Clinical Research Directory

Amyloid PET Imaging in the Baltimore Longitudinal Study of Aging

Background: Some people experience cognitive decline as they age. That is, they lose memory, problem-solving, and other mental abilities. Amyloids are groups of proteins that develop in the brain and increase in number as people age. Researchers want to use imaging scans to track amyloids in people s brains over time. Their goal is to find out if any changes are related to cognitive decline or other medical issues. Objective: To learn how amyloids may affect brain structure and function as people age. Eligibility: People aged 55 years and older who are enrolled in the Baltimore Longitudinal Study of Aging. Design: Participants will have imaging scans and other tests every 1 to 4 years, depending on their age. Those 80 and older will be scanned yearly. These scans will be done during regular BLSA visits. The scans will be positron emission tomography and computed tomography (PET CT). Participants will be given fluid through a tube inserted into a vein in their arm. The fluid is a tracer that will cause the amyloids to light up in the images. Then they will lie on a bed with their head inside a PET CT scanner. They will lie still for about 30 minutes. Participants will have tests to assess their memory and other mental skills. They will answer questions about their mood and daily life. These tests will take about 40 minutes to complete; they may be done in person or by phone. Participants will give a contact number for someone who can answer questions about the participant s daily routine. These questions may be answered in person or by phone. Participants will be in this study for 5 years.

Anti-aging Efficacy Study on One Cosmetic Product Containing Mitopure

The aim of this study is to investigate the impact of a topical product on skin health and aging

Implementation of Routine Walking Speed Measurements in Older Veterans

Walking speed is a powerful predictor of mortality and adverse health consequences (e.g. fall or hospitalization) in older adults. Knowledge of individuals' walking speed can provide unique insight into current physical function and need for healthcare services. Furthermore, walking speed is a modifiable risk factor such that early recognition of physical function decline allows for appropriate and timely intervention prior to the occurrence of adverse health events. Therefore, this proposal seeks to implement routine measures of walking speed into VHA primary care as a 'vital sign' to routinely monitor Veteran physical function and help guide provider referrals.

Memory Enhancement in Aging With Optimal Dosing

This project optimizes high-resolution tACS to improve memory in healthy older adults, advancing drug-free approaches for ADRD. We test stimulation schedules and develop an adaptive, brain-guided tACS system to strengthen memory-supporting networks.

Improving PCP Advance Care Planning for People With ADRD

This study will test the Dementia Advance Care Planning (AD ACP) Toolkit intervention to usual care in facilitating goals of care (GOC) discussions between People Living with Dementia (PLwD) and primary care team members over an 18-month period. The primary outcome is to assess the frequency and quality of GOC discussions with PLwD. Secondary outcomes include the identification of preferred surrogates, assessment of decisional capacity, and the completion of portable ACP orders. This randomized clinical trial aims to determine if the AD ACP Toolkit can enhance ACP practices and improve care planning outcomes for PLwD compared to the standard care approach.

Modulating Neurocognitive Processes of Learning to Trust and Distrust in Aging

Much of human interaction is based on trust. Aging has been associated with deficits in trust-related decision making, likely further exacerbated in age-associated neurodegenerative disease (Alzheimer's disease/AD), possibly underlying the dramatically growing public health problem of elder fraud. Optimal trust-related decision making and avoiding exploitation require the ability to learn about the trustworthiness of social partners across multiple interactions, but the role that learning plays in determining age deficits in trust decisions is currently unknown. Aim: Probe the malleability of the underlying neurocircuitry of trust-learning deficits in aging. This study will utilize real-time fMRI neurofeedback to train older adults in brain activity up-regulation toward enhanced trust-related learning in aging and confirm critical mechanisms of experience-dependent social decisions in aging. Grant R01AG072658 Aim 3: Test the malleability of trust-learning neurocircuitry toward optimized trust-related decision making in aging.

Role of Menopause in Thermoregulation

The frequency and severity of heat waves has increased in the last decades. Older adults (over 65 years) have impaired responses to heat stress making them at increased risk for adverse events. Previous heat waves report that women over 65 experience worse health outcomes than any other age group and age matched men. Aging and reproductive hormones, specifically estrogen, independently alter responses to heat stress. However, the combined effects of low estrogen following menopause and aging on the response to heat stress are unknown. In this study, the investigators will identify the role of estrogen in pre and post menopausal women on thermoregulatory responses to heat stress.

Evaluation of Electroencephalographic Biomarkers in Physiological Aging

Aging is the inevitable biological process that results in a progressive structural and functional decline from the cellular level to whole body function. It is associated with functional changes in the resting brain activity, brain morphology, plasticity, complexity and function. Moreover, aging is the main risk factor for neurodegenerative disease. Understanding the molecular mechanisms underlying the age-related neurophysiological changes and identifying novel biomarkers of healthy brain ageing is thus instrumental for the development of efficient interventions against age-related motor/cognitive impairments. Within this context, there is now a significant literature establishing the enhanced efficacy of secreted exosomes over the stem cells from which they are derived when used as a possible treatment for neurodegenerative disorders. Exosomes are a subgroup of extracellular vesicles which regulate intercellular communication and, unlike stem cells, easily cross into the brain and can be administered in non-syngeneic species without immune rejection. Studies on brain ageing in humans has major limitation in the lack of accessibility of the central nervous system. EEG has allowed the non-invasive assessment of functional changes in the aging brain. In fact, this technique can provide a direct assessment of neural activity and information flow with a higher temporal resolution that is particularly important for investigating the dynamics of brain changes underlying cognitive processing and age-related changes, providing novel biomarkers of brain aging that could be used to unveil differences between healthy and unhealthy processes particularly in the pre-symptomatic and pre-clinical stage. To reach this aim, it is necessary to demonstrate, in experimental models, the relationship between age-dependent changes in brain activity and cellular/molecular processes occurring in aged brain. Our project will pursue this overall goal by: 1\) identifying neurophysiological biomarkers of brain aging in human subjects based on functional network and complexity analyses; 2) characterizing age-dependent changes in brain connectivity and complexity in mice and correlating them to changes in motor and cognitive performances and to molecular alterations occurring in both the brain and blood; 3) evaluating changes of the identified electrophysiological and molecular biomarkers in mice treated with stem cell derived exosomes for the rejuvenation of the aged brain. 4\) designing Artificial Intelligence (AI) predictor of brain age trajectories on individual basis to evaluate individual neural reserve and resilience. This study will identify novel electrophysiological biomarkers of healthy brain ageing and will advance knowledge on cellular/molecular signature of brain aging that could targeted for the preservation of brain health.

The Role of Neutrophils in the Age-driven Decline in Anti-pneumococcal Vaccine Responses

This study focuses on the role of neutrophils in shaping the adaptive immune response to the anti-pneumococcal vaccine Prevnar-13 in young and elderly adults.

IMAT Quality in Aging

This study will test the central hypothesis that fat within the muscle, or intramuscular adipose tissue (IMAT), exhibits elevated damage and pro-inflammatory signaling with aging, both of which are reduced by progressive resistance exercise (PRE). Sixteen older adults 65-80 years old will be recruited and complete a 12 week calf PRE intervention. Calf muscle strength, composition (measured by computed tomography) and muscle biopsies will be collected before and after the intervention. Histology, transcriptomic and secretomic tests will be completed to assess signs of damage and inflammation.

BID WM Digital Intervention in Aging

The goal of this clinical trial is to learn if engaging with an digital intervention may improve cognitive function. The main questions it aims to answer are: 1. Does engagement in with a digital intervention improve working memory? 2. Does engagement in with a digital intervention improve inhibitory control? 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.

The Effect of NAD Supplementation on Brain Vascular Health in Aging

Daily consumption of one of the forms of Vitamin B3, the Nicotinamide Riboside (NR), energizes the body and combats cellular aging. This study is designed to test whether NR can also improve brain health and memory.

Older Adult Traditional Balance Training vs Traditional Balance Training Plus Neck Strengthening

This study promotes greater understanding of factors impacting balance and how neck strength alters specific aspects of impaired balance. This study will help physical therapist protocols target a wholistic approach to treat fall risk individuals.

Effects of Physical Exercise and a Nutritional Supplement on Body Composition, Metabolic Function, and Overall Health in Adults With a Metabolically Challenging Profile

Early-onset metabolic disturbances (such as mild hyperglycemia, subclinical dyslipidemia, excess body fat, and reduced functional capacity) represent one of the major public health challenges among middle-aged and older adults. Although body mass index (BMI) remains the primary clinical criterion for classifying excess weight, growing evidence indicates that BMI does not adequately discriminate cardiometabolic risk, particularly in individuals classified as overweight who present elevated body fat levels (Wu et al., 2024). Several studies have identified altered metabolic phenotypes that do not meet the criteria for obesity, including the so-called "metabolically unhealthy normal weight" (MUNW) or "metabolically unhealthy non-obese" phenotypes. These individuals are characterized by excess body fat, central adiposity, and alterations in glucose and lipid metabolism despite having a non-obese BMI (Stefan, 2020). This profile is associated with increased insulin resistance, low-grade systemic inflammation, and elevated cardiovascular risk, underscoring the need for targeted interventions in "metabolically challenged" individuals. Xiong et al. (2024) demonstrated that metabolic health status independently predicts cardiovascular risk, even when BMI is within non-obese ranges. This evidence supports the rationale of the present project: to intervene in a group of adults without clinical obesity (BMI \< 30 kg/m²) but presenting at least two indicators of mild metabolic dysfunction. Nutritional supplements with thermogenic properties that promote fat oxidation and satiety-such as phenylcapsaicin, an analog of capsaicin designed to improve bioavailability and reduce pungency, thereby enhancing tolerability in adults-may offer a promising complementary strategy. Recent studies have shown that low doses of phenylcapsaicin were sufficient to increase fat oxidation during exercise, reduce respiratory exchange ratio, and lower maximal heart rate during submaximal testing compared with placebo (Jiménez-Martínez et al., 2023a). Furthermore, additional research reported that phenylcapsaicin improved strength performance, reduced perceived exertion, and attenuated markers of muscle damage following resistance training (Jiménez-Martínez et al., 2023b). These findings suggest that thermogenic and fat-oxidation-enhancing supplementation may act as a safe and effective metabolic modulator, particularly when combined with exercise, positioning it as an innovative strategy for adults presenting mild metabolic risk. The present study would integrate: (1) a multicomponent functional exercise program designed to improve strength, balance, and aerobic capacity in older adults; (2) a thermogenic and fat-oxidation-enhancing nutritional supplement as a safe metabolic activation strategy; (3) a standardized dietary control protocol to isolate the specific effects of the supplementation; (4) dual-energy X-ray absorptiometry (DXA) for precise body composition assessment; (5) hormonal and lipid biomarkers to evaluate underlying physiological mechanisms; and (6) validated questionnaires addressing quality of life, sleep, and appetite to capture the holistic dimension of this stage of adulthood. This multidimensional approach would provide an innovative intervention for a growing yet underexplored population: non-obese but metabolically challenged adults at increasing cardiometabolic risk. References: * Jiménez-Martínez P, Sánchez-Valdepeñas J, Cornejo-Daza PJ, Cano-Castillo C, Asín-Izquierdo I, Alix-Fages C, Pareja-Blanco F, Colado JC. Effects of different phenylcapsaicin doses on neuromuscular activity and mechanical performance in trained male subjects: a randomized, triple-blinded, crossover, placebo-controlled trial. Front Physiol. 2023a Aug 2; 14: 1215644. * Jiménez-Martínez P, Cornejo-Daza PJ, Sánchez-Valdepeñas J, Asín-Izquierdo I, Cano-Castillo C, Alix-Fages C, Pareja-Blanco F, Colado JC. Effects of different phenylcapsaicin doses on resistance training performance, muscle damage, protein breakdown, metabolic response, ratings of perceived exertion, and recovery: a randomized, triple-blinded, placebo-controlled, crossover trial. J Int Soc Sports Nutr. 2023b Dec; 20 (1): 2204083. * Stefan N. Metabolically healthy and unhealthy normal weight and obesity. Endocrinol Metab (Seoul). 2020 Sep;35(3):487-493. * Xiong Q, Zang Y, Li J, An Y, and Yu S. Comparison of cardiovascular disease risk association with metabolic unhealthy obesity identified by body fat percentage and body mass index: Results from the 1999-2020 National Health and Nutrition Examination Survey. PLoS One. 2024 Aug 14; 19 (8): e0305592. * Wu Y, Li D, and Vermund SH. Advantages and limitations of the body mass index (BMI) to assess adult obesity. Int J Environ Res Public Health. 2024 Jun 10; 21 (6): 757.

Pain in Aging Former Athletes, Master's Athletes, and Nonathletes

The goal of this clinical trial is to determine how male and female former athletes experience pain and respond to moderate-intensity exercise (strength versus aerobic) compared with both current master's athletes and nonathletes. The main questions this study aims to address are: 1. How do former athletes, master's athletes, and nonathletes experience pain? 2. How do different types of moderate-intensity exercise (strength versus aerobic exercise) influence pain in former athletes, master's athletes, and nonathletes? Participants will complete 3 different testing sessions: 1. Baseline testing including assessments of strength, cardiorespiratory fitness, and pain; 2. Strength exercise: pain assessments will occur before and after moderate-intensity strength training exercise; 3. Aerobic exercise: pain assessments will occur before and after moderate-intensity aerobic exercise. There will be a washout period of approximately one week or greater between each of the three different testing sessions. The order of conditions (strength versus aerobic exercise) will be randomized (crossover randomized trial design).

Skeletal Muscle Aging and Responsiveness in Aged People With MS

The purposes of this study are to: 1) compare baseline muscle and cardiovascular health in older individuals (\>60 years old) diagnosed with MS to age-matched people without MS, 2) determine muscle and whole body changes to an exercise training program, 3) determine if the muscle in a more affected leg in individuals diagnosed with MS is different from the muscle of a less affected leg, and 4) if or how individuals diagnosed with MS adapt differently than age-matched people without MS to exercise training. Participation in this study will average 1.5 hours per visit, 3 visits per week, for approximately 4 months.

Project SIRT6 Activator

The global ageing population is increasingly affected by age-related diseases, which are challenging healthcare systems. Current treatments often extend lifespan without improving healthspan. The geroscience hypothesis suggests that targeting the ageing process could prevent or delay multiple diseases, enhancing healthspan. Fucoidan, a sulfated polysaccharide from brown macroalgae, is a safe dietary supplement with Sirtuin-6 (SIRT6) activating properties, which are linked to longevity. Clinical studies have shown that it reduces inflammatory markers associated with biological aging and frailty and influences DNA methylation in vitro and in vivo; however, its effects on human DNA methylation remain unknown.

Aurora: AI-Based Narrative Intervention to Support Emotional Well-Being in Clinical and Non-Clinical Populations

Aurora is an interdisciplinary project evaluating a chatbot-mediated supportive care intervention designed to promote emotional expression, autobiographical meaning-making, identity processes, and emotional well-being through guided narrative reconstruction. The Aurora system provides a structured, person-centered storytelling process supported by generative AI and human facilitation. Under the supervision of a trained facilitator (licensed mental health professional), participants engage in guided reminiscence and storytelling sessions to co-create a personalized "life book." The chatbot is not a diagnostic or treatment tool; rather, it is intended to support emotional expression, narrative reconstruction, and recovery-oriented processes. The study includes three non-randomized arms implemented sequentially: (1) a single-session arm of healthy adults focused on acceptability, usability, and emotional safety; (2) a four-hour intervention arm of adults with DSM-5 diagnosed mental disorders in residential care; and (3) a four-hour intervention arm of healthy older adults aged 65 years and older. Quantitative outcomes assess affect, mental well-being, and recovery-related constructs. Additional measures include usability, satisfaction, and qualitative feedback. Ecological momentary assessment (EMA) is conducted in Arms 2 and 3.

Using Nicotine to Reverse Age-related Auditory Processing Deficits

The present study will evaluate the effects of both aging and nicotine on psychophysical tasks and electrophysiological measures. Nicotine will be administered to study participants in the form of gum that is available as an over-the-counter medication. The hypothesis is that nicotine will reverse the detrimental effects of aging on auditory processing. The proposed experiments will characterize the effects of nicotine and may eventually lead to improved treatments of hearing loss in a variety of patient populations and in healthy aging.

Guided Episodic Future Thinking to Increase Physical Activity Adherence and Promote Healthy Brain Aging

The goal of this behavioral clinical trial is to learn how to increase physical activity in mid-life adults. Specifically, can guided imagery that includes creating mental pictures increase excitement about working out. Participants will be asked to complete testing at the beginning of the study, following 6-weeks of an in-person exercise program, and 6-weeks after finishing the exercise program. Testing will include an exercise test, MRI, questionnaires, computer tasks, and a blood draw.

Baltimore Longitudinal Study of Aging

Background: \- The Baltimore Longitudinal Study of Aging (BLSA) is a clinical research program on human aging that began in 1958. Volunteers of different ages join the study when they are healthy, and have follow-up visits for life. Visits last for multiple days. Participants are evaluated for many physical elements as well as for brain function. Physical tests are given. Information on mood, personality, and social aspects of life is also collected. This program has contributed more than any other research project to our understanding of aging. Objectives: \- To characterize the many aspects of the aging process and learn how people can successfully adapt to aging. Eligibility: \- Healthy individuals at least 20 years old. Design: * Participants will receive a booklet and video describing the tests they will take. * During a 3-day visit at the study hospital, participants will take the following tests: * Urine will be collected for 24 hours. Blood samples will be taken. A small piece of muscle tissue may be collected by a needle. * A medical questionnaire and a physical exam will be given. * Participants hearts will be tested, including with blood pressure tests and electronic monitors. They will breathe into a tube to test their lungs. * Participants will perform several exercises, including treadmill walking. * Vision, hearing, and taste will be tested. * Bone and joint X-rays may be taken. * Imaging tests will be given, such as an MRI. * Participants will answer questions to test their mental abilities. * Participants will return for follow-up visits every few years for life. The tests listed above will be given at every visit.

Feasibility of A Smartphone Application Intervention in Community Settings: A Pretest-Posttest Pilot Study

The objective of this project is to test the feasibility of using a smartphone app in a community setting through collaborating with community-based organizations. The app is called utmbHealthyBrain and it has three activities: (1) drawing, (2) Tai-Chi and meditation, and (3) prayer reading. It also has a "share" function to enable users to interact with their family and friend. These activities can be translated to humans' well-beings such as a more stable emotion, more muscle movement, and better social engagement. This app does not collect any personal data and users are not required to register an account either. The overall study period is 6 weeks including one introduction session (week 1), four weeks of intervention (week 2 to 5), and final feedback session (week 6).

Effects of Functional Task Training on Muscle Health and Function in Older Adults With Sarcopenia

Sarcopenia is a condition associated with aging that causes a loss of muscle mass, strength, and physical function. This decline limits the ability to perform basic daily activities and increases the risk of falls and dependency. The purpose of this clinical study is to determine the effects of a 12-week Functional Task Training (FTT) program on functional, structural, and physiological biomarkers in older adults with sarcopenia. FTT involves practicing everyday movements, such as standing up from a chair, climbing stairs, walking, and carrying objects. The study aims to answer the following question: Does Functional Task Training performed specifically in optimal muscle power zones offer greater improvements in aging biomarkers compared to standard Functional Task Training or traditional resistance training? The researchers hypothesize that while all exercise interventions will be beneficial, the FTT program focused on power zones will generate the greatest improvements in functional, physiological, and structural biomarkers in older adults with sarcopenia. To test this, 30 older adults (aged 60 and older) will be randomly assigned to one of three active groups for a 12-week period (2 days per week): an FTT group training in power zones, a standard FTT group, or a traditional resistance training group. All exercise groups will use a Functional Electromechanical Dynamometer (DEMF) to precisely measure and control the training loads.

Metabolic Profiling of Hematopoietic Stem Cells in Clonal Hematopoiesis (CHIP)

Bone marrow samples will be collected from patients undergoing hip arthroplasty surgery. Blood and bone marrow samples will be used for metabolic profiling and analysis of relevant CHIP mutations. Combined single-cell transcriptomics and mutation-specific single-cell genotyping (biotin-PCR using mutation-targeted primers followed by sequencing) will subsequently be performed. The gene expression profile of wildtype and mutant hematopoietic stem cells will be compared, performing both broad gene set enrichment analysis and targeted analysis of metabolic pathways.