Clinical Research Directory

PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)

Background: About 5 million adults in the United States have age-related brain disorders. These include Alzheimer disease (AD), mild cognitive impairment (MCI), and other dementias. The number of people with these disorders will likely increase as the population ages and life span increases. Inflammation is thought to play a role in AD and MCI. Researchers want to know if an enzyme called PDE4B increases inflammation in people with AD or MCI. Objective: To test whether medical imaging using a new radiotracer (\[18F\]PF-06445974) can measure PDE4B in the brains of people with AD or MCI. Eligibility: People aged 50 years and older with AD or MCI. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits with 3 imaging scans of the brain. They will have be screened. They will have a physical exam with blood tests. This will include tests of their heart and nerve function, including memory. Participants will have 2 positron emission tomography (PET) scans. One will use a standard radiotracer. The other will use the study radiotracer. They will receive each tracer through a tube attached to a needle inserted into a vein. During the scan with the study tracer, participants will have a second tube inserted into a vein in the wrist; this tube will be used to draw blood during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. These visits will take about 6 hours each. Participants will have 1 magnetic resonance imaging (MRI) scan. They will lie on a bed that slides into a cylinder. This visit will take up to 2 hours....

Superior Parietal iTBS for PD-MCI

The goal of this study is to determine the whether a short-term, high-dose form of non-invasive brain stimulation (intermittent theta burst stimulation; iTBS) is a promising and safe treatment for mild cognitive impairment in Parkinson's disease (PD-MCI).

Study on Ginkgo Biolba Extract Fifty and Mild Cognitive Impairment Associated With CSVD

This study aimed to explore the efficacy and safety of Ginkgo Biolba Extract fifty in treating mild cognitive impairment associated with cerebral small vessel disease (CSVD). Subjects included based on eligibility criteria were randomized into treatment and control groups. Patients will receive the drug or placebo for 12 months. Patients were followed at baseline and at 3 months, 6 months, and 12 months after randomization. The primary outcome was the difference from baseline in the Montreal Cognitive Assessmen (MoCA) score at 12 months after randomization.

MCI Speech in Noise

The purpose of this study is to determine whether people with MCI (Mild Cognitive Impairment) and healthy comparison subjects differ with respect to their ability to hear soft sounds and how their brain understands and processes sound. The investigators are also evaluating, within those with MCI, whether the hearing tests are associated with neurocognitive functioning. The investigators are interested in learning whether changes in cognition in those with MCI can be detected using tests of how the brain processes sound. The investigators hypothesize that participants with MCI will score worse on both hearing tests and neurocognitive tests than participants without MCI. Participants are asked to complete multiple types of hearing tests, take a series of neurocognitive tests, and complete a few questionnaires.

The Effect of Combination of Mediterranean Diet and Oleocanthal in Patients With Mild Cognitive Impairment

BACKGROUND: Mild cognitive impairment (MCI) constitutes a form of preclinical dementia and characterizes a cognitive decline that exceeds what is expected for one's age and education status, but at the same time does not fulfill the criteria for dementia. MCI is considered a prodromal stage of Alzheimer's disease (AD) and the progression to this neurodegenerative disease, renders the patients heavily dependent on their relatives and the society, which creates a huge psychological and financial burden, since no effective treatment exists for MCI and AD to this day. Mediterranean diet (MeDi) displays beneficial effects on the cognitive function of both healthy individuals and cognitive impaired patients. High Phenolic Early Harvest Extra Virgin Olive Oil (HP-EH-EVOO) is a natural product that contains high concentrations of the substance Oleocanthal (OLC), while at the same time it has been shown to exert beneficial properties on the cognitive function of cognitive impaired individuals, as well as on the slowing down of the decline of cognitive function. AIM: The main hypothesis that will be evaluated is whether the combined approach of the MeDi pattern and the concurrent intervention with the administration in a capsule form of the supplement containing olive oil polyphenols with the main substance being Oleocanthal (SUPOL), could constitute a considerable strategy of management of MCI patients. Study Type: Investigational Study Design, Allocantion: Randomized Intervention Model, Parallel Assignment Masking: Double Blind (Subject, Outcome Assessor - Investigator) on Supplement, Primary Purpose: Prevention.

Wake Forest Alzheimer's Disease Clinical Core

Efforts to find treatments for AD have yielded only modest benefits, likely because longstanding AD pathological processes induce irreversible neurological compromise. These processes begin years before the onset of clinical symptoms. This possibility has been incorporated into a model describing stages of AD development, articulated by the NIA/Alzheimer's Association preclinical workgroup of which the Co-Director of the Kulynych Alzheimer's Research Center, Dr. Suzanne Craft, was a member. According to this model, the best hope for countermanding the effects of AD lies in intervening at the earliest possible point in the pathological cascade. There are several important ongoing efforts in adults with preclinical AD that directly target amyloid aggregation. Although this strategy addresses an important aspect of the AD pathological cascade, we believe that addressing metabolic dysfunction affecting glucose and insulin regulation offers a complementary approach, in that it may reduce amyloid burden and toxicity, while also directly enhancing synaptic health, brain metabolism, tau regulation and neurovascular function. The purpose of the ADCC is to identify and characterize early risk factors that predict cognitive decline and dementia in asymptomatic adults and adults with early signs of cognitive impairment. The data obtained from this study, collected at enrollment and follow-up will allow us to examine disease trajectory in individuals with and without prediabetes and other measures of glucoregulatory dysfunction in this process. The enrollees, who will be well-characterized with regard to cognitive and metabolic status through ADCC assessments, will provide an important resource for other local (institution) and national investigations. Data collected from participants enrolled in the ADCC will be stored indefinitely for future investigations.

A Scalable Nutrition Adherence Intervention

Objective 1: To scale-up the nutrition adherence intervention for testing in racially diverse rural communities in North Florida. The investigators hypothesize that: 1\. The protocol will produce at least 75% of participants obtaining measurable levels of urine ketones (e.g., good adherence) in the Modified Mediterranean-Ketogenic diet (MMKD) group and an average score of \>6 on the MEDAS questionnaire in the Mediterranean group during the 10-week program. Further, we hypothesize that the use of ongoing monthly support groups will bolster long-term adherence. Objective 2: To evaluate the effects of adherence to Mediterranean versus MMKD on novel gut-brain axis markers of Alzheimer's disease pathogenesis in individuals with mild cognitive impairment compared to cognitively normal older adults. The investigators hypothesize that individuals with mild cognitive impairment will: 1. Have greater evidence of gut dysbiosis at baseline than cognitively normal controls and 2. Will demonstrate greater increases in beneficial gut microbial metabolites in response to adherence to Mediterranean-Ketogenic nutrition and the Mediterranean diet compared to CN controls.

Impact of Intensive Computerized Cognitive Training

To investigate factors that predict cognitive enhancement following engagement in an intensive Computerized Cognitive Training Protocol.

A Novel Multi-Modal Approach to Promote Functional Outcomes in Cognitively Frail Older Adults

The goal of this clinical trial is to explore the effects of intermittent theta burst stimulation (iTBS) primed with theta burst stimulation (cTBS), on top of aerobic exercise, on cognitive function, mobility, and brain activity in older adults with cognitive frailty. Understanding these effects will help us develop intervention models that benefit cognitively frail older adults. The main questions it aims to answer are: 1. Does the combination of iTBS primed with cTBS and aerobic exercise lead to greater improvements in cognition and mobility in older adults with cognitive frailty compared to non-priming iTBS and sham stimulation? 2. What are the neural mechanisms responsible for the improvements in cognition and mobility associated with the combination of iTBS primed with cTBS and aerobic exercise in older adults with cognitive frailty?

Choose Myself (Before) Losing Myself

The purpose of this study is to see if an educational interactive booklet about how dementia progresses throughout a person's life can be a helpful tool for patients to think about future decisions that might need to be made regarding their medical care and helping patients discuss their diagnosis and possible future medical decisions with their family or future caregivers.

Alzheimer's Disease Neuroimaging Initiative 4

The Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4) is a non-randomized, longitudinal, natural history study designed to validate biomarkers, improve clinical trial design, and advance understanding of Alzheimer's disease across the full disease spectrum. Building on the success of ADNI1, ADNI-GO, ADNI2, and ADNI3, ADNI4 integrates clinical, cognitive, imaging, genetic, and fluid biomarker data to characterize disease progression and predict cognitive decline. ADNI4 includes both in-clinic and remote cohorts and a small complementary sub-cohort, Together Exploring Aging Minds (TEAM-ADNI), which evaluates community-based recruitment and longitudinal data collection approaches.

Disease Modifying Potential of 5mg of Melatonin on Cognition and Brain Health in Aging

The study will examine whether 5mg melatonin (over the counter, OTC) over a 9-month period improves Alzheimer's disease (AD) biomarkers and cognitive function in two groups of individuals: those with mild cognitive impairment (MCI+) and those who are not (MCI-). AD biomarkers will be measured from cerebrospinal fluid (CSF) obtained from lumbar punctures. Cognitive function will be evaluated with routine neuropsychological tests. AS OF AUGUST 2024, THE LUMBAR PUNCTURE PROCEDURES FOR THIS CLINICAL TRIAL HAVE BEEN ELIMINATED. THAT IS, PARTICIPANTS ARE NO LONGER RECEIVING A LUMBER PUNCTURE. BUT ARE CONTINUING TO RECEIVE TWO SEPARATE BLOOD DRAWS FOR BIOMARKER TESTING.

Jigsawdio Multisensory Platform for People With Mild Cognitive Impairment, Alzheimer's Disease, or Related Dementias

This study will evaluate Jigsawdio, a personalized multisensory jigsaw puzzle platform, for adults aged 60 years and older with mild cognitive impairment or mild dementia. Approximately 80 participants will be randomly assigned to either the Jigsawdio group or a control group using standard dementia-friendly jigsaw puzzles. Both groups will complete two 30- to 40-minute puzzle sessions per week for six weeks, for a total of 12 sessions. Jigsawdio combines transparent physical puzzle pieces with personalized images, stories, and audio presented through an iPad. The study will compare changes in depression, anxiety, quality of life, cognition, engagement, satisfaction, and program feasibility. Assessments will be completed at baseline, after the six-week program, and at a 12-week follow-up. Information may also be collected from participants' caregivers or informants.

Memory Support System Feasibility Study

The purpose of this study is to determining the feasibility of providing the Memory Support System (MSS) to individuals with mild cognitive impairment (MCI) and their partners at a clinic in Ontario, Canada. This will involve a) collecting information from patients referred to the a memory clinic and geriatric day hospital about the patient's interest in and the patient's preferred method to administer the MSS; and b) a cost analysis related to implementation of the MSS. The study will also measure efficacy outcomes of the MSS regarding program adherence as well as to self-reported IADLs, self-efficacy for memory, quality of life, mood, anxiety, and caregiver burden among a sample of individuals with MCI and their care partners

2-Hydroxybenzylamine (2-HOBA) Study in Early Alzheimer's Patients

Investigators propose a phase 1b/2a, randomized, double-blind, placebo-controlled, parallel group dose finding and biomarker study to evaluate the safety, tolerability, and biomarker activity of 2-HOBA in 48 MCI/AD participants. Participants will be randomized 1:1:1:1 to receive 250 mg BID, 250 and 500 mg 2-HOBA acetate TID or placebo for 12 weeks. Blood and cerebral spinal fluid (CSF) will be collected to measure markers of protein modification by dicarbonyls (IsoLGs- \& MDA), pTau-181, YKL-40, and NF-L.

Virtual Outreach and Individualized Coaching Extension

This study tests whether a nurse-led program that uses a voice-controlled smart speaker in the home helps older adults better manage their chronic health conditions. It also examines which nursing staff and clinic resources would be needed to offer such a program in regular outpatient care.

The LUCINDA Trial: LeUprolide Plus Cholinesterase Inhibition to Reduce Neurological Decline in Alzheimer's

The LUCINDA Trial is a three-site, phase II, randomized, double-blind, placebo-controlled study of leuprolide acetate (Eligard) in women with Mild Cognitive Impairment or Alzheimer's Disease taking a stable dose of a cholinesterase inhibitor medication like donepezil. Its objective is to assess the efficacy of a 48-week regimen of leuprolide (22.5 mg per 12 weeks) compared to placebo on cognitive function, global function and plasma and neuroimaging biomarkers.

Music for Pain and Dementia

This study aims to provide mechanistic insights into how group drumming as a music-based intervention (MBI) affects pain responses and nociceptive function in individuals with Alzheimer's Disease (AD), mild dementia or mild cognitive impairment (MCI). Heart rate (HR), heart rate variability (HRV), and brain activity will be measured during communal drumming with their dyadic partners and others. Brain activity, blood pressure, cognitive abilities, blood hormone levels, and static and dynamic pain will also be measured during sessions pre and post the 8-week community drum circle. Investigators will leverage various measurement techniques including, but not limited to, electroencephalography (EEG), quantitative sensory testing (QST), behavioral, surveys, and physiological monitoring to study the impact of group drumming on pain and brain activity in AD and inter-dyad synchrony.

Microbiome in Aging of Gut and Brain

The Microbiome in Aging Gut and Brain (MiaGB) Study is an observational study designed to examine whether differences in the microorganisms living in the gut and mouth are associated with cognitive health and cognitive decline. The study includes young healthy adults, cognitively healthy older adults, older adults with mild cognitive impairment (MCI), and older adults with Alzheimer's disease or related dementia. At the baseline visit, participants complete assessments of medical history, cognitive function, physical function, and diet and provide biological samples that may include stool, saliva, oral swabs, blood, and urine. Researchers will study the gut and oral microbiome and related biological factors, including metabolites and markers of intestinal permeability and inflammation, to determine whether these measures differ according to cognitive status. Young healthy adults, cognitively healthy older adults, and participants with MCI will be followed annually for up to 5 years to evaluate changes in the microbiome and cognitive function over time. Participants with Alzheimer's disease or related dementia will participate in the baseline assessment only. No drug, treatment, or other research intervention is assigned as part of this study.

SYNERGIC-2 Trial (SYNchronizing, Exercises and Remedies to GaIn Cognition@Home)

In Canada, 1,700,000 adults are at risk of dementia, half of them with MCI,representing one of the largest groups at risk for an incurable disease. Epidemiological evidence suggests up to 40% of dementia cases might be preventable by targeting modifiable lifestyle and cardiovascular factors. Given that current treatments cannot modify the disease, prevention is critical. SYNERGIC-2 offers a "personalized multidomain intervention" that combines physical and cognitive training, sleep, diet, and vascular-metabolic interventions in individuals with MCI to synergistically enhance their overall brain health including cognition and contributes to maintaining their independence. Importantly, interventions will be provided at home using an existing virtual platform reducing delivery complexity and expanding the accessibility to a wider population, thus decreasing potential inequities. Improving older adults' brain health and achieving even a modest two-year dementia incidence delay will have a projected saving of $218 Billion in Canada's healthcare system over 30 years.

Improving Neurological Health With Acetylcholine Via Neuroplasticity-based Computerized Exercise in Mild Cognitive Impairment

This study is a validation study to evaluate efficacy of two neuroplasticity-based, computerized cognitive training programs to improve neurological and neuropsychological health in older adults with mild cognitive impairment (MCI).

Evaluation of Cerogrin for Auricular Vagus Nerve Stimulation in Vascular Dementia or Vascular Mild Cognitive Impairment

This clinical trial evaluates the preliminary effectiveness and safety of Cerogrin, a medical device developed by Neurogrin Inc. for auricular vagus nerve stimulation, in patients with vascular dementia or vascular mild cognitive impairment. Given the limited availability of effective pharmacological treatments for these conditions, the study aims to assess whether Cerogrin can enhance cognitive function through non-invasive neuromodulation. Twenty-four participants will be randomized to receive either the active Cerogrin device or a sham (non-stimulating) device. Daily use will occur at home for 30 minutes over a four-week intervention period. The full study duration, including baseline assessments and follow-up, will span up to three months. During this period, cognitive function, neural activity, and safety outcomes will be systematically evaluated. This feasibility trial represents a critical step toward expanding therapeutic options for vascular cognitive impairment.

Study of Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of NIO752 in Early Alzheimer's Disease Participants

Phase 1b study to assess the pharmacodynamics, safety, tolerability, and pharmacokinetics of NIO752 in patients with early Alzheimer's disease (AD)

VisMemoPD Protocol: an Observational Pilot Study on Spatial and Topographical Memory in Patients With Parkinson's Disease and Parkinsonism

VISMEMO-PD is an observational pilot study aimed at investigating visuospatial memory in reaching space and topographical memory in navigational space in patients with Parkinson's disease and Parkinsonism. The protocol is based on the hypothesis that topographical memory may deteriorate before visuospatial memory, suggesting that navigational memory impairment could represent an early indicator of disease progression. The study will include 80 participants stratified into four groups: patients with mild Parkinson's disease, patients with moderate-advanced Parkinson's disease, patients with Parkinsonism, and healthy participants. Visuospatial memory will be assessed using the Corsi Block-tapping Test, while topographical memory will be assessed using the Walking Corsi Test. Walking motor patterns will be recorded using wearable inertial sensors from the MOVIT system, and visual exploration strategies will be assessed using a wearable Pupil Labs eye-tracking system. The integration of cognitive, motor, and eye-tracking measures may support the identification of early neuropsychological markers and the development of tailored neurorehabilitation pathways for individuals with Parkinson's disease and Parkinsonism.