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....

Enhancing Frontal Lobes Plasticity in Mild Cognitive Impairment

More than 5 million people live with Alzheimer's dementia (AD) in North America. No effective treatment exists yet probably because by the time AD has developed it is too late to intervene. Mild Cognitive Impairment (MCI) is a clinical state that typically precedes AD. In MCI, the prefrontal cortex supports compensatory mechanisms that depend on robust synaptic plasticity and that delay progression to AD. Using a neurostimulation approach that enhances prefrontal cortical plasticity in vivo, this project aims to enhance prefrontal cortical plasticity and function in patients with MCI. If successful, this project would discover a treatment modality that enhances compensation in MCI and ultimately, prevents progression to AD.

LEADing Dementia End-of-Life Planning Conversations

Advance care planning is important for all adults, but perhaps even more so for the 5.7 million persons with Alzheimer's disease or related dementia (ADRD), due to the progressive and protracted cognitive deterioration associated with the disease process. In the context of ADRD, medical decision-making at the end of life is typically left to one's care partner, who often does not have the knowledge or confidence in their ability to make such decisions. This study will refine and evaluate a web-based platform, called the LEAD Intervention (Life-Planning in Early Alzheimer's and other Dementias), which is designed to help persons in the preclinical or early stage of ADRD engage in conversations about, document, and share their end-of-life values and preferences with a care partner, extended family members, and health care providers.

Prevention of Alzheimer's Disease With CR Plus tDCS in Mild Cognitive Impairment and Depression (PACt-MD)

This 7-year randomized controlled trial will compare the efficacy of non-invasive brain stimulation (trans-cranial Direct Current Stimulation - tDCS) combined with cognitive remediation (CR) versus sham ("placebo") tDCS combined with sham ("placebo") CR in slowing down cognitive decline and preventing Alzheimer's Dementia in older persons with mild cognitive impairment or major depressive disorder with or without mild cognitive impairment.

rTMS to Improve Cognition in Parkinson's

The purpose of this study is to examine safety, feasibility, and the behavioral and brain effects of a non-invasive treatment, repetitive transcranial magnetic stimulation (rTMS), for Veterans with Parkinson's disease or atypical parkinsonism and mild impairments in their thinking. The hypothesis is that rTMS can improve thinking for people with Parkinson's disease or atypical parkinsonism who are experiencing mild problems with their thinking ability.

Metformin in Alzheimer's Dementia Prevention

MAP will be a multisite phase II/III 1:1 randomized controlled trial (RCT) of long acting metformin (reduced mass Glucophage XR) vs. matching placebo in 326 men and women with early and late aMCI, without diabetes, not treated with metformin, overweight or obese, aged 55 years to 90 years. The RCT will last 18 months and have 4 visits: baseline, 6-months, 12-months, and 18-months. The RCT will be preceded by a screening phase followed by randomization and a titration period in which drug/placebo will be titrated from 500 mg a day (one tablet) to 2,000 mg a day (4 tablets), in increments of 500 mg (one tablet) every 10 days. Participants will remain in the RCT on the tolerated dose, and included in analyses on an intent to treat basis. We expect the attrition rate to be 10%/year. Neuropsychological battery, clinical interviews, physical exam, and phlebotomy will be conducted at baseline and every 6 months. Brain MRI will be conducted in approximately half of the participants (186) twice, at baseline, and after the last study visit at month 18. We will also conduct brain amyloid Positron Emission Tomography (PET) using 18F-Florbetaben, and tau PET using 18F-MK6240 in half of the participants at baseline and end of the RCT. The primary clinical outcome of the study will be changes in the Free and Cued Selective Reminding Test. The secondary endpoints are 1) changes in global cognitive performance, measured with the Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC); 2) changes in neurodegeneration, ascertained as cortical thickness in areas affected by AD on brain MRI; 3) changes in cerebrovascular disease, ascertained as white matter hyperintensities (WMH) volume on brain MRI; 4) Changes in whole brain amyloid ß (Aß) SUVR and in incident amyloid positivity; 5) Changes in tau SUVR in a composite brain region comprising medial and inferolateral temporal cortex; 6) Changes in plasma AD biomarkers. The data coordinating center and Imaging Core is located at John Hopkins University. The PET coordinating center is located at UC-Berkeley. The Clinical Coordinating and Monitoring Center and the central laboratory will be located at Columbia. The Research pharmacy function will be shared by the University of Rochester, which will dispense randomization kits, and the University of Iowa, which will receive bulk metformin and identical matching placebo from EMD Serono.

The Swedish BioFINDER - Preclinical AD Study

This research study aims to examine biomarkers of Alzheimer's disease (AD) as early as possible which could potentially be a screening tool for the general population. This observational study will take place at the Skåne University Hospital in Sweden. The study will enroll up to 600 cognitively healthy subjects aged 50 to 80 years with 3/4 having preclinical Alzheimer's disease. Recruitment and enrollment will be ongoing for 2-3 years, and subject participation will be lasting approximately 4 years. Disclosure of AD risk assessments will be an optional procedure.

Human Mesenchymal Stem Cells & Monoclonal Antibodies in the Treatment for Mild Cognitive Impairment or Early Alzheimer's Disease.

The purpose of this study is to test if adding one infusion of (Human Mesenchymal Stem Cells) hMSCs to the treatment with standard of care (SOC) monoclonal antibodies (mAb) will stabilize the rate of cognitive and functional decline associated with mild Alzheimer's Disease.

The Swedish BioFINDER - Memory Clinic Study

The diagnosis of diseases causing memory difficulties or dementia is often challenging. Without the use of advanced methods such as cerebrospinal fluid tests, approximately 25-30% do not receive a correct diagnosis today. However, the investigators have recently developed new blood biomarkers with high diagnostic accuracy, and the investigators now want to investigate whether they can eventually replace cerebrospinal fluid tests. This is because blood tests are much more cost-effective and significantly easier for patients compared to cerebrospinal fluid tests. In this study, 1200 patients undergoing clinical evaluations at the Memory Clinic, Skåne University Hospital in Malmö, are included for blood and cerebrospinal fluid sample collection. The blood samples are sent for analysis using the new blood biomarkers. Subsequently, the results are compared with those from the clinical analysis of cerebrospinal fluid to determine how well they perform in routine clinical practice as an alternative to cerebrospinal fluid tests and whether the blood test improves patient care. This comparison is carried out by the attending physician in three steps: 1. Assessment without access to the results of either the blood test or cerebrospinal fluid test. 2. Assessment with access to only the results of the blood test. 3. Assessment with access to the results of both the blood test and cerebrospinal fluid test. Aim 1) To prospectively validate plasma Alzheimer's disease (AD) biomarkers for diagnosis of patients with cognitive symptoms who are evaluated in a specialist memory clinic. Aim 2) Determine whether blood AD biomarkers improve patient management in specialist memory clinic settings.

Effectiveness of Strength-based Intervention for Elderly With Dementia Living in the Community

In the realm of dementia care, the imperative to intervene at the earliest stages of cognitive decline is paramount. Recognizing this pivotal moment, the development of innovative and effective interventions becomes imperative in delaying dementia progression. Rooted in the Roy Adaptation Model and Zimmer's Theory of Psychological Empowerment, the investigator team has developed the empowerment-based dyadic strength-based intervention, which integrates strength-based and empowerment methodologies. Emphasizing a shift from deficits to capabilities, the strength-based approach fosters awareness of collective strengths within care dyads, facilitating coping mechanisms and resilience in the face of cognitive afflictions.

The Swedish BioFINDER 2 Study

The Swedish BioFINDER 2 study is a new study that will launch in 2017 and extends the previous cohorts of BioFINDER 1 study (www.biofinder.se). BioFINDER 1 is used e.g. to characterize the role of beta-amyloid pathology in early diagnosis of Alzheimer's disease (AD) using amyloid-PET (18F-Flutemetamol) and Aβ analysis in cerebrospinal fluid samples. The BioFINDER 1 study has resulted in more than 40 publications during the last three years, many in high impact journals, and some the of the results have already had important implications for the diagnostic work-up patients with AD in the clinical routine practice. The original BioFINDER 1 cohort started to include participants in 2008. Since then there has been a rapid development of biochemical and neuroimaging technologies which enable novel ways to the study biological processes involved in Alzheimer's disease in living people. There has also been a growing interest in the earliest stages of AD and other neurodegenerative diseases. With the advent of new tau-PET tracers there is now an opportunity to elucidate the role of tau pathology in the pathogenesis of AD and other tauopathies. The Swedish BioFINDER 2 study has been designed to complement the BioFINDER 1 study and to e.g. address issues regarding the role of tau pathology in different dementias and in preclinical stages of different dementia diseases. Further, the clinical assessments and MRI methods have been further optimized compared to BioFINDER 1. Detailed assessments of motor aspects and dual task performance, which is part of a sub-study named Motor-ACT: "Motor aspects and activities in relation to cognitive decline and brain pathologies, has been added to further optimize assessment of motor function.

Prediction of Cognitive Test Performance Using AI-Based Analysis of Narrative Speech

This study aims to evaluate a new artificial intelligence (AI)-based method for measuring cognitive function using speech recordings. Participants will complete a short storytelling task in which they describe a story based on an image while their voice is recorded using a computer or mobile device. The speech recordings will be analyzed using AI technology to identify patterns in speech that may be related to cognitive function. The system will then estimate scores that correspond to commonly used cognitive tests. To evaluate the accuracy of this method, the AI-generated scores will be compared with results from standard cognitive assessments administered by trained researchers. These assessments may include tests commonly used to measure memory, attention, and other cognitive abilities. The goal of this study is to determine whether speech analysis using AI can provide a convenient and efficient approach for cognitive assessment. If successful, this technology may help support early detection of cognitive decline and provide a practical tool for large-scale or remote cognitive screening.

EVASION: Effect of VisuAl Stimulation on attentION

The main objective is to compare changes in information processing speed after 30 days of intervention in participants with a dysexecutive mild cognitive impairment (MCI) and receiving either cognitive stimulation by adapted visual exercises (Emeraude® software) or the broadcasting of a television program without cognitive stimulation. Secondary objectives are: * To compare, after 30 days of intervention, in participants with a dysexecutive MCI and receiving either cognitive stimulation by adapted visual exercises (Emeraude® software), or the broadcasting of a television program without cognitive stimulation : * changes in information processing speed of each subtest, * changes in cognitive performance, * changes in executive functions, * changes in walking performance. * To compare the quality of life, after 30 days of intervention, of participants with a dysexecutive MCI and receiving either cognitive stimulation by adapted visual exercises (Emeraude® software) or the broadcasting of a television program without cognitive stimulation. * In the "Intervention" group, to study correlations between changes in information processing speed index and the final level reached for each cognitive stimulation exercise.

The Swedish BioFINDER - Primary Care Study

The overall aim of the study is to improve the diagnostic accuracy of AD and cognitive impairment in primary care settings to ensure better care and treatment as well as facilitate correct referrals to specialized memory clinics. The investigators will strive to recruit diverse and representative populations of patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and mild dementia. The specific aims of the study are to: 1. Improve the detection of mild cognitive impairment (MCI) and dementia in primary care. 2. Develop and evaluate cognitive tests, blood-based biomarkers and brain imaging methods that are suitable for accurate and early diagnosis of Alzheimer's disease (AD) in primary care. 3. To prospectively validate plasma AD biomarkers for diagnosis of patients with cognitive symptoms who are evaluated in primary care. 4. Determine whether blood AD biomarkers improve patient management in primary care.

Impact of Yoga on Cognitive Function

Mild cognitive impairment is highly prevalent in patients with heart failure and results in poor well-being and quality of life. While yoga has proven effective in promoting cognitive health in older adults through its gentle movements, controlled breathing, and meditation, its effects on patients with heart failure remain unknown. Therefore, this feasibility and pilot study plans to deliver a 12-week yoga intervention and test its effects on cognitive function in patients with heart failure and mild cognitive impairment.

The Digital Memory Notebook

Compensatory aids (e.g., alarms, calendars) play an important supporting role when completing everyday tasks (e.g., appointments, medication management), and there is a growing body of scientific work suggesting that compensatory training improves daily functioning. However, traditional paper-based calendars and to-do-lists have limitations related to accumulation of information, difficulty retrieving information, and remembering to complete activities. Such limitations may be overcome using a digital format through organized digital files, search functions, and alarms. This pilot project proposes to train older adults at risk for cognitive decline to use the Digital Memory Notebook (DMN), a tablet-based application (app), to support everyday functioning. The primary goal is to obtain preliminary evidence that a 6-week, individual and group-based DMN training intervention results in demonstrable changes in target behaviors (e.g., goal-directed DMN use to support everyday activities) among older adults with mild cognitive impairment (MCI) and subjective cognitive complaints (SCC). Participants will complete a curriculum involving 2-hour weekly sessions for 6-weeks. Each week will cover a specific function of the DMN and will include standardized goal-setting and weekly homework targets. Following the 6-week intervention, participants will continue to use the DMN app for 4-weeks to evaluate stability. Participants will complete a questionnaire packet 1 week prior to the 6-week intervention, 1 week after the 6-week intervention, and 5 weeks following the 6-week intervention. MCI and SCC participants will complete separate 6-week individual or group interventions spaced two months apart at UCD.

rTMS in Older Adults With MCI and AUD

Alcohol misuse is a risk factor for early onset cognitive impairment, contributing to 10% of early onset dementia, with risk corresponding to consumption. Additionally, continued drinking risks worsening cognitive decline and dementia progression, while worsening cognitive impairment contributes to drinking escalation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve cognition in Alzheimer's Disease and Related Dimentias (ADRD) and separately reduce heavy drinking in alcohol use disorder. Our objective is to optimize rTMS for simultaneous mitigation of both drinking and cognitive dysfunction in older adults.

Effectiveness of TeleVR App in Cognitive Decline and MCI Patients

The goal of this clinical trial is to evaluate the effectiveness of a telerehabilitation program combined with a virtual reality (VR) app in improving cognitive performance and social skills in patients with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI). The main questions it aims to answer are: Can a VR telerehabilitation program improve cognitive functions and social skills in patients with SCD and MCI? Are there measurable changes in brain activity, eye movements, and gait patterns after the intervention? Researchers will compare telerehabilitation with a VR group (Experimental Group - EG) to a traditional paper-based cognitive rehabilitation group (Active Control Group - aCG) to determine which approach is more effective. Participants will: Undergo an initial assessment, including neurological exams, neuropsychological tests, brain MRI, EEG, eye movement analysis, and gait evaluation. Participate in a 6-week intervention program: EG: Use VR apps on smartphones/tablets at home, guided remotely by a therapist. aCG: Perform traditional cognitive exercises using paper-based tasks. Complete follow-up assessments immediately after the intervention and again after three months. This study will help determine whether telerehabilitation with VR can provide measurable cognitive and social benefits, contributing to improved care strategies for individuals at risk of dementia.

Transcranial Magnetic Stimulation for MCI

The goal of this phase II study is to establish the dose-response curves of a safe and clinically feasible non-invasive brain stimulation technique (accelerated Transcranial Magnetic Stimulation (TMS)) to improve both depression and cognitive function in Mild Cognitive Impairment (MCI) patients with comorbid depression. It is known that TMS can effectively treat depression. Identifying the right dose of accelerated TMS in MCI patients is necessary prior to designing subsequent trials to determine efficacy. These results will inform future clinical trials of accelerated TMS for MCI, with the long-term goal of developing an efficacious treatment to prevent dementia.

BID LTM Digital Intervention in Aging

Healthy aging is typically accompanied by diminished capability for learning and retrieval of high-fidelity long-term memory (LTM). The decline in these faculties is accelerated and becomes significant deficits in LTM and cognitive control functions at the level or a diagnosis of Mild Cognitive Impairment (MCI). Training with the navigation game, relative to training with control games, is expected to improve LTM performance for older adult participants. Researchers will compare two different digital interventions to assess whether they may be helpful in improving cognitive function. Participants will conduct study activities remotely (e.g., at-home): 1. Baseline Assessment. Complete a series of cognitive assessments and surveys. 2. Intervention. Engage in a digital intervention for up to 8 weeks. 3. Post Intervention Assessment. Complete the same cognitive assessments and surveys as the Baseline Assessment. 4. Follow-Up Assessment. Six months after the intervention ends, participants will complete the same cognitive assessments and surveys as the Baseline Assessment.

Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD) Study

The objective of the study is to determine the safety, feasibility, and efficacy of senolytics in older adults with amnestic mild cognitive impairment (MCI) or early-stage AD (Clinical Dementia Rating (CDR)=0.5 or 1) who are tau PET positive

Dementia-friendly Apothecaries as a Resource for Mental Heath in the Elderly

The DARE study (Dementia-Friendly Apothecaries as a Resource for Mental Health in the Elderly) is a multicenter, prospective cohort study aiming to identify individuals with cognitive impairments early in pharmacies and enhance their access to support services. Partner pharmacies are equipped with memory test stations, and pharmaceutical staff are trained to guide participants. The digital memory test evaluates cognitive, psychosocial, and health factors, displaying results in a traffic light graphic. Participants with concerning results are referred to specialists or support services. The study's primary goals are to establish pharmacies as dementia screening hubs, improve care for affected individuals, promote interdisciplinary collaboration, and lay the groundwork for legal and billing frameworks. An optional subproject validates the screening through neurological evaluations.

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

The Comparative Effectiveness Dementia & Alzheimer's Registry

To evaluate the effectiveness of using clinical precision medicine to develop lifecourse interventions for Alzheimer's disease (AD) prevention and treatment. Anthropometrics, blood biomarkers (including genetics), and cognition will measured longitudinally to assess the comparative effectiveness of clinical care.