Obstructive sleep apnea during the chronic stroke recovery period: Comparison between primary haemorrhagic and ischaemic events.

The present study retrospectively determined the incidence of obstructive sleep apnea (OSA) after a primary haemorrhagic event compared to an ischaemic stroke during the post-acute recovery period ( x¯ > 3 months). Consideration of medications taken during the sleep evaluation provided additional information on the association between OSA and pathophysiological conditions that may increase the risk of a repeated cardiovascular event. The medical records from 103 patients that underwent a type I fully attended overnight polysomnography as a standard evaluation procedure at a rehabilitation facility were reviewed. Diagnosis of ischaemic or primary haemorrhagic stroke was obtained from a neurological report that was typically confirmed by imaging. Medications taken at the time of the sleep study were documented. Age-adjusted assessment of sleep-disordered breathing revealed a higher incidence of apnea and hypopnea in the ischaemic stroke group (p < 0.005). Patients with ischaemic stroke were also more likely to have severe OSA (p < 0.005). In comparison, a higher percentage of patients with haemorrhagic stroke had an apnea-hypopnea index <5 events/hr (p < 0.005). Those with an ischaemic stroke were taking more lipid lowering agents (p < 0.05). Results suggest that apnea is less prevalent after a haemorrhagic stroke, independent of hypertension, compared to an ischaemic stroke. An increase in predictive values for OSA was observed for indicators of diabetes (p < 0.05). These data indicate that it is relevant to consider stroke type when determining the risk of OSA during the chronic recovery period thus facilitating new strategies for stroke recurrence prevention.

Prevalence of growth hormone deficiency in middle-age adults recovering from stroke.

Objective: The prevalence of chronic growth hormone deficiency (GHD) and its association with other hormonal deficiencies was determined in middle-aged patients post-stroke with and without consideration of body mass index (BMI).Methods: Clinical records were reviewed to determine pituitary function at least 3 months post-stroke. Patients with a history of endocrine anomalies were excluded. GHD was determined by utilizing standard peak GH cutoffs following the glucagon stimulation test. A secondary analysis was conducted with stricter BMI-adjusted cutoffs. The accuracy of IGF-1 in predicting GHD was also examined.Results: GHD was diagnosed in 54% of patients (≥5.0 µg/L), with 32% falling into the severe (≤3 µg/L) category. Patients with GHD had lower levels of FSH, T3, LH, and SHBG. Analyzes of BMI-adjusted GH levels, revealed that 14% of patients were GHD. These patients had higher prolactin. IGF-1 values were not predictive of GHD. Latency to be admitted to post-acute rehabilitation was greater in patients with GHD.Conclusions: Evidence suggests patients with stroke may be at risk for developing GHD. GHD was associated with decreased levels of other hormones. Co-morbidities for stroke and neuroendocrine dysfunction overlap and may have implications for recovery following stroke.

First Do No Harm: An Opinion on Bundled Care for Stroke Patients.

The Center for Medicare and Medicaid Innovation under the Centers for Medicare and Medicaid Services has invited institutions to demonstrate ways to bundle services into a 90-day episode of acute care that will lower costs and hospital re-admission rates. While these goals are laudable, they overlook the need for and value attained in postacute treatment. This article argues for elimination of the diagnosis of stroke from the proposed demonstration project due to misaligned financial incentives that will severely compromise patient outcomes.

The influence of post-acute rehabilitation length of stay on traumatic brain injury outcome: a retrospective exploratory study.

OBJECTIVE: Data regarding length of stay (LOS) in a rehabilitation programme after traumatic brain injury (TBI) are limited. The goal of this study was to examine the effect of LOS and disability on outcome following TBI. METHODS: Records from patients in a multidisciplinary rehabilitation programme at least 3 months after TBI were analysed retrospectively to study the influence of LOS on functional outcome at different levels of disability. Functional status was determined by the Mayo-Portland Adaptability Inventory (MPAI) and the Community Integration Questionnaire (CIQ). Patients were further grouped by time since injury of 3-12 months or over 1 year. RESULTS: Those with a mild and moderate disabilities and over 1 year chronicity showed improvements after 90 days of rehabilitation. Patients with a severe disability and over 1 year chronicity required at least 180 days to show improvements. Moderately and severely disabled patients with an injury chronicity of 3-12 months showed improvements in the MPAI after 90 days. However, further improvement was observed after 180 days in the severely disabled group. CONCLUSIONS: Results suggest that both, level of disability and injury chronicity, should be considered when determining LOS. Data also show an association between LOS and changes in the MPAI and CIQ.

Post-traumatic hypopituitarism and fatigue.

Post-traumatic hypopituitarism (PTH) associated with chronic cognitive, psychiatric, and/or behavioural sequelae is common following moderate to severe traumatic brain injury (TBI). More specifically, due to a cascade of hormonal deficiencies secondary to PTH, individuals with TBI may experience debilitating fatigue that can negatively impact functional recovery, as it can limit participation in brain injury rehabilitation services and lead to an increase in maladaptive lifestyle practices. While the mechanisms underlying fatigue and TBI are not entirely understood, the current review will address the specific anatomy and physiology of the pituitary gland, as well as the association between pituitary dysfunction and fatigue in individuals with TBI.

Neuropsychological and physiological correlates of fatigue following traumatic brain injury.

BACKGROUND: Fatigue is a common and debilitating phenomenon experienced by individuals with traumatic brain injury (TBI) that can negatively influence rate and extent of functional recovery by reducing participation in brain injury rehabilitation services and increasing maladaptive lifestyle practices. The underlying mechanisms of TBI-related fatigue are not entirely understood and focused research on symptom reduction or prevention is limited. REVIEW: The current review of the literature suggests that the aetiology of TBI-related fatigue can be viewed as a multifactorial and complex model impacting physiological systems (i.e. endocrine, skeletal muscle and cardiorespiratory) that can be directly or indirectly influenced by neuropsychological correlates including cognitive and psychological impairment. Distinguishing central from peripheral fatigue is helpful in this regard. Potential therapeutic strategies and pharmacological agents to help alleviate fatigue in this patient population are discussed.

Prevalence of fatigue and cognitive impairment after traumatic brain injury.

BACKGROUND: Following traumatic brain injury (TBI) some patients develop lingering comorbid symptoms of fatigue and cognitive impairment. The mild cognitive impairment self-reported by patients is often not detected with neurocognitive tests making it difficult to determine how common and severe these symptoms are in individuals with a history of TBI. This study was conducted to determine the relative prevalence of fatigue and cognitive impairment in individuals with a history of TBI. METHODS: The Fatigue and Altered Cognition Scale (FACs) digital questionnaire was used to assess self-reported fatigue and cognitive impairment. Adults aged 18-70 were digitally recruited for the online anonymous study. Eligible participants provided online consent, demographic data, information about lifetime TBI history, and completed the 20 item FACs questionnaire. RESULTS: A total of 519 qualifying participants completed the online digital study which included 204 participants with a history of TBI of varied cause and severity and 315 with no history of TBI. FACs Total Score was significantly higher in the TBI group (57.7 ± 22.2) compared to non-TBI (39.5 ± 23.9; p<0.0001) indicating more fatigue and cognitive impairment. When stratified by TBI severity, FACs score was significantly higher for all severity including mild (53.9 ± 21.9, p<0.0001), moderate (54.8 ± 24.4, p<0.0001), and severe (59.7 ± 20.9, p<0.0001) TBI. Correlation analysis indicated that more severe TBI was associated with greater symptom severity (p<0.0001, r = 0.3165). Ancillary analysis also suggested that FACs scores may be elevated in participants with prior COVID-19 infection but no history of TBI. CONCLUSIONS: Adults with a history of even mild TBI report significantly greater fatigue and cognitive impairment than those with no history of TBI, and symptoms are more profound with greater TBI severity.

Growth hormone treatment for neurologic symptoms of post-acute sequelae of COVID-19.

Following SARS-CoV-2 infection, some patients develop lingering neurologic symptoms of post-acute sequelae of COVID-19 (PASC) that commonly include fatigue and "brain fog." PASC symptoms are also linked with reduced growth hormone (GH) secretion, but GH treatment has not been tested to relieve symptoms. We enrolled 13 adults with neurologic PASC symptoms and peak stimulated GH secretion less than 10 ng/mL (glucagon stimulation) in a pilot study to receive 9 months of daily GH injections and an additional 3 months of off-treatment assessment. We compared peak stimulated GH secretion at baseline and 12 months and assessed measures of cognition, metabolism, body composition, and physical performance over the first 6 months of treatment. Patient-reported outcomes of fatigue, quality of life, sleep, and mood were recorded at baseline and compared with timepoints at 6, 9, and 12 months. GH treatment was associated with significantly improved scores for Brief Fatigue Inventory, Multidimensional Fatigue Symptom Inventory, Quality of Life Assessment of Growth Hormone Deficiency in Adults, Profile of Mood States, and Beck Depression Inventory-II, with no significant change in Pittsburgh Sleep Quality Index. Six months of adjunct GH treatment was not associated with significant changes in cognition, body composition, resting energy expenditure, or physical performance. Peak stimulated GH secretion was not altered at 12 months following 9 months of GH treatment. GH treatment significantly improved neurologic symptoms in PASC patients but cognition, sleep, and physical performance were not significantly altered.

The altered TBI fecal microbiome is stable and functionally distinct.

Introduction: Patients who suffer a traumatic brain injury (TBI) often experience chronic and sometimes debilitating sequelae. Recent reports have illustrated both acute and long-term dysbiosis of the gastrointestinal microbiome with significant alterations in composition and predicted functional consequences. Methods: Working with participants from past research, metagenomic stability of the TBI- associated fecal microbiome (FMB) was evaluated by custom qPCR array comparing a fecal sample from 2015 to one collected in 2020. Metatranscriptomics identified differently expressed bacterial genes and biochemical pathways in the TBI FMB. Microbiota that contributed the largest RNA amounts identified a set of core bacteria most responsible for functional consequences of the TBI FMB. Results: A remarkably stable FMB metagenome with significant similarity (two-tail Spearman nonparametric correlation p < 0.001) was observed between 2015 and 2020 fecal samples from subjects with TBI. Comparing the 2020 TBI FMB metagenome to FMBs from healthy controls confirmed and extended the dysbiotic genera and species. Abundance differences between average TBI and healthy FMBs revealed Bacteroides caccae, B. uniformis, Blautia spp., Collinsella spp., Dialister spp., and Ordoribacter spp. were significantly different. Functionally, the Parabacteroides genus contributed the highest percentage of RNA sequences in control FMBs followed by the Bacteroides genus as the second highest contributor. In the TBI FMB, the Corynebacterium genus contributed the most RNA followed by the Alistipes genus. Corynebacterium and Pseudomonas were distinct in the top 10 contributing genera in the TBI FMB while Parabacteroides and Ruminococcus were unique to the top 10 in controls. Comparing RNA profiles, TBI samples had ∼1.5 fold more expressed genes with almost 700 differently expressed genes (DEGs) mapped to over 100 bacterial species. Bioinformatic analysis associated DEGs with pathways led identifying 311 functions in the average TBI FMB profile and 264 in the controls. By average profile comparison, 30 pathways had significantly different abundance (p < 0.05, t-test) or were detected in >80% of the samples in only one of the cohorts (binary distinction). Discussion: Functional differences between TBI and healthy control FMBs included amino acid metabolism, energy and carbon source usage, fatty acid metabolism, bacterial cell wall component production and nucleic acid synthesis and processing pathways. Together these data shed light on the functional consequences of the dysbiotic TBI FMB decades after injury.

Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study.

OBJECTIVE: To determine if patients that develop lingering neurologic symptoms of fatigue and "brain fog" after initial recovery from coronavirus disease 2019 (COVID-19) have persistent low growth hormone (GH) secretion as seen in other conditions with similar symptom etiology. DESIGN: In this case-control observational pilot study, patients reporting lingering neurologic post-acute sequelae of SARS-CoV-2 (PASC, n = 10) symptoms at least 6 months after initial infection were compared to patients that recovered from COVID-19 without lingering symptoms (non-PASC, n = 13). We compared basic blood chemistry and select metabolites, lipids, hormones, inflammatory markers, and vitamins between groups. PASC and non-PASC subjects were tested for neurocognition and GH secretion, and given questionnaires to assess symptom severity. PASC subjects were also tested for glucose tolerance and adrenal function. RESULTS: PASC subjects reported significantly worse fatigue, sleep quality, depression, quality of life, and gastrointestinal discomfort compared to non-PASC. Although PASC subjects self-reported poor mental resilience, cognitive testing did not reveal significant differences between groups. Neurologic PASC symptoms were not linked to inflammatory markers or adrenal insufficiency, but were associated with reduced growth hormone secretion. CONCLUSIONS: Neurologic PASC symptoms are associated with gastrointestinal discomfort and persistent disruption of GH secretion following recovery from acute COVID-19. (www. CLINICALTRIALS: gov; NCT04860869).

Efficient assessment of brain fog and fatigue: Development of the Fatigue and Altered Cognition Scale (FACs).

Debilitating symptoms of fatigue and accompanying "brain fog" are observed among patients with various chronic health conditions. Unfortunately, an efficient and psychometrically sound instrument to assess these co-occurring symptoms is unavailable. Here, we report the development and initial psychometric properties of the Fatigue and Altered Cognition Scale (the FACs), a measure of self-reported central fatigue and brain fog. Traumatic brain injury (TBI) was chosen to model and develop the FACs due to research team expertise and established links between TBI and the symptom complex. Potential items were generated by researchers and clinicians with experience treating these symptoms, drawing from relevant literature and review of patient responses to measures from past and current TBI studies. The 20 candidate items for the FACs-ten each to assess altered cognition (i.e., brain fog) and central fatigue-were formatted on an electronic visual analogue response scale (eVAS) via an online survey. Demographic information and history of TBI were obtained. A total of 519 participants consented and provided usable data (average age = 40.23 years; 73% female), 204 of whom self-reported a history of TBI (75% reported mild TBI). Internal consistency and reliability values were calculated. Confirmatory factor analysis (CFA) examined the presumed two-factor structure of the FACs and a one-factor solution for comparison. A measurement invariance test of the two latent constructs (altered cognition, fatigue) among participants with and without TBI was conducted. All items demonstrated normal distribution. Cronbach's alpha coefficients indicated good internal consistency for both factors (α's = .95). Omega reliability values were favorable (α's = .95). CFA supported the presumed two-factor model and item loadings which outperformed the one-factor model. Measurement invariance found the two-factor structure was consistent between the two groups. Implications of these findings, study limitations, and potential use of the FACs in clinical research and practice are discussed.

Traumatic brain injury, abnormal growth hormone secretion, and gut dysbiosis.

The gut microbiome has been implicated in a variety of neuropathologies with recent data suggesting direct effects of the microbiome on host metabolism, hormonal regulation, and pathophysiology. Studies have shown that gut bacteria impact host growth, partially mediated through the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, no study to date has examined the specific role of GH on the fecal microbiome (FMB) or the changes in this relationship following a traumatic brain injury (TBI). Current literature has demonstrated that TBI can lead to either temporary or sustained abnormal GH secretion (aGHS). More recent literature has suggested that gut dysbiosis may contribute to aGHS leading to long-term sequelae now known as brain injury associated fatigue and cognition (BIAFAC). The aGHS observed in some TBI patients presents with a symptom complex including profound fatigue and cognitive dysfunction that improves significantly with exogenous recombinant human GH treatment. Notably, GH treatment is not curative as fatigue and cognitive decline typically recur upon treatment cessation, indicating the need for additional studies to address the underlying mechanistic cause.

Is there a role for growth hormone replacement in adults to control acute and post-acute COVID-19?

The SARS-CoV-2 pandemic created a multitude of medical crossroads requiring real time adaptations of best practice covering preventative and interventional aspects of care. Among the many discoveries borne from efforts to address the myriad clinical presentations across multiple organ systems was a common impact on tissues with cells that express the ACE-2 receptor. The vast majority of acute infections began and often ended in the respiratory tract, but more recent evaluations have confirmed significant extrapulmonary manifestations including symptom clusters that extend beyond the acute phase of infection collectively referred to as "post-acute sequelae SARS-CoV-2 infection" (PASC) or more commonly as "long (-haul) COVID". Both acute SARS-CoV-2 infection and PASC are associated with gut microbiome dysbiosis and alterations in the gut-brain and HPA-axis in a subset of the infected. Mounting evidence suggests these extrapulmonary manifestations may ultimately lead to reduced growth hormone (GH) secretion as demonstrated following stimulation tests. Disrupted GH secretion could cause or exacerbate long lasting neuropsychological symptoms as seen in other similar manifesting conditions. Ongoing clinical research has shown promising improvement in PASC patients with fatigue and cognition complaints can be achieved via GH replacement therapy. GH stimulation testing should be considered in PASC workups and future research should delve deeper into the mechanistic effects of GH on acute COVID and PASC.

What are critical outcome measures for patients receiving pituitary replacement following brain injury?

There are scant prospective studies defining improvements in critical outcome measures with hormone replacement in hypopituitarism secondary to brain injury. We review the tests of cognition and physical function and summarize their use for subjects that are deficient in anterior hormone production during anterior pituitary hormone replacement in brain injury and propose these as the minimal tests that are feasible for a physician to perform in a clinical setting. We summarize the studies conducted to assess outcome measures after brain injury and also report preliminary findings for improvements in cognition and physical function in subjects with brain injury and GH deficiency.

A consensus on optimization of care in patients with growth hormone deficiency and mild traumatic brain injury.

OBJECTIVE/DESIGN: Approximately 2.9 million children and adults in the US experience traumatic brain injuries (TBIs) annually, most of which are considered mild. TBI can induce varying consequences on pituitary function, with growth hormone deficiency (GHD) among the more commonly reported conditions. Panels of pediatric and adult endocrinologists, neurologists, physical medicine and rehabilitation specialists, and neuropsychologists convened in February and October 2020 to discuss ongoing challenges and provide strategies for detection and optimal management of patients with mild TBI and GHD. RESULTS: Difficulties include a low rate of seeking medical attention in the population, suboptimal screening tools, cost and complexity of GHD testing, and a lack of consensus regarding when to test or retest for GHD. Additionally, referrals to endocrinologists from other specialists are uncommon. Recommendations from the panels for managing such patients included multidisciplinary guidelines on the diagnosis and management of post-TBI GHD and additional education on long-term metabolic and probable cognitive benefits of GH replacement therapy. CONCLUSION: As patients of all ages with mild TBI may develop GHD and/or other pituitary deficiencies, a multidisciplinary approach to provide education to endocrinologists, neurologists, neurosurgeons, traumatologists, and other providers and guidelines for the early identification and management of persistent mild TBI-related GHD are urgently needed.

Serum IGF-1 concentrations in a sample of patients with traumatic brain injury as a diagnostic marker of growth hormone secretory response to glucagon stimulation testing.

OBJECTIVE: The diagnosis of growth hormone deficiency (GHD) in adults is established through growth hormone (GH) stimulation testing, which is often complex, expensive, time-consuming and may be associated with adverse side effects. The decision to perform GH provocative testing is influenced by clinical findings, medical history and biochemical evidence. We report in this study our experience using the glucagon stimulation test (GST) in assessing GHD in adult patients with traumatic brain injury (TBI) as it relates to baseline serum insulin-like growth factor-1 (IGF-1) concentrations. DESIGN: A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal IGF-1 cut-off for diagnosis of GHD at different potential diagnostic GST cut-off values (<3, <5, & <10 µg/l). PATIENTS: One hundred and thirty-eight patients (98 men and 40 women) with a documented history of moderate to severe TBI were assessed for GHD using serum IGF-1 concentrations and the GST. MEASUREMENTS: IGF-1 values were compared with peak GH values obtained following the GST. RESULTS: An IGF-1 cut-off value of 175 µg/l minimized the misclassification of GHD patients and GH-sufficient patients and provided a sensitivity of 83% and specificity of 40%, as well as a negative predictive power of 90% considering a criterion for peak GH response of <3 µg/l. CONCLUSIONS: Our current findings are consistent with previous work assessing peak GH response using the insulin tolerance test (ITT) in a non-TBI sample, suggesting that diagnostic accuracy may be optimized if the GST is used when obtained serum IGF-1 concentrations are below 175 µg/l. While the decision to perform provocative testing to assess GHD in adult patients should be based on the clinician's clinical impression, the findings from this retrospective study can provide useful clinical information and serve as a guide.

Hyperbaric oxygen therapy for traumatic brain injury: still an enigma.

With their article on the use of HBOT for post TBI dysautonomia, Lv and colleagues discuss a novel use for this form of treatment. Although HBOT has been a part of our TBI treatment armamentarium for many years, its use remains a very controversial issue. In this commentary, the science and research studies behind HBOT for TBI are reviewed, hopefully leaving the reader with an adequate knowledge base to answer a patient or family's inquiries as to the usefulness of HBOT for TBI.

Balint's syndrome and post-acute brain injury rehabilitation: a case report.

BACKGROUND: Balint's syndrome includes the clinical symptom triad of simultagnosia, ocular apraxia and optic ataxia. These symptoms, in combination, are rare and can be quite debilitating as they impact visuospatial skills, visual scanning and attentional mechanisms. CASE STUDY: The literature addressing rehabilitation of individuals with Balint's syndrome is sparse. The current case report describes the outcome of a 58-year old male who presented with Balint's syndrome secondary to severe traumatic brain injury and following completion of a comprehensive post-acute brain injury rehabilitation programme. The patient was 4-months post-injury onset upon admission and received 6 months of rehabilitation services as an inpatient. The patient's comprehensive rehabilitation programme involved a 3-pronged approach including the implementation of (a) compensatory strategies, (b) remediation exercises and (c) transfer of learned skills in multiple environments and situations with implementation of psychoeducation and psychotherapy. Comprehensive neuropsychological and occupational therapy evaluations were performed at admission and at discharge in order to monitor cognitive, affective, neurological and functional change over time. CONCLUSIONS: Neuropsychological test improvements were noted on tasks that assess visuospatial functioning, although most gains were noted for functional and physical abilities.

Endurance training and cardiorespiratory conditioning after traumatic brain injury.

OBJECTIVE: To examine the importance of cardiorespiratory conditioning after traumatic brain injury (TBI) and provide recommendations for patients recovering from TBI. METHOD: Review of literature assessing the effectiveness of endurance training programs. MAIN OUTCOMES AND RESULTS: A sedentary lifestyle and lack of endurance are common characteristics of individuals with TBI who have a reduction in peak aerobic capacity of 25% to 30% compared with healthy sedentary persons. Increased physical activity and exercise training improves cardiorespiratory fitness in many populations with physical and cognitive impairments. Therefore, increasing the endurance and cardiorespiratory fitness of persons with TBI would seem to have important health implications. However, review of the TBI literature reveals that there have been few well-designed, well-controlled studies of physiologic and psychological adaptations of fitness training. Also lacking are long-term follow-up studies of persons with TBI. CONCLUSIONS: Assessing endurance capacity and cardiorespiratory fitness early in the TBI rehabilitation process merits consideration as a standard of care by professional rehabilitation societies. Also, providing effective, safe, and accessible training modalities would seem to be an important consideration for persons with TBI, given the mobility impairments many possess. Long-term follow-up studies are needed to assess the effectiveness of cardiorespiratory training programs on overall morbidity and mortality.

Effect of recombinant growth hormone replacement in a growth hormone deficient subject recovering from mild traumatic brain injury: A case report.

OBJECTIVE: To assess the effects of growth hormone (GH) replacement in an individual who sustained mild traumatic brain injury (mTBI) as an adult and was found to have GH deficiency by glucagon stimulation testing. PARTICIPANT: A 43-year old woman who sustained a mild TBI at age 37 years. She was 6.8 years post-injury when she began supplementation. INTERVENTION: Recombinant human GH (rhGH) subcutaneously per day for 1 year. MAIN OUTCOME MEASURES: Single fibre muscle function was evaluated from muscle biopsies. Body composition, muscle strength and peak aerobic capacity were also measured. In addition, neuropsychological tests of memory, processing speed and motor dexterity and speed, as well as a self-report depression inventory were administered. All assessments were performed at baseline and after 6 and 12 months of rhGH replacement therapy. RESULTS: Single muscle fibre changes were greatest at 6 months. Body composition showed continuous improvement. Muscle strength improved for knee extension. Peak oxygen consumption increased at 6 months and total work and ventilatory equivalents continued to improve at 12 months. Significant improvements in neuropsychological test performance were not found, with the exception of performance on a test of motor dexterity and speed. CONCLUSION: rhGH replacement in a subject with GH deficiency after mild TBI improves muscle force production, body composition and aerobic capacity. Reliable improvements on tests of cognition were not found in this subject.