Alzheimer Dementia (AD)

Down syndrome (DS) is typically caused by an extra chromosome 21 in the cell nucleus (trisomy 21, or T21). T21 is both the most common cause of genetically defined intellectual disability and the earliest documented cause of Alzheimer's disease (AD)-type pathology. Currently, all presymptomatic individuals with DS are classified as having 'Stage 0' DS-associated AD (DSAD). DSAD pathology evolves inexorably, with virtually all individuals with DS developing AD pathology by age 40, and approximately 50% meeting clinical dementia diagnosis criteria at 55 years of age. This study will test the hypothesis that the FDA-approved AD drug memantine, at higher-than-standard doses, may be effective as a cognitive enhancer in young adults with DS. The primary goal of this phase 1b clinical trial will be the assessment of the safety and tolerability of three memantine doses in persons with DS. In addition, we will assess the effect of this drug on cognitive test scores and plasma biomarkers of AD in the study participants. Finally, we will also investigate steady-state plasma levels of memantine and the time course of memantine plasma levels after a single dose in the study participants (pharmacokinetics, or PK). The data generated through this phase 1b study will provide the essential safety, PK, and preliminary efficacy signals required to advance a phase 2 trial evaluating high-dose memantine as a first-in-class therapeutic strategy in DS.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with the accumulation of abnormal proteins, including amyloid-beta and tau, in the brain. Recent evidence suggests that the glymphatic and meningeal lymphatic systems, which contribute to the removal of waste products from the brain, may play a role in AD. In particular, impaired drainage through the deep cervical lymphatic system may contribute to the accumulation of disease-related proteins. The LymphDAD study is a prospective, single-center pilot study designed to explore whether surgically improving cervical lymphatic drainage may be associated with changes in biological markers, brain imaging, and cognitive and clinical measures in selected patients with AD who are not eligible for currently available disease-modifying treatments. Five participants with AD will undergo a minimally invasive microsurgical procedure called lymphovenous anastomosis (LVA), in which small cervical lymphatic vessels are connected to nearby small veins to facilitate lymphatic drainage. During the procedure, a small sample of lymphatic fluid will also be collected for exploratory analysis of amyloid-beta and tau proteins. Participants will undergo clinical and neuropsychological assessments, blood sampling, magnetic resonance imaging (MRI), and amyloid positron emission tomography (PET) before the procedure and during follow-up. Follow-up assessments will be performed at 1, 3, 6, and 12 months after surgery. The study is exploratory and is not designed to demonstrate a definitive clinical benefit. Its primary purpose is to obtain preliminary information on the feasibility, safety, and possible biological and clinical effects of cervical LVA in AD, which may support the design of future controlled studies.

The goal of this clinical trial is to evaluate whether a virtual reality (VR) based social platform can improve mental health and social connection for older adults who receive in-home care. Specifically, the study aims to determine if the VR program reduces loneliness, depressive symptoms, and boredom while increasing social connection and well-being among older adult participants. It also explores whether access to the VR program reduces caregiver burden and depressive symptoms for family caregivers. Researchers will compare an immediate-start group to a waitlist control group to assess whether the VR program improves outcomes compared to standard home care alone. Both groups will eventually receive the intervention. Older adult participants will use a VR headset at home to join group activities three times a week. These sessions include social activities with local peers and live-hosted group activities. A family caregiver or home care professional may be present during sessions if needed for support. Over a 12-week study period, older adult participants will complete three surveys assessing their mood, social connection, and well-being. Family caregivers of participating older adults are also invited to join an optional caregiver substudy. Caregivers who enroll in the substudy will not participate in the VR activities themselves, but will complete three surveys at the same time points over the 12 weeks to share their own well-being and caregiving experiences.

The aim of the study is to evaluate the clinical and biological efficacy, as well as predictors of efficacy, of a home-based intervention combining transcranial alternating current stimulation (tACS) with individualized computerized cognitive training in patients with mild Alzheimer's disease (AD). In neurodegenerative diseases, including AD, neurodegeneration is accompanied by alterations in brain oscillatory activity. Restoration of these oscillations through neuronal entrainment has shown beneficial effects in animal models, while previous studies in patients with AD have demonstrated that gamma-frequency tACS applied over the precuneus is safe and well tolerated and is associated with improvements in cognitive performance and cholinergic function, as well as modulation of brain oscillatory activity. Cognitive rehabilitation may also improve memory performance in patients with mild AD. Based on this evidence, the present study investigates a multimodal approach combining gamma-tACS with individualized computerized memory training. The study is a multicenter, randomized, placebo-controlled, double-blind trial involving 30 participants with mild AD. Participants will be randomly assigned to one of two groups: Group 1 will receive real gamma-tACS for 8 weeks (5 sessions/week, 60 minutes/session) combined with cognitive training (2 sessions/week, 30 minutes/session); Group 2 will receive sham tACS according to the same schedule, combined with the same cognitive training. tACS will be applied over the precuneus. Treatment will initially be performed in the hospital and will subsequently be administered at home under remote supervision by the study team. Assessments will be performed at baseline (T00), after 8 weeks of treatment (T08), and at follow-up visits at 16 weeks (T16) and 24 weeks (T24) from baseline. At each time point, participants will undergo clinical and neuropsychological assessment, blood sampling, and transcranial magnetic stimulation (TMS). The occurrence of adverse events will be monitored throughout the duration of the study. The main objectives of the study are: 1) to evaluate the short- and long-term effects of the combined intervention on cognitive performance; 2) to investigate intervention-induced changes in biological markers of neurodegeneration, inflammation, and synaptic function; 3) to evaluate the effects of the intervention on cholinergic transmission through the TMS short-latency afferent inhibition (SAI) measure; and 4) to investigate potential predictors of treatment efficacy.

Alzheimer's disease (AD) is the most common cause of dementia. Despite major research efforts, effective treatments that slow or stop disease progression remain limited. Growing evidence suggests that inflammation in the brain and the body plays a key role in the onset and progression of AD. In particular, immune cells called regulatory T cells (Tregs), which normally help control inflammation, are impaired in AD individuals. This leads to increased activity of harmful immune pathways that worsen brain injury. Interleukin-2 (IL-2) is a drug that can restore the function of Tregs. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, are a class of drugs currently used to treat diabetes and obesity. Beyond their metabolic effects, GLP-1RAs also reduce inflammation, protect brain cells, and improve cellular energy balance. Laboratory studies, including our own, show that combining IL-2 with semaglutide has stronger effects than either drug alone. Together, they enhance Treg function, dampen harmful inflammatory responses, and improve cell survival. These findings support testing IL-2 plus semaglutide as a novel combination therapy for AD. We now propose a clinical trial to evaluate the safety, feasibility, and biological effects of this strategy. The study will enroll 30 individuals with AD, ages 50 to 86, who have a confirmed diagnosis by amyloid PET brain imaging and a Mini-Mental State Exam score between 16 and 26. Participants will be randomly assigned to one of three groups: (1) placebo, (2) low-dose IL-2 alone, or (3) IL-2 combined with semaglutide. Throughout the trial, participants will undergo regular medical exams, blood tests, and safety monitoring. We will measure how the treatment affects Tregs and other immune cells, inflammatory markers in blood and CSF, and established Alzheimer's biomarkers such as amyloid beta, tau, and neurofilament light chain. Cognitive and functional assessments will also be conducted to explore potential benefits on memory and daily living skills. If successful, this study will provide the first evidence that a dual immunotherapeutic strategy can safely modify disease-related processes in AD. Such findings would lay the foundation for larger clinical trials and could open the door to a new, multimodal approach to slowing or preventing Alzheimer's progression.

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.

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.

The goal of this clinical study is to investigate the effectiveness of non-invasive stimulation to enhance cognitive control abilities in older adults with and without cognitive impairment. The main questions it aims to answer are: * whether it is possible to restore various cognitive functions in older adults by delivering theta burst stimulation (TBS), a form of transcranial magnetic stimulation, and * whether closed-loop TBS is able to induce therapeutic benefits that outperform open-loop TBS. Participants play a cognitive video game while a brain-computer interface (BCI) analyzes their electroencephalogram (EEG) signals and decodes the presence or absence of the contingent negative variation (CNV) potential, a marker of cognitive control. The BCI triggers TBS when its outputs indicate that the participant is not engaged properly in the video game. Researchers will compare the effects of closed-loop and open-loop TBS using the outcome metrics described below to see how much cognitive restorations is achievable with each stimulation modality.

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.

This pilot randomized controlled trial evaluates the feasibility and preliminary efficacy of VICA, an AI-powered virtual care assistant that delivers evidence-based education, symptom monitoring, and coaching to informal caregivers of people living with Alzheimer's disease and related dementias (ADRD). Sixty caregiver-patient dyads will be randomized 1:1 to VICA or an attention-control education app (Dementia Guide Expert) for 3 months. The study will assess recruitment, VICA acceptance/usability, and engagement (Aim 1), and estimate effect sizes for reducing patient behavioral and psychological symptoms of dementia (BPSD) and caregiver distress (Aim 2).

To evaluate the safety and tolerability of low-dose whole brain radiotherapy (WBRT) delivered as an induction course of 0.3 Gy × 10 fractions (3.0 Gy total) followed by 12 months of monthly maintenance LDRT (0.3 Gy × 10 fractions; 3.0 Gy total) in patients with Alzheimer's disease or dementia with inflammatory components

The goal of this observational study is to learn about the ability of a point risk score prediction model, developed using electronic medical record data, to predict the risk of progression from geriatric depression to dementia in older Chinese adults. The main questions it aims to answer are: Does a higher point risk score increase the risk of developing dementia in older adults with depression? What is the accuracy of the point risk score prediction model in identifying individuals at high risk of dementia among older adults with depression? Participants will receive their usual medical care as they normally would. No new treatments, tests, or procedures will be performed specifically for this study. The research team will collect data from their electronic medical records, including depression diagnoses, dementia diagnoses, comorbidities, medication records, and follow-up information. The point risk score will be calculated based on these routinely collected clinical data.

This study aims to evaluate the efficacy and safety of non-invasive brain-computer interface (BCI) neuromodulation technique combined with 40Hz audio-visual stimulation on cognitive function in patients with Alzheimer's disease (AD). This is a single-center, randomized, double-blind, sham-controlled trial. A total of 90 participants with Aβ-PET positive AD diagnosed according to NIA-AA criteria will be enrolled and randomly assigned to three groups in a 1:1:1 ratio: (1) 40Hz stimulation group (fixed 40Hz audio-visual stimulation, 60 minutes daily for 6 months), (2) individualized stimulation group (closed-loop BCI with real-time EEG feedback to adjust stimulation parameters, 60 minutes daily for 6 months), and (3) sham stimulation group (inactive stimulation, same duration). The primary outcome is the change in MoCA-B score from baseline to 6 months. Secondary outcomes include changes in cognitive domain-specific assessments (AVLT, STT, DST), multimodal brain imaging, EEG parameters, peripheral blood AD biomarkers, safety, tolerability, and comparison of efficacy between open-loop and closed-loop stimulation.

This research proposal outlines a multi-center, randomized, trial. Patients diagnosed with early-to-moderate Alzheimer's Disease will be recruited. Participants will be randomly assigned to receive either Lecanemab. The study will run over a period of 24 months, with evaluations conducted at baseline, 6 months, and 12 months, 18 months and 24 months. Data from multiple omics layers will be integrated to assess both the efficacy and safety of the treatment. The primary aim of this study is to assess the efficacy and safety of Lecanemab in patients with Alzheimer's Disease, leveraging multi-omics approaches. Specifically, the study will integrate data from OCT/OCTA imaging of the eye and MRI imaging of the brain, as well as cognitive measures such as ADAS-Cog, MoCA and CDR scores. Furthermore, the presence of ARIA-a significant safety concern in amyloid-targeting therapies-will be closely monitored. The study seeks to provide a more robust understanding of Lecanemab's impact on disease progression, cognition, and potential adverse effects, contributing to a more informed clinical application of this treatment in Alzheimer's care.

The aim of this study is to identify genetic factors that contribute to risk and progression of early-onset dementia (loss of memory function before the age of 70 years) across all ethnic groups, including Alzheimer's Disease, mild cognitive impairment and other dementias.

The goal of this study is to use ultra-high-resolution (UHR) PET imaging to better understand how the brain and spinal cord change in healthy aging and in neurological and psychiatric disorders such as Alzheimer's disease (AD), Parkinson's disease and related movement disorders, amyotrophic lateral sclerosis (ALS), and psychotic disorders. Researchers will use the NeuroExplorer PET/CT system, a new scanner that can show very small structures in the brain and spinal cord in much more detail than regular PET. The main questions this study aims to answer are: * How do small but important brain regions (like the locus coeruleus, substantia nigra, and thalamic nuclei) change in healthy aging? * What early brain changes occur in neurodegenerative and psychotic disorders, and can they help improve early diagnosis? Participants will: * Undergo PET and MRI brain scans using different tracers that measure brain metabolism (18F-FDG), synaptic density (¹⁸F-SynVesT-1), dopamine transporters (¹⁸F-PE2I), and tau protein buildup (¹⁸F-MK6240). * Complete cognitive and clinical assessments related to memory, mood, and motor or psychiatric symptoms, depending on their group. This study will include healthy volunteers and patients with mild cognitive impairment due to Alzheimer´s disease, ALS, Parkinson's disease and related disorders, or psychotic disorders. The results will help create detailed brain imaging maps for healthy aging and identify early biomarkers for different diseases to support better diagnosis and treatment in the future.

Alzheimer's disease is the most common cause of dementia and affects a growing number of older adults. Although harmful proteins build up in the brain, we still do not fully understand why some brain regions are affected earlier or more severely than others. Many people with Alzheimer's disease also have problems with blood flow and sugar handling in the brain, and these changes may play an important role in disease development. People with type 2 diabetes are at especially high risk of developing Alzheimer's disease and often experience a more severe disease course. This pilot study aims to improve our understanding of how brain blood flow and sugar use are altered in Alzheimer's disease, and whether these changes differ in people with and without type 2 diabetes. We will study three groups: people with Alzheimer's disease without diabetes, people with Alzheimer's disease and type 2 diabetes, and healthy older individuals. By comparing these groups, we aim to identify early brain changes that may contribute to cognitive decline. Participants will undergo advanced brain imaging using positron emission tomography (PET) scans. One scan uses a radioactive sugar tracer to measure how the brain takes up and uses glucose. Importantly, a new non-invasive method will also allow us to estimate how efficiently glucose is transported from the blood into the brain. This is a key process that may be impaired in Alzheimer's disease, but has previously required invasive procedures. The new approach avoids arterial cannulation, making the study safer and more comfortable for participants. A second PET scan will assess brain blood flow and blood vessel function, including how well the vessels can respond to increased demand. Participants will also complete cognitive tests to assess memory and thinking abilities. Ultimately, this research may contribute to earlier diagnosis, better monitoring of disease progression, and development of new treatment strategies for Alzheimer's disease.

Alzheimer's disease causes progressive memory and cognitive decline, driven in part by the buildup of a protein called β-amyloid in the brain. New antibody therapies - lecanemab and donanemab - can remove amyloid and slow down the disease in its early stages. However, it is still unclear how long each patient should continue treatment or when it is safe to stop, because amyloid is cleared at different rates across individuals. Today, amyloid Positron Emission Tomography (PET) scans are used to measure whether amyloid has been removed from the brain, but these scans are expensive, not always available, and expose patients to radiation. Since repeated PET scans are not ideal, doctors need better ways to monitor treatment progress. This study will use advanced brain Magnetic Resonance Imaging (MRI) and blood tests to create personalized prediction models. These models will simulate how amyloid spreads or clears in each person's brain and help identify when treatment is still needed. With this approach, monitoring becomes safer, more efficient, and more affordable - helping ensure that each patient receives the right treatment for the right amount of time. This prospective monocenter study investigates the role of 3Tesla MRI-based predictive modeling in predicting treatment response to anti-amyloid monoclonal antibodies (lecanemab or donanemab administered as clinical practice) in 50 patients with early Alzheimer's disease (AD) at IRCCS Ospedale San Raffaele (Milan, Italy). Advanced MRI techniques, including high- resolution structural imaging for cortical thickness and volumetric atrophy, diffusion imaging for structural connectivity, and resting-state functional MRI for functional network analysis, will be acquired at baseline, 6, 12, and 18 months. These multimodal MRI measures will be integrated into computational approaches, such as the Aggregation Network Diffusion (AND) model, to simulate individual disease trajectories and predict the probability of achieving negativity at amyloid PET under treatment. While serial \[¹⁸F\]Flutemetamol PET will be performed as part of standard clinical practice to confirm amyloid removal, the focus of the study is on developing MRI- derived predictive biomarkers. The ultimate goal is to establish robust, non-invasive models capable of guiding individualized treatment monitoring and supporting evidence-based decisions on treatment discontinuation Overall, the project aims to support more precise care for people with early Alzheimer's disease, while reducing unnecessary procedures and improving quality of life.

This project aims to improve knowledge regarding Alzheimer's dementia and related dementias (ADRD) among older adults and their caregivers in Vietnam and promote the early diagnosis of ADRD using a digital storytelling intervention.

The purpose of this study is to evaluate whether levetiracetam can prevent epileptic seizures in patients with Alzheimer's disease associated with Down syndrome. It will also analyze whether it can delay the neurodegeneration associated with this disease. Patients will be randomly assigned to one of two groups: one group will receive the active drug (levetiracetam), and the other will receive a placebo. Both groups will receive the treatment for 96 weeks. Each patient will participate for a total of 2 years and 5 months.

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.

The purpose of this study is to test a new procedure to treat Alzheimer's disease. The procedure is called intermittent Deep Brain Stimulation (DBS) of the nucleus basalis of Meynert. There will be up to six participants enrolled at Wellstar MCG Memory Clinic. There will be another six participants similarly enrolled to act as a control group that does not receive DBS. This second group will document the course of progression of Alzheimer's disease under the normal standard of care. The main goal of the study is to determine if DBS can sustain or improve cognition in Alzheimer's disease for at least two years. Participant data, with identifying information removed, may be shared with online repositories for comparison with trials with similar subjects.

This study evaluates whether the combined treatment of methylphenidate and non-invasive brain stimulation, called intermittent theta burst stimulation, can effectively treat apathy in individuals with Alzheimer's disease or mixed AD/vascular dementia

TPS is a non-invasive therapeutic modality that uses focused, low-energy pulse stimulation to stimulate tissue regeneration and reduce inflammation. In the context of neurological disorders, it is hypothesized that TPS can modulate neuronal activity, enhance synaptic plasticity, and reduce neuroinflammation. It is a relatively new application in neurological disease treatment and is still under intense investigation.

Although life expectancy is increasing, the risk of dependence and/or loss of autonomy is increasing too with ageing. Alzheimer's disease affects many people and this kind of disease is constantly growing. Today, relatives of these sick people are increasingly taking on the role of carer to help them remain at home as long as possible. This situation of assistance has often a negative impact on the quality of life of the caregiver, which in some cases can lead to the caregiver burnout and increase the risk factors for developing pathological ageing. This situation can also damage the relationship and the quality of interactions between patient/caregiver dyad. Non-pharmacological therapies and the use of digital tools appear to be promising avenues to fight psychological distress and social isolation, but also to improve the quality and duration of homecare services, by promoting the autonomy of the patient. The MUSIQUAL+ study aims to evaluate the impact of music listening offered to caregivers, alone or with their sick relative, on the quality of life and the exhaustion felt by the caregiver. Three times 20-minute sessions a week of music listening at home through the use of a tablet application, for 12 weeks, will be proposed. In addition to the collection of subjective feelings of the caregivers, a neuropsychological evaluation of the patient and the caregiver will be carried out on 90 dyads divided. Finally, in order to better understand the cerebral mechanisms involved and to provide evidence of the effect of this intervention, an EEG recording will be made before and after the musical listening. This study proposes a therapeutic and preventive alternative to drug treatments and to the currently unsatisfactory support of patients and their caregivers in distress; its benefits will be assessed too.