Clinical Research Directory

ToolBox Detect: Low Cost Detection of Cognitive Decline in Primary Care Settings

Our study objective is to widely implement and evaluate a user-centered, scalable, electronic health record (EHR)-linked strategy for the routine detection of cognitive decline among diverse primary care settings. This strategy, called ToolboxDetect, will provide an efficient and sensitive cognitive screen that can be easily implemented in everyday clinical settings, and is responsive to patient, family, and caregiver concerns for potential symptoms of cognitive decline (CD) and cognitive impairment (CI).

A Study of Donanemab (LY3002813) in Participants With Early Cognitive Decline (TRAILBLAZER-ALZ 7)

The main purpose of this study is to evaluate whether treatment with donanemab slows the progression of cognitive (how we think, learn, remember, pay attention, and make decisions) and functional (how we are able to perform daily activities) decline. For each participant, the study will last one and a half years.

PREsurgical Cognitive Evaluation Via Digital clockfacEdrawing

This study leverages a modernized digital version of a well-known cognitive screening tool to examine pre and post operative cognitive function after surgery in adults age 65 years or more. Machine learning algorithms will be applied to the hospital wide standard of care cognitive metric to identify risk for post-operative cognitive complications.

Efficacy of Gamma Auditory Stimulation for Cognitive Decline in Older Adults (Study 1)

Animal studies have shown that 40 Hz auditory stimulation alone can improve spatial memory and reduce Aβ deposition. However, human studies using 40 Hz auditory stimulation alone remain limited. Therefore, this study will use a randomized, double-blind, placebo-controlled design to investigate the effects of 40 Hz auditory stimulation on cognitive function, EEG activity, sleep quality, and quality of life in older adults with mild cognitive impairment (MCI) or mild dementia.

ME/CFS Brain Fog: Cognitive Rehabilitation Trial

The purpose of this study is to compare two approaches to cognitive rehabilitation in adults with post-viral cognitive syndrome, which resulted in brain fog. All participants will be screened for eligibility prior to participation. Most of the procedures will take place over a phone call or secure telehealth platform (i.e., Zoom). However, participants will be asked to visit UAB on three occasions for blood sample collection and brain imaging (about 2 hours each). Online testing will happen one month before treatment, one day before treatment, one day afterwards, and 6 months afterwards. The study will utilize two different forms of rehabilitation training to improve participants' cognitive ability. Participants will be randomized to one of the two treatment groups. The first treatment approach, known as Constraint-Induced Cognitive Therapy (CICT), will feature (A) web-based computer "games" that trains how quickly individuals process information that they receive through their senses; (B) online training on everyday activities with important cognitive components, (C) procedures designed to transfer improvements in cognition from the treatment setting to everyday life, and (D) a non-invasive form of vagus nerve stimulation, also known as trans-auricular VNS (taVNS). The second approach, known as Brain Fitness Training (BFT), will include (A) web-based computer "games" that train reaction time and eye-hand coordination; (B) in-lab training on relaxation, breathing, healthy nutrition, and healthy sleep, (C) education about how relaxation, breathing, nutrition, and sleep are connected to thinking effectiveness, and (D) taVNS. Approximately 30 hours of training will be conducted over a secure telehealth platform (i.e., Zoom) in the span of two- to four- weeks. A typical CICT session will consist of one hour of gaming, with the bulk of the session being spent on cognitive training of the target behaviors and procedures designed to promote transfer of therapeutic gains to daily life. ta-VNS will be administered for 10 minutes before gaming and in-lab target behavior training. A typical BFT session will consist of one hour of gaming, training on healthy lifestyle behaviors (i.e., healthy sleep, nutrition, and relaxation habits), as well as procedures designed to promote transfer of behavior changes to daily life. Ta-VNS will be administered for 10 minutes before gaming and in-lab target behavior training. Training sessions in both conditions will be scheduled based on participants' availability, with the options for sessions scheduled to be as close as every weekday over 2 weeks or as loosely as every other weekday (i.e., over a 4-week span). If a caregiver is available, they will receive training on how to best support participants in their therapeutic program. After the training ends, both groups will receive 4 follow-up phone calls approximately one week apart to promote integration of the gained skills into everyday life. Outcomes measured will include cognitive processing speed, cognitive function on laboratory tests, and spontaneous performance of everyday activities with important cognitive components in daily life.

Vanderbilt Memory and Aging Project

This study will use an observational cohort to cross-sectionally and longitudinally relate vascular health to clinical, imaging, and biological markers of early Alzheimer's disease and cerebrovascular disease among aging adults. Adjusting for relevant clinical covariates, we will test the hypothesis that vascular health is associated with clinical, brain magnetic resonance imaging (MRI), neuropsychological, and cerebrospinal fluid markers of early cerebrovascular and Alzheimer's disease changes (i.e., prior to the onset of significant cognitive decline or dementia). Secondarily, we will examine medical and genetic factors that might mediate associations between vascular health and brain aging, such as inflammatory processes, insulin resistance, and genetic factors (e.g., APOE, a susceptibility risk factor for dementia). Findings will advance knowledge regarding the role that vascular health plays in brain aging.

Cognitive Impairment in Colorectal Cancer Patients Receiving Cytotoxic Chemotherapy

The purpose of this research study is to see how the brain changes in patients receiving chemotherapy (cytotoxic drug) treatment for colon or rectal cancer at Parkview Cancer Institute. This information will be used to identify helpful tests to diagnose individuals at risk for developing difficulties with thinking and memory due to their cancer treatments.

Interventions in Mathematics and Cognitive Skills

The purpose of this study is to investigate neurocognitive mechanisms underlying response to intervention aimed at enhancing, and remediating weaknesses in, numerical skills in children, including those with mathematical learning disabilities (MLD).

High-Intensity Exercise to Combat Vascular and Cognitive Dysfunction in Adults With HIV

This is a single site, randomized exercise trial with individuals at least 50 years of age living with HIV who experience suboptimal cognition. The overall goals of this proposal are to determine whether 16 weeks of structured high-intensity interval training (HIIT) can overcome vascular and cognitive impairments (Aim 1) to a greater extent than continuous moderate exercise. Additionally, investigator will seek to identify barriers to engagement in exercise and the participants' perceptions of the study and exercise interventions (Aim 2). This study will enroll 60 participants in Birmingham, Alabama. Data collection will occur at each visit, with baseline data collected at the initial visit with a 3-month follow-up occurring following completion of the intervention.

Network-targeted Theta-burst Stimulation for Episodic Memory Improvement in Mild Cognitive Impairment

The purpose of this study is to see if stimulation of the brain can improve memory. The investigators will use a device called transcranial magnetic stimulation that can stimulate and activate a specific part of the brain that is important for memory. The study will enroll MCI subjects and subjects with subjective memory complaints who will be randomly assigned to receive active or sham brain stimulation. 'Blinded' or 'sham-controlled' means that the subject will not know whether the treatment they receive is the active treatment or the non-active stimulation. In the 'sham' condition, the stimulator will turn on but will not actually be stimulating the target brain region.

Cognitive Effects of Hesperidin in Overweight/Obese Older Adults

A randomized, double-blind, placebo-controlled trial was designed to test whether two doses of hesperidin (a natural flavonoid from citrus fruits) improve cognitive function in overweight and obese older adults. A total of 105 participants, aged 55-75 years with a BMI ≥24 kg/m² or elevated waist circumference, will be randomly assigned to one of three 10-week treatments: placebo, low-dose hesperidin (300 mg/day), or high-dose hesperidin (600 mg/day). The primary aim is to see if hesperidin supplementation enhances cognitive performance - specifically executive function, memory, and attention - and to explore any dose-response relationship. Secondary aims include examining changes in gut microbiota composition and related metabolites, as well as exploring potential mechanisms behind any observed effects. The findings are expected to provide scientific evidence on whether hesperidin could serve as a nutritional strategy to support cognitive health in this population.

Protocolized Receptive Music Intervention to Reduce Care Refusal in Nursing Home Residents With Major Neurocognitive Disorders

The goal of this randomized study is to find out whether using a structured, protocolized music program (MUSIC CARE©) during daily hygiene care can reduce care refusal in older adults with dementia (memory and thinking conditions) who live in nursing homes (EHPADs). What is "care refusal"? Care refusal (also called resistance to care) happens when a person with dementia refuses or becomes distressed during everyday care activities such as bathing, dressing, or taking medications. It is a very common situation in nursing homes that can be stressful for both residents and care staff. The main questions this study aims to answer are: * Can a structured, daily music program reduce care refusal during bathing and hygiene care compared to current practice? * Does using music for 20 minutes during the care session work as well as - or differently from - using it both before and during care (40 minutes total)? * Does the music program also reduce distressing behavioral symptoms in residents? * Does it reduce the need for sedative or psychiatric medications? * Does it reduce professional burnout in caregivers who perform hygiene care? Researchers will compare three groups: * Group 1 (Control): Current practice - care staff may use MUSIC CARE© at their own discretion, as they already do * Group 2 (Music During Care): Structured use of MUSIC CARE© for 20 minutes during every hygiene care session, daily for 4 weeks * Group 3 (Music Before + During Care): Structured use of MUSIC CARE© for 20 minutes before and 20 minutes during every hygiene care session (40 minutes total), daily for 4 weeks Nursing homes (not individual residents) are randomly assigned to a group. Residents and their caregivers will: * Have their level of care refusal recorded daily for 4 weeks * Have neuropsychiatric symptoms and medication use assessed at the start, Week 4, and Week 8 * Caregivers will also complete a confidential and anonymous professional burnout questionnaire at 3 time points

Transcranial Direct Current Stimulation for Long COVID Brain Fog and Fatigue

Long COVID can cause persistent symptoms such as fatigue, cognitive difficulties commonly described as brain fog, reduced exercise tolerance, and impaired quality of life. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that may help modulate brain activity in regions involved in cognition, fatigue, and executive function. The NEUROSTIM-LC study will evaluate the feasibility and potential effects of repeated tDCS sessions in adults with long COVID presenting fatigue and/or brain fog. Participants will receive 30 sessions of tDCS applied over the left dorsolateral prefrontal cortex. Assessments will be performed before and after the intervention to evaluate changes in quality of life, fatigue, cognitive function, brain metabolism, physical performance, autonomic function, sleep quality, psychological symptoms, respiratory function, and blood biomarkers.

FitMi AD Home Therapy for Individuals With MCI or Mild Dementia Due to Alzheimer's Disease

This study will investigate the efficacy of a newly developed exercise device (FitMi AD) for individuals with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease. FitMi AD uses embedded sensors that can track and record the patient's direction and degree of movement while performing exercises described on a computer.

Neurocognitive Assessment CNSL and LGG

This study is to determine whether self-administered digital cognitive tests can serve as accurate and reliable alternatives to established neuropsychological tests for evaluating cognitive functioning in participants with primary central nervous system lymphoma and low-grade gliomas.

The Better, Harder, Faster, Stronger Study

The purpose of this study is to evaluate changes in the electronic Frailty Index (eFI) score following 3-4 cycles of neoadjuvant chemotherapy (NACT) in participants with advanced ovarian and endometrial cancer.

A Multi-Dimensional Comparative Study of Exercise Psychological Experience Under AI Fitness Companion and Human Coach Paradigms

This study conducted a comparative analysis of subjective exercise experiences between an AI-based fitness companion and traditional human coaching among 98 university students participating in a standardized 20-minute functional circuit training session. Participants were evaluated across three psychological dimensions: Emotional Resonance (ER), Interactive Dynamics (InD), and Embodied Presence (EP). The results indicated that human coaching elicited significantly higher levels of Emotional Resonance, whereas AI-based companions demonstrated superior performance in Interactive Dynamics. No significant differences were observed in Embodied Presence, suggesting that contemporary AI systems can provide spatial immersion and body-awareness comparable to human coaches. These findings indicate that AI and human coaches offer distinct psychological strengths, suggesting that AI should be viewed as a complementary, scalable tool for exercise guidance rather than a direct replacement for human emotional support.

Non-randomized Clinical Trial on Cognitive Stimulation With Virtual Reality in Patients With Mild Cognitive Impairment

The purpose of this study is to find out if adding virtual reality (VR) to a cognitive training program helps improve cognitive performance in older adults with mild cognitive impairment (MCI). In this study, all participants will take part in a 12-week computer-based cognitive rehabilitation program. One group will also use immersive VR for 15-20 minutes at the end of each session. Participants will attend 2 sessions per week, completing at least 20 sessions and up to 22, depending on the clinic's schedule. Researchers will measure changes in attention, memory, and thinking skills using standard cognitive tests. They will also collect feedback on how participants experience the VR exercises.

Health Ahead Comparative Effectiveness Study

The Health Ahead Comparative Effectiveness Study is a pragmatic, parallel-arm interventional platform that systematically compares successive changes to preventive health screening - each isolated as a single variable against current practice - on the path toward a fully automated screening system deployable in any environment, including the most isolated and resource-limited communities. Each comparison is evaluated with a common set of engagement, behavior-change, experience, cost, and longitudinal outcome measures, allowing results to accumulate on a consistent yardstick across the life of the platform. The first comparison evaluates static versus interactive personalized health report delivery. Subsequent pre-planned comparisons, added by protocol amendment, evaluate mobile community versus fixed laboratory screening; and a hybrid medical-droid plus human-delivery model versus human-only screening. All participants are simultaneously enrolled in the 100-Year Human Aging Study and the Human Observatory Study, contributing individual longitudinal and population-level causal inference data through those protocols.

Promoting Goals-of-Care Discussions for Patients With Memory Problems and Their Caregivers

The goal of this clinical trial is to improve communication among clinicians, patients with memory problems, and their family members. We are testing a way to help clinicians have better conversations to address patients' goals for their healthcare. To do this, we created a simple, short guide called the "Jumpstart Guide." The goal of this research study is to show that using this kind of guide is possible and can be helpful for patients and their families. Patients' clinicians may receive a Jumpstart Guide before the patient's clinic visit. Researchers will compare patients whose clinician received a Jumpstart Guide to patients whose clinician did not receive a guide to see if more patients in the Jumpstart Guide group had conversations about the patient's goals for their healthcare. Patients and their family members will also be asked to complete surveys after the visit with their clinician.

Psychological Impacts of Exercise Snacks Versus Traditional Exercise: A Comparative Study

This study investigates the comparative psychological impacts of a high-frequency "Exercise Snacks" (ESG) protocol versus a traditional continuous exercise (TEG) regimen on healthy young adults. Utilizing a randomized controlled trial design over a 4-week longitudinal period, 180 participants were allocated into two groups of 90, with a standby recruitment protocol employed to ensure sample size stability. The intervention was standardized to equate total weekly exercise volume at 90 minutes. The TEG cohort performed 30-minute continuous cycling sessions three times per week, whereas the ESG cohort executed 15-minute distributed cycling sessions six times per week. To ensure physiological homogeneity and precision in workload prescription, individual baseline maximal aerobic capacity was assessed via incremental cardiopulmonary exercise testing. Based on these individual thresholds, exercise intensity for both cohorts was rigorously maintained at 40% of their respective maximal aerobic capacity throughout the intervention. Psychometric outcomes were evaluated within 24 hours of the intervention's conclusion, focusing on three dimensions: Perceived Stress, Decision Fatigue and Cognitive Load, and Physical Activity Enjoyment. By applying Lazarus and Folkman's Transactional Model of Stress and Coping, Sweller's Cognitive Load Theory, and Self-Determination Theory, this research examines how fragmented exercise protocols interact with daily workflow and self-regulatory resources. The findings provide critical insights into the real-world viability, behavioral resistance, and psychological divergence associated with high-frequency, fragmented exercise routines compared to conventional models.

Human Observatory Study

The Human Observatory Study is a prospective observational and ecological surveillance study building a continuously-updating world model for human health, disease, and death at the individual and population level. Individual multi-system clinical data from enrolled participants are linked to a continuously-ingested ecological data infrastructure spanning environmental exposures, social determinants, genealogical and family history records, mortality data, and population health databases at geographic resolutions from home address to global scale and beyond. The resulting model generates individual screening recommendations informed by population-level causal estimates, and population-level causal forecasts anchored by present-timepoint individual clinical biology. Thus creating a feedback architecture designed to improve both simultaneously.

Feasibility Study on the Use of Redormin®500 on Day-time Cognition

Randomized, double-blind, parallel groups, placebo-controlled, baseline/run-in period of 21 days followed by trial period of 21 days, digital phenotyping (sleep, cognitive/psychological parameters and HRV). The aim of this study is to determine the feasibility of investigating the effects of Redormin® 500 on day-time cognition and to assess psychological parameters (subjective cognitive performance, tiredness, mood, stress level, quality of life, motivation), in people with occasional sleep problems. Sleep tracking data will be collected using consumer devices of the Charge series by Fitbit.

Polyphenols and Cognitive Decline

Globally, populations are aging thereby increasing healthcare burden, overall cognitive impairment, and dementia including Alzheimers diseases (AD). The lack of effective treatments makes it essential to develop new strategies for healthy cognitive aging, including interventions to slow or prevent cognitive decline. A traditional Mediterranean diet, rich in polyphenols (PPs), may prevent or delay the onset of cognitive dysfunction in older adults, preserving healthy brain structure and function, and lowering the risk of AD. These effects, mediated in part by gut microbiome-derived PP metabolites, highlight the role alterations in the brain-gut microbiome system play in neurodegeneration. Moreover, high levels of circulating phenyl-y-valerolactones, neuroprotective compounds, exclusively produced by gut microbiota from flavan-3-ol-rich foods (e.g., cocoa, tea, berries) are associated with delaying the onset of cognitive dysfunction in older adults. Intake of such PPs can also change gut microbial composition and function, altering the physiology of the hosts secondary bile acid (BA) pool, affecting regulatory and signaling functions in the brain as well as cognitive decline and AD. The investigators hypothesize that, in older adults with enhanced AD risk, dietary intake of PPs maintains healthier brain features and cognitive function, and that this beneficial effect is mediated by gut microbiota metabolites of PPs and BAs. In this multi-PI application by leaders in the field of brain-gut microbiome interactions, the investigators will conduct a year-long, multi-center, randomized double-blind placebo-controlled study in 300 older adults in the United States (validation sample of 100 from Northern Ireland) who are at enhanced risk of developing AD. Ultimately, the investigators will establish the protective effects of regular dietary PP intake on cognitive function and on brain-gut microbiome interactions, ideally allowing the development of effective dietary regimes to prevent of delay the onset of AD in at-risk elderly, thereby reducing cognitive decline and healthcare costs. Participants will be asked to provide information about their diet, mood, and behaviors via food diaries, physical body measures (e.g. height, weight, etc.), and online questionnaires collected before each in-clinic appointment, as well as monthly online questionnaires. MR imaging will be collected on participants to assess neurocognitive changes as a result of the supplement. Participants will be asked to provide both stool and blood samples. Participants will be randomly assigned to either the Juice Plus+ intervention group or the placebo treatment group and then asked to take their respective supplement 4 pills twice a day. All participants will be asked to come in for 4 in-clinic appointments, including 3 brain MRI scans and 3 cognitive testing appointments, collect 3 stool samples with corresponding diet diaries, and provide 3 blood samples over the course of 12 months. Participants will also meet with a nutritionist 3 times over the 12 months to discuss diet to ensure study eligibility and any questions about the supplement.