Clinical Research Directory

Brain Boosters 2 in Persons at Risk for Alzheimer's Disease: a Digital Application Supported Intervention

The purpose of this research is to determine if training in memory support aids and healthy lifestyle activities (physical exercise, mentally stimulating activities and stress management) can have a positive effect on memory, thinking, and activities that people do every day. Participation in this study will involve being placed into one of two groups: a Self-Guided Intervention Group or a Structured Intervention Group. Both groups will be asked to attend group sessions in which they will be provided education on memory support strategies and lifestyle changes. The Structured Intervention Group will also be provided with an iPad and a digital application (called EMMA) to track their activity. Study participation involves a 6-month intervention and completing outcome measures at 4 different time points for up to a year.

Auditory-Cognitive Optimization Care Program for Older Adults With Hearing Loss and Cognitive Impairment

Hearing loss and cognitive impairment are common and interrelated health problems that may affect communication, information processing, attention, psychological well-being, daily functioning, and quality of life. This study aims to develop and evaluate a comorbidity-oriented Auditory-Cognitive Optimization Care Program (A-COP) for individuals with hearing loss and cognitive impairment. The A-COP will be developed based on evidence from a literature review and findings from qualitative research involving individuals with hearing loss and cognitive impairment and their caregivers. The program integrates hearing-related care and cognitive stimulation strategies to address the combined needs associated with hearing and cognitive difficulties. In the intervention phase, participants will be randomly assigned to either the A-COP intervention group or an active control group in a two-arm, parallel-group randomized controlled trial. The study will evaluate changes in cognitive function, hearing and communication-related outcomes, depressive symptoms, and quality of life from baseline through the 6-month follow-up. The findings will provide evidence regarding the effects of the A-COP in individuals with hearing loss and cognitive impairment.

Technology Assisted Cognitive Behavioural Therapy Intervention for Anxiety in People Living With Cognitive Impairment

This study is a randomized controlled trial (RCT) of a remotely-delivered, technology-assisted psychotherapy program, supported by an innovative software platform for people with cognitive impairment experiencing anxiety.

COgnitive and Physical Exercise to Improve Outcomes After Surgery (COPE-iOS) Study

The COgnitive and Physical Exercise to improve Outcomes after Surgery (COPE-iOS) study is testing the hypothesis that a pragmatic program combining computerized cognitive training and physical training throughout the perioperative period will improve long-term cognitive and disability outcomes in older surgical patients at high risk for decline. To accomplish these goals, the Investigators are randomizing 250 patients ≥60 years old undergoing elective major non-cardiac surgery with expected hospitalization ≥3 days to a pragmatic comprehensive training program (computerized cognitive training and supervised progressive physical exercise) or to active control (control computer game, stretching exercises) for 2-4 weeks prior to surgery and for 3 months after discharge. At baseline and after discharge, the Investigators will assess global cognition, activities of daily living, depression, endothelial and blood brain barrier function (blood biomarkers), and neuroimaging (anatomical and functional MRI). In this early stage trial, the Investigators will determine if certain subgroups benefit most, program aspects with greatest effect on outcomes, mechanistic associations with outcomes, and additional exploratory analyses.

Epigenetic Enhancement of Cognitive Training in Aging Mood and Schizophrenia Spectrum Disorder Populations

The aim of this clinical trial is to investigate the effects of a three-week virtual reality-based cognitive remediation training (VR-CRT) programme in combination with daily intake of a histone deacetylase inhibitor (HDACi) sodium butyrate on cognition in symptomatically stable patients with mood (depression or bipolar disorder; MD) or schizophrenia spectrum disorders. The investigators hypothesize that the VR-based cognitive remediation training (VR-CRT) combined with HDACi butyrate vs. a VR-based control treatment combined with placebo will improve global cognition (primary outcome measure) over three weeks. Secondly, the investigators hypothesize that VR-CRT with placebo will improve cognition relative to the VR control treatment with placebo, although to a lesser extent than VR-CRT with HDACi butyrate. Thirdly, the investigators hypothesize that the HDACi butyrate with VR control treatment will not produce cognitive improvements relative to placebo with VR control treatment. Finally, the investigators hypothesize that the combined treatment (VR-CRT + HDACi butyrate) will enhance neuroplasticity (exploratory outcome) vs. VR control with placebo, as indicated by increase in hippocampal volume and/or memory-related activity shown with structural and functional MRI.

Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen in Norway: A Prospective Cohort Study

This study evaluate use of a translated Norwegian version of the Edinburgh cognitive and behavioral amyotrophic lateral sclerosis screen (ECAS-N) as an early predictor in car-driving, working and use of advanced life-prolonging therapy.

Beta-1 Band Functional Connectivity Mediates the Effects of Acute Exercise on Cognitive Flexibility in Older Adults With Cognitive Impairment: A Randomized Controlled Trial

Objective: The effects of different exercise modalities (mind-body, aerobic, and resistance training) on cognitive flexibility and brain functional connectivity in cognitively impaired older adults are unknown, and the mechanistic relationships linking acute exercise, cognitive flexibility, and neural connectivity remain unclear. Methods: A total of 60 older adults with cognitive impairment were recruited and randomly assigned to a Baduanjin group (n = 15), a brisk walking group (n = 15), a resistance band group (n = 15), or a control group (n = 15). Five-minute resting-state electroencephalography signals were collected and cognitive flexibility was assessed before and after the intervention. All exercise interventions were performed at a moderate intensity and lasted 30 minutes.

NEURO-COGS: Neurometabolic Mechanisms of Cognitive Training in Schizophrenia

This study will examine brain metabolic and excitatory/inhibitory mechanisms related to cognitive and visual functioning in adults with schizophrenia and healthy control participants. Participants will complete behavioral assessments, cognitive testing, electroencephalography, magnetic resonance imaging, and magnetic resonance spectroscopy assessments. After baseline assessments, participants will be randomly assigned to one of two computerized cognitive training programs: perceptual discrimination training or cognitive control training. Each training program will include approximately 10 hours of training over 2 to 6 weeks. The study will evaluate changes in cognitive and visual task performance, EEG measures, and brain metabolite concentrations before and after cognitive training. Some participants may also complete optional extended baseline assessments before cognitive training.

Psychological Interventions for Multiple Sclerosis: Effects on Anxiety, Depression, and Cognition.

This study evaluated the efficacy of two structured psychological interventions in individuals with relapsing-remitting multiple sclerosis (RRMS). The main objective was to evaluate whether Group-Based Cognitive-Behavioral Therapy (CBT) and Psychophysiological Regulation Therapy (PRT) improved emotional well-being and objective cognitive functioning compared with Standard Care (SC). A total of 153 individuals with RRMS were assessed for eligibility, of whom 148 were randomized to one of three study conditions: Group-Based CBT, PRT, or SC (waiting-list control). Participants were allocated using a simple computer-generated randomization sequence with a 1:1:1 allocation ratio. Both active interventions were delivered in small groups over 12 weekly sessions. CBT and PRT shared a common therapeutic framework comprising psychoeducation, mindfulness, psychophysiological regulation strategies, and homework assignments. The CBT condition additionally incorporated specific cognitive-behavioral components during sessions 4-10. Assessments were conducted at baseline and immediately after completion of the 12-week intervention period using standardized psychological and neuropsychological measures. The study evaluated treatment effects across complementary domains of emotional functioning and objective cognitive performance.

Impact of a Multimodal Lifestyle Intervention on Dementia Risk Factors and Attitude Related to Dementia Risk: A Logistical Pilot Study

Many individuals develop dementia, and dementia has multiple causes, yet we currently have limited treatment options. A critical observation of the effectiveness of the available dementia treatments is that they tend to be more effective when started early. Previous studies have shown that multimodal lifestyle interventions can significantly delay the onset of Alzheimer's dementia in individuals with high risk for Alzheimer's or with Mild Cognitive Impairment (MCI). These interventions may be less effective when initiated after dementia has already been diagnosed or is more advanced. This study has two primary goals. The first goal is to assess attitudes around dementia risk for participants throughout the study as they learn of their personalized risk and possible lifestyle factors that may modify that risk. The second goal is to serve as a logistical pilot for the implementation of data collection and processing and multimodal lifestyle intervention to reduce the risk factors of dementia in individuals without current cognitive impairment but who are at high risk of progression to dementia. Secondary goals of this study include better defining what factors contribute the most risk to dementia and identifying sub-types of dementia defined by different genetic and molecular risk factors.

Biomarkers as Prognostic Factors of Silent, Cerebral Infarctions in Patients Undergoing High-thromboembolic-risk Transcatheter Interventions

Background: The transcatheter interventions with high thromboembolic risk, as transcatheter carotid angioplasty or transcatheter ablation of cardiac arrhythmias are associated with asymptomatic strokes- silent strokes. The silent strokes are cerebral infarctions with small diameter which are diagnosed with computed tomography or magnetic resonance imaging (MRI). Silent cerebral infarctions (SCIs) are associated with neurological deficits, cognitive impairment, high mortality and high risk of dementia. There are biomarkers, as neuron specific enolase (NSE) and neurofilaments (NFLs) which are indicated for the prognosis of these patients. Aim: The aim of this study is the prognostic role of biomarkers NSE and NFLs in patients undergoing high-thromboembolic-risk transcatheter interventions. This study will assess the hypothesis that the level of these biomarkers could predict the development of SCIs and the long-term cognitive impairment. Study type - materials: This study is a prospective, observational study. Patients undergoing highthromboembolic-risk transcatheter interventions will be included in this study. Protocol: All the demographic and clinical characteristics of patients will be recorded. Blood samples will be obtained, 24 hours pre-interventionally and 24 hours post-interventionally. The blood samples will be centrifugated and will be freezed at -80 οC for the measurement of biomarkers. MRI will be conducted 24 hours pre- and postinterventionally. The neurological assessment will be conducted with the use of Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) questionnaires, 24 hours pre-interventionally, 24 hours and 6 months postinterventionally. Outcomes: The primary outcome is the association between level of biomarkers and the development of SCIs in MRI post-procedurally. Secondary outcomes concern the probable association of biomarkers with the cognitive impairment. The data will be assessed with statistical analysis and will be interpreted. The results of this study will be published with the view to create algorithms and prognostic tools for appropriate management of these patients.

Anesthesia and Perioperative Neurocognitive Disorders in the Elderly Patients Undergoing Hip Fracture Surgery Platform Trial (ANDES Platform Trial)

The ANDES Platform Trial is a pragmatic, multicenter, adaptive randomized controlled platform trial in patients aged 65 years or older undergoing surgery for hip fracture. The trial evaluates whether enhanced anesthesia techniques reduce perioperative neurocognitive disorders compared with standard anesthesia care. The platform includes two randomization processes. In the first randomization, eligible participants are assigned to an active platform intervention-currently a preoperative regional nerve block or perioperative intravenous lidocaine infusion-or to a shared standard-anesthesia control. Participants for whom general anesthesia is planned may also enter a second, nested randomization and are assigned in a fixed 1:1 ratio to total intravenous anesthesia or volatile inhalational anesthesia, regardless of whether they participate in the first randomization. A non-surgical cognitive control cohort is included to characterize changes in cognitive test performance over time without exposure to surgery or study interventions. The Data Monitoring Committee reviews accumulating trial data and makes recommendations to the Trial Steering Committee, which determines whether platform interventions should continue, be modified, advance, or stop.

Benefits of Nicotinamide Riboside Upon Cognition and Sleep

Poor sleep quality and short sleep duration may be a mechanistic component of cognitive impairment in older adults, associated with a decline in brain-derived neurotrophic factor. Increasing the availability of nicotinamide adenine dinucleotide (NAD+) with supplementation of its precursor, nicotinamide riboside (NR), a form of vitamin B3 may increase the expression of brain-derived neurotrophic factor. This study proposes to examine the benefits of NR supplementation on sleep and cognitive function in older adults with comprehensive subjective and objective measures and to explore its impacts on serum brain-derived neurotrophic factor.

Cognitive Assessment And Post-Operative Complications After Surgery: Linking Anaesthesia And Risk

Many older people can experience confusion, memory problems, or a decline in their thinking after major surgery. These problems are sometimes called 'postoperative neurocognitive disorders' or PND and can affect recovery and a person's ability to live independently. The investigators want to find out the best way to study these problems in older patients undergoing surgery. This is a 'feasibility study', which means we are testing the research methods. The investigators want to see if it is possible to ask participants to do memory tests and give blood samples before and after their operation. The investigators are hoping to include around 40 patients over 2 years in this study. The investigators will compare performance in memory (cognitive assessment) findings before and after surgery and link this to data taken from the anaesthetic, including the types of drugs used, duration, brain features from processed electroencephalogram monitoring and standard recommended monitoring. In addition the investigators will link this to blood sample markers of brain health and function (biomarkers). The results of this study will help the investigators plan a much larger study in the future, with the ultimate goal of making surgery safer for the brain.

Effect of Metformin on Behaviour and the Brain in Children Treated for a Brain Tumour

The efficacy of treatment with metformin for promoting cognitive recovery and brain growth in children/adolescents treated for a brain tumour will be investigated in a multi-site Phase III randomized double-blind placebo-controlled parallel arm superiority trial. Specifically, in children/adolescents aged 7 years to 21 years and 11 months who have completed treatment for a brain tumour, is oral administration of metformin for 16 weeks associated with greater improvement of cognitive function and brain growth compared to placebo administered for 16 weeks?

Influencing Factors of Cerebrovascular Disease and Cognition in Hemodialysis Patients

In this observational study, the investigators evaluate the influencing factors of cerebrovascular disease and cognition in hemodialysis patients.

Nurse-Led Active Music Program in Older Adults With Cognitive Impairment

This pilot study evaluated the feasibility and acceptability of a structured, nurse-led active music program for older adults with cognitive impairment living in a long-term care facility. Participants took part in eight group music sessions delivered twice weekly over four consecutive weeks. The program included singing, rhythmic activities, seated movement, music-based reminiscence, cognitive stimulation, and social interaction. Feasibility and acceptability were the primary domains of interest. Cognitive function, depressive symptoms, active participation, sustained attention, and social interaction were also assessed as exploratory outcomes.

Efficacy and Safety Study of Digital Cognitive Training and PCSK9 Inhibitor-Enhanced Lipid-lowering Strategy in Patients With Intracranial Atherosclerotic Stenosis: A 2x2 Factorial, Randomized, Parallel-Group, Multicenter Trial

This study aims to evaluate whether digital cognitive training and/or PCSK9 inhibitor-enhanced lipid-lowering therapy on top of moderate-intensity statin can improve cognitive function in patients with intracranial atherosclerosis (ICAS). ICAS is a common cause of stroke and is also linked to thinking and memory problems. The study will enroll 440 adults aged 55-80 years who have 50-99% narrowing of an intracranial artery, subjective memory complaints, and LDL cholesterol ≥1.8 mmol/L, but who are not demented. Participants will be randomly assigned to one of four groups in a 2×2 factorial, parallel-group design: No cognitive training + moderate-intensity statin therapy Cognitive training + moderate-intensity statin therapy No cognitive training + moderate-intensity statin plus PCSK9 inhibitor Cognitive training + moderate-intensity statin plus PCSK9 inhibitor Cognitive training consists of 30 minutes of tablet-based exercises, 5 days per week for 24 weeks (first 12 weeks as the intensive phase, followed by 12 weeks continuation phase). The PCSK9 inhibitor (Recaticimab) is administered subcutaneously according to the product label, on top of moderate-intensity statin. The main outcome is change in a composite cognitive score from baseline to 24 weeks. Secondary outcomes include changes in specific cognitive domains, serum LDL-C, MRI markers of brain structure and function, and safety measures. The study is multicenter, open-label with blinded outcome assessment, and is conducted under the approval of the ethics committee of Peking Union Medical College Hospital.

Theta Deep Brain Stimulation for Cognitive Enhancement in Parkinson's Disease

Cognitive impairment is common in Parkinson's disease. A recent study demonstrated 40% of people with PD suffer from mild cognitive impairment and \> 80% of patients develop dementia after a disease duration of 20 years. Cognitive impairment significantly impairs quality of life and has limited treatment options. While the pathophysiology of cognitive symptoms in PD is multifactorial, one contributing factor is dysfunction in subthalamic-cortical loops. The subthalamic nucleus (STN) receives input from distributed regions of the cortex, forming partially segregated parallel networks with sensorimotor regions, associative (cognitive) cortical regions, and limbic cortical regions. These subthalamic-cortical networks are thought to play a domain general role in inhibitory control, which is a fundamental mechanism underlying flexible behavior across motor, cognitive, and affective domains. Information processing in these subthalamic-cortical networks is expressed through oscillatory activity within distinct frequency bands. For example, communication between the STN and prefrontal regions involved in executive function is thought to occur through coherence in the theta (4-8 Hz) frequency band. As a result of these observations, stimulation of the STN at a theta frequency has been investigated as a method of modulating cognitive processes. Theta stimulation of the STN has been shown to enhance coherence in subthalamic-cortical networks, facilitating information processing and modulating behavior. For example, a recent study demonstrated that theta stimulation of the STN improved working memory performance in PD subjects, while no effect was seen for other frequency bands. The authors performed a post-hoc analysis and found that the effect may be mediated by connectivity between the stimulated STN region and the right dorsolateral prefrontal cortex (DLPFC). While these studies have demonstrated proof of principle, they are limited by small sample sizes and post-hoc analyses assessing the relationship between stimulation location and outcomes. Further research is needed to directly test the hypothesis that theta stimulation of the STN can improve executive control in PD patients by modulating associative STN circuitry.

Synbiotic LA-5 and Agave Inulin for Mild Cognitive Impairment

This pilot randomized, double-blind, crossover clinical trial will evaluate the effect of a synbiotic containing Lactobacillus acidophilus LA-5 and agave inulin on mild cognitive impairment (MCI) in adults aged 60-75 years attending the Defense Medical Specialties Unit. Forty participants with MCI will be randomized into two groups of 20 participants. The intervention will consist of daily administration of L. acidophilus LA-5 (4 × 10⁹ CFU), 7 g of agave inulin, and almond powder for 12 weeks, while the control group will receive almond powder as the vehicle. After a two-week washout period, participants will cross over to the alternate intervention for an additional 12 weeks. Cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA), Memory Alteration Test (M@T), and Mini-Mental State Examination (MMSE). Secondary assessments will explore potential mechanisms of the microbiota-gut-brain axis by measuring fecal L. acidophilus LA-5 and butyrate, as well as serum BDNF and inflammatory biomarkers including IL-1β, IL-6, IL-10, and TNF-α. The study aims to determine whether synbiotic supplementation improves cognitive performance in older adults with MCI and whether these changes are accompanied by modifications in gut microbial activity, short-chain fatty acid production, neurotrophic signaling, and systemic inflammation.

Assess the Effect of Metaxalone 640 mg (M640) Compared to Tizanidine 8 mg on Truck Driving Ability and Cognition

Every participant will receive active study drug and one (1 )comparator, in two (2) stages, one after the other. Each drug will be taken one (1) time after a high fat meal. Vital signs and discussion of medications, illness or injury are considered safety assessments and will be discussed at every visit. There will be ( four (4) visits.

Memantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases

This randomized phase III trial compares memantine hydrochloride and whole-brain radiotherapy with or without hippocampal avoidance in reducing neurocognitive decline in patients with cancer that has spread from the primary site (place where it started) to the brain. Whole brain radiotherapy (WBRT) is the most common treatment for brain metastasis. Unfortunately, the majority of patients with brain metastases experience cognitive (such as learning and memory) deterioration after WBRT. Memantine hydrochloride may enhance cognitive function by binding to and inhibiting channels of receptors located in the central nervous system. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Using radiation techniques, such as intensity modulated radiotherapy to avoid the hippocampal region during WBRT, may reduce the radiation dose to the hippocampus and help limit the radiation-induced cognitive decline. It is not yet known whether giving memantine hydrochloride and WBRT with or without hippocampal avoidance works better in reducing neurocognitive decline in patients with brain metastases.

Immersive Virtual Reality for Older Adults in Long-Term Care Settings

The goal of this clinical trial is to learn if an immersive virtual reality mindfulness meditation program is feasible and acceptable for older adults living in long-term care settings in Quebec who have mild to moderate neurocognitive disorder. It will also learn about the safety and potential effects of the program on well-being. The main questions it aims to answer are: * Is the virtual reality mindfulness meditation program feasible and acceptable for residents and staff in long-term care settings? * Does the adapted version of the program show potential benefits for well-being, including depression, anxiety, quality of life, mindfulness, pain, and loneliness? * What practical challenges, user experiences, and side effects, such as cybersickness, occur during the program? Researchers will compare the Toujours Dimanche virtual reality mindfulness meditation program designed for older adults with mild to moderate neurocognitive disorder, and standard care alone to see if the adapted program is feasible, acceptable, and potentially helpful. Participants will: * Take part in up to 8 virtual reality mindfulness meditation sessions over 4 weeks, if assigned to a virtual reality group * Complete questionnaires before and after the 4-week study period * Share feedback about their experience, when possible * Be observed by staff or research team members to document feasibility, acceptability, user experience, and safety

Methylphenidate to Address Attention and Executive Deficits Among Children With Sickle Cell Disease

The purpose of this study is to determine if patients with sickle cell disease (SCD) can consistently take a drug called Methylphenidate (MPH) daily, once a day for 4 weeks to help with any thinking, attention or schoolwork problems and if they have any side effects. The study will assess any thinking or attention problems participants may have both before taking this drug and after. Additionally, the study will assess the decision-making process of the caregiver that may influence using this drug or not. Primary Objective: • Assess the feasibility, acceptability, and adherence to MPH treatment in children with SCD and EF deficits. Secondary Objective: • Evaluate neurobehavioral and safety outcomes following MPH treatment. Exploratory Objective: • Evaluate decision-making and determinants influencing methylphenidate utilization among caregivers.