Mild Cognitive Impairment (MCI)

This is an eight-week pilot research study designed to test whether simple changes to the bedroom environment along with brief sleep hygiene strategies, can improve sleep in older adults who live alone, have memory concerns, and experience insomnia symptoms. Older adults may be eligible to participate. The intervention will take 8 weeks, which includes 1-2 in-person visits from the research team at the participant's residence (evaluate the bedroom environment, install participant-agreed bedroom changes, deliver target sleep hygiene strategy) and 2 virtual or telephone calls (support environmental and sleep hygiene strategies) over 8 weeks. Sleep and environment data will be collected at screening/baseline, mid-intervention (4-week) and post-intervention (8-week)

The goal of this clinical trial is to learn if a wearable ultrasound device, called ATTN201, is safe and easy to use. The study is for adults ages 65 and older who have mild cognitive impairment (MCI) and a buildup of a protein called amyloid in the brain. Amyloid buildup is an early sign of Alzheimer's disease. The ATTN201 device sends low-intensity sound waves to a deep area of the brain that helps control sleep. The aim is to boost deep-sleep brain waves. These brain waves may help the brain clear away waste, including amyloid. The main questions it aims to answer are: 1. What, if any, issues do participants have when using the ATTN201 device? 2. Can participants complete the full study schedule? Researchers will compare focused ultrasound to unfocused ultrasound. Unfocused ultrasound is a look-alike treatment. It feels and sounds the same but is not aimed at the brain target. The comparison will show if the focused treatment changes sleep brain waves, blood markers of Alzheimer's disease, or memory and thinking. Participants will: * Visit the study site for memory and thinking tests, blood draws, a health check, and MRI scans of the brain * Record their sleep at home for at least 5 days with a sleep diary, a watch-like sensor, and a headband that measures brain waves * Be assigned by chance to focused or unfocused ultrasound * Take part in 10 nap sessions over 2 weeks while wearing the device, at the study site or at home * Return for a final visit to repeat the first tests, and may return for an optional visit 3 months later

The goal of this international observational study is to evaluate long-term disease outcomes and treatment safety in people with Alzheimer's disease (PwAD), by collecting real-world data from routine clinical practice across global clinical centers. The InRAD Registry Observational Study has several aims: * To collect medical information for many years from a large group of people with Alzheimer's disease. This will be used for research, which will support improved understanding about the disease. * To enable researchers to look at the effectiveness, usefulness and safety of treatments for Alzheimer's disease. * To enable researchers to answer similar research questions and compare results in many different areas of the world. People with Alzheimer's disease who meet the eligibility criteria and agree to participate in the Study will be asked to visit their doctor (e.g. psychiatrist, geriatrician, or neurologist) at least once a year, or as frequently as is needed for their care. During or after their appointments they may be offered assessments, tests, medications, and treatments as determined by their doctor and their team. This is an observational data collection.

The purpose of the study is to evaluate the preliminary efficacy of RP902 Tablets in participants with Alzheimer's disease (AD)-derived mild cognitive impairment (MCI) and provide a design basis for the Phase III study. This Phase II study plans to enroll 360 participants and will be conducted at approximately 50 sites in China. The study consists of a Screening Period (up to 4 weeks) and a double-blind treatment period (48 weeks). After completing the 48-week double-blind treatment period, participants may choose to continue into an extension treatment period (96 weeks) or undergo safety follow-up (4 weeks after the last dose).

The aging of the U.S. population, combined with health care workforce shortages and insufficient access to effective fall prevention and exercise programs, has contributed to a high burden of fall-related injuries in older adults, especially in those with Mild Cognitive Impairment (MCI), a precursor of Alzheimer's dementia (AD) and related dementias (ADRD). There is an urgent need for scalable, evidence-based interventions that can be delivered efficiently in the home setting. This study aims to evaluate the efficacy and impact of a comprehensive digital fall prevention program (Digital STEADI) delivered through a technology platform with two conversational agents that leverage generative artificial intelligence (gen-AI) with human oversight to increase program access, enhance adherence to clinical fall prevention protocols and best practices, and reduce fall risk among community-dwelling older adults.

The goal of this clinical trial is to learn if photobiomodulation therapy (PBMT) can help treat mild cognitive impairment and mild Alzheimer's disease in adults aged 50 to 85 years. It will also learn about the safety of PBMT. The main questions it aims to answer are: Does PBMT improve cognitive function in adults with mild cognitive impairment or mild Alzheimer's disease? What medical problems do participants have when using PBMT? Researchers will compare an active PBMT device to a sham (look-alike) device that delivers no active light therapy to see if PBMT improves cognitive function. Participants will: Use a transcranial near-infrared light therapy device (or a matching sham device) once a day for 20 minutes, 5 days a week, for 6 months Visit the clinic for cognitive, mood, sleep, and daily-function assessments at the start of the study, at Month 3, and at Month 6 Have brain MRI scans at the start of the study, at Month 3, and at Month 6

The Combating Alzheimer's through Sleep and Exercise (CASE) study is an exploratory, hypothesis-generating trial designed to: (1) assess whether improvements in sleep are associated with improvements in cognitive performance and cardiovascular and metabolic health; (2) evaluate the effects of structured, moderate-level aerobic and anaerobic exercise on cognitive performance and cardiovascular and metabolic health; (3) examine the combined, potentially synergistic effects of both interventions on cognitive performance and cardiovascular and metabolic health; and (4) investigate the role of light exposure as a potential modulator of sleep parameters.

The goal of this observational study is to learn how well a multimodal "Progression and Risk" (PR) model can predict and stage early mild cognitive impairment (MCI) due to Alzheimer's disease in cognitively normal or very mildly impaired ApoE4-positive adults aged 55 and older. The main questions it aims to answer are: Can a prespecified proteogenomic PR model accurately predict conversion from cognitively normal (CN) or very mildly impaired status to pTau217-positive MCI Stage I within 24 months in ApoE4-positive adults? Does adding digital monitoring features (e.g., sleep, activity, speech), EMR-lifestyle risk scores, and plasma biomarkers to a polygenic risk score (PRS) meaningfully improve risk stratification and time-to-conversion prediction compared with simpler models (e.g., PRS alone or standard clinical risk factors)? If there is a comparison group: Researchers will compare performance of the full multimodal PR model (integrating PRS, plasma proteomics and other omics, digital monitoring, and EMR-lifestyle data) with simpler or reduced models (for example, PRS-only, biomarker-only, or models without continuous digital monitoring) to see if the full model provides higher discrimination (AUC/ROC), better calibration, and improved time-to-conversion prediction for CN to pTau217-positive MCI transitions. Participants will: Provide prior genomic data (ApoE genotype and whole-genome sequencing or high-density genotyping array data) for calculation of an ancestry- and sex-normalized Alzheimer's disease PRS and assignment to PRS-based risk strata. Attend an in-person baseline visit and follow-up visits at months 6, 12, 18, and 24 (±2 months) for clinical evaluation, neurocognitive testing (including CDR and digital cognitive batteries), and venous or capillary blood collection for plasma pTau217 and other AD biomarkers, proteomic and methylome panels, and routine safety labs when indicated. Use digital devices (e.g., Oura Ring and smartphone-based tools) for continuous or frequent remote monitoring of sleep, activity, heart rate metrics, mobility/location, and speech-linked digital cognitive tasks, with adherence checks at study visits. Undergo optional or sub-cohort procedures as clinically indicated or as resources allow, such as EEG, retinal hyperspectral imaging, MRI, or amyloid PET, and optionally allow clinically indicated lumbar puncture CSF samples and external clinical data to be shared with the study for exploratory biomarker analyses.

A multi-center prospective, open-label, parallel-group randomized controlled trial is conducted to investigate the cognitive-protective efficacy of a novel, diabetes-specific virtual reality (VR)-based cognitive training system integrated with diet management modules, relative to frequency- and duration-matched traditional paper-and-pencil cognitive training, in adults aged 45-80 years with T2DM and amnestic/mixed mild cognitive impairment (MCI). A total of 40 eligible participants are randomly assigned 1:1 to either the intervention group (24 weeks of individualized VR training with dynamic difficulty, 2 sessions/week, 45-60 minutes/session) or the active control group (standardized paper-and-pencil cognitive tasks). All participants maintain stable glucose-lowering regimens for ≥3 months and receive standardized weekly diabetes health education. The primary endpoint is the between-group difference in the change in MoCA total score from baseline to the 24-week follow-up. Secondary endpoints include changes in individual cognitive domains (memory, executive function, attention, processing speed), Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) Score , Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) Score , Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score, olfactory threshold/identification/recall, brain structural volumes and resting-state functional connectivity (assessed via 3.0T fMRI), glycemic control (HbA1c, fasting/postprandial glucose), lipid profile, body composition, sleep quality, anxiety and depressive symptoms, and diabetes self-management behaviors. The safety and participant adherence to the VR intervention are also systematically monitored.

This Phase 1, randomized, double-blind, placebo-controlled trial evaluates the cognitive and neurophysiological effects of a dietary supplement containing cat's claw (Uncaria tomentosa) bark extract and oolong tea extract, in adults aged 40-85 with self-reported mild cognitive impairment (MCI). The study employs a decentralized design leveraging remote monitoring technologies. Participants will self-administer the study supplement or a matched placebo daily for 6 months. The primary outcome is cognitive performance assessed by digital Montreal Cognitive Assessment (MoCA) at baseline, Month 3, and Month 6. Secondary outcomes include objective sleep and autonomic metrics from Oura Ring wearables (heart rate variability, sleep architecture) and self-reported brain health using the Brain Health Index. An exploratory sub-study will measure plasma biomarkers of neurodegeneration (pTau-217) at baseline and Month 6 in a subset of participants to explore potential mechanisms of action. The study aims to provide preliminary evidence for Percepta's efficacy in improving cognitive function and supporting brain health in individuals with MCI, while evaluating safety and biological plausibility through mechanistic biomarkers.

This study tests an innovative system and service for collecting objective, consistent, and in-community gait parameters suitable for use as AD/ADRD biomarkers. The system is designed to be affordable, scalable, and practical for longitudinal, unsupervised, in-community use by older adults, including those with dementia symptoms. This study will be performed in two parts and involves collecting gait data from participants using the leg module and insole device either (1) for several hours in a lab setting (in-lab testing) or (2) within their home and community for 1 week (in-community testing). Thirty people who are healthy, have mild cognitive impairment, or who have Alzheimer's disease or related dementia will be recruited to participate in the in-lab testing, in which they will perform walking tasks and cognitive testing for several hours within a lab environment. After completion of in-lab testing, 120 individuals who are healthy, have mild cognitive impairment, or who have Alzheimer's disease or related dementia will be recruited to participate in the in-community testing, in which they will wear the insole and ankle device within their community for 1-week for collection of gait data in real world settings.

The goal of this one-arm clinical trial is to determine whether participants with mild cognitive impairment (MCI) can successfully navigate a virtual reality (VR) maze. The VR maze is designed as a training tool aimed at improving participants' spatial navigation abilities. Main Aims: 1. To determine whether at least 70% of older adults enrolled in the study can complete twenty-four 50-minute training sessions over a 4-month period. 2. To assess whether combining virtual reality with EEG recordings can be used to measure brain activation and changes in brain activation associated with spatial navigation learning. Participants will: 1. Walk in an open, unobstructed space while wearing VR goggles. 2. Explore up to fifty different virtual mazes in sequence and attempt to find their way through each one.

Memory problems can range from normal aging to mild cognitive impairment (MCI) to dementia. This study looks at three ways of measuring what is happening in the brain at each of these stages: a blood test (GFAP), a brain MRI scan, and a brain wave test (EEG). The goal is to see whether combining these three tests can help doctors tell the difference between normal aging, MCI, and dementia more accurately, and whether this approach works well in an Egyptian population, including all common causes of dementia (not only Alzheimer's disease). Adults aged 50 to 85 will be placed into one of three groups: those with normal memory, those with mild memory problems (MCI), and those with dementia. Everyone will have a memory and thinking assessment, a blood draw, a brain MRI, and a brain wave (EEG) recording. No new medication or treatment is given as part of this study; it involves only assessment and testing. The information gathered may help doctors diagnose memory problems earlier and more accurately in the future.

The research aims to investigate the effectiveness of a new short-term multicomponent intervention to promote the bio-psycho-social-spiritual health of older adults with MCI to improve their cognitive abilities. In this study, the multicomponent intervention consists of healthy lifestyle psychoeducation and cognitive stimulation. This study is a double-blind, clustered, randomized, controlled, four-arm parallel group study. 200 eligible older adults with MCI are openly recruited into activity groups in local elderly centres. The activity groups are randomly allocated to three intervention groups (i.e., multicomponent intervention, cognitive stimulation and lifestyle psychoeducation) and a control group in a 1:1:1:1 ratio. The participants with MCI are blinded on group allocation and kept uninformed which type of intervention they are receiving. An investigator, blinded to group allocation and intervention, assess outcomes using standardized assessment tools before and after the intervention and after 3 months.

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 observational study will enroll approximately 100 participants evenly split by cognitive status (Cognitively Impaired vs Non-Cognitively Impaired), and involves four clinic visits over one year (at baseline, 3, 6, and 12 months), each followed by 7 days of remote monitoring to assess the long-term feasibility of PAMSys+ (Physical Activity Monitoring System).

This randomized placebo-controlled clinical study, called the LpD3.5 Intervention Study in Older Adults (LISA), aims to evaluate whether a heat-inactivated postbiotic of human origin (LpD3.5) can serve as a non-pharmacological intervention to reduce gut permeability and inflammation in older adults with mild cognitive impairment (MCI). The study will assess the effects of LpD3.5 supplementation on markers associated with gut health, inflammation, microbiome composition, and cognitive function. Participants aged 60 years or older with clinically diagnosed MCI will receive either LpD3.5 capsules or placebo capsules for 60 days, followed by a 30-day follow-up period. Biological samples and clinical assessments will be collected to evaluate changes in gut permeability, inflammatory markers, microbiome characteristics, and cognitive outcomes. The findings from this study may provide insight into the potential role of postbiotics as a dietary intervention to improve gut health and related outcomes in older adults with MCI.

This study aims to evaluate whether individualized hippocampal transcranial temporal interference stimulation (tTIS) combined with Tai Chi training can improve cognitive function and dual-task performance in individuals with mild cognitive impairment. Participants will be randomly assigned to receive either active or sham individualized tTIS combined with Tai Chi training for 8 weeks. The study will also investigate changes in brain structure and function using neuroimaging and assess whether the intervention effects are maintained during follow-up.

This randomized controlled trial examines the mechanisms of conversational AI-based interventions for early dementia prevention in socially isolated older adults.

Gut problems, such as constipation, can have an important impact on quality of life of people who have them, and have been associated with higher risk of developing neurological diseases such as Parkinson's or Alzheimer's disease. Recent studies suggest that gut problems may also have implications for the progression of these diseases, as constipation is a risk factor for faster Parkinson's and Alzheimer's progression. However, how constipation and brain diseases are linked is unknown. Previous research has suggested that gut changes may lead to inflammation, which could play a role in accelerating the progression of both movement and memory problems in Parkinson's and memory and thinking problems in people with cognitive impairment. Methane is a gas that is naturally produced by microorganisms in the gut. Levels of methane can be measured using a simple breath test. Higher methane levels in the breath are thought to be more common in people with Parkinson's disease (PwP) when compared to people without Parkinson's (healthy controls) and have been associated with gut symptoms, particularly constipation, as well as worse movement problems in PwP, although they are less understood in conditions that affect memory and thinking (like dementia or mild cognitive impairment). The investigators want to better understand the changes in the gut of PwP and people with cognitive impairment (e.g. mild cognitive impairment or dementia). They will compare breath methane levels in PwP, people with cognitive impairment, people with REM Sleep Behaviour Disorder (a sleep condition linked to a higher risk of developing Parkinson's) and healthy participants. Participants will be followed-up over time to assess how methane levels are linked to changes in the blood and the stools, gut function, and clinical symptoms. This study has 2 components: Component 1: observational study, where the study investigators will follow 200 participants over 2 visits, 18 months apart. The study will recruit 4 groups of people: 50 people with Parkinson's disease, 50 people at high risk of developing Parkinson's disease (people with REM Sleep behaviour disorder), 50 people with other conditions affecting cognition (e.g. dementia, mild cognitive impairment), and 50 healthy controls. Component 2: study with 15 people with Parkinson's, who produce high methane levels, to test whether a probiotic (Lactobacillus reuteri) affects how much methane is produced.

Mild and Moderate cognitive impairment is a condition characterized by a noticeable decline in cognitive abilities, including memory and thinking skills, which is greater than expected for an individual's age but does not significantly interfere with daily life. Early intervention is essential to prevent further cognitive decline and progression to dementia. Dual-task training has emerged as an effective rehabilitation approach that combines cognitive and motor tasks to enhance neuroplasticity and improve both physical and cognitive performance. This study is designed to investigate the effectiveness of dual-task training compared to conventional therapy in individuals with mild cognitive impairment. Participants meeting the inclusion criteria will be recruited and randomly allocated into intervention and control groups. The intervention group will receive structured dual-task training, which may include activities such as walking while performing cognitive tasks (e.g., counting, word recall), balance exercises combined with mental tasks, and functional activities requiring divided attention. The control group will receive standard rehabilitation or single-task training. The intervention will be conducted over a specified duration (e.g., several weeks), with sessions held multiple times per week. Outcome measures will be assessed at baseline and after completion of the intervention. The primary outcome will be cognitive function measured using the Mini-Mental State Examination (MMSE). Secondary outcomes may include balance, mobility, and functional performance. Data will be analyzed to determine the effectiveness of dual-task training in improving cognitive and functional outcomes. The results of this study may contribute to evidence-based rehabilitation practices and support the use of dual-task interventions in clinical settings.

The goal of this 26-week trial is to learn if creatine supplementation and resistance training (i.e., weightlifting; exercise that increases muscle mass), alone and together, impact cognition, brain health, and physical function in older adults with mild cognitive impairment. Previous studies have shown that resistance training improves cognition and brain health in older adults. Creatine is naturally occurring in the human body and is known to decline with age. Studies have shown that creatine increases muscle mass and bone density in older adults when supplemented. Some research has suggested that creatine may also improve cognition and brain health. However, little is known about how creatine supplementation affects the aging brain and body alone and when combined with resistance training, especially in those with known cognitive impairment. In this study, participants will be randomly assigned to one of four groups: 1) creatine and resistance training, 2) placebo and resistance training, 3) creatine and active control (balance and tone classes), or 4) placebo and active control. Participants in the creatine groups will take creatine every day during the study. Participants in the placebo groups will take a look-alike substance that contains no drug every day during the study. Participants in the resistance training groups will attend three 60-minute classes per week that target each major muscle group and will increase in difficulty during the study. Participants in the active control group will attend three 60-minute classes per week that will consist of balance, stretching, and range of motion exercises. This group accounts for variables such as physical training received by traveling to the training centres, social interaction, and changes in lifestyle secondary to study participation. Researchers will collect information before and after the 26 weeks to see if creatine supplementation and/or resistance training have any effects on cognition, brain health, and/or physical function. The investigators suspect that both creatine supplementation and resistance training will improve cognition, brain health, and physical function alone. However, it is thought that the combination of creatine supplementation and resistance training will improve cognition, brain health, and physical function more.

This trial aims to investigate whether a single session of 40 Hz hippocampal temporal interference stimulation can improve memory function and dual-task postural control among older adults with mild cognitive impairment (MCI). The primary research questions to be addressed are as follows: * Can 40 Hz hippocampal temporal interference stimulation boost memory test performance in older adults with MCI? * Can 40 Hz hippocampal temporal interference stimulation improve walking and balance ability under dual-task conditions in older adults with MCI? Researchers will compare active 40 Hz hippocampal temporal interference stimulation against sham stimulation to identify whether this intervention yields positive immediate effects on memory function and dual-task postural control. Participants will be required to: * Attend three laboratory visits over approximately three weeks, and receive one session of active stimulation and one session of sham stimulation in random order, with an interval of at least seven days between the two stimulation visits; * Complete memory and motor function assessments before and after each stimulation session; * Undergo functional magnetic resonance imaging (fMRI) scans to detect changes in brain activity.

A multicenter phase III clinical study evaluating the diagnostic performance and safety of PET for the deposition of Aβ plaques in the brain of participants with normal cognitive function, MCI and AD using \[18F\]Fluorbetazine injection.

Alzheimer's Disease (AD) is associated with impairments in both gait and cognition, significantly increasing fall risk. Falls are a leading cause of injury-related disability in older adults, and individuals with AD experience a nearly threefold higher rate of falls compared to neurotypical older adults. There is an urgent need for fall prevention interventions tailored to the unique deficits of individuals with AD. Converging evidence suggests that interventions aiming to reduce fall risk in AD should target both gait and cognition. Rhythmic music interventions, such as Rhythmic Auditory Stimulation (RAS) can harness global brain activation and auditory-motor entrainment to facilitate high-intensity exercise to alleviate AD-related neurocognitive and gait dysfunction. This study aims to assess the neural correlates of gait dysfunction in people with AD, evaluate if baseline neurocognitive impairment is predictive of the effects of RAS, and evaluate RAS benefits for individuals with AD.