Neuroprotective Agent

Researchers are evaluating the use of [18F]-MFBG PET scans to assess heart nerve activity in people with Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), and Alzheimer's disease (AD). The study compares this method with the current standard [123I]-MIBG SPECT scans, focusing on distinguishing between PD and MSA as well as DLB and AD. This is a prospective study conducted at two centers, aiming to validate the accuracy and feasibility of [18F]-MFBG PET for these neurological conditions. Participants will undergo several imaging tests including dynamic cardiac [18F]-MFBG PET, [123I]-MIBG SPECT, and cerebral [18F]-PE2I PET scans. Healthy volunteers and patients with confirmed diagnoses will be included, with groups divided by age and disease duration. A dosimetry study will also be conducted for healthy volunteers to measure radiation exposure from [18F]-MFBG. Multiple visits to the hospital are required for scans and assessments. During the study, participants will have thorough neurological assessments, brain MRI scans, and blood sampling alongside PET and SPECT imaging. Researchers will evaluate diagnostic accuracy, effect size of tracer uptake changes, and relationships between heart nerve imaging and brain dopamine transporter changes and autonomic dysfunction. The study includes monitoring for safety and will analyze regional heart uptake patterns. Participants can expect 3 to 4 hospital visits with detailed imaging and clinical evaluations over the study period.

Researchers are evaluating the use of PET imaging with the radioligand [18F]PI-2620 to detect tau protein deposits in people with Alzheimer's disease and healthy controls. This open-label, multi-center, non-randomized Phase 3 study aims to compare PET imaging results during life with brain tissue analysis after death to better understand tau pathology in Alzheimer's. The study is sponsored by Lantheus Biosciences Ltd. and focuses on diagnostic accuracy and safety of this imaging technique. Participants receive an intravenous injection of [18F]PI-2620 at a dose of 185 MBq ± 20%. The study involves a PET scan procedure that participants must tolerate, including lying still in the scanner. There are no randomized groups or placebo controls as this is an open-label study. The research compares the PET imaging findings with post-mortem brain autopsy results to evaluate the ability of this imaging to detect tau deposits accurately. During the study, participants undergo PET imaging and are monitored for their ability to tolerate the scan. Brain donation consent is required for post-mortem histopathological comparison. Researchers assess the diagnostic performance of the PET scan in correctly identifying tau-related pathology and Alzheimer's disease changes. The primary outcome focuses on the accuracy of visual assessment of PET images compared to autopsy findings, with follow-up continuing until study completion and an average of one year after death.

Researchers are evaluating the Green Activity Program designed for people living with memory challenges, such as mild cognitive impairment, Alzheimer's disease, and subjective cognitive decline. This program focuses on "green activities," which are nature-based activities like dog walking, hiking, outdoor yoga, and gardening that participants enjoy and can do with others or pets. The study aims to see if the program is doable and enjoyable, helping participants stay active and improve their health and well-being. The study is a single arm pre/post feasibility trial lasting up to 1 year, involving 40 pairs of participants and their study partners (80 people total). The Green Activity Program includes a 12-week intervention with 4-8 virtual or phone coaching sessions focused on evaluation, goal-setting, strategy training, and outdoor activity planning. Outdoor activity professionals also participate, receiving training and conducting site evaluations. Feedback is collected through surveys, phone interviews, and informal conversations to refine the program. Participants and their partners will complete assessments before, during, and after the 12-week program, including physical activity tracking, heart rate monitoring, cognitive function tests, and questionnaires on health, well-being, social participation, depression, and sleep. Follow-up interviews occur up to one month post-intervention to evaluate sustained behavior change and program acceptability. The total participation time can last up to one year, with detailed monitoring and evaluation throughout.

Researchers are evaluating the safety of LY3954068 in people with early symptomatic Alzheimer's Disease. This study also examines how much of the drug enters the bloodstream and its effects on Alzheimer's markers. It is a Phase 1 trial sponsored by Eli Lilly and Company focused on participants aged 50 to 85 years with early signs of the disease. The study includes two parts: Part A and Part B. In Part A, each participant receives a single dose of LY3954068 or placebo injected into the spinal fluid. In Part B, participants receive two doses of either LY3954068 or placebo administered the same way. There is an optional bridging period after Part B where participants may receive LY3954068 in a separate study. Part A lasts about 45 weeks including screening, and Part B lasts about 100 weeks including screening. Participants will undergo regular assessments such as safety monitoring for adverse events related to the study drug, blood and spinal fluid sampling to measure drug levels and effects on tau proteins, and imaging with Flortaucipir F18 PET scans for tau pathology. Cognitive tests like the Mini Mental State Examination and Clinical Dementia Rating will be used. Safety and drug effects will be followed up to 24 weeks in Part A and up to 52 weeks in Part B, with additional monitoring during the bridging period if chosen.

Researchers are investigating the relationship between gut microbiota dysfunction and Alzheimer's disease (AD), focusing on how gut-derived short-chain fatty acids (SCFAs) may influence brain function through the "gut microbiota-SCFAs-brain networks" pathway. This observational study will explore differences in SCFAs among people across the AD spectrum, including cognitively normal individuals, those with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD dementia. The project aims to clarify the interactions between gut microbiome, metabolites, and brain changes using high-throughput metabolomics and multi-modal MRI techniques. Participants will be grouped into four categories: cognitively normal, SCD, MCI, and AD dementia. The study involves collecting multi-omics data, including gut microbiome analysis, metabolomics, and neuroimaging, to establish a diagnostic model for SCD due to preclinical AD using machine learning methods. The study spans five years, during which gut microbiome changes, SCFAs levels, and multi-omics biomarkers related to cognitive impairment conversion will be monitored. Participants will undergo cognitive tests and brain imaging scans, along with gut microbiome and metabolite sample collection. Researchers will assess the interaction mechanisms of the gut microbiota-SCFAs-brain networks over five years. The study includes both healthy volunteers and patients aged 60 to 80. Outcome measures focus on changes in gut microbiome, SCFAs, and biomarkers linked to cognitive decline, with long-term follow-up to better understand the disease progression and its early detection.

Researchers are investigating the effects of a multidomain lifestyle intervention to slow cognitive decline and dementia risk in elderly residents aged 60 to 80 in Zhejiang Province, China. The study builds on findings from Finland, where a similar approach combining physical activity, nutrition, cognitive training, social activities, and vascular risk management showed promise in healthy older adults at risk of cognitive decline. This trial aims to explore how such an intervention may change brain structure and function as well as cognitive abilities in an Asian population. Participants are randomly assigned to either a structured multidomain intervention group or a self-guided control group. The intervention group receives tailored nutritional guidance, cognitive training, physical exercises, and vascular risk monitoring, all adapted to Chinese cultural norms. The control group receives regular health education campaigns and basic health monitoring every 6 to 12 months. This trial runs for two years with ongoing assessments to evaluate the impact of these lifestyle changes. During the study, participants undergo various evaluations including cognitive tests measuring global and domain-specific cognition, neuroimaging scans like MRI and fMRI, laboratory blood tests, and physical performance measures such as grip strength and gait speed. Questionnaires assess quality of life, depression, sleep quality, and daily activities. Researchers also monitor cardiovascular health, dementia onset, and falls. This comprehensive monitoring will help determine the intervention's effects on brain health and daily functioning over the 24-month period.

Researchers are evaluating whether a combined approach using multifocal non-invasive brain stimulation and brain recording with cognitive training can help reduce cognitive and emotional symptoms in people with mild cognitive impairment and early dementia. The study aims to understand if this treatment affects cognition and depression symptoms, and how factors like education and cognitive reserve influence outcomes. It also investigates brain activity measures to identify who responds best to the treatment. Participants will receive two treatment cycles involving either real or placebo multifocal transcranial direct current stimulation (tDCS) over the left frontal and temporal brain areas, twice a week for two months each cycle. Along with the brain stimulation, all participants will undergo cognitive training involving exercises targeting memory, attention, and executive functions. The study uses a crossover design where each participant experiences both real and placebo stimulation cycles. During the trial, participants will complete detailed cognitive and mood assessments before treatment and after each cycle, including tests like the Montreal Cognitive Assessment and Geriatric Depression Scale. EEG brain recordings will monitor brain activity at specific sessions. Caregivers will provide information on daily living activities. The study measures changes in cognition, mood, and functional independence over an 8-week intervention period with regular evaluations.

Researchers are evaluating the safety and effectiveness of rotigotine combined with rivastigmine in people with mild to moderate Alzheimer's disease. This phase III, 24-week study compares this combination to rivastigmine with a placebo patch. The study design is randomized and double-blind to reduce bias and improve reliability of results. Participants will receive either a rotigotine 4 mg/24 hours transdermal patch or a placebo patch, alongside rivastigmine, for 24 weeks. The study includes baseline assessments followed by treatment visits at Weeks 6, 12, and 24. EEG exams and plasma biomarker collections happen at the start and end of the study. Caregivers will also be contacted by phone between visits and additional visits may occur if safety concerns arise. During the study, participants will have physical and neurological exams, vital signs measured, and adverse events recorded at screening and each visit. Cognitive and behavioral assessments will measure changes in frontal lobe function, daily living activities, cognition, memory, and apathy. The total participation time is 24 weeks, with close monitoring to ensure safety and collect comprehensive data on treatment effects.

Researchers are evaluating the safety and effectiveness of KarXT combined with KarX-EC in adults aged 55 to 90 who experience agitation linked to Alzheimer's Disease. This phase 3 trial aims to understand how these treatments impact agitation symptoms in this population. The study is sponsored by Bristol-Myers Squibb and uses rigorous methods to compare the investigational drugs against a placebo. Participants will receive either the combination of Xanomeline/Trospium Chloride capsules (KarXT + KarX-EC) or a placebo, with doses given on specified days. The study is randomized, double-blind, and placebo-controlled, ensuring objective assessment of treatment effects over a 14-week period. The trial includes a parallel group design where participants are assigned to either the experimental treatment group or placebo group. During the study, participants will be assessed for changes in agitation using the Cohen-Mansfield Agitation Inventory and other related scales at week 14. Researchers will monitor safety through adverse event reports, clinical labs, vital signs, ECGs, and specific rating scales up to week 18. Caregivers will assist by attending visits and reporting on participant status. Total participation involves regular visits and assessments over the course of the trial.

Researchers are evaluating the safety and effectiveness of a combination treatment called KarXT and KarX-EC for adults aged 55 to 90 who have agitation linked to Alzheimer's Disease. This Phase 3 study aims to understand how this treatment may help manage agitation symptoms in this population, with careful monitoring of side effects and overall safety. Participants will receive either the KarXT plus KarX-EC treatment or a placebo, with doses given on specified days as capsules. The study is randomized and double-blind, meaning neither participants nor researchers know who receives the active treatment or placebo. The treatment period lasts 14 weeks, during which participants are closely observed. During the study, participants will undergo various assessments including the Cohen-Mansfield Agitation Inventory-International Psychogeriatric Association (CMAI-IPA) score to measure agitation changes at week 14. Additional evaluations include clinical global impressions, neuropsychiatric inventories, safety monitoring through lab tests, vital signs, body measurements, and assessment of side effects up to week 18. Caregivers will also report on participants' status, and safety will be closely followed throughout the trial.