Neuroprotective Agent

Researchers are evaluating the use of 18F-MFBG PET scans to assess heart nerve activity in people with Parkinsons disease PD, multiple system atrophy MSA, dementia with Lewy bodies DLB, and Alzheimers 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 18FPI-2620 to detect tau protein deposits in people with Alzheimers 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 Alzheimers. 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 18FPI-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 Alzheimers 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 and their study partners. The program includes outdoor nature activities such as dog walking, hiking, yoga, and gardening, aiming to help participants stay active and improve their health and well-being. This feasibility study focuses on whether participants can complete and enjoy the program, supporting their participation in nature activities. The study involves a single group of 40 pairs dyads consisting of individuals with memory challenges and their study partners. Over 12 weeks, participants engage in 4 to 8 virtual or phone sessions lasting 30 to 90 minutes each, plus 2 additional check-ins of 15 to 30 minutes. Outdoor activity professionals also participate by evaluating sites for safety and accessibility, receiving dementia training, and learning strategies to tailor activities and provide behavioral support. Participants complete evaluations before and after the 12-week program, including surveys, brief phone interviews, and physical activity and health assessments. Researchers measure feasibility, acceptability, behavior change, physical activity, well-being, social participation, depression, cognitive function, and other health-related outcomes. Feedback from study partners and outdoor professionals is also collected. The total study duration for participants may last up to one year to include all evaluations and follow-ups.

Researchers are evaluating the safety of LY3954068 in people with early symptomatic Alzheimers Disease. This study also examines how much of the drug enters the bloodstream and its effects on Alzheimers 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 Alzheimers 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 interventions 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 Alzheimers 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 mg24 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 have agitation related to Alzheimers Disease. This Phase 3, randomized, double-blind, placebo-controlled study aims to address agitation symptoms in this population by comparing the investigational drugs with a placebo. The study is sponsored by Bristol-Myers Squibb and uses established diagnostic criteria for Alzheimers Disease. Participants will receive either the combination of XanomelineTrospium Chloride capsules KarXT KarX-EC or a placebo with specified doses on designated days. The study includes a parallel group design and treatment lasts for 14 weeks. The main focus is to assess changes in agitation using the Cohen-Mansfield Agitation Inventory-International Psychogeriatric Association CMAI-IPA total score. During the study, participants will undergo regular assessments including cognitive and behavioral evaluations, safety monitoring through vital signs, laboratory tests, electrocardiograms, and rating scales for movement disorders and suicidal ideation. Caregivers will be involved to help monitor participant status and medication compliance. The primary outcome is measured at Week 14, with safety follow-up extending to Week 18. Participants are expected to be engaged throughout the treatment period and follow-up assessments.

Researchers are evaluating the long-term effectiveness of donanemab combined with usual care compared to usual care alone in people with early symptomatic Alzheimers disease. This observational study is designed to reflect real-world medical practice by using ongoing assessments and linking to past and future electronic health records. The study will last about 273 weeks and may involve up to 28 visits. Participants will either receive open-label donanemab administered intravenously along with usual care, or they will receive usual care alone, which may include medications excluding amyloid-targeting agents or non-drug therapies like watchful waiting. The study groups are observed prospectively without blinding. During the study, participants will be monitored regularly through various assessments including the Dependence Scale, Functional Assessment Questionnaire, and Neuropsychiatric Inventory, among others, up to five years. Researchers will track changes in cognition, independence, living situation, and caregiver burden. Electronic health records will be accessed throughout, and safety and outcome data will be collected over the long term.