Clinical Research Directory

Eye-Movement Intervention for Cognitive Impairment Across Schizophrenia Spectrum

The goal of this clinical trial is to determine whether a gamified eye-movement intervention can improve cognitive function in individuals across the schizophrenia spectrum, including clinical high-risk individuals, first-episode schizophrenia patients, and chronic schizophrenia patients. The main questions it aims to answer are: * Does eye-movement training improve cognitive performance measured by the MATRICS Consensus Cognitive Battery (MCCB)? * Does eye-movement training improve oculomotor functions and clinical symptoms across different illness stages? Researchers will compare an eye-movement intervention group with an active control group receiving matched finger-controlled game training to determine whether the eye-movement intervention produces greater improvements in cognitive function and eye-movement performance. Participants will: * Receive either gamified eye-movement training or matched finger-controlled game training for 4 weeks. * Complete cognitive assessments using the MCCB before and after the intervention. * Complete standardized eye-tracking tasks, including fixation stability, smooth pursuit, antisaccade, and free-viewing tasks, to evaluate changes in oculomotor control and visual exploration patterns. * Complete clinical symptom assessments using SOPS or PANSS according to illness stage.

METformin and FINGER Intervention to Prevent Cognitive Impairment and Disability in Older Adults at Risk for Dementia

Dementia is the main cause of disability in older adults, currently affecting about 50 million people world-wide with this number estimated to triple in the next 30 years. In MET-FINGER, we aim to understand whether the FINGER 2.0 multidomain intervention, combining healthy lifestyle changes and a drug for diabetes (metformin), may help reduce the risk of dementia and improve health and independence among older adults. The study primary objective is to test the effect of the intervention, compared to healthy lifestyle advice, on the change in cognition, measured as a composite score including 14 of neuropsychological/cognitive tests. The secondary objective is to test the intervention effect on change in individual cognitive domains, functioning level, and risk factors for dementia (e.g., lifestyle, medical, and psychosocial). To this aim, a range of personal/health-related data and blood samples, will be collected. Potential interactions between metformin and lifestyle changes; potential disease-modifying effects; and feasibility of the metformin + lifestyle combination will be explored. 600 older people with risk factors for dementia, but without dementia/substantial cognitive impairment, will be recruited in the United Kingdom, Finland, and Sweden (at least 50% with higher genetic risk of Alzheimer's Disease/dementia based on the Apolipoprotein E (APOE) gene). Participants will be randomly assigned 1:1 to either a self-guided multidomain lifestyle intervention or to the FINGER 2.0 multidomain lifestyle-based intervention. Outcome assessors will be blinded to group allocation. Within the FINGER 2.0 intervention group, participants at increased risk of diabetes, will be randomly assigned 1:1:1 to either the metformin 2000mg/day, metformin 1000mg/day, or placebo group (double blinded). The intervention duration is 24 months. The lifestyle intervention includes four main components: physical exercise, diet, brain training and health checks. In the self-guided group, participants will create their own program, based on health advice and recommendations which will be provided during the study. In the FINGER 2.0 intervention group, participants will receive intensive lifestyle guidance, and participate in structured activities, which will be as tailored as possible on each person's daily habits and needs. Over the 2-year study period, all participants will attend four assessment visits: baseline, 6-, 12-, and 24-months.

Orthopedic Procedures and Postoperative Delirium in Older Adults in the Czech Republic

This multicenter, prospective, non-interventional observational study (ORTOPODCZ) investigates the association between preoperative cognitive impairment and postoperative delirium (POD) in older adults undergoing elective total hip arthroplasty in the Czech Republic. Postoperative delirium is a frequent and serious neurocognitive complication in senior surgical patients and is associated with increased morbidity, mortality, prolonged hospitalization, and impaired functional and cognitive outcomes. Despite international recommendations, routine preoperative cognitive screening remains insufficiently implemented. The study evaluates the predictive value of the ALBA test, a brief cognitive screening tool, performed during the pre-anesthetic assessment. Postoperative delirium will be assessed using the validated CAM-ICU instrument for up to 72 hours after surgery. Secondary objectives include assessing the relationship between POD and frailty, polypharmacy, comorbidities, type of anesthesia, intraoperative hemodynamics, blood loss, vasoactive support, and postoperative complications. Approximately 300-400 participants aged ≥65 years will be enrolled across seven centers. No additional procedures, biological sampling, or deviations from standard clinical care are required. Data will be collected in REDCap and analyzed according to a predefined statistical analysis plan. The study aims to provide robust evidence supporting the integration of cognitive screening into routine preoperative evaluation and to describe feasibility and implementation requirements for the ALBA test in clinical practice.

Brain Health in Breast Cancer Survivors

Endocrine therapy (ET) is widely used to treat hormone receptor positive breast cancer and prevent recurrence by downregulating estrogen function. However, ETs readily cross the blood brain barrier and interfere with the action of estrogen in the brain. Estrogen supports cognition and menopausal status is closely linked to cognitive health in women. This has raised concern that anti-estrogen ETs may affect cognition and brain health in breast cancer survivors. However, evidence across existing studies is inconsistent and these effects remain poorly understood. The incomplete understanding of the effects of ET are likely due to limitations of earlier studies - namely, the under-appreciation of the role of menopausal status and insensitivity of standard cognitive measures. This research project will address these earlier limitations by specifically comparing ET effects by menopausal status, and using highly sensitive, task-related functional magnetic resonance imaging (fMRI) measures to assess the effects of ET on brain function.

Cognitive Task-Based Walking Effects on Cognition, Mood, Sleep, and Quality of Life in Older Adults With Brain Fog

This randomized controlled trial aims to investigate the effects of cognitive task-based walking exercise on cognitive function, depressive symptoms, sleep quality, and quality of life in older adults experiencing brain fog. Eligible participants will be randomly assigned to either a cognitive task-based walking exercise group or a walking-only exercise group. The intervention will be conducted under physiotherapist supervision, three times per week for four weeks. Outcome measures will be assessed at baseline and after the intervention period to compare the effectiveness of the two exercise approaches.

The Care for America's Aging Study

Care for America's Aging is a randomized pilot study investigating whether a home health aide training intervention consisting of enhanced dementia-specific curriculum content will improve: 1) behavioral symptoms of older adult persons living with dementia or cognitive impairment (PLWD/CI) and 2) global health-related quality of life among PLWD/CI and their care partners.

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 parents.

Efficacy of Bright Light Therapy on Cognitive Impairment in Major Depressive Disorder and Its Neuroimaging Mechanisms: Protocol for a Randomised Controlled Trial

This study aims to validate the therapeutic efficacy and safety of bright light therapy (BLT) in ameliorating cognitive impairment (CI) in major depressive disorder (MDD), characterize the functional and structural features of the hippocampus (HPC)-dorsolateral prefrontal cortex (dlPFC) neural circuitry in MDD participants with CI and examine the mediating effect of the HPC-dlPFC neural circuit on CI induced by BLT treatment in MDD participants. MDD participants will be required to only receive selective serotonin reuptake inhibitors (SSRIs) as monotherapy for at least four weeks, or medication-free status before enrollment. Eligible participants will be randomly assigned to the experimental group and the control group. The experimental group will receive the intervention of BLT, and the control group will receive the intervention of dim red light (DRL). The intervention will last for four weeks, 6 days per week, with 40 minutes each day between 7 am and 10 am. The MDD participants will be followed once in the end of each week during the 4-week intervention and in the end of the 4th week after intervention. Demographic information will be collected at baseline; cognitive function will be evaluated at baseline, weeks 2, 4, and 8 after intervention beginning; and other symptoms such as depression, anxiety and sleep were assessed at baseline, weeks 1, 2, 3, 4, and 8 after intervention beginning. Moreover, structural and functional MRI scans will be made at baseline and post-intervention. During the intervention, MDD participants will be required to keep a record of daily light exposure duration and complete the daily sleep diary as well.

Cognitive Function and Quality of Life in Obstructive Sleep Apnea

Obstructive Sleep Apnea (OSA) is a common condition that disrupts normal breathing during sleep. Beyond causing daytime tiredness, OSA can also impact a person's cognitive functions, such as their attention span, memory, and problem-solving skills, which may in turn affect their overall quality of life. The main purpose of this study is to compare the thinking and memory skills of adults recently diagnosed with OSA against a control group of healthy adults without the condition. Furthermore, the researchers aim to understand how specific cognitive challenges (like difficulty sustaining attention) relate to a patient's physical and mental well-being. Participants in the study will undergo an overnight sleep test (diagnostic polysomnography) at a sleep clinic. Shortly after the sleep test, participants will complete a series of short, computer-based tasks designed to measure their attention, memory, and executive function. They will also be asked to fill out standard questionnaires regarding their daily sleepiness, mood, and health-related quality of life.

Polyamine Treatment in Elderly Patients With Coronary Artery Disease

The present study is testing spermidine treatment in elderly patients with coronary artery disease. The study is a randomized, double-blind, placebo-controlled, two-armed, parallel-group, single centre, clinical study.

A Mechanistic Study to Investigate tDCS and Working Memory in MCI Patients

The current study is a mechanistic study to evaluate working memory gains from application of transcranial direct current stimulation (tDCS) in older adults with mild cognitive impairments (MCI) compared to cognitively healthy control

Neurologic Stem Cell Treatment Study

This is a human clinical study involving the isolation of autologous bone marrow derived stem cells (BMSC) and transfer to the vascular system and inferior 1/3 of the nasal passages in order to determine if such a treatment will provide improvement in neurologic function for patients with certain neurologic conditions. http://mdstemcells.com/nest/

Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H)

We aim to determine whether cognitive impairment attributable to cerebral hemodynamic impairment in patients with high-grade asymptomatic carotid artery stenosis is reversible with restoration of flow. To accomplish this aim CREST-H will add on to the NINDS-sponsored CREST-2 trial (parallel, outcome-blinded Phase 3 clinical trials for patients with asymptomatic high-grade carotid artery stenosis which will compare carotid endarterectomy plus intensive medical management (IMM) versus IMM alone (n=1,240), and carotid artery stenting plus IMM versus IMM alone (n=1,240) to prevent stroke and death). CREST-H addresses the intriguing question of whether cognitive impairment can be reversed when it arises from abnormal cerebral hemodynamic perfusion in a hemodynamically impaired subset of the CREST-2 -randomized patients. We will enroll 385 patients from CREST-2, all of whom receive cognitive assessments at baseline and yearly thereafter. We anticipate identifying 100 patients with hemodynamic impairment as measured by an inter-hemispheral MRI perfusion "time to peak" (TTP) delay on the side of stenosis. Among those who are found to be hemodynamically impaired and have baseline cognitive impairment, the cognitive batteries at baseline and at 1 year will determine if those with flow failure who are randomized to a revascularization arm in CREST-2 will have better cognitive outcomes than those in the medical-only arm compared with this treatment difference for those who have no flow failure. We hypothesize that hemodynamically significant "asymptomatic" carotid disease may represent one of the few examples of treatable causes of cognitive impairment. If cognitive decline can be reversed in these patients, then we will have established a new indication for carotid revascularization independent of the risk of recurrent stroke.

Primary Care Detection of Cognitive Impairment Leveraging Health & Consumer Technologies in Underserved Communities: The MyCog Trial

Our study intends to offer 'real world' evidence of a viable, sustainable means to mobilize primary care via a comprehensive strategy for detecting cognitive impairment and dementias, advancing next steps for referral, and participating in the care planning and management of affected patients and caregivers. We will conduct a clinic-randomized, pragmatic trial testing the effectiveness and fidelity of our NIH Toolbox-derived paradigm to improve early detection and management of cognitive impairment/dementia in primary care settings serving health disparate patient populations.

Brain Functional Connectivity Mechanism of Cognitive Flexibility Impairment and rTMS Intervention in Major Depressive Disorder

Major depressive disorder (MDD) often involves cognitive deficits, particularly in cognitive flexibility, which is inadequately addressed by standard antidepressants. This study tests an innovative brain stimulation regimen: individualized dual-target repetitive transcranial magnetic stimulation (rTMS) to improve cognitive flexibility in MDD patients. This is a randomized, double-blind, sham-controlled trial that plans to enroll 105 MDD patients with cognitive flexibility impairment. Participants will be randomly assigned to one of three groups: (1) Active dual-target group - receiving active rTMS over both the left inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (DLPFC); (2) Active single-target group - receiving active rTMS over the left IPL and sham stimulation over the right DLPFC; (3) Sham control group - receiving sham stimulation over both targets. All participants will continue their stable antidepressant medication (SSRI or SNRI). The rTMS intervention lasts 10 days, with 5 stimulation sessions per day. Cognitive flexibility, depressive symptoms, and brain functional connectivity will be assessed at baseline, immediately after the 10-day treatment, and at 2-week and 4-week follow-ups using neurocognitive tests, clinical rating scales (e.g., HAMD), and functional MRI. The results will help confirm the role of the IPL-DLPFC connectivity in cognitive flexibility and may establish a new treatment target for cognitive dysfunction in MDD.

Harmonization of Teleneuropsychological Assessment in Dementia

The prevention and management of cognitive decline and dementia represent major healthcare challenges. Neuropsychological assessment is a key component of current diagnostic criteria for Mild Neurocognitive Disorder (mNCD) due to Alzheimer's disease (AD), supporting both diagnosis and patient follow-up. It enables the evaluation of cognitive domains, monitoring of disease progression, and assessment of treatment effects. Digital tools offer standardized, objective, and scalable methods for cognitive evaluation. The growth of telemedicine and the widespread adoption of digital technologies, accelerated by the COVID-19 pandemic, have increased acceptance of remote healthcare solutions, including teleneuropsychology. Recent advances in mobile technology, together with lower costs and greater accessibility, have facilitated the large-scale implementation of digital cognitive assessments. Tablet-based teleneuropsychological platforms are particularly advantageous for older adults, providing user-friendly interfaces and improving access to care for individuals with mobility limitations or those living in underserved areas. To promote harmonized neuropsychological assessment within the Italian Neuroscience and Neurorehabilitation Network (RIN), this multicenter study aims to establish normative data and clinically validate Tenèpsia®, an innovative tablet-based teleneuropsychological platform certified as a Class IIa Medical Device. The study will support its clinical and research use while evaluating its diagnostic performance in patients with neurocognitive disorders.

Robot-Assisted Meditation for Older Adults With Cognitive Concerns

While traditional app-based mindfulness meditation programs relying solely on audio guidance have shown potential benefits for older adults, the apps often face challenges such as low compliance. Participants frequently report difficulties in maintaining focus during meditation sessions, which can limit its effectiveness in improving outcomes such as stress reduction and sleep quality. Recognizing these limitations, this study explores whether a haptic-enabled handheld robot can enhance meditation practices by providing both haptic and audio guidance. The robot, designed to foster sustained attention and encourage rhythmic breathing, may offer a novel, multidimensional approach that addresses compliance issues and supports deeper engagement in mindfulness meditation. The study primarily seeks to answer the question: Does robot-guided meditation, combining both haptic and audio guidance, improve the sleep quality of older adults living alone with subjective cognitive decline more effectively than traditional audio-based mindfulness meditation guidance? Furthermore, the study examines a secondary question: Is the effect of robot-guided meditation on sleep quality mediated by reductions in stress? By investigating these questions, the research aims to offer insights into whether haptic-enabled meditation technology can overcome common barriers to mindfulness practices among older adults and serve as an innovative tool to improve physical, emotional, and cognitive well-being.

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 original Toujours Dimanche virtual reality mindfulness meditation program, an adapted version of Toujours Dimanche 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

Hypnosis in Working Memory Rehabilitation

Establishment of effective, efficient, and evidence-based interventions in rehabilitation of working memory (WM) deficits after acquired brain injury (ABI) is sorely needed. Despite robust evidence for the usefulness of clinical hypnosis in a wide range of clinical conditions, and improved understanding of mechanisms underlying it ́s effects, the potential of clinical hypnosis in cognitive rehabilitation is virtually unexplored. The current study seeks to replicate resent intriguing findings where large effects of hypnotic suggestion were seen on WM capacity following ABI, and further, explore underlying mechanisms of change.

Managing the Needs of Care Home Residents With Dementia Through a Music Therapy Intervention

The purpose of this study is to implement and evaluate a music therapy intervention in care homes. The primary aim is to assess whether implementing the intervention will have an impact on unmet in care homes for people living with dementia. Researchers will also examine the feasibility of a music therapy programme in care homes and its effects on care staff and residents with cognitive impairment. Care home staff will also receive training with music therapists via video communications to help staff use music therapy techniques to support people living with dementia.

pBFS-guided iTBS Over the Left DLPFC for Chronic PSCI

The study aims to investigate the efficacy and safety of intermittent theta burst stimulation (iTBS) guided by the personalized Brain Functional Sector (pBFS) technique in the treatment of patients with chronic post-stroke cognitive impairment.

Music Improvisation Training on Cognitive Function in Older Adults

This project will study the effects and mechanisms of a music improvisation training intervention on self-regulation of older adults with and without MCI. The investigator's overall hypothesis is that improvisation training will lead to improvements in self-regulation, compared to controls, and that improvisation training will be associated with specific changes in prefrontal brain networks and ultimately cognitive engagement.

REpeated ASSEssment of SurvivorS in Intracerebral Hemorrhage Study

The investigators propose to perform serial detailed cognitive, motor, behavioral, and blood collection follow-up using longitudinal structured telephone interviews of an anticipated 350 ICH survivors enrolled in Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE) III and ENRICH trials to identify specific cognitive and motor impairment and to perform RNA sequencing to evaluate for evidence of chronic inflammation. The investigators' expected sample size in 2022 accounts for mortality attrition of 10%/year.

Neuroimaging Study

The researchers are trying to gather information and learn more about imaging tests in racially different people who are cognitively normal or have dementia.