Cognitive Impairment

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.

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.

Family caregivers of people living with Alzheimer's disease and related dementias often experience conflicts and communication challenges when coordinating care, making decisions, and interacting with family members and healthcare providers. These challenges can contribute to caregiver burden, stress, anxiety, and reduced well-being. The purpose of this study is to evaluate the effectiveness of NegotiAge, an online negotiation and communication training program designed for family caregivers. NegotiAge provides education and interactive practice exercises to help caregivers develop negotiation, problem-solving, conflict-resolution, and communication skills that can be applied to real-world caregiving situations. Approximately 200 family caregivers will be randomly assigned to either the NegotiAge intervention or an attention-control educational website. Participants will complete online surveys before the intervention, immediately after the intervention, and at 1-month and 3-month follow-up time-points. The study will examine whether NegotiAge reduces caregiver burden and improves communication, conflict-management behaviors, self-efficacy, stress, anxiety, fatigue, and well-being. Findings from this research may help improve support programs for family caregivers of people living with Alzheimer's disease and related dementias.

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.

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.

This cross-sectional study aims to determine the prevalence of cognitive impairment and evaluate its relationship with activities of daily living among older adults with hematologic malignancies receiving chemotherapy.

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.

Dementia is a leading cause of death in the UK, and long waits for diagnosis can delay access to care and treatment. The SANDBOX study is a research study in NHS Memory Clinics investigating whether providing clinicians with additional test results could help them diagnose dementia earlier. Adults aged 50 or over who have been referred to a Memory Clinic by their GP may be invited to take part. Taking part is voluntary and will not affect a participant's care. Participation adds to their NHS care and does not replace or delay it. Participants complete three assessments: a blood test that measures two proteins which can indicate whether Alzheimer's-related changes may be happening in the brain (not currently available on the NHS); a genetic test for the APOE gene, which influences Alzheimer's risk; and a cognitive assessment of memory and thinking that includes a recorded speech task analysed for subtle language changes. All results are shared with the participant's clinician. This research will help determine whether this approach can support earlier dementia diagnosis and improve care for patients across the UK.

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.

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.

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?

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

This study aims to understand how memory and thinking abilities (cognition) are affected in patients with heart conditions, and to find out if early detection and interventions can improve health outcomes.

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.

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.

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.

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

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.

The goal of this observational study is to learn if an artificial intelligence (AI)-based speech analysis tool can identify which patients with memory problems need specialist evaluation at a memory clinic. The main questions it aims to answer are: Can the AI model accurately distinguish between patients who need referral to a memory clinic (those with dementia or Mild Cognitive Impairment) and patients who don't (those with normal cognition or memory problems from other causes like depression)? Which speech patterns and cognitive test features are most useful for making this distinction? Researchers will compare speech recordings and cognitive test results from patients diagnosed with dementia or MCI to those from patients with normal cognition or non-neurodegenerative cognitive impairment to see if the AI model can reliably predict who needs specialist dementia care. Participants will: Complete standard cognitive tests at the memory clinic Perform structured speech tasks while being audio-recorded Receive their usual clinical evaluation and diagnosis from memory clinic specialists The results of this study will help develop a tool that can assist doctors in making faster, more accurate decisions about which patients need specialist dementia evaluation, potentially leading to earlier diagnosis and better patient outcomes.

This study is a multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial designed to evaluate the safety and potential efficacy of endovascular recanalization strategies in patients with symptomatic non-acute carotid artery occlusion and cognitive impairment. Eligible participants will be randomly assigned to best medical treatment alone, endovascular recanalization without proximal protection plus best medical treatment, or endovascular recanalization with proximal balloon protection plus best medical treatment. The study will assess whether endovascular recanalization improves cognitive function and whether proximal protection reduces procedure-related new ischemic lesions on diffusion-weighted magnetic resonance imaging.

MARKERS-NDD is a prospective, observational, longitudinal study, which aims to collect data from patients affected by neurodegenerative diseases (NDD) followed longitudinally for routine examinations performed as part of normal clinical practice. Data collected from clinical evaluations, movement analysis, brain imaging, neuropsychological and electroencephalographic assessments, blood chemistry tests will be analysed to carry out statistical investigations and predictive analyses, also using artificial intelligence systems, which allow the identification of new early markers of diagnosis and prognosis of neurodegenerative diseases.

older adults with mild and moderate cognitive impairment. compare immediate vs progressive standing dual-task training. assess balance, cognition, executive function, mobility, and quality of life.

While traditional app-based mindfulness meditation programs relying solely on audio guidance have shown potential benefits for older adults, the programs often face challenges such as low engagement. 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. To address these limitations, this study examines whether a haptic robot that provides both tactile and audio guidance can enhance meditation. The robot's expansion and contraction movements help users pace and sustain rhythmic breathing, while gentle vibrations signal phase transitions without disrupting concentration. These haptic features are intended to anchor attention and support a more embodied practice. The study primarily seeks to answer the following questions: Does a haptic enabled meditation intervention reduce perceived stress in older adults living alone with subjective cognitive decline more effectively than an audio only mindfulness meditation guidance provided by a non-moving robot? To what extent does enhanced attentional anchoring mediate the intervention's effect on perceived stress in this population? By addressing these questions, the research aims to determine whether haptic enabled meditation technology can overcome common barriers to mindfulness practice among older adults and serve as an innovative tool to reduce perceived stress, and ultimately improve their sleep quality and physical, emotional, and cognitive well being.

CONVERGE-HF is a 4-center pilot phase IIb randomized control trial in ambulatory patients with chronic heart failure (≥ 6 months) and mild-to-moderate cognitive impairment.

The purpose of the study is to examine the effect of Problem Adaptation Therapy for Pain (PATH-Pain) on cognitive functioning, depression and pain-related disability in 100 older adults with cognitive impairment, chronic pain, and depression. The study will test if PATH-Pain has better cognitive, affective, and functional outcomes than Attention Control Usual Care.