Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial.

In our previous randomized controlled trial, we documented significant improvements in cognitive, psychiatric, fatigue, sleep, and pain symptoms among long Coronavirus disease 2019 (COVID) patients who underwent hyperbaric oxygen therapy (HBOT). The primary objective of the present study was to evaluate the enduring 1 year long term effects of HBOT on long COVID syndrome. This longitudinal long-term follow-up included 31 patients with reported post COVID-19 cognitive symptoms, who underwent 40 daily sessions of HBOT. Participants were recruited more than one year (486 ± 73) after completion of the last HBOT session. Quality of life, assessed using the short form-36 (SF-36) questionnaire revealed, that the long-term results exhibited a similar magnitude of improvement as the short-term outcomes following HBOT across most domains. Regarding sleep quality, improvements were observed in global score and across five sleep domains with effect sizes of moderate magnitude during the short-term evaluation, and these improvements persisted in the long-term assessment (effect size (ES1) = 0.47-0.79). In the realm of neuropsychiatric symptoms, as evaluated by the brief symptom inventory-18 (BSI-18), the short-term assessment following HBOT demonstrated a large effect size, and this effect persisted at the long-term evaluation. Both pain severity (ES1 = 0.69) and pain interference (ES1 = 0.83), had significant improvements during the short-term assessment post HBOT, which persisted at long term. The results indicate HBOT can improve the quality of life, quality of sleep, psychiatric and pain symptoms of patients suffering from long COVID. The clinical improvements gained by HBOT are persistent even 1 year after the last HBOT session.

Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial.

Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection. Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1-3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = - 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001). Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate. These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT's beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.

The Montreal Cognitive Assessment Test (MoCA) as a screening tool for cognitive dysfunction in fibromyalgia.

OBJECTIVES: Cognitive dysfunction is one of the criteria for the diagnosis of fibromyalgia (FM) and is typically based on self-report questionnaires such as the Symptom Severity Scale. However, recent studies have shown that there is no correlation between these subjective measures of cognitive dysfunction and more lengthy objective measures of cognitive functioning. This points to the need for a briefer valid evaluation tool for cognitive dysfunction in FM. The aim of this study is to examine whether the Montreal Cognitive Assessment (MoCA) test is a valid measure of cognitive assessment in FM patients, by comparing it to a comprehensive computerised cognitive assessment battery. METHODS: Sixty-two FM patients (55 women, 7 men, mean age = 46.17 years, sd=12.56) were administered the MoCA and a computerised cognitive assessment battery. FM symptoms were assessed on the Fibromyalgia Impact Questionnaire (FIQ), the Widespread Pain Index (WPI), the Symptom Severity Scale (SSS), and the Beck Depression Inventory (BDI-2). Patient effort was controlled on the TOMM (Test of Memory Malingering). RESULTS: Moderate positive correlations were found between the MoCA and the computerised cognitive scores as follows: Global Cognitive Score (r=0.493**, p=0.00), Memory Index Score (r= 0.384**, p=0.002), Executive Function Index Score (r=0.461**, p=0.00), Attention Index Score (r=0.310*, p=0.016), Information Processing Speed Index Score (r=0.435**, p=0.001), and Motor Skills (r=0.406**, p=0.002). CONCLUSIONS: The MoCA is an acceptable cognitive screening test for the cognitive evaluation of FM patients.

Estimating the X chromosome-mediated risk for developing Alzheimer's disease.

Parental lineage has been shown to increase the risk of Alzheimer's disease (AD) in the offspring, with greater risk attributed to maternal lineage. While 40 genes/loci have been linked to the risk of developing AD, none has been found on the X chromosome. We propose a new method to estimate the risk for developing AD mediated by the X chromosome in a subgroup of late-onset AD (LOAD) patients with amnestic mild cognitive impairment (aMCI) or early AD and unilateral ancestral history of AD or dementia, and pilot-test it on our clinic data. Records of patients aged 55-80 years presenting to our Memory Disorders Clinic with aMCI or early AD between May 2015 and September 2020, were reviewed, counting patients with a family history of AD or dementia and unilateral ancestral lineage. The X chromosome-attributable relative risk was estimated by calculating the following odds ratio (OR): (women with paternal lineage:women with maternal lineage)/(men with paternal lineage:men with maternal lineage). The proportion of genetic risk borne by the X chromosome is equal to (OR-1)/OR. 40 women aged 66.1 ± 5.1 years (mean ± standard deviation) and 31 men aged 68.1 ± 6.5 were identified. The OR was (18:22)/(6:25) = 3.4 (95% confidence interval 1.1-10.1; p = 0.027). The estimated proportion of genetic risk borne by the X chromosome in this population is 70% (95% CI 12-90%). This paper presents the first application of a new method. The numbers are small, the confidence intervals wide. The findings need to be replicated. The method may be generalizable to other diseases.

A modified version of the 2016 ACR fibromyalgia criteria cognitive items results in stronger correlations between subjective and objective measures of cognitive impairment.

OBJECTIVES: In a previous study, we showed that the subjective item assessing cognitive impairment (SSS-Cog) for fibromyalgia (FM) did not correlate with the objective cognitive measures. In the current study, we describe two modifications designed to enhance this correlation: extending the SSS-cog scale from 0-3 to 1-5, and administration of a new questionnaire that specifically targets the cognitive impairments associated with FM. METHODS: Sixty-two FM patients underwent a computerised cognitive assessment battery. FM symptoms were assessed on the Fibromyalgia Impact Questionnaire (FIQ); the Widespread Pain Index (WPI); the Symptom Severity Scale (SSS), the new SSS-Cog scale ranging from 1 to 5, the Beck Depression Inventory (BDI) and the new cognitive questionnaire developed by the authors. RESULTS: Significant correlations were found between the new SSS-Cog, the global cognitive score and all indices [Global Score r=-0.532, p=0.00; Indices: Memory r=-0.305, p=.01; Executive function r=-0.514, p=0.00; Attention r=-0.471, p=0.00; Processing Speed r=-0.468, p=0.00; Motor Skills r=-0.495, p=.00]. Significant correlations were found between the new questionnaire and the global cognitive score and all indices except the memory index [Global Score r=-0.522, p=0.00; Indices: Memory r=-0.163, p=0.212; Executive function r=-0.477, p=0.00; Attention r=-0.439, p=0.00; Processing Speed r=-0.496, p=0.00; Motor Skills r=-0.532, p=0.00]. CONCLUSIONS: Given the simplicity involved in extending the scale, we suggest incorporating this modification into the FM diagnostic criteria of the American College of Rheumatology (ACR).

Does the cognitive index of the symptom severity scale evaluate cognition? Data from subjective and objective cognitive measures in fibromyalgia.

OBJECTIVES: The current provisional diagnostic criteria for the fibromyalgia syndrome (FM) include a cognitive index score (SSS-Cog), which constitutes a part of the Symptom Severity Scale (SSS). The current study aimed at assessing the validity of the cognitive index score, by comparing this subjective measure of cognitive impairment with an objective measure of cognitive functioning, collected through comprehensive computerised cognitive testing and assessment. METHODS: 50 FM patients underwent a computerised cognitive assessment battery, including testing in domains of memory, executive function, attention and information processing speed (NeuroTraxCorp.). Age and education standardised scores were computed. FM symptoms were assessed by the Fibromyalgia Impact Questionnaire (FIQ), Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), a Visual Analog Scale (VAS) of clinical pain and the Beck Depression inventory (BDI-II). RESULTS: The index score for subjective assessment of cognitive decline (SSS-Cog) was not correlated with any of the objective cognitive measures. However, a positive correlation was found between the SSS-Cog and the FIQ, the WPI and the VAS measures, all reflecting subjective overall functional ability. CONCLUSIONS: No significant relationship was found between FM patients' subjective appraisal of cognitive deficit and objective cognitive scores on all computerised subtests. However, subjective appraisal of cognitive impairment was found to be strongly and significantly related to patients' functional ability. Therefore, we suggest reconsidering the definition of this index score (SSS-Cog) and propose developing novel and more accurately defined tools in order to measure cognitive impairment in FM patients, for both diagnostic and epidemiological purposes.

Cognitive functioning in fibromyalgia: The central role of effort.

OBJECTIVE: Fibromyalgia syndrome (FM) patients demonstrate deficits in tests of attention, executive functioning and verbal memory. We assessed the role of effort in the cognitive impairment in FM patients, alongside common symptoms of pain, fatigue and depression. METHOD: 50 FM patients underwent a computerized cognitive assessment battery including memory, executive function, attention and information processing speed (NeuroTrax Corp.). Age and education standardized scores were computed. Effort was assessed by the Test of Memory Malingering (TOMM). FM symptoms were assessed by the Fibromyalgia Impact Questionnaire (FIQ), Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), a Visual Analog Scale (VAS) of clinical pain and the Beck Depression Inventory (BDI-2). RESULTS: FM patients showed impaired performance on the memory, attention and information processing speed domains. According to the TOMM, sub-optimal effort was shown by 16% of patients. TOMM scores were not associated with pain, fatigue or depression. After controlling for effort, no significant impairment was found in memory scores; however attention and information processing speed scores remained significantly low. Multiple regressions analysis, performed in order to evaluate the contribution of effort, pain, fatigue and depression, found effort to be the only significant variable accounting for variance of cognitive scores on all domains. CONCLUSION: The findings confirm impaired attention and processing speed in FM patients, independent of effort level. Nonetheless, the findings point to a general and strong effect of effort on neuropsychological performance in FM patients, especially in the domain of memory, emphasizes the importance of effort testing in this population.

Hypoxemia correlates with attentional dysfunction in patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea is associated with cognitive impairment, but whether hypoxemia or repeated arousals and sleepiness are the underlying mechanism is controversial. Studies using a wide range of attention and executive functions tests in patients with severe sleep apnea are lacking. METHODS: In a prospective cohort study, 40 patients aged 30-70 years, diagnosed with obstructive sleep apnea (apnea-hypopnea index ≥5) were recruited. Patients with known cardiovascular, pulmonary, psychiatric, or neurological disease, and or patients receiving anti-psychotic, sedatives, or stimulant medications were excluded. Patients underwent full overnight polysomnography including continuous oxygen saturation measurements followed by extensive neuropsychological testings in attention and executive function domains. The correlation between sleep apnea severity and patients' performance on the neuropsychological tests was examined. RESULTS: The patients' performance on measures of attention and executive function was significantly worse compared to the average in a normal population. Attention, as reflected by the number of omissions and by the reaction time on the Conners' Continuous Performance Test correlated significantly with the apnea-hypopnea index (r = 0.6, p < 0.001 and r = 0.48, p = 0.003, respectively) and with parameters of hypoxemia, namely the average SpO(2) (r = -0.51, p = 0.002 and r = -0.39, p = 0.02, respectively) and the percent time spent with SpO(2) < 90% (r = 0.57, p < 0.001 and r = 0.39, p = 0.02, respectively), but not with the degree of sleepiness. Executive dysfunction did not correlate with sleep parameters. DISCUSSION: Attention is the predominant cognitive function affected in patients with obstructive sleep apnea and correlates primarily with nocturnal hypoxemia rather than daytime sleepiness or sleep fragmentation. Executive functions, while below average in some patients, do not correlate with polysomnographic parameters.

Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer's disease: a proof of concept study.

The current drug treatment for Alzheimer's disease (AD) is only partially and temporary effective. Transcranial magnetic stimulation (TMS) is a non-invasive technique that generates an electric current inducing modulation in cortical excitability. In addition, cognitive training (COG) may improve cognitive functions in AD. Our aim was to treat AD patients combining high-frequency repetitive TMS interlaced with COG (rTMS-COG). Eight patients with probable AD, treated for more than 2 months with cholinesterase inhibitors, were subjected to daily rTMS-COG sessions (5/week) for 6 weeks, followed by maintenance sessions (2/week) for an additional 3 months. Six brain regions, located individually by MRI, were stimulated. COG tasks were developed to fit these regions. Primary objectives were average improvement of Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) and Clinical Global Impression of Change (CGIC) (after 6 weeks and 4.5 months, compared to baseline). Secondary objectives were average improvement of MMSE, ADAS-ADL, Hamilton Depression Scale (HAMILTON) and Neuropsychiatric Inventory (NPI). One patient abandoned the study after 2 months (severe urinary sepsis). ADAS-cog (average) improved by approximately 4 points after both 6 weeks and 4.5 months of treatment (P < 0.01 and P < 0.05) and CGIC by 1.0 and 1.6 points, respectively. MMSE, ADAS-ADL and HAMILTON improved, but without statistical significance. NPI did not change. No side effects were recorded. In this study, rTMS-COG (provided by Neuronix Ltd., Yokneam, Israel) seems a promising effective and safe modality for AD treatment, possibly as good as cholinesterase inhibitors. A European double blind study is underway.