The goal of this clinical trial is to learn if stem cell therapy works to treat brain inflammation in adults. Inflammation in the brain may be involved in adults who have memory or thinking problems. The stem cells will be taken from participant's fat samples, processed and given back to participants, so they are their own donor. The main questions this trial aims to answer are:
* Does stem cell therapy reduce inflammation in the brain?
* Does stem cell therapy improve brain activity?
* Does stem cell therapy slow down progression to Alzheimer's disease?
Participants will:
* Have a small fat biopsy taken at a doctor's office to process stem cells
* Receive 4 infusions of stem cells, through a vein in the arm over 12 weeks
* Visit the clinic every 2-4 weeks for the first 4 months and then every 1-2 months for 8 months for checkups and tests
Cognitive Dysfunction· Paul E Schulz· Houston, Texas· Ages 60–80
The purpose of this study is to assess the efficacy and safety of trontinemab in participants with early symptomatic Alzheimer's disease (AD) (mild cognitive impairment \[MCI\] to mild dementia due to AD).
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.
Alzheimer Dementia (AD)· The Methodist Hospital Research Institute· Houston, Texas· Ages 50–86
The main purpose of this study is to determine if participants who previously took donanemab get clinical benefit when they receive annual doses. For each participant, the study will last up to 2.5 years and will include 6 visits.
Alzheimer Disease· Eli Lilly and Company· Phoenix, Arizona · Huntington Beach, California +3 more
Researchers want to know if the study treatment called MK-2214 works to slow certain changes in the brains of people with Alzheimer's disease (AD). AD is a type of dementia that can cause loss of memory, communication (such as speech), and decision-making skills. It can limit a person's ability to do daily tasks. MK-2214 is a study treatment designed to slow down AD.
The goals of the study are to learn:
* If MK-2214 slows the spread of tau in the brain compared to placebo. Tau is a protein that accumulates in AD \& damages brain cells. A placebo looks like the study treatment but has no study treatment in it. Using a placebo helps researchers better understand the effects of a study treatment.
* About the safety of MK-2214 and if people tolerate it
Early Alzheimer's Disease· Merck Sharp & Dohme LLC· Irvine, California · Long Beach, California +3 more· Ages 50–85
The purpose of this study is to evaluate the long-term efficacy and safety of combined formulation of xanomeline tartrate/trospium chloride in an immediate release (IR) capsule (KarXT) and xanomeline enteric capsules (KarX-EC) in participants with agitation associated with Alzheimer's Disease who completed the parent studies CN012-0023 or CN012-0024.
This is a study to evaluate the efficacy, safety, and tolerability of BMS-986368, a FAAH/MAGL inhibitor, for the treatment of agitation in participants with Alzheimer's Disease.
Alzheimer's disease (AD) is characterized by the accumulation of tau pathology, and blood-based biomarkers such as phosphorylated tau-217 (pTau217) have been identified as sensitive and specific predictors of AD risk. Recent studies suggest that individuals with elevated pTau217 levels may be at increased risk for developing AD and cognitive dysfunction. This observational study will examine donated human plasma samples to determine whether some units of donated blood contain abnormally elevated pTau217 concentrations. The overarching goal is to evaluate whether transfusion of blood with higher pTau217 may pose risks to recipients and whether such units should be avoided in clinical use.
Alzheimer&Amp;#39;s Disease· The University of Texas Health Science Center, Houston· Houston, Texas
Inflammation occurs in many brain diseases including Alzheimer's disease. In Alzheimer's disease, an abnormal protein called amyloid starts accumulating decades before the start of forgetfulness. However, scientists have reported that inflammation but not amyloid is linked to forgetfulness and the topography of brain inflammation and tau buildup are closely correlated in patients with mild cognitive impairment due to Alzheimer's disease. New medications are under development to help healing and prevent permanent damage in the brain. To see if inflammation is improving or getting worse with these medications, investigators can watch inside of the brain using a special camera called positron emission tomography (PET). It is currently possible to watch inflammation in the brain by taking pictures of a molecule called translocator protein (TSPO). But the problem is that by imaging TSPO, investigators can catch changes in more than one kind of cells. The information is not specific to each cell type. Such vague information is not completely useful to monitor the effect of new medications for inflammation. This proposal attempts to develop a novel method to capture changes in each of two major players in inflammation, microglia and astrocytes. To do so, investigators will take selective pictures of one cell type by using a novel imaging agent for PET. Investigators will also take PET pictures of TSPO. Investigators will process these two kinds of PET pictures using advanced mathematical methods and extract specific information on microglia and astrocytes. Our novel method will be useful to monitor new therapies to treat inflammation in the brain.
Alzheimer Disease· The Methodist Hospital Research Institute· Houston, Texas· Ages 18–90
The purpose of this study is to assess the efficacy and safety of trontinemab in participants with early symptomatic Alzheimer's disease (AD) (mild cognitive impairment \[MCI\] to mild dementia due to AD).
The goal of this clinical trial is to learn if repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, can improve short-term memory in people with early Alzheimer's disease (AD). The study will also evaluate the safety of this approach.
The main questions it aims to answer are:
* Does rTMS applied to the cerebellum improve short-term memory in people with early AD?
* How does this stimulation affect brain activity and connectivity measured by MRI?
Researchers will compare active rTMS to sham rTMS (a look-alike procedure that does not deliver brain stimulation) to see if rTMS works to improve memory.
Participants will:
* Complete a screening visit with medical and memory assessments
* Be randomly assigned to receive either active rTMS or sham rTMS (neither participants nor researchers will know the assignment during treatment)
* Receive 20 rTMS sessions over 4 weeks (about 20 to 30 minutes per session)
* Undergo two MRI scans, one before and one after treatment
* Complete memory and thinking tests and questionnaires at baseline, immediately after treatment, and at 3- and 6-month follow-up visits
Participation in the study will last about 6 months.
The rTMS is generally well tolerated. The most common side effects include mild headache and scalp discomfort during treatment, which are usually short-lasting. MRI is non-invasive and safe for most people. Study procedures will be reviewed to ensure participant safety.
Participants may or may not benefit directly from this study. People who receive active rTMS may experience improvement in memory. This research may help improve understanding of memory function in AD and support development of new treatments.
Alzheimer s Disease· Chi-Ying (Roy) Lin· Houston, Texas· Ages 55–90
Study AACU determines rates of cognitive worsening in participants within elevated and not elevated plasma P-tau217 cohorts.
Participation in AACU will last approximately 7 years.
Alzheimer Disease· Eli Lilly and Company· Houston, Texas· Ages 55–75
The purpose of this study is to evaluate the efficacy and safety of KarXT + KarX-EC in adult participants with agitation related to Alzheimer's Disease.
Alzheimer's Disease· Bristol-Myers Squibb· Chandler, Arizona · West Hills, California +3 more· Ages 55–90
The goal of this pilot study is to test a combination of two non-invasive brain stimulation methods, called iTBS (intermittent theta burst stimulation) and tDCS (transcranial direct current stimulation), in people with Alzheimer's Disease (AD) and related dementias (ADRD). This study will also explore whether the combined treatment shows promise for reducing neuropsychiatric symptoms like mood swings, apathy, and agitation, and will evaluate the impact of the treatment on caregivers.
The main questions the study aims to answer are:
1. Is the combined brain stimulation treatment practical and well-tolerated?
2. Do preliminary results suggest that this treatment could help manage neuropsychiatric symptoms and support a larger study?
Participants will:
* Attend nine in-person visits over three months.
* Complete one week of in-clinic brain stimulation sessions (iTBS) followed by four weeks of daily at-home brain stimulation sessions (tDCS).
* Take part in brain scans, questionnaires, and brain activity tests before and after the treatment.
This pilot study is a first step to assess whether this combined treatment approach is practical and whether it has potential to improve symptoms, laying the groundwork for larger studies in the future.
Alzheimer&Amp;#39;s Disease-related Dementia· Baylor College of Medicine· Houston, Texas· Ages 65–85
The purpose of this study is to evaluate the safety and efficacy of KarXT in adult participants with mild to severe Alzheimer's Disease (AD) with moderate to severe psychosis related to AD.
The purpose of this study is to evaluate the efficacy and safety of KarXT + KarX-EC in adult participants with agitation related to Alzheimer's Disease.
The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY4006895. Part A will administer a single-ascending dose in healthy participants or Part B will administer multiple-ascending doses in participants with early symptomatic Alzheimer's Disease (AD).
Blood tests will be performed to check how much LY4006895 gets into the bloodstream and how long it takes the body to eliminate it.
This is a 2-part study and will last approximately 29 weeks for Part A and 61 weeks for Part B, including a screening period for each part.
Alzheimer Disease· Eli Lilly and Company· Los Alamitos, California · Lady Lake, Florida +3 more· Ages 45–85