Clinical Research Directory

Effects of Real vs. Soundless Acoustic Stimulation During Deep Sleep on Brain Activity, Memory, and Blood Biomarkers in Older Adults (60-85) With Mild Memory Impairment

This study aims to explore a non-invasive way to improve memory and slow cognitive decline in older adults by enhancing sleep quality. Dementia, a leading cause of death worldwide, is often associated with disturbed sleep, particularly the loss of deep, slow-wave sleep (SWS). SWS is important for memory and clearing waste from the brain. Poor SWS can worsen memory loss and allow harmful waste to build up, which may increase the risk of dementia. The investigators are testing whether phase-locked auditory stimulation (PLAS) can improve SWS in people at a mild stage of cognitive impairment. PLAS uses short sounds played at specific moments to strengthen slow-wave brain activity during sleep. The investigators previous laboratory based research has shown that this can improve memory and help with clearing waste from the brain. Now, the investigators want to test this in a real-world setting, over a longer period, which is unfeasible in a laboratory setting. In this study, 60 older adults will use home-use devices that deliver either real or sham (soundless) PLAS across two different 4-week periods. Memory will be tested using engaging "serious games." Before and after each experimental period, blood samples will be taken to measure dementia-related markers, and cognitive batteries will be performed. The investigators expect that PLAS will improve sleep, and that this will have a downstream effect on memory and brain clearance, potentially slowing the process of cognitive decline. If successful, this could lead to the development of an affordable treatment that helps people maintain brain health and prevent dementia.

Effect of Acupuncture on Psychoneurological Symptom Cluster in Breast Cancer Survivors

This clinical trial aims to assess whether electroacupuncture (EA) can alleviate the psychoneurological symptom cluster (including pain, fatigue, insomnia, anxiety, depression and subjective cognitive decline) in breast cancer survivors, and to evaluate the safety of this therapy. Researchers will conduct a randomized controlled trial of electroacupuncture (EA) as compared to sham electroacupuncture (SA) in breast cancer survivors with the psychoneurological symptom cluster who are currently being treated with endocrine therapy. Participants will receive 16 treatments over 8 weeks. The EA group will receive true acupuncture with continuous wave stimulation (2Hz, intensity as tolerated) administered for 30 minutes per session. The SA group will receive sham acupuncture using blunt (non-penetrating) needles that contact the skin without penetration, along with a 30-second transient device activation instead of the 30-minute continuous stimulation. Treatment outcomes for pain, fatigue, insomnia, anxiety, depression and subjective cognitive function will be assessed. The primary outcome is response rate of the psychoneurological symptom cluster after 8 weeks of treatment. Secondary outcomes include changes from baseline in the scores of each of the six psychoneurological symptoms.

Art of Memory for Cognitive Enhancement in the Monza Brain Health Service

The goal of this pilot interventional clinical trial (non-drug study) is to learn whether memory techniques (mnemonics) can improve cognitive performance in adults over 50 years old with subjective cognitive decline who are followed at the Brain Health Service of Monza. The study will also evaluate the feasibility of this intervention and explore which biological or clinical factors may influence its effects. The main questions it aims to answer are: * Do memory techniques improve overall cognitive performance, measured by a composite score from a neuropsychological test battery, after 6 months? * Are any cognitive benefits maintained over time (up to 9 months)? * Do biomarkers (such as blood p-tau217 levels, APOE genotype, or brain atrophy on MRI) influence the response to memory training? * Do memory techniques improve subjective cognitive complaints and performance on sensitive memory and cognitive-motor tests? Researchers will compare a memory training group to a control group receiving information only to see whether structured mnemonic training leads to greater improvement in cognitive outcomes. Participants will be randomly assigned to either the memory training group or the control group. Both groups will undergo complete cognitive assessments at baseline, 6 months, and 9 months. If assigned to the training group, participants will attend two in-person group sessions to learn basic and advanced memory techniques, participate in two additional online group meetings, access online video materials, and practice memory exercises on a dedicated online platform for about 20 minutes per day. If assigned to the control group, participants will receive general information about memory techniques but no structured training or platform access. A total of 80 participants (40 per group) will be enrolled. This pilot study will help estimate the size of the effect and determine whether a larger future study is feasible.

Lombard Cohort of Brain Health Services

The goal of this multicenter prospective observational cohort study is to better understand the clinical, neuropsychological, and biological characteristics of individuals attending Brain Health Services (BHS) in the Lombardy region. The study focuses on adults with subjective cognitive decline (SCD), functional cognitive disorder (FCD), or "well worried" individuals without objective cognitive impairment. The main questions it aims to answer are: * What clinical, cognitive, and biological differences exist between individuals who are positive versus negative for Alzheimer's disease (AD) plasma biomarkers (p-tau217) at baseline? * What factors predict positivity to AD biomarkers at baseline? * How does communication of biomarker results (risk disclosure) affect psychological well-being shortly after receiving results? * What factors predict longitudinal changes in AD biomarkers over 5 years? * Do baseline biomarkers predict the development of mild cognitive impairment (MCI) or dementia during follow-up? Participants will: * Undergo standard clinical evaluation at their local BHS * Provide blood samples for plasma biomarker analysis (e.g., p-tau217, GFAP, NfL, ApoE) * Undergo neuropsychological testing and cognitive screening * Complete questionnaires assessing psychological impact and risk perception (before and after biomarker disclosure) * Undergo additional center-specific procedures when clinically indicated (e.g., MRI, lumbar puncture, polysomnography) * Be followed annually for 5 years The study plans to enroll approximately 1000 participants across multiple BHS in Lombardy and will follow them for a total duration of 7 years. The results will help clarify the role of biomarkers in early cognitive complaints and support the development of preventive strategies within BHS.

Chinese Classics Recitation Training in Subjective Cognitive Decline

Subjective cognitive decline (SCD) is considered a preclinical condition associated with an increased risk of dementia and Alzheimer's disease. Effective early behavioral interventions remain limited, and the neurobiological mechanisms underlying cognitive training effects are not fully understood, particularly in culturally specific educational contexts. This randomized, assessor-blinded, controlled clinical trial will enroll 60 individuals with SCD to evaluate the effects of a six-month structured Chinese Classics recitation training program. Participants will be randomly assigned to either an intervention group or a non-active control group. Assessments will be conducted at baseline, immediately post-intervention, and during annual follow-up. Multimodal evaluations will include neuropsychological testing, functional magnetic resonance imaging (fMRI), electroencephalography (EEG), blood biomarker profiling, gut microbiota analysis, and fecal metabolomics. The study aims to examine clinical outcomes and explore potential neurobiological and systemic correlates associated with culturally adapted cognitive training.

Increasing Physical Activity Through Social Support and Stress Resilience

The goal of this clinical trial is to learn the effects of technology enhancements when combined with basic education, goal-setting, and self-monitoring to increase physical activity among older adults living alone, experiencing subjective cognitive decline, and currently engaging minimal physical activity (60 minutes or less of moderate to vigorous physical activity). Further, we will examine key psychosocial mechanisms believed to contribute to successful promotion of physical activity, which include social support and stress resilience. The primary questions are to determine whether * the tech-enhanced condition lead to greater physical activity over time? * the tech-enhanced condition lead to social support and stress resilience over time? * social support and stress resilience mediate the relationship between the study condition and physical activity? All participants will engage in self-monitoring of physical activity, will receive weekly text reminders of their physical activity goals for the week, and will receive basic education about the importance of physical activity, social support, and stress resilience for cognitive, physical, and psychological health. Participants in the tech-enhanced condition will also receive access to a study-specific website and virtual coaching to reinforce the information presented. Researchers will then compare the tech-enhanced condition to the basic education condition to determine the benefits of technology to deliver the intervention materials in order to increase physical activity, social support, and stress resilience. Participants will: * Use a Garmin wearable device to monitor their physical activity * Be randomly assigned to a basic education condition or tech-enhanced condition * Set achievable goals for weekly physical activity, with incremental increases to achieve 7000 average daily steps by the end of the study * Respond to surveys to monitor their social support, stress resilience, quality of life, and depression. The sample has several risk factors for Alzheimer's disease and related dementias: low physical activity, social isolation risk via living alone, and subjective cognitive impairment. Therefore, a long-term goal includes the determination of the intervention's effectiveness at increasing physical activity, social support, and stress resilience to reduce risk for developing dementia.

Physiological Effect of Non-invasive Photobiomodulation on Cognition and Mood in Older Adults With Subjective Cognitive Impairment

Subjective cognitive impairment (SCI) is a non-clinical condition manifesting as a self-reported decline in cognitive function without objective clinical evidence, and is prevalent among older adults and strongly associated with declining mood. This study explores the potential of photobiomodulation (PBM) as a therapeutic intervention for SCI. PBM, using near-infrared light, is a non-invasive neuromodulation approach that has shown promise in improving neuronal function, blood flow, and reducing inflammation in both healthy adults and patients with neurological conditions, including dementia and depression. This study proposes investigating the potential of forehead (tPBM), intranasal (iPBM) and vagal (vPBM) PBM to enhance mood and cognitive function in individuals with SCI as a proof of concept for the future use of PBM as therapy for cognitive decline in general. This study will recruit approximately 80 participants with SCI for the study, and the total expected duration of the participant\'s participation in the study is 5 weeks. The active and sham Neuro 5T device consisting of a headset with a built-in controller, nasal and neck applicators will be used. The nasal and neck applicators each contains a single LED and will be placed into the nostril or neck and secured into place. The headset contains multiple LEDs in a wearable applicator and may be adjusted. The Neuro 5T also contains telemetry features to allow documentation of patient usage of the device. LEDs are semiconductor electronic components that emit light. Participants will be given PBM devices for in-home usage, 2 times a day, 7 days a week, for 5 weeks. Participants will undergo EEG, MRI, cognitive and nasal microbiome assessments before and after the 5-week period.

Study of Bedroom Environment Sleep Intervention at Home for Older Adults Living Alone With Memory Concerns

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 Signature of Alzheimer's Disease in Subjective Cognitive Decline

This study focuses on improving early detection of Alzheimer's disease (AD) in patients with subjective cognitive decline (SCD), a preclinical stage of cognitive impairment, in the context of emerging disease-modifying therapies (DMTs). Current biomarkers, such as brain MRI, PET scans, and cerebrospinal fluid (CSF) markers, are highly accurate but costly, invasive, and not widely accessible. The study aims to provide cost-effective, scalable tools for early identification of individuals at risk, enabling personalized assessment and timely DMT administration. Objectives: * Evaluate the accuracy of innovative, easily accessible biomarkers in predicting biologically confirmed AD. * Assess the predictive utility of previously studied methods for SCD patients. * Explore new approaches, including automated speech analysis, to identify cognitive decline. * Evaluate genetic contributions to AD risk. * Integrate data from these various modalities using machine learning to create a predictive model for AD in SCD patients. Study Design: This is a multicenter, longitudinal, low-intervention study conducted at IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy (UO1) and the Center for Research and Innovation in Dementia, Careggi Hospital, Florence, Italy (UO2). Eligible participants are adults with SCD, intact daily functioning, and Mini-Mental State Examination (MMSE) scores \>24. Exclusion criteria include neurological or systemic diseases, major psychiatric disorders, substance use, or prior head injury. Participants undergo: * Detailed medical and family history collection. * Comprehensive neuropsychological, personality, and independence in daily activities assessment * EEG recording in resting state. * Blood sampling for plasma biomarkers (Aβ42, Aβ40, p-tau181, p-tau217, t-tau, NfL, GFAP). * CSF biomarker analysis (Aβ42, Aβ40, p-tau, t-tau). * Genetic analysis of AD-related genes (PSEN1, PSEN2, APOE, TREM2, ABCA7, BDNF, HTT). * Speech recording and analysis using standardized tasks to extract features for automated evaluation. The study expects to create a machine learning-based predictive model combining biomarker, neuropsychological, EEG, speech, and genetic data to improve early detection and guide personalized patient care. Procedures: * Neuropsychological evaluations occur at baseline and two-year follow-up. * Language recordings are conducted in controlled settings using standardized picture description tasks. * EEG is recorded using 21-channel systems. * Blood and CSF samples are collected, processed, and stored at -80°C for subsequent analysis at respective institutional laboratories. * Plasma biomarkers are analyzed with Simoa technology; CSF biomarkers are analyzed using chemiluminescent enzyme immunoassay (CLEIA). * Genetic analyses employ PCR, high-resolution melting analysis (HRMA), sequencing, and capillary electrophoresis as appropriate for specific genes or polymorphisms. The study expects to create a machine learning-based predictive model combining biomarker, neuropsychological, EEG, speech, and genetic data to improve early detection and guide personalized patient care.

Personalized Digital Training for COGnitive FITness in Mild Cognitive Impairment

The goal of this clinical trial is to determine whether a home-based digital cognitive-training program called RICORDO can enhance patients' ability to manage their own health and daily life when they have Mild Cognitive Impairment (MCI) or Subjective Cognitive Decline (SCD) and are 50 years of age or older. The main questions it aims to answer are: Does using RICORDO for five weeks raise the Patient Activation Measure (PAM) score more than an at-home paper-and-video education program called S.A.M.B.A.? Does RICORDO also improve cognition, everyday functioning, quality of life and mood compared with S.A.M.B.A.? Researchers will compare individuals who train with RICORDO to those who follow S.A.M.B.A. to determine which approach is more effective. Participants will be randomly assigned to one of the two groups and complete three 45-minute sessions per week at home for five weeks. They will also visit the clinic at the beginning and end of the program to complete questionnaires and take brief thinking tests.

High Frequency Stimulation to Improve Cognition, Mobility, and Affect in Individuals With Subjective Cognitive Decline

The goal is to determine whether three months of at least three times / week of sensory flicker stimulation improves cognition, mobility, and affect in older adults with Subjective Cognitive Decline (SCD), relative to an SCD control group receiving white noise sensory stimulation. Investigators will also determine whether the intervention slows cortical thinning and declines in brain functional network segregation and changes in blood biomarkers of Alzheimer's Disease (AD).

LETHE-AT: a Personalized Multidomain Lifestyle Intervention for Individuals at Increased Risk of Memory Impairment.

The goal of this clinical trial is to learn whether a hybrid multidomain lifestyle program can prevent cognitive decline and reduce dementia risk in community-dwelling adults in mid- to late life who are at increased risk of Alzheimer´s disease or related dementias but do not yet have significant cognitive impairment. The main question the study aims to answer are: * Whether the structured hybrid multidomain lifestyle intervention is feasible (e.g., adherence and retention rate), and how well the digital components are accepted and implemented in the intervention group. * Does the intervention reduces the overall burden of modifiable dementia risk factors and improves global cognitive performance compared with usual care. Researchers will compare participants assigned to the tailored hybrid multidomain lifestyle intervention group with those in a self-guided multimodal lifestyle advice group. Participants assigned to the intervention group will receive a plan adjusted to their individual dementia risk profile. A physician trained in motivational interviewing will review their progress continuously. The self-guided multimodal lifestyle advice group will receive rigid but comprehensible lifestyle health advice with reduced access to digital support tools. Participants will: * Complete an initial risk assessment that uses machine-learning triage to identify and prioritize their most important modifiable dementia risk factors. * Receive personalized recommendations for gradual lifestyle change, including physical activity, nutrition, cognitive training, other dementia risk-factor management (e.g. hearing impairment), stress \& sleep management, and social activities. * Use a smartphone and smartwatch to passively collect digital biomarkers and to complete questionnaires at regular intervals, so that physicians trained in motivational interviewing can adapt goals through shared decision making. * Use a study app as the central access point for the program, including educational content, progress tracking, and gamified challenges with social comparison and incentives.

Comprehensive Assessment of Neurodegeneration and Dementia

This is a longitudinal observational study recruiting individuals between the ages of 50 and 90 with different types of dementia as well as a comparison group without cognitive deficits. Participants are/will be recruited at sites across Canada and will undergo assessments, neuroimaging, and biological sample collection.

Electro-acupuncture for SCD With Depression

The goal of this clinical trial is to evaluate the efficacy and safety of electroacupuncture in treating adults with subjective cognitive decline accompanied by depression. The main objectives are to answer the following questions: 1. Can electroacupuncture improve cognitive function and depressive symptoms in individuals with subjective cognitive decline accompanied by depression? 2. Does electroacupuncture alleviate subjective cognitive decline with depression by modulating the amygdala-entorhinal circuit, and if so, what is the specific mechanism involved? Researchers will compare real electroacupuncture therapy with sham electroacupuncture therapy to determine whether real electroacupuncture can effectively improve symptoms in patients with subjective cognitive decline accompanied by depression. Additionally, multimodal magnetic resonance imaging (MRI) technology will be used to assess changes in the amygdala-entorhinal circuit following electroacupuncture intervention. Participants will: 1. Receive either real or sham electroacupuncture treatment once daily, 3-5 times per week, for a total treatment duration of 8 weeks. 2. Undergo cognitive function and depression assessments before and after treatment. 3. Complete multimodal cranial magnetic resonance imaging examinations before and after treatment.

Positive Psychology for Early Cognitive Decline: Effects on Cognitive and Brain Function

This randomized study tests whether a new multicomponent Positive Psychology program can improve cognition and wellbeing in older adults at the earliest stages of dementia-related decline. About 128 participants with Subjective Cognitive Decline or Mild Cognitive Impairment will be enrolled. Half will be randomized to the Positive Psychology program and half to Treatment As Usual (TAU). The program consists of weekly, small-group online sessions for \~24 weeks plus brief home practices. All participants (both arms) will complete questionnaires and cognitive tests at baseline, during treatment, post-treatment, and 9-month follow-up. Primary question: Do participants receiving the Positive Psychology program show better cognitive and brain-function outcomes than TAU at post-treatment and at 9 months? Secondary question: Are effects larger for SCD than MCI? No medicines are used and risks are minimal. If effective, this scalable, low-cost, non-pharmacological approach could complement usual care for people in very early cognitive decline.

An Open Label Trial Evaluating the Efficacy of Lacticaseibacillus Paracasei PS23 on Cognition

This open label study aims to evaluate whether the consumption of probiotics can improve symptoms and overall quality of life in individuals experiencing cognitive decline symptoms, as well as to evaluate the effects of probiotics on blood-related biomarkers.

Effect of Accelerated Neuromodulation of Anterior Cingulate Cortex to Enhance Cognition in Older Adults With Mild Memory Problems

The goal of this clinical trial is to test whether an accelerated deep Transcranial Magnetic Stimulation (dTMS) protocol in combination with cognitive training can improve cognitive abilities in older adults with Subjective Cognitive Decline (SCD) or Mild Cognitive Impairment (MCI). The study will look at whether it is safe and tolerable to use accelerated dTMS to enhance the benefits of cognitive training in older adults, and will also gather early information on the effects of accelerated dTMS on memory and other cognitive abilities.

A Feasiblity Study of Green Activity Program for People Living With Memory Challenges

The purpose of this study is to test the Green Activity Program that was designed with people living with memory challenges and their study partners to see if it can be done and if they enjoy the program. "Green activities" are nature activities that the person enjoys and can be done with other people or pets. For example, dog walking, hiking, outdoor yoga, and gardening are all green activities. The purpose of the program is to help people living with memory challenges participate in nature activities they enjoy. The goal of the program is to help people stay active and improve their health and well-being.

InRAD Observational Study

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.

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.

Predictors Of Cognitive Decline Using Digital Devices

The overall aim of this study is to find out if people with cognitive difficulties will wear and use different types of digital technology, and if they will allow data from that technology and their clinical profile to be collected. Participants will be patients in Essex Memory clinic and their partners/carers. The digital technology used will include a smartwatch, a sleep headband and two smartphone applications, which have been selected as part of the Early Detection of Neurodegenerative Disease (EDoN) initiative. The investigators will also investigate how the digital data can be analyzed together with routinely captured clinical data using machine learning models, a complex type of statistical analysis. The aim of the wider EDoN initiative is to combine digital and clinical data to develop machine learning models which can predict individuals' risk of developing dementia decades before the onset of symptoms.

Sleep Stimulation to Enhance Waste Clearance in the Brain

This study aims to examine whether multi-night closed-loop auditory stimulation (CLAS) during sleep can enhance waste clearance and memory consolidation in healthy adults and older adults with subjective cognitive decline or mild cognitive impairment who exhibit elevated brain amyloid levels identified through prior clinical screening. Specifically, the study investigates whether sleep stimulation increases the clearance of plasma biomarkers related to neurodegeneration, improves the brain's waste clearance system, and supports memory consolidation. Participants will undergo five nights each of CLAS and sham (no stimulation) interventions, with a washout period in between. They will also complete clinical assessments, including MRI scans, blood sample collection, and cognitive testing, and will keep track of subjective sleep quality, sleepiness, mood, and fatigue throughout the interventions.

Neural Mechanisms of Cognitive Assessment and Rehabilitation for Cognitive Decline

This study investigates the neural mechanisms of cognitive function decline, cognitive assessment methods for subjects with mild cognitive dysfunction (Mild cognitive impairment, MCI, or cognitive decline milder than MCI), and the approaches used to improve and restore cognitive function.

Korean Joint Registry for Alzheimer's Treatment and Diagnostics (JOY-ALZ)

The purpose of this research is to investigate the long-term effectiveness and safety of new Alzheimer's disease treatments, particularly monoclonal antibody therapies like lecanemab and donanemab, as well as to enhance diagnostic methods for Alzheimer's disease by collecting real-world data from Korean Alzheimer's patients. The goal is to contribute to the precision of Alzheimer's treatment and to evaluate the impact of these new therapies and diagnostic techniques in clinical practice.