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.

Music Improvisation Training on Cognitive Function in Older Adults

This project will study the effects and mechanisms of a music improvisation training intervention on self-regulation of older adults with and without MCI. The investigator's overall hypothesis is that improvisation training will lead to improvements in self-regulation, compared to controls, and that improvisation training will be associated with specific changes in prefrontal brain networks and ultimately cognitive engagement.

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.

Italian Validation of the dNA Scale and Its Correlation With Neurocognitive Variables

The goal of this experimental multicentric intervention study is to validate, in Italian, the dynamic Neurocognitive Adaptation (dNA) Scale, which has already been validated in English, among a healthy elderly population (aged 65 and older) residing in Italy and patients with dementia or Alzheimer's Disease. dNA is a questionnaire designed to assess both current and past levels of engagement in physical, cognitive, creative, and social activities. The study aims to recruit a total of 265 participants with mild cognitive impairment, subjective memory complaints, or dementia. These participants will be distributed among the 8 recruitment centers. Neuropsychological data, subjective measures, and MRI data will be collected and analyzed to address the following research questions: 1) Is there a positive correlation between scores on the dNA Scale and cognitive efficiency, as reflected in neuropsychological measures, such as episodic memory and executive functions? 2) Is there a correlation between dNA scores and improved functional connectivity within neural networks, such as the Default Network (DN)? Participants recruited at the participating clinical centers will undergo: * A clinical interview, during which demographic and medical history information will be collected. The dNA Scale will be administered, along with a questionnaire assessing adherence to dietary habits typical of a Mediterranean diet (14-Item Mediterranean Diet Adherence Screener; MEDAS). * A neuropsychological assessment, aimed at evaluating general cognitive function with a particular focus on episodic memory and executive functions. The following tests will be administered: Mini-Mental State Examination (MMSE) or, alternatively, Montreal Cognitive Assessment (MoCA); Rey Auditory Verbal Learning Test (RAVLT); Trial Making Test (TMT) Form B; Digit Span Forward and Backward (WAIS or WAIS-III); and the Stroop Test. * Self-report questionnaires designed to assess depressive symptoms using the Geriatric Depression Scale (GDS) and anxiety symptoms using the Geriatric Anxiety Scale (GAS) (or alternatively the State-Trait Anxiety Inventory, STAI). Finally, the Cognitive Reserve Index Questionnaire will be administered to estimate Cognitive Reserve (CRIq). * Where available, MRI data previously acquired for clinical or diagnostic purposes will be included in the study and analyzed by the principal investigator.

ACHIEVE Hearing Intervention Follow-Up Study

The ACHIEVE Hearing Intervention Follow-Up study is a randomized trial of a telehealth versus conventional clinic-based hearing healthcare (HHC) delivery model among older adults who are existing hearing aid users to determine if a telehealth HHC model improves hearing aid use and other communication outcomes compared to clinic-based HHC.

Identifying the Limits of Survivability in Heat-exposed Older Females

Climate change increases extreme heat events, elevating global heat-illness risk. Females have reduced heat loss capacity (\~5%) compared to males, driven by differences in skin blood flow and sweating responses. While findings on sex-mediated mortality are mixed, some studies suggest older females (≥65 years), face higher heat-related mortality/morbidity risks, evidenced by disproportionate female deaths in the 2021 Western Heat Dome. The effects of extreme uncompensable heat on older females remain understudied. Heat exposure initially causes net heat gain, raising core/skin temperatures and triggering heat-loss responses. Under compensable heat stress, heat loss balances gain, stabilizing core temperature. Uncompensable heat stress (exceeding maximal dissipation capacity) causes continuous core temperature rise, posing severe health risks. The specific temperature and relative humidity (RH) limits where compensability is lost are critical survival determinants, influenced by age and sex. Ramping protocols identify these limits: participants face progressively increasing heat stress (e.g., staged humidity rises) while core temperature is monitored. Core temperature typically stabilizes initially, then exhibits an abrupt rapid increase at an inflection point, operationally defined as the limit of compensability. Despite increasing use, ramping protocol validity for accurately identifying this threshold remains unverified. This project assesses ramping protocol validity for determining uncompensable conditions in older females and evaluates cumulative thermal and cardiovascular strain, as well as psychological and cognitive responses to both uncompensable and compensable heat. Participants will complete five trials. Trial 1 (Ramping): Rest at 42°C, 28% RH for 70min, then incremental RH increases (3% every 10min) to 70% RH. Individual core temperature (rectal) inflection points are identified from the ramping trial. Trials 2-5 (Fixed Conditions, Randomized): i) \~10% below inflection; ii) \~5% below inflection; iii) \~5% above inflection; iv) Thermo-neutral control (26°C, 45% RH). Comparing the rate of rectal temperature change and cumulative strain during prolonged fixed exposures (especially below vs. above inflection) will validate if the ramping inflection point represents the true limit of compensability for older females.

A Social Media Game to Increase Physical Activity Among Older Adult Women

This study will test the effects of a social media game on the physical activity of older adult women. The game will consist of playful weekly challenges that require sharing photographs on a private social media group and also wearing an activity monitor to track steps. Participants will be randomized to this game group or to receive the activity monitor only.

Enhancing Heat Resiliency in Older Adults During Indoor Overheating Via Heat Acclimation by Warm Water Immersion

As overheating in buildings is expected to increase as global warming continues, proactive measures to increase heat resiliency in heat-vulnerable older people are needed, especially for those without access to home cooling or reliable sources of electricity. While short-term heat acclimation through exercise in the heat has been shown to increase heat dissipation and decrease both the physical and mental stress imposed on individuals exposed to heat, such protocols are not tenable for older, sedentary adults. A recent report showed that seven consecutive days of warm-water immersion improved whole-body heat loss and reduced physiological strain as assessed during an exercise-heat stress in habitually active older men This represents a critical finding as an increase heat-loss capacity would serve as an important safeguard for older adults exposed to indoor overheating due to lack of air-conditioning. While this preliminary data highlights passive hot water immersion as a promising strategy for increasing heat-resilience in vulnerable adults, work is needed to confirm its efficacy in more "real-world" environments. Thus, this study aims to assess the effectiveness of a 7-day passive heating (warm-water immersion with core temperature clamped at \~38.5°C for the final 60 minutes) protocol in mitigating increases in thermal and cardiovascular strain in older females exposed to daylong (10-hours) indoor overheating (36°C, 45% relative humidity) prior to and following the passive heating intervention. Relative to males, females have a reduced heat loss capacity (\~5%), which is driven by differences in the activation of heat loss responses (i.e., skin blood flow and sweating). Although there have been mixed findings with regards to the influence of sex as a mediating factor for heat-related mortality, some studies suggest that females are at a higher risk of heat-related mortality and morbidity compared to males, especially amongst older individuals (≥65 years). Notably, a greater proportion of older females died compared to their male counterparts during the 2021 Western Heat Dome. While the underlying causes for these differences remain unclear, greater cardiovascular strain may place females at higher mortality risk during extreme heat.

100-Year Human Aging Study

The 100-Year Human Aging Study is a prospective, pragmatic, observational trial enrolling participants across fixed and mobile clinical sites to undergo comprehensive multi-system health screening and longitudinal follow-up until death. Participants are followed to determine whether measurements taken at enrollment and repeated across the lifespan - individually and in combination - predict all-cause mortality, cause-specific mortality, incident serious disease, and functional disability. The study is designed to generate the surrogate endpoint validation data that longevity medicine currently lacks.

Everolimus Aging Study

The objective of this project is to determine if mTORC1 inhibition by 24 weeks of daily (0.5 mg/day) or weekly (5 mg/week) everolimus can safely improve physiological and molecular hallmarks of aging in humans. Participants who are 55-80 years old and insulin resistant or prediabetic will be randomized to treatment and can expect to be on study for up to approximately 38 weeks. Participants aged 18-35 will not receive the intervention and can expect to be on study for up to approximately 8 weeks.

Glycine Supplementation Improves Cognitive Performance in Mexican Older Adults

The purpose of this study was to evaluate the effects of daily glycine supplementation on metabolic health and cognitive performance in older adults. Over a period of six months, participants received 1,000 mg of glycine per day to determine if this amino acid could improve markers of insulin resistance, glucose metabolism, and cognitive functions such as memory and executive tasks. The research aimed to identify whether this nutritional intervention provides a safe and effective strategy to support healthy aging, focusing on the link between metabolic balance and brain health in the elderly population.

Isa-Pom-Dex in Elderly/Frail Subjects With RRMM

This research study aims to evaluate the safety and effectiveness of the combination of isatuximab, pomalidomide, and dexamethasone (Isa-Pd) for the treatment of relapsed or refractory multiple myeloma (RRMM), which refers to multiple myeloma that has returned or has not responded to prior treatment. The study will specifically investigate the impact of administering lower-than-standard doses of pomalidomide and dexamethasone. Using lower doses of pomalidomide and dexamethasone in this setting has not been approved by the Food and Drug Administration (FDA).

Aerobic Exercise and Cerebrovascular Function

This proposal will evaluate two brain health measures, cerebrovascular perfusion and cerebrovascular reactivity (CVR), before and after a proven, interval-based, aerobic exercise intervention in older Veterans. The hypothesis is that the 12-week aerobic exercise intervention (Spin) will increase perfusion and improve CVR in brain regions susceptible to age-related decline. This information will inform the impact of exercise on cerebrovascular health which is known to be negatively impacted in aging and implicated in the development of neurodegenerative disease. This information will also aid the investigators' continued efforts of clinical implementation of evidence-based exercise interventions in the local Atlanta VA and surround region.

Effects of a Powered Lower-Limb Exoskeleton on Walking Performance in Older Adults

The goal of this clinical trial is to learn whether a powered wearable lower-limb exoskeleton can improve walking performance in independently ambulatory older adults aged 65 to 75 years. The main questions it aims to answer are: * Does use of a powered lower-limb exoskeleton increase comfortable walking speed over 10 meters? * Does use of a powered lower-limb exoskeleton increase average walking speed during a 400-meter walk? Researchers will compare walking performance in older adults during walking with the powered exoskeleton and walking without the device to determine whether the exoskeleton improves mobility. Young-adult reference participants will also complete walking assessments to provide reference values for walking performance. Participants will: * Attend a screening and familiarization visit. * Complete walking assessments with and without the powered exoskeleton in randomized order (older adults only). * Perform a 10-meter walk test, a 400-meter walk test, and other physical performance assessments. * Complete questionnaires about balance confidence, fear of falling, and device usability. * Be monitored for safety events during testing.

Prepare for Your Diabetes Care

As adults with type 2 diabetes age, they are increasingly vulnerable to treatment-related hypoglycemia and its related complications (including hospitalization and death). This study proposes to evaluate, in a randomized clinical trial, a strategy of expanded advance care planning to support older adults in value-aligned re-assessment of diabetes treatment regimens with their primary care team. If the aims of this project are achieved and incidence of clinically-significant hypoglycemia is reduced, this Prepare for Your Diabetes web-based patient educational care strategy could be scaled and applied in a wide variety of healthcare settings and chronic conditions in which evolving risks, benefits, and consequences of treatment require re-assessment with age.

Spinal Networks of Balance Learning and Retention in Older Adults

Age-related balance and walking issues increase fall risks, leading to injuries, higher healthcare costs, reduced quality of life, and increased morbidity/mortality rates. Preserving functional ability is a crucial public health priority, with the potential to reduce healthcare costs and enhance older adults' quality of life. Declines in balance and walking ability threaten independence. These declines are attributed to spinal network impairments and may be mitigated by targeted interventions aimed at addressing age-related spinal cord impairment to enhance functional outcomes. However, there is a lack of research into how the aging spinal cord affects balance/walking. In older adults, the spinal cord is less excitable, conducts signals more slowly, and is subject to neural noise. Intervening on age-related impairment of the spinal cord to improve balance/walking ability is a very promising but untapped area of research. A therapeutic approach that combines dynamic balance training with non-invasive electrical spinal stimulation may be effective in preserving functional abilities. This study tests whether electrical stimulation of the spinal lumbar regions is more beneficial than sham stimulation.

Far Red Light to Improve Functioning in PAD

The LIGHT PAD Trial is a Phase II multi-centered randomized clinical trial to collect preliminary data to test whether daily far red light treatment of the lower extremities in people with PAD improves six-minute walk distance, lower extremity perfusion, and ischemia-related damage in gastrocnemius muscle at four-month follow-up, compared to a sham control. Participants will complete 10 minutes of twice daily home treatment with either far red light or a sham light for four months.

Walking Sensation Study

The primary objective of this new line of research is to test whether augmenting sensory information from the legs, using Walkasins sensory neuroprosthesis, can enhance performance of a complex walking task in older adults with foot sensory impairment. The overarching hypothesis is that Walkasins will enhance the automaticity and reduce cognitive demand of walking in older adults with foot sensory impairments, as measured by reduced prefrontal activity, decreased dual-task costs, and lower gait variability.

Strength and Pain-Coping Through Resilience and Knowledge

Older adults who are 50 years of age and older with depressive symptoms, pain and difficulty with mobility will participate in the SPARK intervention study that includes 8 nurse visits in participants' homes to help participants with participants' pain and mood.

Walking and Thinking - Brain Activity During Complex Walking in Stroke

Everyday life requires individuals to function in complex environments and perform tasks that involve the integration of motor and cognitive abilities. However, stroke often leads to impairments in motor-cognitive interaction, which can negatively affect mobility, balance, attention, and the ability to live independently. Although motor-cognitive performance has been identified as an important rehabilitation target after stroke, limited knowledge exists regarding the underlying brain function associated with these difficulties and how rehabilitation and exercise interventions can best address them. Improving treatment for motor-cognitive difficulties after stroke, such as dual-task walking and navigation, remains a major challenge. An important step is developing assessment methods that accurately capture these impairments in ecologically valid settings that reflect real-world mobility demands. The investigators therefore aim to explore brain function during complex walking after stroke by investigating motor-cognitive performance and its neural correlates during three walking conditions: dual-task walking, navigation, and a combination of both. Non-invasive measures of brain activity using functional near-infrared spectroscopy (fNIRS) together with advanced real-time gait analysis will be used to better understand how stroke affects motor-cognitive functioning during complex walking tasks.

Effect of Gerofit Exercise on Cognition in Older Veterans

Over 50% of the Veterans enrolled for VA health care are over the age of 65. Dementia prevalence increases with age, and with the increase in the population of people ages 65 and older, the total number of people with dementia is also increasing. Older Veterans often have comorbid PTSD, major depression and traumatic brain injury so that they are at 2 to 5 times the risk for cognitive impairment and dementia compared to the general population. There is evidence that exercise interventions in sedentary older adults could improve both physical and cognitive function. However, there have been very few studies on the effects of exercise on cognition in older Veterans and do not reflect the broader ethnic and health-status diversity of Veterans. Thus, improved knowledge of the role of exercise on cognition as well as the predictive power of biomarkers could have a major beneficial impact on Veterans' functional independence and quality of life. The investigators hypothesize that participation in the VA Gerofit exercise program will improve cognitive function in older Veterans and that blood and muscle biomarkers will predict these improvements.

RESTOR: PK/PD mTORi Inhibition in Older Adults

As people get older, there are changes in their cells and tissues that may affect their ability to function. This can lead to increased death and age-associated disorders, like heart disease, cancer, and Alzheimer's disease. Studies in animal models have been able to identify drugs that slow the aging process, leading to a longer, healthier life. This study is focused on one such family of drugs, called mTOR inhibitors, and the investigators' goal is to test two of these drugs, Rapamycin (Sirolimus) and Everolimus (Afinitor), in healthy older adults to find a dose and dose timing that can be used to safely inhibit mTOR to the levels seen in young healthy persons. The investigators expect that the dose that works well in women may differ from the one that is best in men, so it is important to include both sexes in this research.

ACHIEVE Brain Health Follow-Up Study

The ACHIEVE Brain Health Follow-Up Study is a 3-year follow-up to the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) randomized study to determine the long-term effect of hearing intervention vs. successful aging/delayed hearing intervention on rates of cognitive decline and incident mild cognitive impairment or dementia.

Reducing Blood Pressure in Mid-life Adult Binge Drinkers

This study has two phases: Phase 1 is to examine blood pressure, microvascular function, and sympathetic nerve activity in mid-life adult binge drinkers vs. alcohol abstainers/moderate drinkers. Phase 2 is to examine the effect of 8-week aerobic exercise training on blood pressure, microvascular function, and sympathetic nerve activity in mid-life adult binge drinkers