Clinical Research Directory

Personalized Closed-Loop Brain Stimulation for Patients With Mild Cognitive Impairment

This research study investigates the feasibility and efficacy of a personalized, closed-loop electroencephalogram-transcranial electrical stimulation (EEG-tES) intervention for individuals with mild cognitive impairment (MCI), addressing the inconsistent results of generic brain stimulation protocols. By integrating artificial intelligence (AI)-derived insights with real-time data, the study aims to customize transcranial electrical stimulation (tES) parameters, including electrode placement, intensity, and frequency to target the specific brain regions responsible for abnormal signaling in each participant. Over the intervention period paired with computerized cognitive training, the project will evaluate improvements in learning, memory, and functional connectivity, while simultaneously identifying clinical and physiological predictors to determine the viability of transitioning this low-cost, non-invasive technology into a remotely supervised, home-based therapy setting. The study duration will be a total of 6-8 weeks.

Exploring the Utility of [18F]3F4AP for Demyelination Imaging

The overall objective is to obtain an assessment of the pharmacokinetics of \[18F\]3F4AP in healthy volunteers and subjects with demyelinating diseases such as mild cognitive impairment (MCI), Alzheimer's Disease (AD), Multiple Sclerosis (MS), Spinal Cord Injury (SCI) and Spinal radiculopathy (SR).

A Pivotal Study of Sensory Stimulation in Alzheimer's Disease (HOPE Study)

This is a randomized, double-blind, sham-controlled pivotal study of sensory stimulation in subjects with mild to moderate AD. Up to approximately 670 subjects will be treated with either Active or Sham investigational device, Spectris™ AD, for 60 minutes daily for approximately 12 months. Efficacy will be measured using the Integrated Alzheimer's Disease Mini-Mental State Exam (MMSE) Activities of Daily Living (ADCS-ADL) Rating Scale (iADMARS).

Tau PET Imaging in the NACC Study Cohort

The purpose of this study is to measure the amount of a protein in the brain known as tau using an imaging procedure called Positron Emission Tomography (PET/CT). 18F-AV-1451 is a specialized radioactive PET imaging agent that is able to detect the presence of tau in the brain. In this study, the investigator will use the 18F-AV-1451 to capture images of tau in the brain. Findings from this study will likely provide insight into the mechanisms and distinctions of age-related cognitive decline and that of very early Alzheimer's disease.

Accelerating Cognitive Gains From Digital Inverventions With Noninvasive Brain Stimulation

The overall goal of this project is to collect pilot feasibility and early efficacy data showing improvements in cognition and wellbeing in adults with mild cognitive impairment (MCI) through a combination treatment of non-invasive brain stimulation (transcranial alternating current stimulation (tACS)) and a one of two digital cognitive interventions.

Enhancing Attention and Wellbeing Using Digital Therapeutics

The goals of the proposed research are to first determine the minimal and/or optimal dose of a digital intervention required for cognitive enhancement, and then to examine the impact of several potential moderators of treatment effects (i.e., cognitive decline, AD polygenic hazard score, cardiovascular risk, and race/ethnicity). This knowledge gained from his high-impact study with transform the field of cognitive interventions, paving the way for a precision medicine model for cognitive enhancing interventions that improve quality of life for older adults and individuals with cognitive deficits at risk of developing dementia.

Studying the Effects of Digital Interventions on Cognition, Wellbeing, Stress, and Sleep in Older Adults

The goal of this proposed research is to collect pilot data to test the hypothesis that treatment with a novel form of closed-loop digital meditation (MediTrain) will lead to a greater magnitude of gains in cognitive abilities in patients with mild cognitive impairment (MCI), compared to OA without cognitive impairment, and will lead to improvements in quantitative measures of sleep.

Developing and Testing an AI-Based Cognitive Intervention Program

The goal of this clinical study is to learn if an artificial intelligence (AI)-assisted lifestyle intervention program can help protect memory and thinking skills in adults aged 40 years and older who do not have severe cognitive impairment. It will also learn whether the program can help people maintain healthier lifestyle habits and whether it affects blood markers related to Alzheimer's disease. The main questions it aims to answer are: Can the AI-assisted program help participants improve their lifestyle, including diet, exercise, mental activities, social participation, sleep, smoking, alcohol use, and stress? Does a healthier lifestyle help maintain memory and thinking skills over 1 year? Are healthier lifestyle habits related to changes in blood markers such as p-tau217, which may be related to Alzheimer's disease? Does the effect differ for people who carry the APOE ε4 gene, a gene that may increase the risk of Alzheimer's disease? Researchers will compare participants with healthier lifestyles to those with less healthy lifestyles, to see whether healthier lifestyles are linked to better memory and thinking and different blood marker levels. Participants will: Join an online lifestyle intervention program for 1 year. Receive personalized advice about diet, exercise, mental activities, and social participation through an online platform, WeChat tools, an AI assistant, and online messages. Complete memory and thinking tests and lifestyle questionnaires at the start of the study, at 6 months, and at 12 months. Give blood samples at the start of the study and at 12 months for tests related to Alzheimer's disease. Have APOE gene testing at the start of the study.

Cognitive-Motor Training for AD/ADRD Prevention

Alzheimer's disease and related dementias (AD/ADRD) greatly affect memory and daily activities in older adults. Mild Cognitive Impairment (MCI) is an early stage of dementia, affecting about 17% of older adults. People with MCI often show problems with gait and balance, which doubles their risk of falling compared to cognitively healthy peers. Falls can cause injuries, increase sedentary behavior, and reduce physical activity. This decline in activity can also speed up the progression from MCI to dementia. Exercise can help older adults make healthy lifestyle changes; however, most of the existing exercise programs focus mainly on physical movement rather than cognitive function. Therefore, the investigators developed a new program that uses computer vision and a cloud-based system to provide more scalable, engaging, and personalized cognitive-motor training for OAwMCI. The purpose of this study is to investigate the short- and long-term effects of a novel CogXergaming training (CXT) paradigm for improving the cognitive-motor function, physical activity, falls efficacy, and quality of life.

Neuromodulation of Memory in Aging

The proposed research will use closed-loop transcranial magnetic stimulation (TMS) based on individualized brain networks to establish parameters that can reliably control brain states. This will be tested in healthy aging and mild cognitive impairment (MCI) cohorts. The investigators will study network activation and neural oscillatory mechanisms underlying the network that regulates working memory and then target this network using closed-loop TMS to the Prefrontal Cortex. Investigators will measure the impact of TMS on working memory performance and task-based neural activity. The project will use brain stimulation and network modeling techniques to enhance working memory in healthy older adults and MCI and will demonstrate the value of closed-loop, network-guided TMS for future clinical applications.

Prevalence of Mild Cognitive Impairment and Dementia in Patients Admitted to Non-neurological Rehabilitation Wards

Cognitive impairment is common among older adults hospitalized for non-neurological conditions but often goes unrecognized, particularly in rehabilitation settings where clinical attention is mainly focused on physical recovery. The COGinREHAB study is a multicenter, prospective, longitudinal interventional study conducted at three rehabilitation centers of the Fondazione Don Carlo Gnocchi in Italy (Florence and Milan). The study will enroll 384 patients aged 45 years or older who are hospitalized for at least 7-10 days in cardiac, pulmonary, or orthopedic intensive rehabilitation units, or in intermediate care units, for conditions unrelated to the nervous system. At admission, all participants undergo a clinical and cognitive screening visit. Patients whose screening results suggest possible cognitive impairment then undergo a more extensive neuropsychological evaluation. In those with confirmed cognitive impairment, additional blood tests are performed to measure biomarkers of neurodegeneration (GFAP, neurofilament light chain, and phosphorylated tau-217), together with APOE genotyping and a non-contrast brain CT scan. In a subset of these patients, resting-state EEG, auditory event-related potentials, actigraphy, and overnight polysomnography are also performed. Patients with confirmed cognitive impairment are invited to a follow-up visit 12 months later to assess whether their cognitive profiles and biological markers have changed. The main purpose of the study is to estimate how frequently cognitive impairment occurs among patients admitted to non-neurological rehabilitation units, including how often it was previously undiagnosed. The study will also describe the clinical, biological, and neurophysiological profile of these patients and examine how cognitive impairment evolves over one year.

The Effects of Some Antihyperglycemic Drugs on Cognitive Function and Risk of Depression of Diabetic Patients

The study aims to investigate the effects of DPP-4 Is+ metformin versus SGLT2 Is + metformin on the risk of cognitive decline and depression in patients with T2DM.

The Effect of Lavender Aromatherapy on Cognitive Function in Older Adults With Mild Cognitive Impairment

1. To analyze the therapeutic effects of lavender aromatherapy on memory function and overall cognitive function in older adults with Mild Cognitive Impairment (MCI); 2. To analyze whether lavender aromatherapy improves executive function, language ability, attention, visuospatial ability, anxiety, depression, quality of life, and sleep in older adults with MCI.

Validation and Reliability of the Turkish Version of the Montreal Cognitive Assessment-Basic (MoCA-B) in Individuals With Low Educational Level

This study aimed to evaluate the validity, reliability, and diagnostic accuracy of the Turkish version of MoCA-B in distinguishing healthy controls, mild cognitive impairment (MCI), and dementia patients within a low-education population.

Telehealth-Adapted Compensatory Training and Intervention for Cognition

The goal of this clinical trial is to develop a five-week virtual cognitive training intervention for people with Mild Cognitive Impairment (MCI) based off an existing eight-week intervention. The main question it aims to answer is: • Is five weeks of training as good as eight weeks in improving cognition, quality of life, daily functioning, and mood, and in reducing caregiver burden? Researchers will compare five weeks of cognitive training to eight weeks of training to see if the shorter version is as effective as the full training. Participants will complete all activities virtually: * Complete a screening visit with a study partner (typically a family member, roommate, or close friend) to determine eligibility to participate in the study * Complete some tests of memory and thinking and some questionnaires * Attend weekly two-hour group cognitive training sessions with a trained group leader, for five or eight weeks * Redo the questionnaires and tests of memory and thinking immediately after completing the training, and three months after completing the training

Tailored Brain Health Insights Through Nurturing Knowledge-based Change - Stakeholder-driven, Human-centered, AI-powered Refinement for Prevention

The goal of this clinical trial is to evaluate whether an AI-powered digital brain health coaching intervention can improve modifiable brain health risk factors in community-dwelling adults aged 40 and above in Singapore. The main question it aims to answer is: does the use of BLAZE, an AI-powered digital brain health coaching intervention, lead to a greater improvement in Brain Care Score (BCS) compared to usual care at 6 months? Researchers will compare participants receiving BLAZE to those receiving usual care (waitlist control) to see if BLAZE leads to greater improvements in brain health risk factors, behavioural outcomes, quality of life, and cost-effectiveness. Participants will: * Be randomly assigned to either receive BLAZE immediately for 12 months or be placed on a waitlist receiving usual care for the first 6 months before receiving BLAZE for a further 6 months * Complete a series of assessments at baseline, 6 months, and 12 months including the Brain Care Score, physical function tests, cognitive assessments, quality of life measures, and lifestyle behaviour questionnaires * If assigned to the intervention group, interact with BLAZE via a WhatsApp-based platform that delivers personalised brain health recommendations, behavioural nudges, educational content, and goal-setting support based on their individual Brain Care Score profile

Acute Oral Ketone Monoester Supplementation and Resting-state Brain Connectivity

The primary objectives of this pilot study are to test if a single dose of an oral ketone monoester supplement will increase blood flow and connectivity in the brain in adults with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). The main questions it aims to answer are: Does a single dose of an oral ketone supplement increase global cerebral blood flow (CBF)? Does a single dose of an oral ketone supplement improve resting-state functional connectivity in the Default Mode Network (DMN)? Does the increase in CBF positively correlate with improved functional connectivity in the DMN? Participants will: * Attend one 2-hour session, which includes: * Neurocognitive assessment * MRI Scans (two, each 15 Minutes) * Capillary blood ketone level measurements * Hemodynamic assessment (blood pressure, heart rate)

A Phase I Study of [18F]Flortaucipir PET Imaging in Chinese Subjects: Safety, Pharmacokinetics, Biodistribution, Radiation Dosimetry, and Preliminary Diagnostic Efficacy

This is a non randomized, open-label Phase I study in Chinese participants. The goal of this clinical trial is to evaluate the safety and tolerability of a radioactive imaging agent called \[18F\]Flortaucipir Injection, which is used during a PET scan. The study will also measure how the agent moves through the body (pharmacokinetics), where it goes (biodistribution), the amount of radiation exposure (radiation dosimetry), and how well it may help detect signs of disease (preliminary diagnostic efficacy).

Accexible Speech Analysis for MCI Detection and Monitoring in Colombia

Mild Cognitive Impairment (MCI) is frequently underdiagnosed due to its subtle clinical presentation. This study evaluates the diagnostic performance of AcceXible, a speech analysis-based machine learning platform, compared to the Montreal Cognitive Assessment (MoCA) for MCI detection and monitoring in Colombian patients. A diagnostic test accuracy study will be conducted within a primary care setting (EPS Sanitas), including prior validation of the AcceXible protocol in the Colombian healthcare context. The study pursues two primary aims: (1) to validate the AcceXible tool in a Colombian population, and (2) to demonstrate that AcceXible achieves high diagnostic accuracy for early MCI detection and longitudinal monitoring relative to the MoCA.

Ketogenic Diet to Reduce Osteoarthritis Pain in MCI

Osteoarthritis and mild cognitive impairment are common conditions that share underlying biological processes related to metabolism and inflammation. This study will examine whether a well-formulated ketogenic diet influences pain, physical function, and cognitive outcomes in adults with osteoarthritis and mild cognitive impairment. Participants will follow a supervised ketogenic dietary intervention, with assessments conducted before and after the intervention to evaluate changes in symptoms and related biological markers. The goal of this study is to better understand shared mechanisms between joint pain and cognitive health and to explore whether a ketogenic dietary approach may support symptom management in these populations.

FACE Phase II (a Stage II Trial)

How to ensure adherence to computerized cognitive training in unsupervised circumstances (e.g., at-home, self-administered) in older adults at risk for Alzheimer's disease (AD) or AD related dementia (AD/ADRD) is understudied. The objective of the R33 study is to test a novel facial expression-based personalization engine (FPE) for monitoring and modulating real-time effective engagement, with an ultimate goal of enhancing long-term adherence in unsupervised cognitive training in older adults at risk for AD/ADRD. Here, Effective engagement is defined as the extent to which someone is actively engaged and performing with significant attention and enjoyment while training, addressing a balance between adherence and cognitive gains/plasticity from the training. Based on previous work, the hypotheses include that (1) mental fatigue revealed in facial expressions will reflect a trainee's degree of effective engagement, which can be modified by modulating task novelty; (2) the proposed FPE will ensure the effective engagement in cognitive training by monitoring trainee facial expressions and modulating training in response, promoting the trainee's long-term adherence to the training and cognitive plasticity. A Stage II intervention efficacy study will be conducted to compare effective engagement and adherence in unsupervised cognitive training between training programs with vs. without FPE in older adults at risk for AD/ADRD. The proposed FPE may assist in monitoring and improving effective engagement and adherence in older adults with unsupervised cognitive training. In the current application, FPE in a cognitive training program called speed of processing training will be tested. However, such FPE may be embedded to any computerized cognitive training in future studies to help address adherence related issues.

Impact of Nutrition, Sleep, and Physical Activity on Intellectual Function and Muscle Mass in Older Adults

The goal of this prospective, single site, interventional randomized control trial is to treat age related health conditions in adults older than 65 years and functional independence. The main question of the study is to answer the effectiveness of notification on activity, sleep, and nutrition based on wearable device Fitbit recorded data for the improvement of health conditions including intellectual property and physical function, compared to usual care. Participants in the intervention arm will be given a Fitbit Charge 5 device and asked to wear this for the duration of the study, including during sleep. The study intervention will run for 6 months. Notifications will be issued using a monitoring software in Japanese, and issued automatically to participants. Participants in the control arm will be given a routine care and health-related information. Researchers will compare cognitive performance, muscle mass and physical activity between the two groups to see if the notification based on Fitbit data would promote the health conditions of older adults.

Neurocognitive Assessment Platform 4 Alzheimer

The aging population in Europe is leading to an increase in neurodegenerative diseases, such as Alzheimer's disease (AD), which is expected to affect 152 million people worldwide by 2050. In Italy, there are approximately 1.2 million cases of dementia, with 600,000 attributed to AD. Given the limited effectiveness of current pharmacological treatments, there is a growing need for early, non-pharmacological interventions to slow disease progression and improve the quality of life for patients and caregivers. The Neurocognitive Assessment Platform 4 Alzheimer (NAP4A) study aims to create a digital platform for the early detection of amnestic mild cognitive impairment (MCIa), considered an intermediate stage between normal aging and dementia. The platform uses non-invasive biometric tools, including EEG, blood flow sensors, and eye-tracking devices, to collect neurophysiological and behavioral data. The study will involve 100 participants aged 55 to 80, divided into two groups: one with individuals diagnosed with MCIa and a control group of healthy participants. Over 12 months, regular assessments will be conducted to identify markers that predict the progression from MCIa to AD. The goal is to develop advanced diagnostic tools that support early and targeted interventions.

Validation of the Montreal Cognitive Assessment (MoCA) Version 8.x and MoCA-MIS in Greece.

Objective: The purpose of this study is to assess the psychometric qualities of the Montreal Cognitive Assessment (MoCA) version 8.x in Greek, including the MoCA-MIS. We intend to examine the tool's reliability (internal consistency, test-retest reliability) and validity (construct validity, concurrent validity, and known-group validity). Aim: The findings will support the tool's application for early cognitive impairment identification in clinical and research settings.