Clinical Research Directory

Predicting Pre-dementia

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.

Efficacy of Lecanemab at Different Therapeutic Doses for Alzheimer's Disease (AD) in Real-World Practice

This study will analyze the clinical indicators, imaging data, and serum biomarkers of Alzheimer's disease (AD) patients receiving different doses of the medication before and after treatment. It aims to clarify whether the therapeutic efficacy in the low-dose group is equivalent to that in the recommended-dose group, and meanwhile to determine the optimal dose range for effective pharmacotherapy.

Brain NAD in Alzheimer's Disease

The goal of this observational study is to learn about the levels of nicotinamide adenine dinucleotide (NAD) in the brains of people with Alzheimer's disease. The study aims to determine if brain NAD levels are lower in people with Alzheimer's disease compared with people of the same age group who do not have Alzheimer's disease. Participants with or without Alzheimer's disease will have a brain imaging session where NAD will be measured using magnetic resonance spectroscopy (MRS). Eight months later, they will have a second, similar, brain imaging session.

Arlington Longitudinal Optimal Healthy Aging Study (ALOHA)

The Arlington Longitudinal Optimal Healthy Aging (ALOHA) Study is a community-based research project led by the Marymount University Center for Optimal Aging (MCOA). The study is designed to help older adults in the Washington, D.C., Maryland, and Virginia (DMV) area maintain independence, mobility, wellbeing and brain health as they age. Adults aged 50 years and older will receive a comprehensive health assessment at the study site, Center for Optimal Aging- ALOHA Lab at Marymount University (MU) Ballston Campus in Arlington, Virginia. The assessment includes physical and cognitive testing, health and medical history, lifestyle surveys, and biometric measures such as blood pressure, grip strength, body composition by the InBody system, balance and gait speed. Participants will receive their results in a personalized "Health Passport," which summarizes findings and provides tailored recommendations to help manage modifiable health risk factors-such as those linked to Alzheimer's disease, cardiovascular disease, frailty syndrome, and depression. Participants will return annually for up to 5 years to repeat assessments and receive updated health and wellness recommendations. The study will track changes in health over time and explore the impact of the Health Passport on health behaviors, functional independence, and quality of life. ALOHA will also evaluate the cultural appropriateness of the Health Passport for diverse populations in Northern Virginia. The program incorporates an interprofessional research model, engaging researchers from multiple health professions to work alongside older adults, supporting both participants' wellness and optimal aging.

Generation of Synthetic [18F]FDG PET From Early-Phase Amyloid PET in Alzheimer's Disease

This study aims to test a new artificial intelligence (AI) method to create brain scan images without needing an extra scan. Currently, patients with memory problems often undergo two types of PET scans (Amyloid PET and FDG PET) to assess Alzheimer's disease. This study will use existing scan data from patients who already had both scans as part of their routine care. The AI model will try to generate the FDG PET image using only the Amyloid PET scan and an MRI. If successful, this method could reduce radiation exposure, costs, and time for future patients by eliminating the need for a separate FDG injection and scan. No new scans, injections, or procedures will be performed for this study. All data will be fully anonymized (personal information removed) before analysis. The study involves approximately 35 adult patients (age 50+) whose data were collected between January 2025 and December 2025 at IRCCS Ospedale San Raffaele in Milan, Italy.

BioMIND (Biomarkers for the Molecular Identification of Neurodegenerative Dementia) - Improving Access to Alzheimer's Disease Diagnostics: A Pragmatic System Level Intervention

The BioMIND (Biomarkers for the Molecular Identification of Neurodegenerative Dementia) pilot study was launched at Parkwood Hospital in response to national calls for implementation of biomarker diagnostics in Canada. It evaluated the feasibility, impact, and equity of introducing blood biomarker testing, lumbar punctures, and amyloid Positron Emission Tomography (PET) scans into clinical pathways. The study found that the Biomarker-First pathway significantly reduced the time from referral to diagnosis (195 versus 533 days - a difference of 318 days), demonstrating the value in implementing clinical biomarkers to bypass bottlenecks created by the need for specialist assessments. Building on these findings, the next phase of BioMIND is aimed at reducing wait times for biomarker diagnostics for patients with symptoms suggestive of mild cognitive impairment (MCI) and early AD. The aim is to understand these wait times to biomarker testing using a nurse-led triage support tool. Group A participants will be pre-screened using this tool that includes the eligibility criteria for the study. This will help understand, out of everybody coming to the Aging Brain and Memory Clinic (ABMC) who've indicated interest in research, which people would be eligible to receive AD biomarkers if they were clinically available. Comparison of Group A's time to diagnosis with Group B and C's, who would have had a specialist appointment within 18 months and were referred to research to receive AD biomarkers through this study.

Effectiveness of Genistein in Mild Cognitive Impairment

Randomized, placebo-controlled, double-blind, multicenter clinical trial with two parallel study arms (experimental and placebo) to assess the efficacy of genistein extract consumption over 18 months on cognitive decline in patients with prodromal Alzheimer's disease.

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.

LEvetiracetam to Prevent Seizures in Symptomatic Alzheimer's Disease in Adults With Down Syndrome

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.

Daridorexant for Alzheimer Disease Prevention

This study will evaluate whether daridorexant, a DORA sleep medication, can support brain health by promoting the clearance of proteins linked to the development and progression of Alzheimer's disease. The trial is preventive and is open to participants who do not have Alzheimer's disease dementia, regardless of whether or not they experience sleep problems.

Tributyrin Treatment in Mild Alzheimer Disease: Assessment of Butyrate Effects Via the Gut-Brain

The goal of this clinical trial is to learn if tributyrin can help prevent or mitigate cognitive decline in individuals with mild Alzheimer's disease (AD). The trial will also examine the safety and effects of tributyrin on inflammation and gut microbiota. The main questions it aims to answer are: Does tributyrin reduce inflammation and neurodegeneration markers? How does tributyrin affect gut microbiota and intestinal permeability? Researchers will compare tributyrin to a placebo (a look-alike substance that contains no active ingredient) to evaluate its effectiveness. Participants will: Take tributyrin or a placebo every day for 12 weeks. Undergo assessments of cognitive function, blood markers (such as NfL and pTau217), and gut health. The findings are expected to provide insight into the potential of tributyrin as a preventive intervention for Alzheimer's disease.

A Pilot Study to Examine the Effect of Egb761 on Plasma Biomarker Levels and on Cognitive Function in Patients With MCI

The goal of this clinical trial is to learn if the drug Egb761, produced from Ginkgo Biloba extract, works to improve the blood level of a biomarker of Alzheimer's disease, called phosphorylated-tau217 (p-tau217), which serves as a biomarker for disease activity in the brain. The main questions it aims to answer are: Does drug Egb761 lower the plasma level of p-tau217 in patients with mild cognitive impairment? Does drug Egb761 improve cognitive and behavioral functions in these patients? Does Egb761 affect the blood levels of neurofilament-light (Nfl) and glial-fibrillary-acidic-protein (GFAP), which serve as additional biomarkers for brain disease activity? Participants will: Take Egb761 twice daily for 6 months Visit the clinic once every 3 months for checkups and tests Keep a diary of their symptoms

Understanding the Lived Experience and Bereavement of Caregivers of People With Alzheimer's Disease

The main objective of this study is to explore the lived experience of caregivers and family members of people with Alzheimer's disease (AD), from the beginning of caregiving through the bereavement process following the patient's death. Using a mixed-methods design, qualitative data will be collected through in-depth interviews and combined with quantitative data obtained from standardized scales. The results will aim to determine whether prolonged caregiving significantly affects the caregiver's or family member's personal, emotional, and occupational well-being, as well as whether it leads to a reorganization of activities of daily living (ADL), an increased perception of burden, and/or a decreased quality of life. The study will also examine the presence of positive adaptation experiences.

REAl World Dementia OUTcomes: Observational Study

READ-OUT observational study will investigate blood-based biomarkers for dementia in real-world clinical settings. This 3-year observational study will include 3165 people, males or females aged 45 years or older, with cognitive impairment of any severity. Participants provide blood samples and complete questionnaires about quality of life and healthcare use, with some having additional follow-ups at 2 weeks and 1 year. The study will assess reliability and accuracy of blood tests in diagnosing dementia.

DUVAX: A Phase 1 Alzheimer's Vaccine Study Targeting Amyloid-Beta and Tau

This Phase 1 study will test the safety and immune response of the investigational vaccine DUVAX in healthy adults. Participants will be randomly assigned to receive either DUVAX or placebo by intramuscular injection. The study will evaluate how well the vaccine is tolerated and whether it produces antibodies against Alzheimer's disease-related proteins.

Intravenous Infusion of Umbilical Cord Blood as an Adjunctive Treatment for Alzheimer's Disease

This study is a single-center, prospective, double-blind, randomized controlled clinical trial (RCT). Employing a parallel-group design, the trial plans to enroll 30 clinically diagnosed AD patients, who will be randomly assigned via a computerized randomization tool into three equal groups: low-dose, high-dose, and control (10 patients per group). The blinded clinical trial consists of three phases: \*\*Screening Phase\*\*: All enrolled patients must provide fully informed consent and meet inclusion criteria while avoiding exclusion criteria. Baseline assessments will be recorded, and single-cell omics samples will be collected. Patients may voluntarily opt for cerebrospinal fluid (CSF) sampling. The umbilical cord blood (UCB) used clinically is sourced from the Shandong Cord Blood Hematopoietic Stem Cell Bank. Following erythrocyte and granulocyte depletion via lymphocyte separation and density gradient centrifugation, the UCB is purified to reduce immunogenicity and undergoes genetic screening to exclude the APOE4 risk allele. \*\*Treatment Phase\*\*: In addition to standard care, patients will receive intravenous infusions at weekly intervals for four sessions. A fifth infusion will be administered one month after the fourth. The low-dose group receives 1×10⁸ UCB-derived mononuclear cells (UCB-MNCs) per infusion, the high-dose group receives 3×10⁸ UCB-MNCs, and the control group receives an equivalent volume of saline placebo. All clinically administered UCB-MNCs undergo genetic screening to exclude the APOE4 risk allele. \*\*Follow-up Phase\*\*: Assessments will be conducted at 30 days (1 month), 60 days (2 months), 90 days (3 months), and 180 days (6 months) post-initial infusion, including: 1. CDR-SB scale scoring; 2. Total and subdomain scores of the Activities of Daily Living (ADL) scale; 3. Serum inflammatory cytokines (IL-1, IL-2, IL-6, IL-8, IL-10, TNF-α), AD biomarkers (P-tau181, P-tau217), and other relevant markers; 4. Single-cell omics sample collection; 5. Optional CSF sampling per patient preference. After database lock, unblinding will occur for subsequent analysis.

Therapeutic Efficacy of Monoclonal Antibody Drugs for Alzheimer's Disease Based on PET Research

Preliminary clinical trial results indicate that Aβ-targeting monoclonal antibody drugs can delay disease progression more effectively. However, some patients still progress slowly to the moderate stage during treatment despite maintaining low Aβ/tau pathological protein loads. For such cases, patients and their families are fully informed about the potential lack of efficacy with continued treatment, and the decision is left to their discretion. Information regarding whether treatment is continued is documented and followed up to determine whether sustained benefits can be achieved. Previous further studies on lecanemab suggest that patients with low or absent tau pathology derive more significant clinical benefits, though large-sample validation remains lacking. This project will therefore enroll patients at clinical stages 3-4 (0.5 ≤ CDR ≤ 1) and monitor those progressing to moderate AD (CDR = 2) during monoclonal antibody therapy. Using tau pathology stratification, the study aims to identify which AD patients are most suitable for monoclonal antibody treatment and evaluate whether therapy continuation yields sustained benefits in patients progressing to moderate dementia, as well as whether patient selection should integrate both pathological (a-c stage) and clinical diagnoses.

Impact of a Multimodal Lifestyle Intervention on Dementia Risk Factors and Attitude Related to Dementia Risk: A Logistical Pilot Study

Many individuals develop dementia, and dementia has multiple causes, yet we currently have limited treatment options. A critical observation of the effectiveness of the available dementia treatments is that they tend to be more effective when started early. Previous studies have shown that multimodal lifestyle interventions can significantly delay the onset of Alzheimer's dementia in individuals with high risk for Alzheimer's or with Mild Cognitive Impairment (MCI). These interventions may be less effective when initiated after dementia has already been diagnosed or is more advanced. This study has two primary goals. The first goal is to assess attitudes around dementia risk for participants throughout the study as they learn of their personalized risk and possible lifestyle factors that may modify that risk. The second goal is to serve as a logistical pilot for the implementation of data collection and processing and multimodal lifestyle intervention to reduce the risk factors of dementia in individuals without current cognitive impairment but who are at high risk of progression to dementia. Secondary goals of this study include better defining what factors contribute the most risk to dementia and identifying sub-types of dementia defined by different genetic and molecular risk factors.

Improved Treatment and Monitoring of Alzheimer's Disease

In the world's high-income countries, Alzheimer's disease and other dementia diseases are currently the second most common cause of death. This is a recent change, as strokes in the form of blood clots or bleedings in the brain previously were the second most common cause of death. In Denmark 90,000 live with dementia and life expectancy after dementia diagnosis is 5 to 8 years. Of these, 50,000 have Alzheimer's disease. By 2040 due to a steep increase of the elderly population, the number of people with dementia in Denmark is expected to profoundly increase to 120,000-146,000. This is a concerning forecast which calls for action for several reasons. First and foremost, for the sake of the many thousands of persons who will experience dementia. Every three hours, a Dane dies of dementia. There is currently no cure for Alzheimer's disease and there is a need for the development of an effective therapy. The use of cholinesterase inhibitors, such as donepezil, galantamine and rivastigmine, and the NMDA receptor antagonist memantine, may relieve symptoms, but cannot stop disease progression. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are among the promising therapies for repurposing as a treatment for Alzheimer's disease. Dementia rate was significantly lower both in type 2 diabetic patients randomized to GLP-1 RAs versus placebo (hazard ratio: 0.47) and in a nationwide Danish registry-based cohort (HR: 0.89) with yearly increased exposure to GLP-1 RAs in a publication on pooled data from three randomized double-blind placebo-controlled trials (15,820 patients) and the cohort (120,054 patients). It is not known whether treatment with GLP-1 RAs may reduce the incidence of dementia in patients without diabetes. There are ongoing studies of whether the GLP-1 RA semaglutide (Rybelsus®), which has a 94% similarity to the naturally occurring human GLP-1 hormone, has a positive effect on early Alzheimer's disease, namely the EVOKE and EVOKE Plus clinical trials. In this present placebo-controlled clinical trial, the effect of semaglutide (Rybelsus®) on cognitive impairment in Alzheimer's disease will be investigated. The primary hypothesis is that treatment with semaglutide (Rybelsus®) in combination with other treatments will reduce the progression of the cognitive impairment compared to the control group. In comparison with the EVOKE trials focusing on semaglutide as monotherapy, this present trial will investigate the effect of semaglutide both alone and combined with other treatments. The secondary hypothesis is that patients with mild cognitive impairment and Alzheimer's disease have a more frequent incidence of gingivitis and periodontitis, especially with the bacterium Porphyromonas gingivalis producing its toxins in the oral cavity. Recent research has indicated that this bacteria from the mouth and gingiva through the bloodstream can spread to the brain and be a trigger for Alzheimer's disease. Lactobacillus rhamnosus (LGG) has demonstrated to decrease the level of Porphyromonas gingivalis in plaque along with reduction in gingivitis. Further hypotheses tested in this trial * Administration of candesartan to patients with biomarker-confirmed initial-stage Alzheimer's disease will decrease levels of amyloid markers, improve cognitive function, and enhance brain connectivity. * Daily multivitamin-mineral, including vitamin D and calcium supplementation, will improve global cognition, episodic memory, and executive functions in older adults. * Alzheimer's disease is associated with certain abnormalities of vision and of the structure of the visual system, both of which can precede the development of symptoms of cognitive decline. Hard drusen are yellow deposits under the retina typically made up of lipids and proteins, which may predict retinal pathology, were more commonly found in the temporal region of Alzheimer's disease retinas compared to retinas of normal older patients. Retinal nerve fiber layer thickness will be measured, retinal drusen, retinal hyper-reflective foci, and foveal avascular zone area in patients with treated Alzheimer's disease compared to controls. * Gait analysis will be performed and may be particularly sensitive to early symptoms of dementia development. * • Biomarkers (p-beta-amyloid, p-tau217 and p-tau181) in cerebrospinal fluid (CSF) will be measured to support suspected Alzheimer's disease.

Use of a Product Containing the Cannabinoids CBD and THC as a Treatment Strategy for Alzheimer's Disease - Alzheimer's Disease and Cannabis Clinical Trial (DAZACANN) Open-Label Phase

Alzheimer's Disease (AD) has become a significant public health issue due to the increase in its incidence from 2.0 to 16.8 cases per thousand people in a year, based on 2022 data. As many countries experience population aging, there is an increase in the prevalence of AD cases, which is the main form of dementia in the elderly. It commonly begins around the age of 60, with aging being the primary risk factor. AD is a neurodegenerative disorder characterized by the presence of extracellular beta-amyloid plaques and intracellular neurofibrillary tangles of Tau protein. Among the main symptoms of AD is progressive memory loss, with varying degrees of cognitive impairment. These symptoms share common clinical features such as a progressive decline in cognitive functions, including abstract thinking, judgment, language, personality changes, and behavioral symptoms, as well as the emergence of certain comorbidities. As there are currently no curative treatments for this disease, pharmacotherapy aims to control the progressive symptoms, improving cognitive and functional aspects in patients, and consequently their quality of life. In this context, there is a need for further research to identify effective drugs that can delay or alleviate symptoms. This study is part of the second phase of the project entitled: Use of a Product Containing the Cannabinoids CBD and THC as a Treatment Strategy for Alzheimer's Disease - Alzheimer's Disease and Cannabis Clinical Trial (DAZACANN): A randomized, double-blind, placebo-controlled clinical trial previously approved by the Human Ethics Committee - CEP (CAAE 60167722.6.0000.0107). The trial is being finalized at the Laboratory of Medicinal Cannabis and Psychedelic Science, located in the city of Foz do Iguaçu, Paraná, and will continue with a new experimental design, now as an open-label trial (all participants will receive the extract and will be informed about the formulation they are receiving). The objective of this study remains to evaluate the clinical and biochemical effects of using cannabinoid-based products with low doses of purified CBD and THC, both individually and in combination, in patients with AD.

Aβ PET and Tau PET Imaging in the Diagnosis and Progression Assessment of Alzheimer's Disease

This prospective study recruited 20 healthy volunteers and 50 patients diagnosed with Alzheimer's disease (AD) and mild cognitive impairment (MCI) according to clinical guidelines. Participants underwent AV45/AV-1 and AV1451 PET imaging to obtain information on Aβ protein deposition, tau protein distribution, and structural and functional information. The study aims to evaluate the value of multimodal imaging features in the diagnosis and progression assessment of AD, providing imaging evidence for novel treatment modalities such as lecanemab therapy and deep cervical vein-lymphatic anastomosis.

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.

Alzheimer's Disease Treated With Vagus Nerve Stimulation

The goal of this clinical trial is to evaluate the safety and efficacy of vagus nerve stimulation (VNS) for treating Alzheimer's disease (AD) in patients aged 50-80 years with mild cognitive impairment to moderate Alzheimer's disease. The main questions it aims to answer are: Is the change from baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) score at 6 months post-randomization better in the VNS group compared to the sham stimulation group? Is the change from baseline in scores of other cognitive function, neuropsychiatric symptom, or activities of daily living scales at 6 months post-randomization better in the VNS group compared to the sham stimulation group? Researchers will compare the group receiving vagus nerve stimulation (active VNS group) and the group receiving sham vagus nerve stimulation (sham VNS group) to see if VNS is more effective in improving cognitive function, neuropsychiatric symptoms, or activities of daily living. Participants will: Undergo screening assessments (including medical history, physical exams, cognitive and behavioral scale assessments, imaging, etc.). Undergo surgery for VNS device implantation. Be randomized to either the active VNS or sham VNS group and receive the corresponding stimulation treatment for 6 months (while continuing standard AD medication). Attend multiple follow-up visits during the study (baseline, randomization day, 3 months, and 6 months post-randomization) for clinical scale assessments. Potentially provide biological samples (blood, CSF) and undergo additional auxiliary examinations (e.g., MRI, EEG, PET) at specific time points.

Safety, PK and Biodistribution of 18F-OP-801 in Patients With ALS, AD, MS, PD and Healthy Volunteers

This is a Phase 1/2 study to evaluate the safety and tolerability of 18F-OP-801 in subjects with ALS, AD, MS, PD and age-matched HVs. 18F-OP-801 is intended as a biomarker for PET imaging of activated microglia and macrophages in regions of neuroinflammation.