scholarly journals Acute cognitive effects of the hypocretin receptor antagonist almorexant relative to zolpidem and placebo: a randomized clinical trial

SLEEP ◽  
2020 ◽  
Vol 43 (10) ◽  
Author(s):  
Thomas C Neylan ◽  
Anne Richards ◽  
Thomas J Metzler ◽  
Leslie M Ruoff ◽  
Jonathan Varbel ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Receptor Antagonist ◽  
Verbal Memory ◽  
Motor Coordination ◽  
Human Subjects ◽  
Controlled Trial ◽  
Benzodiazepine Receptor ◽  
Impaired Performance ◽  
Receptor Modulator ◽  
Benzodiazepine Receptor Agonist

Abstract Study Objectives Hypnotic medications can adversely affect behavior during unanticipated awakenings during the night. Animals treated with the hypocretin (Hcrt) receptor antagonist almorexant (ALM) have less acute cognitive impairment compared to the GABAA receptor modulator zolpidem (ZOL). This study aimed to determine whether ALM produces less acute cognitive impairment than ZOL in human subjects. Methods Healthy, young adult, unmedicated male and female subjects participated in a controlled trial of a single dose of ALM 100 mg (N = 48), ALM 200 mg (N = 53), ZOL 10 mg (N = 49), and placebo (PBO, N = 52). Results ZOL and both doses of ALM produced similar levels of subjective sleepiness and impaired the ability of subjects to remain awake in a dark, low-stimulus setting relative to PBO. For most cognitive measures, performance under ZOL was significantly worse than ALM or PBO. For tasks involving verbal memory or visual-motor coordination, ZOL impaired performance, whereas the two doses of ALM were no different than PBO. For tasks involving higher-order executive function, ZOL produced impairment in processing speed and inhibitory control, whereas the two doses of ALM were no different than PBO. Performance decrements for ALM were less than ZOL but greater than PBO for some reaction time measures. Conclusions The data provide support for the hypothesis that Hcrt receptor antagonists produce less functional impairment than a benzodiazepine receptor agonist (BzRA). These observations are particularly relevant to patients treated with sedative-hypnotics who are at elevated risk for falls and other untoward events during the intended hours for sleep.

scholarly journals Methylphenidate for Mild Cognitive Impairment: An Exploratory 3-Day, Randomized, Double-Blind, Placebo-Controlled Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
Yan Press ◽  
Boris Punchik ◽  
Ella Kagan ◽  
Alexander Berzak ◽  
Tamar Freud ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Adverse Events ◽  
Verbal Memory ◽  
Cognitive Assessment ◽  
Controlled Trial ◽  
Immediate Release ◽  
Cognitive Outcome ◽  
Double Blind ◽  
Double Blind Placebo

Background: To evaluate the efficacy, safety and tolerability of methylphenidate (MPH) for cognitive function in older patients with mild cognitive impairment (MCI).Methods: Male and female subjects aged 65 years and older with a clinical diagnosis MCI were included in an exploratory randomized, double-blind, placebo-controlled trial. Eligible subjects were assigned to either treatment with immediate-release MPH or placebo. The active compound was administered in an increasing-dose stepwise fashion, namely 10 mg MPH on day 1, 20 mg on day 2, and 30 mg on day 3. Subjects remained under observation for 4 h following drug administration and were monitored for changes in blood pressure and for adverse events. Cognitive outcome measures included the Montreal Cognitive Assessment (MoCA) and the Neurotrax Mindstreams computerized cognitive assessment battery.Results: Of 17 subjects enrolled, 15 subjects completed the study, 7 in the active MPH group and 8 in the placebo group. The average age of the participants was 76.1 ± 6.6 years and 10 (66.7%) were men. Following the final dose a significant benefit on memory (predominantly non-verbal memory) was found in the MPH group. While 12 adverse events were reported, they were all rated as mild to moderate.Conclusions: Our finding of modest beneficial effects of MPH on memory tests in older subjects with MCI in this exploratory study is of interest and should be investigated in further studies.

scholarly journals Randomised controlled trial of Compensatory Cognitive Training and a Computerised Cognitive Remediation programme

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Frances Dark ◽  
Ellie Newman ◽  
Victoria Gore-Jones ◽  
Veronica De Monte ◽  
Marta I. Garrido ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Randomised Controlled Trial ◽  
Outcome Measures ◽  
Cognitive Training ◽  
Controlled Trial ◽  
Schizophrenia Spectrum Disorders ◽  
Cognitive Interventions ◽  
Schizophrenia Spectrum ◽  
Spectrum Disorders ◽  
Randomised Controlled

Abstract Background Compensation and adaptation therapies have been developed to improve community functioning via improving neurocognitive abilities in people with schizophrenia. Various modes of delivering compensation and adaptation therapies have been found to be effective. The aim of this trial is to compare two different cognitive interventions, Compensatory Cognitive Training (CCT) and Computerised Interactive Remediation of Cognition–Training for Schizophrenia (CIRCuiTS). The trial also aims to identify if mismatch negativity (MMN) can predict an individual’s response to the compensation and adaptation programmes. Methods This study will use a randomised, controlled trial of two cognitive interventions to compare the impact of these programmes on measures of neurocognition and function. One hundred clinically stable patients aged between 18 and 65 years with a diagnosis of a schizophrenia spectrum disorder will be recruited. Participants will be randomised to either the CCT or the CIRCuiTS therapy groups. The outcome measures are neurocognition (BACS), subjective sense of cognitive impairment (SSTICS), social functioning (SFS), and MMN (measured by EEG) in people with schizophrenia spectrum disorders. Discussion This trial will determine whether different approaches to addressing the cognitive deficits found in schizophrenia spectrum disorders are of comparable benefit using the outcome measures chosen. This has implications for services where cost and lack of computer technology limit the implementation and dissemination of interventions to address cognitive impairment in routine practice. The trial will contribute to the emerging evidence of MMN as a predictor of response to cognitive interventions. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000161224. Registered on 2 February 2018. Protocol version: 4.0, 18 June 2018.

Increasing Life-Space Mobility in Community-Dwelling Older Persons With Cognitive Impairment Following Rehabilitation: A Randomized Controlled Trial

2020 ◽  
Author(s):  
Phoebe Ullrich ◽  
Christian Werner ◽  
Martin Bongartz ◽  
Tobias Eckert ◽  
Bastian Abel ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Older Persons ◽  
Controlled Trial ◽  
Intervention Group ◽  
Community Dwelling ◽  
Control Group ◽  
Life Space ◽  
Home Based ◽  
Independent Life

Abstract Background Community-dwelling older persons with cognitive impairment (CI) following discharge from geriatric rehabilitation are at high risk of losing life-space mobility (LSM). Interventions to improve their LSM are, however, still lacking. The aim of this study was to evaluate the effects of a CI-specific, home-based physical training and activity promotion program on LSM. Methods Older persons with mild-to-moderate CI (Mini-Mental State Examination: 17–26 points) discharged home from rehabilitation were included in this double-blinded, randomized, placebo-controlled trial with a 12-week intervention period and 12-week follow-up period. The intervention group received a CI-specific, home-based strength, balance, and walking training supported by tailored motivational strategies. The control group received a placebo activity. LSM was evaluated by the Life-Space Assessment in Persons with Cognitive Impairment, including a composite score for LSM and 3 subscores for maximal, equipment-assisted, and independent life space. Mixed-model repeated-measures analyses were used. Results One hundred eighteen participants (82.3 ± 6.0 years) with CI (Mini-Mental State Examination: 23.3 ± 2.4) were randomized. After the intervention, the home-based training program resulted in a significant benefit in the Life-Space Assessment in Persons with Cognitive Impairment composite scores (b = 8.15; 95% confidence interval: 2.89–13.41; p = .003) and independent life-space subscores (b = 0.39; 95% confidence interval: 0.00–0.78; p = .048) in the intervention group (n = 63) compared to control group (n = 55). Other subscores and follow-up results were not significantly different. Conclusions The home-based training program improved LSM and independent life space significantly in this vulnerable population. Effects were not sustained over the follow-up. The program may represent a model for improved transition from rehabilitation to the community to prevent high risk of LSM restriction.

scholarly journals Association of Cognitive Function Screening Results with Adherence and Performance in a Pedometer-Based Intervention

2021 ◽  
pp. 1-9
Author(s):  
Anoop Sheshadri ◽  
Piyawan Kittiskulnam ◽  
Cynthia Delgado ◽  
Rebecca L. Sudore ◽  
Jennifer C. Lai ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Physical Performance ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Controlled Trial ◽  
Cognitive Status ◽  
Dialysis Patients ◽  
Exercise Interventions ◽  
And Performance

<b><i>Introduction:</i></b> A randomized, controlled trial of a pedometer-based walking intervention with weekly activity goals led to increased walking among dialysis patients. We examined whether impairment per cognitive function screening is associated with adherence and performance in the intervention. <b><i>Methods:</i></b> Thirty dialysis patients were randomly assigned to a 3-month pedometer-based intervention with weekly goals. Participants were administered the Telephone Interview of Cognitive Status (TICS), a test of global mental status. We examined the association of levels of impairment on the TICS (≥33: unimpaired, 26–32: ambiguous impairment, 21–25: mild cognitive impairment [MCI]) with adherence, achieving weekly goals, and increasing steps, physical performance (Short Physical Performance Battery, SPPB), and self-reported physical function (PF) through multivariable linear mixed-model and logistic regression analyses adjusted for age, sex, BMI, dialysis modality, baseline steps, baseline SPPB, and stroke status. <b><i>Results:</i></b> One-third of participants were unimpaired, and 13% had MCI. Participants with worse results on cognitive function screening missed more calls and completed fewer weekly goals than participants with better results. During the intervention, a worse result on cognitive function screening was associated with smaller increases in steps compared to those without impairment: (ambiguous: −620 [95% CI −174, −1,415], MCI: −1,653 [95% CI −120, −3,187]); less improvement in SPPB (ambiguous: −0.22 points [95% CI −0.08, −0.44], MCI: −0.45 [95% CI −0.13, −0.77]); and less improvement in PF (ambiguous: −4.0 points [95% CI −12.2, 4.1], MCI: −14.0 [95% CI −24.9, −3.1]). During the postintervention period, a worse result on cognitive function screening was associated with smaller increases in SPPB (ambiguous: −0.54 [95% CI −1.27, 0.19], MCI: −0.97 [95% CI −0.37, −1.58]) and PF (ambiguous: −3.3 [95% CI −6.5, −0.04], MCI: −10.5 [95% CI −18.7, −2.3]). <b><i>Discussion/Conclusion:</i></b> Participants with worse results on cognitive function screening had worse adherence and derived less benefit from this pedometer-based intervention. Future exercise interventions should be developed incorporating methods to address cognitive impairment, for example, by including caregivers when planning such interventions.

scholarly journals Can we decrease the duration of basal thumb joint distraction for early osteoarthritis from 8 to 6 weeks? Study protocol for a non-inferiority randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Janna S. E. Ottenhoff ◽  
Teun Teunis ◽  
Assa Braakenburg ◽  
Aebele B. Mink van der Molen
Keyword(s):  
Physical Function ◽  
Human Subjects ◽  
Controlled Trial ◽  
Central Committee ◽  
Ethics Committees ◽  
Randomized Controlled ◽  
Joint Distraction ◽  
New Treatment ◽  
Thumb Carpometacarpal ◽  
Medical Research Ethics

Abstract Background To our knowledge, to date, 52 patients with thumb carpometacarpal osteoarthritis (CMC1 OA) were treated with joint distraction. So far, most patients experienced improved physical function and less pain. After 2 years, only 1 patient proceeded to trapeziectomy. This study assesses if we can safely lower the distraction duration from 8 to 6 weeks for CMC1 joint distraction, maintaining the improvement in physical function and pain. Methods This is a monocenter randomized controlled non-inferiority trial that includes patients younger than 65 years of age with ongoing symptoms of CMC1 OA and an established indication for surgery. All patients will be treated with CMC1 joint distraction. The primary outcome is to assess whether 6 weeks of joint distraction is not inferior to 8 weeks in terms of physical function at 1 year after surgery. Secondary outcomes will identify differences between groups at 1 year in pain intensity, patient satisfaction, hand health status, adverse event rates, treatment failure, differences in thumb strength and range of motion, and radiographic changes. Discussion If safe, the duration of basal thumb joint distraction can be reduced to 6 weeks, reducing patient burden. Because this is a relatively new treatment, this trial will provide greater knowledge of potential adverse events. This knowledge allows for more informed decision making for patients considering CMC1 distraction treatment. Future studies can directly compare joint distraction to other treatments of CMC1 joint arthritis like splinting and trapeziectomy. Trial registration Central Committee on Research Involving Human Subjects (CCMO), NL68225.100.18; registered on 9 August 2019. Medical Research Ethics Committees United (MEC-U), R19.003; registered on 9 August 2019. Netherlands Trial Register, NL8016; registered on 15 September 2019.

scholarly journals Event-related potential and EEG oscillatory predictors of verbal memory in mild cognitive impairment

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Jiangyi Xia ◽  
Ali Mazaheri ◽  
Katrien Segaert ◽  
David P Salmon ◽  
Danielle Harvey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Verbal Memory ◽  
Verbal Learning ◽  
Event Related Potential ◽  
Single Trial ◽  
Prodromal Alzheimer’S Disease ◽  
Alpha Beta

Abstract Reliable biomarkers of memory decline are critical for the early detection of Alzheimer’s disease. Previous work has found three EEG measures, namely the event-related brain potential P600, suppression of oscillatory activity in the alpha frequency range (∼10 Hz) and cross-frequency coupling between low theta/high delta and alpha/beta activity, each of which correlates strongly with verbal learning and memory abilities in healthy elderly and patients with mild cognitive impairment or prodromal Alzheimer’s disease. In the present study, we address the question of whether event-related or oscillatory measures, or a combination thereof, best predict the decline of verbal memory in mild cognitive impairment and Alzheimer’s disease. Single-trial correlation analyses show that despite a similarity in their time courses and sensitivities to word repetition, the P600 and the alpha suppression components are minimally correlated with each other on a trial-by-trial basis (generally |rs| &lt; 0.10). This suggests that they are unlikely to stem from the same neural mechanism. Furthermore, event-related brain potentials constructed from bandpass filtered (delta, theta, alpha, beta or gamma bands) single-trial data indicate that only delta band activity (1–4 Hz) is strongly correlated (r = 0.94, P &lt; 0.001) with the canonical P600 repetition effect; event-related potentials in higher frequency bands are not. Importantly, stepwise multiple regression analyses reveal that the three event-related brain potential/oscillatory measures are complementary in predicting California Verbal Learning Test scores (overall R2’s in 0.45–0.63 range). The present study highlights the importance of combining EEG event-related potential and oscillatory measures to better characterize the multiple mechanisms of memory failure in individuals with mild cognitive impairment or prodromal Alzheimer’s disease.

scholarly journals Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e041500
Author(s):  
Zoe Menczel Schrire ◽  
Craig L Phillips ◽  
Shantel L Duffy ◽  
Nathaniel S Marshall ◽  
Loren Mowszowski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Feasibility Trial ◽  
Controlled Study ◽  
Brain Oxidative Stress ◽  
Randomised Controlled

IntroductionMelatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher dose (25 mg) melatonin to target brain oxidative stress and sleep disturbance in older adults with mild cognitive impairment (MCI).Methods and analysisThe study design is a randomised double-blind, placebo-controlled, parallel group trial. Forty individuals with MCI will be recruited from the Healthy Brain Ageing Clinic, University of Sydney and from the community, and randomised to receive either 25 mg oral melatonin or placebo nightly for 12 weeks. The primary outcomes are feasibility of recruitment, acceptability of intervention and adherence to trial medication at 12 weeks. Secondary outcomes will include the effect of melatonin on brain oxidative stress as measured by magnetic resonance spectroscopy, blood pressure, blood biomarkers, mood, cognition and sleep. Outcomes will be collected at 6 and 12 weeks. The results of this feasibility trial will inform a future conclusive randomised controlled trial to specifically test the efficacy of melatonin on modifiable risk factors of dementia, as well as cognition and brain function. This will be the first trial to investigate the effect of melatonin in the population with MCI in this way, with the future aim of using this approach to reduce progression to dementia.Ethics and disseminationThis protocol has been approved by the Sydney Local Health District Ethics Committee (X18-0077). This randomised controlled trial will be conducted in compliance with the protocol published in the registry, the International Conference for Harmonisation on Good Clinical Practice and all other applicable regulatory requirements. The findings of the trial will be disseminated via conferences, publications and media, as applicable. Participants will be informed of results of the study at the conclusion of the trial. Eligible authors will include investigators who are involved in the conception and design of the study, the conduct of the trial, the analysis of the results, and reporting and presentation of study findings.Trial registration numberAustralian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190).Protocol versionV.8 15 October 2020.

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