Severe obstructive sleep apnea in patients with chronic obstructive pulmonary disease is associated with an increased prevalence of mild cognitive impairment

BackgroundChronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are associated with mild cognitive impairment (MCI). However, this association is unclear. This study aimed to assess the prevalence of MCI in patients with overlap syndrome, determine whether OSA increases the risk of MCI in patients with COPD, and investigate the potential mechanisms for this association.MethodsParticipants with stable Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2–4 COPD and complaints of snoring in 2016–2018 were enrolled in this cross-sectional observational study. All were free of asthma, acute left-sided congestive heart failure, unstable coronary heart disease, uncontrolled hypertension, diabetes, encephalitis, and epilepsy. They underwent pulmonary function tests and overnight polysomnography and completed the Montreal Cognitive Assessment (MoCA). MCI was defined by an MoCA score of <23, while OSA was defined by an apnea-hypopnea index (AHI) of ≥15 per hour. The association between MCI, demographics, and comorbidities was tested by logistic regression analysis with adjustment for confounders. Sleep-disordered breathing measures were investigated as potential mechanisms underlying this relationship.ResultsMCI was significantly more common in patients with overlap syndrome than in those with COPD (40.6% [43/106] vs 24.6% [42/171]). After adjustment, severe OSA was an independent contributor to MCI (odds ratio, OR 2.27; 95% confidence interval, CI 1.12–4.62). Increased percent of night-time spent with oxygen saturation <90% (TSat₉₀) was associated with increased odds of MCI (odds ratio 4.75, 95% CI 2.73–11.13).ConclusionsMCI is more prevalent in overlap syndrome than in COPD. OSA may contribute to MCI in COPD. The mechanism may involve TSat₉₀.     

Association Between Dietary Copper Intake and Cognitive Decline: A Perspective Cohort Study in Chinese Elderly

ObjectiveThe association between dietary copper (Cu) intake and cognitive decline remains uncertain. We aim to investigate the longitudinal association of dietary Cu with cognitive decline in Chinese elderly.MethodsA total of 3,106 Chinese adults aged older than or equal to 55 years from China Health and Nutrition Survey (CHNS) were included. Dietary nutrients information was collected by 24-hours dietary recalls in combination with a food-weighted method. The 5-year change rates in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status–modified (TICS-m) was calculated as the last-survey score minus the baseline score, then divided by the follow-up time (unit, years) and multiplied by five.ResultsThe median follow-up duration was 5.9 years. There was a nonlinear association of dietary Cu intake with the 5-year change rates in global or composite cognitive scores, with the inflection point at approximately 1.3 mg/day of dietary Cu intake. Accordingly, for the composite cognitive score, compared to the first quantile (<1.28 mg/day), those with dietary Cu in quantiles 2–8 (≥1.28 mg/day) had a significantly slower cognitive decline rate (B, 0.30; 95% CI, 0.13, 0.47). Similar results were found for the global cognitive score. Moreover, the inverse association between dietary Cu and cognitive decline was stronger in those with lower dietary fat intake and lower levels of physical activity (All p-interactions <0.05).ConclusionThere was a nonlinear inverse association of dietary Cu intake with cognitive decline in the elderly, with an inflection point at approximately 1.3 mg/day of dietary Cu intake.     

Validation in French of the Montreal Cognitive Assessment 5-Minute,a brief cognitive screening test for phone administration

BackgroundThe prevalence of cognitive impairment and dementia is high and steadily increasing. Early detection of cognitive decline is crucial since some interventions can reduce the risk of progression to dementia. However, there is a lack of manageable scales for assessing cognitive functions outside specialized consultations. Recently, the MoCA-5 min, a short version of the Montreal Cognitive assessment (MoCA), phone-administered, was validated for screening for vascular cognitive impairment. The aim of the present study was to validate the MoCA-5 min in French in diverse clinical populations.MethodsThe Cantonese version of the MoCA-5 min was adapted for French language. Healthy volunteers and patients with possible or established cognitive impairment (Alzheimer's disease or related disorders, Parkinson's disease, Huntington's disease, type-2 diabetes) participated in the study. The original MoCA and the MoCA-5 min were administered, by phone, with a 30-day interval. Alternate forms were used to reduce learning effects.ResultsThe scores of the original MoCA and MoCA-5 min correlated significantly (Spearman rho = 0.751, P < 0.0001, 95% confidence interval 0.657 to 0.819). Internal consistency was good (Cronbach alpha = 0.795). The area under the ROC curve was 0.870 and the optimal cut-off value for separating patients with and without cognitive impairment with the MoCA-5 min was ≤ 27 with 87.32% sensitivity and 76.09% specificity. Interrater and test-retest reliability were adequate.ConclusionThis study demonstrates that the French version of the MoCA-5 min is a valid and reliable scale for detecting cognitive impairment in different clinical populations. It is administrable by phone and thus suitable for remote assessment as well as for large-scale screening and epidemiological studies.     

Predictive factors for the development of epilepsy after ischemic stroke

ObjectivesIschemic stroke is one of the most common causes of epilepsy in adults. The incidence of post-stroke epilepsy (PSE) is approximately 7%. Risk factors are higher stroke severity, cortical localization, higher National Institute of Health Stroke Scale (NIHSS) upon admission and acute symptomatic seizures. We analyzed the predictive factors of PSE development in our population.Materials and methodsRetrospective observational cohort of adult patients (age ≥ 18 years) with ischemic stroke assessed between January 2012 and June 2020. Patients with personal history of epilepsy and potentially epileptogenic structural injury other than acute or chronic stroke were excluded. Demographic, clinical and imaging variables were evaluated in a multivariate analysis for independent risk factors associated with PSE.ResultsMedical records of 1586 stroke patients were reviewed, 691 met the inclusion criteria and had at least one year of follow-up. Of them, 428 (61.9%) were males. During follow-up, 6.2% had diagnosis of PSE (42/691) with a higher frequency of: previous ischemic stroke, higher NIHSS upon admission, treatment with rt-PA, higher Fazekas scale grade, cortical involvement, hemorrhagic transformation, acute symptomatic seizures, longer hospitalization and higher modified Rankin Scale (mRS) at discharge compared to the group without PSE. In a multivariate analysis, acute symptomatic seizures (OR=3.22, p: 0.033), cortical involvement (OR=0.274, p < 0.05), Fazekas scale score (OR=0.519, p < 0.05) and mRS at discharge (OR=1.33, p: 0.043) were independent risk factors.ConclusionsThe variables related to higher risk of PSE were similar to those reported in the literature, highlighting the importance of neuroimaging findings, acute symptomatic seizures during hospitalization and neurological deficit at discharge. The data obtained will serve as the basis for construction of predictive models, allowing to individualize PSE probability in our population.     

Predictors of CPAP adherence following stroke and transient ischemic attack

ObjectiveContinuous positive airway pressure (CPAP) has been shown to improve functional, motor and cognitive outcomes in post-stroke obstructive sleep apnea (OSA). However, rates of CPAP adherence are often low and factors impacting CPAP adherence remain under-explored. Our objective was to determine predictors of CPAP adherence in patients who had a stroke or transient ischemic attack (TIA).MethodsWe screened 313 stroke/TIA patients for OSA using in-hospital polysomnography or the ApneaLink home sleep apnea test. Potential predictors were recorded at baseline and adherence to CPAP was recorded during a six-month follow-up visit. Selected variables from our univariate analyses were included in multivariate regression models to determine predictors of CPAP adherence. For our logistic regression analyses, CPAP adherence (CPAP use of ≥4 h per night) was the dependent outcome variable. In our linear regression analyses, total CPAP use per week (recorded in hours) was the dependent outcome variable.ResultsEighty-eight patients (mean age 67.81 ± 13.09 years, 69.32% male, mean body mass index 27.93 ± 5.23 kg/m²) were diagnosed with OSA, prescribed CPAP, and assessed for adherence at a six-month follow-up visit. In these 88 patients, 46 (52.27%) were adherent with CPAP therapy. From our regression models, two significant predictors of CPAP adherence were identified: greater functional status (p = 0.04) and not endorsing daytime tiredness (p = 0.047) post-stroke/TIA.ConclusionPatients with greater functional capacity and those with less daytime fatigue demonstrated stronger adherence to CPAP therapy. Our findings may facilitate future treatment strategies for enhancing CPAP adherence in the vulnerable stroke/TIA population.     

Effect of repetitive transcranial magnetic stimulation combined with robot-assisted training on wrist muscle activation post-stroke

ObjectiveTo compare the effects of active assisted wrist extension training, using a robotic exoskeleton (RW), with simultaneous 5 Hz (rTMS + RW) or Sham rTMS (Sham rTMS + RW) over the ipsilesional extensor carpi radialis motor cortical representation, on voluntary wrist muscle activation following stroke.MethodsThe two training conditions were completed at least one week apart in 13 participants >1-year post-stroke. Voluntary wrist extensor muscle activation (motor unit (MU) recruitment thresholds and firing rate modulation in a ramp-hold handgrip task), ipsilesional corticospinal excitability (motor evoked potential [MEP] amplitude) and transcallosal inhibition were measured Pre- and Post-training.ResultsFor MUs active both Pre and Post training, greater reductions in recruitment thresholds were found Post rTMS + RW training (p = 0.0001) compared to Sham rTMS + RW (p = 0.16). MU firing rate modulation increased following both training conditions (p = 0.001). Ipsilesional MEPs were elicited Pre and Post in only 5/13 participants. No significant changes were seen in ipsilesional corticospinal excitability and transcallosal inhibition measures (p > 0.05).ConclusionsFollowing a single rTMS + RW session in people >1-year post-stroke, changes were found in voluntary muscle activation of wrist extensor muscles. Alterations in ipsilesional corticospinal or interhemispheric excitability were not detected.SignificanceThe effects of rTMS + RW on muscle activation warrant further investigation as post-stroke rehabilitation strategy.     

EEG and behavioural correlates of mild sleep deprivation and vigilance

ObjectiveThe current study investigated the behavioral, cognitive, and electrophysiological impact of mild (only a few hours) and acute (one night) sleep loss via simultaneously recorded behavioural and physiological measures of vigilance.MethodsParticipants (N = 23) came into the lab for two testing days where their brain activity and vigilance were recorded and assessed. The night before the testing session, participants either slept from 12am to 9am (Normally Rested), or from 1am to 6am (Sleep Restriction).ResultsVigilance was reduced and sleepiness was increased in the Sleep Restricted vs. Normally Rested condition, and this was exacerbated over the course of performing the vigilance task. As well, sleep restriction resulted in more intense alpha bursts. Lastly, EEG spectral power differed in Sleep Restricted vs. Normally Rested conditions as sleep onset progressed, particularly for frequencies reflecting arousal (e.g., delta, alpha, beta).ConclusionsThe findings of this study suggest that only one night of mild sleep loss significantly increases sleepiness and, importantly, reduces vigilance. In addition, this sleep loss has a clear impact on the physiology of the brain in ways that reflect reduced arousal.SignificanceUnderstanding the neural correlates and cognitive processes associated with loss of sleep may lead to important advancements in identifying and preventing deleterious or potentially dangerous, sleep-related lapses in vigilance.     

Early life Adversity,functional connectivity and cognitive performance in Schizophrenia: The mediating role of IL-6

ObjectiveExposure to childhood trauma (CT) is associated with cognitive impairment in schizophrenia, and deficits in social cognition in particular. Here, we sought to test whether IL-6 mediated the association between CT and social cognition both directly, and sequentially via altered default mode network (DMN) connectivity.MethodsThree-hundred-and-eleven participants (104 patients and 207 healthy participants) were included, with MRI data acquired in a subset of n = 147. CT was measured using the childhood trauma questionnaire (CTQ). IL-6 was measured in both plasma and in toll like receptor (TLR) stimulated whole blood. The CANTAB emotion recognition task (ERT) was administered to assess social cognition, and cortical connectivity was assessed based on resting DMN connectivity.ResultsHigher IL-6 levels, measured both in plasma and in toll-like receptor (TLR-2) stimulated blood, were significantly correlated with higher CTQ scores and lower cognitive and social cognitive function. Plasma IL-6 was further observed to partly mediate the association between higher CT scores and lower emotion recognition performance (CTQ total: β_indirect −0.0234, 95% CI: −0.0573 to −0.0074; CTQ physical neglect: β_indirect = −0.0316, 95% CI: −0.0741 to −0.0049). Finally, sequential mediation was observed between plasma IL-6 levels and DMN connectivity in mediating the effects of higher CTQ on lower social cognitive function (β_indirect = −0.0618, 95% CI: −0.1523 to −0.285).ConclusionThis work suggests that previous associations between CT and social cognition may be partly mediated via an increased inflammatory response. IL-6′s association with changes in DMN activity further suggest at least one cortical network via which CT related effects on cognition may be transmitted.     

Wake-up stroke is not associated with obstructive sleep apnea

Objective/BackgroundObstructive sleep apnea is a risk factor for stroke. This study sought to assess the relationship between obstructive sleep apnea (OSA) and wake-up strokes (WUS), that is, stroke symptoms that are first noted upon awakening from sleep.Patients/methodsIn this analysis, 837 Brain Attack Surveillance in Corpus Christi (BASIC) project participants completed an interview to ascertain stroke onset during sleep (WUS) versus wakefulness (non-wake-up stroke, non-WUS). A subset of 316 participants underwent a home sleep apnea test (HSAT) shortly after ischemic stroke to assess for OSA. Regression models were used to test the association between OSA and WUS, stratified by sex.ResultsOf 837 participants who completed the interview, 251 (30%) reported WUS. Among participants who underwent an HSAT, there was no significant difference in OSA severity [respiratory event index (REI)] among participants with WUS [median REI 17, interquartile range (IQR) 10, 29] versus non-WUS (median REI 18, IQR 9, 30; p = 0.73). OSA severity was not associated with increased odds of WUS among men [unadjusted odds ratio (OR) 1.011, 95% confidence interval (95% CI) 0.995, 1.027] or women (unadjusted OR 0.987, 95% CI 0.959, 1.015). These results remained unchanged after adjustment for age, congestive heart failure, body mass index, and pre-stroke depression in men (adjusted OR 1.011, 95% CI 0.994, 1.028) and women (adjusted OR 0.988, 95% CI 0.959, 1.018).ConclusionsAlthough OSA is a risk factor for stroke, the onset of stroke during sleep is not associated with OSA in this large, population-based stroke cohort.     

Real-time feedback on mobile application use for emergency management affects the door-to-needle time and functional outcomes in acute ischemic stroke

ObjectivesTime from onset to reperfusion affects mortality and favorable outcomes in patients with acute ischemic stroke (AIS). To evaluate effects of a real-time feedback mobile application on critical time intervals and functional outcomes in stroke emergency management.MethodsWe recruited patients with clinically suspected acute stroke from December 1st, 2020 until July 30st, 2022. All Patients had a non-contrast computed tomography (CT) and were included only if they had AIS. We divided the patients into two groups based on the date of availability on mobile application: pre-APP group and post-APP group. Onset to Door time (ODT), Door to Imaging Time (DIT), Door to Needle Time (DNT), Door to Puncture Time (DPT), Door to Recanalization Time (DRT), National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were compared between two groups.ResultsWe retrospectively enrolled 312 AIS patients who were assigned into the pre-APP group (n = 159) and post-APP group (n = 153). The median ODT time and median admission NIHSS score were not significantly different between the two groups at baseline assessment. The median (IQR) DIT [44 (30-60) min vs 28 (20-36) min, P < 0.01] and DNT [44 (36.25-52) min vs 39 (29-45) min, P = 0.02] both decreased significantly in two groups. However, median DPT and DRT time showed no significant differences. The proportion of mRS score of 0 to 2 at day 90 was significantly higher in the post-App group than in the pre-App group, at 82.4% and 71.7%, respectively (dominance ratio OR=1.84, 95% CI: 1.07 to 3.16, P = 0.03).ConclusionThe present findings indicate that the real-time feedback of stroke emergency management used by a mobile application have potential for shortening the DIT and DNT time and improve the prognosis of stroke patients.     

Immune markers are associated with cognitive performance in a multiethnic cohort: The Northern Manhattan Study

ObjectiveTo determine whether immune protein panels add significant information to correlates of cognition.BackgroundImmune mechanisms in vascular cognitive aging are incompletely characterized.Design/methodsA subsample of the prospective Northern Manhattan Study underwent detailed neuropsychological testing. Cognitive scores were converted into Z-scores and categorized into four domains (memory, language, processing speed, and executive function) based on factor analysis. Blood samples were analyzed using a 60-plex immunoassay. We used least absolute shrinkage and selection operator (LASSO) procedures to select markers and their interactions independently associated with cognitive scores. Linear regression models assessed cross-sectional associations of known correlates of cognition with cognitive scores, and assessed model fit before and after addition of LASSO-selected immune markers.ResultsAmong 1179 participants (mean age 70 ± 8.9 years, 60% women, 68% Hispanic), inclusion of LASSO-selected immune markers improved model fit above age, education, and other risk factors (p for likelihood ratio test < 0.005 for all domains). C–C Motif Chemokine Ligand 11 (CCL 11, eotaxin), C-X-C Motif Chemokine Ligand 9 (CXCL9), hepatocyte growth factor (HGF), and serpin E1 (plasminogen activator inhibitor-1) were associated with each of the domains and with overall cognitive function. Immune marker effects were comparable to conventional risk factors: for executive function, each standard deviation (SD) increase in CCL11 was associated with an effect equivalent to aging three years; for memory, HGF had twice the effect of aging.ConclusionsImmune markers associate with cognitive function in a multi-ethnic cohort. Further work is needed to validate these findings and determine optimal treatment targets.     

Cognitive effort decreases beta,alpha, and theta coherence and ends afterdischarges in human brain

ObjectiveMental activation has been reported to modify the occurrence of epileptiform activity. We studied its effect on afterdischarges.MethodIn 15 patients with implanted electrodes we presented cognitive tasks when afterdischarges occurred. We developed a wavelet cross-coherence function to analyze the electrocorticography before and after the tasks and compared findings when cognitive tasks did or did not result in afterdischarge termination. Six patients returned for functional MRI (fMRI) testing, using similar tasks.ResultsCognitive tasks often could terminate afterdischarges when direct abortive stimulation could not. Wavelet cross-coherence analysis showed that, when afterdischarges stopped, there was decreased coherence throughout the brain in the 7.13–22.53 Hz frequency ranges (p values 0.008–0.034). This occurred a) regardless of whether an area activated on fMRI and b) regardless of whether there were afterdischarges in the area.ConclusionsIt is known that cognitive tasks can alter localized or network synchronization. Our results show that they can change activity throughout the brain. These changes in turn can terminate localized epileptiform activity.SignificanceCognitive tasks result in diffuse brain changes that can modify focal brain activity. Combined with a seizure detection device, cognitive activation might provide a non-invasive method of terminating or modifying seizures.     

Comparison of clinical outcomes with two Transcranial Magnetic Stimulation treatment protocols for major depressive disorder

BackgroundTranscranial magnetic stimulation (TMS) is an effective treatment for major depressive disorder (MDD). The rest time between pulse trains is the inter-train interval (ITI). Since 2016, some TMS clinicians have adopted a stimulation protocol with shorter ITIs than were used in regulatory clinical trials.ObjectiveTo contrast treatment outcomes with the Standard TMS protocol (38.5 min per session) and the “Dash” protocol, which, at the shortest ITI, has a session duration of 18.75 min.MethodsRegistry data were collected at 103 practice sites. Of 7759 participants, 5010 were included in an intent-to-treat (ITT) sample, defined as a primary MDD diagnosis, age ≥ 18, and completion of the PHQ-9 before TMS and with at least one PHQ-9 assessment after baseline. Completers (N = 3814) were responders or had received ≥ 20 sessions and had an end of acute treatment PHQ-9 assessment. Within the ITT sample, 613 patients were treated with the Standard NeuroStar 38-min protocol and 1493 patients with the new Dash protocol. CGI-S ratings were obtained in smaller samples. Treatment outcomes were also examined in subgroups considered Completers, as well as the subgroups who met criteria for Full Adherence to the Standard or Dash protocol parameters.ResultsIn the ITT, Completer, and Fully Adherent samples, response (58–72%) and remission (28–53%) rates were notably high across PHQ-9 and CGI-S ratings. The Standard and Dash protocols did not differ in number of treatment sessions, and both manifested strong antidepressant effects.ConclusionsThe Standard and Dash protocols did not meaningfully differ in efficacy.     

Plasma Pro-Enkephalin A and Ischemic Stroke Risk: The Reasons for Geographic and Racial Differences in Stroke Cohort

ObjectivesThe opioid neuropeptide pro-enkephalin A (PENK-A) may be a circulating marker of cardiovascular risk, with prior findings relevant to heart failure, kidney disease, and vascular dementia. Despite these findings, the association of PENK-A with ischemic stroke is unknown, so we examined this association in a prospective cohort study and analyzed differences by race and sex.Materials and MethodsThe REasons for Geographic and Racial Differences in Stroke study (REGARDS) is a prospective cohort study of 30,239 Black and White adults. Plasma PENK-A was measured in 473 participants that developed first-time ischemic stroke over 5.9 years and 899 randomly selected participants. Cox models adjusted for demographics and stroke risk factors were used to calculate hazard ratios (HRs) of stroke by baseline PENK-A.ResultsPENK-A was higher with increasing age, female sex, White race, lower body mass index, and antihypertensive medication use. Each SD higher increment of PENK-A was associated with an adjusted HR of 1.20 (95% CI 1.01-1.42) for stroke, with minimal confounding by stroke risk factors. Spline plots suggested a U-shaped relationship, particularly in White men, with an adjusted HR 3.88 (95% CI 1.94-7.77) for the 95^th versus 50^th percentile of PENK-A in White men.ConclusionsHigher baseline plasma PENK-A was independently associated with future stroke risk in REGARDS. This association was most apparent among White men. There was little confounding by established stroke risk factors, suggesting a possible causal role in stroke etiology. Further research is needed to understand the role of endogenous opioids in stroke pathogenesis.     

Central sleep apnea is uncommon after stroke

Objective/backgroundStroke is often considered a risk factor for central sleep apnea (CSA). The goal of this study was to determine the prevalence and clinical correlates of CSA in patients with ischemic stroke.Patients/methodsIn this analysis, 1346 participants in the Brain Attack Surveillance in Corpus Christi (BASIC) project underwent a home sleep apnea test shortly after ischemic stroke. Respiratory events during sleep were classified as central apneas, obstructive apneas, or hypopneas. Central apnea index (CAI) was defined as number of central apneas divided by recording time. CSA was defined as CAI ≥5/hour with at least 50% of all scored respiratory events classified as central apneas. Demographics and co-morbidities were ascertained from the medical record.ResultsMedian CAI was 0/hour. Nineteen participants (1.4%) met criteria for CSA. Participants with CSA were more likely to be male, and had lower prevalence of obesity than participants without CSA. There was no association between CSA and other co-morbidities.ConclusionsCSA was uncommon in this large cohort of patients with recent ischemic stroke.     

Denial of Cerebrovascular Events in a National Clinical Quality Registry for Stroke: A Retrospective Cohort Study

ObjectivesTo investigate cerebrovascular event (CVE) denials reported by registered patients to the Australian Stroke Clinical Registry, and to examine the factors associated with CVE denial.Material and methodsCVE denials reported from January 1, 2017 to June 30, 2018 were followed up with hospitals to verify their discharge diagnosis. CVE denials were compared with all non-CVE denial registrants and a 5% random sub-sample of non-CVE deniers according to patient and clinical characteristics, quality of care indicators and health outcomes. Multilevel, multivariable logistic regression models were used. Factors explored were age, sex, stroke severity, type of stroke, treatment in a stroke unit, length of stay and discharge destination. Level was defined as hospital.ResultsOverall, 339/23,830 (<2%) CVE denials were reported during the 18-month period. Hospitals confirmed 117 (61%) of CVE denials as a verified diagnosis of stroke or transient ischaemic attack (TIA). Compared to non-CVE deniers, CVE deniers were younger, had a shorter median length of stay (four days versus one day) and were more likely to be diagnosed with a TIA (64%) compared to the other types of stroke (11% intracerebral haemorrhage; 20% ischaemic; 5% undetermined).ConclusionVery few patients denied their CVE, with the majority of denials subsequently confirmed as eligible for registry inclusion. Diagnosis of a TIA and shorter length of stay were associated with CVE denial. These findings provide evidence that very few cases are incorrectly entered into a national registry, and highlight the characteristics of those unlikely to accept their clinical diagnosis where further education of diagnosis may be needed.     

Difference in acute and chronic stage ischemic stroke metabolic markers with controls

BackgroundAcute Ischemic Stroke (AIS), a major cause of disability, was previously associated with multiple metabolomic changes, but many findings were contradictory. Case-control and longitudinal study designs could have played a role in that. To clarify metabolomic changes, we performed a simultaneous comparison of ischemic stroke metabolome in acute, chronic stages of stroke and controls.MethodsThrough the nuclear magnetic resonance (NMR) platform, we evaluated 271 serum metabolites from a cohort of 297 AIS patients in acute and chronic stages and 159 controls. We used Sparse Partial Least Squares-Discriminant analysis (sPLS-DA) to evaluate group disparity; multivariate regression to compare metabolome in acute, chronic stages of stroke and controls; and mixed regression to compare metabolome acute and chronic stages of stroke. We applied false discovery rate (FDR) to our calculations.ResultsThe sPLS-DA revealed separation of the metabolome in acute, chronic stages of stroke and controls. Regression analysis identified 38 altered metabolites. Ketones, branched-chain amino acids (BCAAs), energy, and inflammatory compounds were mostly elevated, while alanine and glutamine were decreased in the acute stage. These metabolites declined/increased in the chronic stage, often to the same levels as in controls. Levels of fatty acids, phosphatidylcholines, phosphoglycerides, and sphingomyelins did not change between acute and chronic stages, but were different comparing to controls.ConclusionOur pilot study identified metabolites associated with acute stage of ischemic stroke and those that are altered in stroke patients comparing to controls regardless of stroke acuity. Future investigation in a larger independent cohort is needed to validate these findings.     

Geriatric nutrition risk index predicts prolonged post-stroke dysphagia in acute ischemic stroke

BackgroundPost-stroke dysphagia (PSD) is a common complication after stroke. Malnutrition inhibits stroke recovery and is associated with stroke mortality. However, no studies have investigated the effects of nutritional state at admission on prolonged PSD.MethodsWe retrospectively analyzed ischemic stroke patients in our institute from January 2018 to December 2020. Swallowing function was assessed using the Food Oral Intake Scale; prolonged PSD was defined as levels 1–3 at 14 days after admission. The Geriatric Nutritional Risk Index (GNRI) was used to assess nutritional risks, which were classified as follows: >98, no nutritional risk; 92–98, mild nutritional risk; 82–92, moderate nutritional risk; and <82, severe nutritional risk. The association between GNRI and prolonged PSD was assessed.ResultsOf 580 patients (median age, 81 years; male, 53%), prolonged PSD was detected in 117 patients. Patients with severe dysphagia had older age, higher pre-stroke modified Rankin Scale score, lower GNRI, and higher National Institutes of Health Stroke Scale score. Logistic regression analysis revealed that lower GNRI was independently associated with prolonged PSD (continuous value; adjusted odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00–1.05). In addition, when "severe" and "moderate" nutritional risk was analyzed as a single class, moderate or severe nutritional risk (GNRI < 92) was independently associated with prolonged PSD (adjusted OR 2.50, 95% CI 1.29–4.87), compared with no nutritional risk patients (GNRI > 98).ConclusionsIn acute ischemic stroke, lower GNRI at admission was independently associated with prolonged PSD, suggesting that GNRI at admission might identify patients at risk of prolonged PSD.     

Looking for opportunities to co-enroll: The DISCOVERY study experience

BackgroundConducting high-quality stroke trials is complex and costly. Often these trials compete for the attention of researchers and the availability of patients. Enrolling patients in more than one study concurrently has the potential to accelerate recruitment into individual studies. DISCOVERY is a multicenter, inception cohort study of cognitive impairment and dementia following ischemic or hemorrhagic stroke. At the request of site investigators, a DISCOVERY committee reviews individual studies for approval of possible concurrent co-enrollment into DISCOVERY. The purpose of this report is to summarize the characteristics and outcomes of studies reviewed by committee for possible co-enrollment.MethodsThis analysis covers studies reviewed from 07/01/2020 to 04/26/2022 by the Site Management Committee (SMC) of the DISCOVERY Recruitment and Retention Core. Characterization of each study included study type, number and length of follow-up visits, and whether there were protocol-required blood draws, brain imaging studies, or cognitive tests. Studies were scored for patient burden and scientific overlap with Discovery. The primary outcome was SMC approval to co-enroll.Results59 studies were reviewed, and 69.5% (n = 41, 21 clinical trials; 20 observational studies) were found by the SMC to be appropriate for co-enrollment. Higher patient burden and greater scientific overlap with DISCOVERY reduced the rates of approval for co-enrollment.ConclusionA large number of diverse stroke studies are being run concurrently across the DISCOVERY study network, however, about two-thirds of the studies were considered appropriate for consideration of co-enrollment. Future studies should study how co-enrollment might improve trial network efficiency.     

Early transcranial direct current stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in hospitalized patients with stroke: A randomized,multicentre, double-blind,clinical trial

BackgroundConstraint-induced movement therapy (CIMT) and transcranial direct current stimulation (tDCS) are used to reduce interhemispheric imbalance after stroke, which is why the combination of these therapies has been used for neurological recovery, but not in the acute phase.ObjectivesTo evaluate the effectiveness of combining active or sham bihemispheric tDCS with modified CIMT (mCIMT) for the recovery of the Upper Limb (UL) in hospitalized patients with acute and subacute stroke.MethodsThis randomized controlled, double-blind, placebo-controlled, parallel group clinical trial was executed between September 2018 to March 2021 recruited 70 patients. The patients were randomized to one of two groups to receive treatment for 7 consecutive days, which included 20 min of active or sham bihemispheric tDCS daily (anodal ipsilesional and cathodal contralesional), with an mCIMT protocol. The primary outcome was the difference in the evolution of motor and functional upper limb recovery with assessment on days 0, 5, 7, 10 and 90. The secondary outcomes were independence in activities of daily living (ADL) and quality of life.ResultsThe active group presented a statistically significant gap compared to the simulated group throughout the trend in the scores of the FMA (motor function and joint pain) and WMFT (functional ability and weight to box) (p < 0.05) and showed a minimal clinically important difference (FMA: difference between groups of 4.9 points [CI: 0.007- 9.799]; WMFT: difference between groups of 6.54 points [CI: 1.10-14.15]). In the secondary outcomes, there was a significant difference between the groups in ADL independence (Functional Independence Measure: difference of 8.63 [CI: 1.37-18.64]) and perceived recovery of quality of life evaluated at 90 days (p = 0.0176).ConclusionsCombining mCIMT with bihemispheric tDCS in patients hospitalized with acute-subacute stroke allows us to maximize the motor and functional recovery of the paretic upper limb in the early stages and independence in ADL, maintaining the effects over time.