Emma B., et al.
Humans experiencing hypoxic conditions exhibit multiple signs of cognitive impairment, and high altitude expeditions may be undermined by abrupt degradation in mental performance. Therefore, the development of psychometric tools to quickly and accurately assess cognitive impairment is of great importance in aiding medical decision-making in the field, particularly in situations where symptoms may not be readily recognized. The present study used the Defense Automated Neurobehavioral Assessment (DANA), a ruggedized and portable neurocognitive assessment tool, to examine cognitive function in healthy human volunteers at sea level, immediately after ascending to an elevation over 5000 m, and following 16 days of acclimatization to this high altitude. The DANA battery begins with a simple reaction time test (SRT1) which is followed by a 20-min series of complex cognitive tests and ends with a second test of simple reaction time (SRT2). Tabulating the performance scores from these two tests allows the calculation of an SRT change score (dSRT =SRT1–SRT2) that reflects the potential effect of mental effort spent during the 20-min testing session. We found that dSRT, but not direct SRT in comparison to sea-level baseline performance, is highly sensitive to acute altitude-related performance deficits and the remission of impairment following successful acclimatization. Our results suggest that dSRT is a potentially useful analytical method to enhance the sensitivity of neurocognitive assessment.
“An Evaluation of the Consistency and Reliability of the Defense Automated Neurocognitive Assessment Tool.” Applied Psychological Measurement (2015): 0146621615577361
Russo, C. R., and C. E. Lathan.
A durable, portable, and field-hardened computerized neurocognitive test (CNT) called the Defense Automated Neurobehavioral Assessment (DANA) tool was recently developed to provide a practical means to conduct neurological and psychological assessment in situ. The psychometric properties of the DANA have been previously described. This present work discusses the test–retest reliability of the DANA Rapid test battery, as administered to a homogeneous population of U.S. Air Force Academy football team players (N = 162) across the duration of the season. The intraclass correlation coefficient (ICC) metric of the DANA is compared with that from two different CNTs recently reported in Cole et al., and the implications of using the metric to interpret comparative test reliability among different CNTs are discussed.
Neurocognitive and Fine Motor Deficits in Asymptomatic Adolescents during the Subacute Period after Concussion Journal of Neurotrauma. Apr 2018.
Servatius Richard J., Spiegler Kevin M., Handy Justin D., Pang Kevin C.H., Tsao Jack W., and Mazzola Catherine A.
Adolescents are at high risk for sustaining concussions. There is considerable controversy regarding the sensitivity of neurocognitive tests to detect and track dysfunction in the aftermath of concussion. Two neurocognitive test batteries were compared during the subacute phase of recovery from concussion to determine sensitivity to concussion. Adolescents (ages 11–17 years) with a concussion diagnosis (eight males, seven females, 9–69 days after injury) were recruited through a concussion clinic and compared with community nonconcussed volunteers (11 males, three females). Adolescents completed the online version of the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) on a desktop computer and the Defense Automated Neurobehavioral Assessment (DANA) on a handheld device, as well as the Grooved Pegboard Test, which assessed manual dexterity and motor speed. There were no differences in self-reported symptoms on the Post-Concussion Symptom Scale comparing concussed and nonconcussed adolescents. No significant between-groups differences were observed in ImPACT performance. Performance deficits were apparent for the DANA assessment, reflecting lower throughput scores for simple reaction time and response inhibition parameters in those with concussion. Concussed adolescents also had slower Grooved Pegboard Test performance when using the nondominant hand. Both the DANA test battery and the Grooved Pegboard Test appear to have promise as tools to detect persistent cognitive and motor dysfunction in the subacute period after concussion.
(2017) Stress-Related Mental Health Symptoms in Coast Guard: Incidence, Vulnerability, and Neurocognitive Performance. Front. Psychol. 8:1513. doi: 10.3389/fpsyg.2017.01513
Servatius RJ, Handy JD, Doria MJ, Myers CE, Marx CE, Lipsky R, Ko N, Avcu P, Wright WG and Tsao JW
U.S. Coast Guard (CG) personnel face occupational stressors (e.g., search and rescue) which compound daily life stressors encountered by civilians. However, the degree CG personnel express stress-related mental health symptoms of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) is understudied as a military branch, and little is known concerning the interplay of vulnerabilities and neurocognitive outcomes in CG personnel. The current study addressed this knowledge gap, recruiting 241 active duty CG personnel (22% female) to assess mental health, personality, and neurocognitive function. Participants completed a battery of scales: PTSD Checklist with military and non-military prompts to screen for PTSD, Psychological Health Questionnaire 8 for MDD, and scales for behaviorally inhibited (BI) temperament, and distressed (Type D) personality. Neurocognitive performance was assessed with the Defense Automated Neurobehavioral Assessment (DANA) battery. Cluster scoring yielded an overall rate of PTSD of 15% (95% CI: 11–20%) and 8% (95% CI: 3–9%) for MDD. Non-military trauma was endorsed twice that of military trauma in those meeting criteria for PTSD. Individual vulnerabilities were predictive of stress-related mental health symptoms in active duty military personnel; specifically, BI temperament predicted PTSD whereas gender and Type D personality predicted MDD. Stress-related mental health symptoms were also associated with poorer reaction time and response inhibition. These results suggest rates of PTSD and MDD are comparable among CG personnel serving Boat Stations to those of larger military services after combat deployment. Further, vulnerabilities distinguished between PTSD and MDD, which have a high degree of co-occurrence in military samples. To what degree stress-related mental healthy symptoms and attendant neurocognitive deficits affect operational effectiveness remains unknown and warrant future study.
“The Impact of Multiple Concussions on Emotional Distress, Post-Concussive Symptoms, and Neurocognitive Functioning in Active Duty United States Marines Independent of Combat Exposure or Emotional Distress.” Journal of neurotrauma 31.22 (2014): 1823-1834.
Spira, James L., et al.
Controversy exists as to whether the lingering effects of concussion on emotional, physical, and cognitive symptoms is because of the effects of brain trauma or purely to emotional factors such as post-traumatic stress disorder or depression. This study examines the independent effects of concussion on persistent symptoms. The Defense Automated Neurobehavioral Assessment, a clinical decision support tool, was used to assess neurobehavioral functioning in 646 United States Marines, all of whom were fit for duty. Marines were assessed for concussion history, post-concussive symptoms,emotional distress, neurocognitive functioning, and deployment history. Results showed that a recent concussion or ever having experienced a concussion was associated with an increase in emotional distress, but not with persistent post concussive symptoms (PPCS) or neurocognitive functioning. Having had multiple lifetime concussions, however, was associated with greater emotional distress, PPCS, and reduced neurocognitive functioning that needs attention and rapid discrimination, but not for memory-based tasks. These results are independent of deployment history, combat exposure, and symptoms of post-traumatic stress disorder and depression. Results supported earlier findings that a previous concussion is not generally associated with post-concussive symptoms independent of covariates. In contrast with other studies that failed to find a unique contribution for concussion to PPCS, however, evidence of recent and multiple concussion was seen across a range of emotional distress, post-concussive symptoms, and neurocognitive functioning in this study population. Results are discussed in terms of implications for assessing concussion on return from combat.
“AltitudeOmics: the integrative physiology of human acclimatization to hypobaric hypoxia and its retention upon reascent.” PloS one9.3 (2014): e92191.
Subudhi, Andrew W., et al.
An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 964 mmHg to 4564 while PaCO2 dropped a further 663 mmHg to 2163, and [Hb] rose 1.860.7 g/dL to 1662 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 868% (all changes p,0.01). Upon renascent,we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention.