Clinical Research Directory

Dopaminergic Dysfunction in Late-Life Depression

Late-Life Depression (LLD), or depression in older adults, often presents with motivational deficits, deficits in performance in cognitive domains including processing speed and executive dysfunction, and mobility impairments. This triad of findings implicate dopaminergic dysfunction as a core pathophysiologic feature in depression, and may contribute to cognitive decline and motor disability. Normal aging results in brain-wide dopamine declines, decreased D1/D2 receptor density, and loss of dopamine transporters. Although brain changes associated with depression and aging converge on dopamine circuits, the specific disturbances in LLD and how responsive the system is to modulation remain unclear. In this study, investigators are testing integrative model that aging, in concert with pro-inflammatory shifts, decreases dopamine signaling. These signally changes affects behaviors supported by these circuits, in the context of age-associated cortical atrophy and ischemic microvascular changes, resulting in variable LLD phenotypes. Investigators propose a primary pathway where dopaminergic dysfunction in depressed elders contributes to slowed processing speed and mobility impairments that increase the effort cost associated with voluntary behavior. The central hypothesis of this study is that late-life depression is characterized by dysfunction in the dopamine system and, by enhancing dopamine functioning in the brain. By improving cognitive and motor slowing, administration of carbidopa/levodopa (L-DOPA) will improve depressive symptoms.

Effects of Comprehensive Community Support Programs on Cognitive Function and Quality of Life in Older Adults

This prospective observational study aims to investigate the effects of a multidomain community-based support program on cognitive function and quality of life in older adults attending the Vefahane Life Center in Istanbul, Türkiye. The study will compare elderly individuals actively participating in community-based social, cognitive, physical, and supportive activities with individuals registered at the center but not actively participating during the study period. Participants will undergo neuropsychological and psychosocial assessments at baseline and after 3 months. The primary outcome is change in global cognitive performance measured by the Mini Mental State Examination (MMSE). Secondary outcomes include memory, executive functions, depression, neuropsychiatric symptoms, and quality of life measures.

Digitally Supported Lifestyle Programme to Promote Brain Health Among Older Adults

Previous research has shown that a healthy lifestyle, including a balanced diet, physical and social activity, and management of vascular risk factors can support both cardiovascular and brain health. In a landmark Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a multimodal lifestyle programme had clear benefits on older adults' cognition, functioning, and quality of life. The LETHE study utilises novel technologies and digital tools to deliver an optimised and more personalised FINGER-type multimodal lifestyle intervention. A total of 160 digitally skilled older adults (age 60-77) with risk factors for dementia but without substantial cognitive impairment will be recruited in Austria, Finland, Italy, and Sweden. Participants will be randomly assigned in a 1:1 ratio to the structured ICT-assisted multimodal lifestyle program (intervention group) or a self-guided lifestyle program (control group). Duration of the study and the intervention is 24 months. The multimodal lifestyle program covers the following domains: physical activity, nutrition, cognitive activity, vascular risk management, social interaction, sleep, and relaxation. The structured intervention program follows a hybrid model where regular in-person, individual and group-based intervention activities led by professionals are supported with activities in the LETHE mobile phone application. The self-guided (control) group receives relevant health advice and is recommended and encouraged to independently implement healthy lifestyle changes that are suitable and fit in with their daily routine. Control group will have access to a simplified version of the LETHE app without any structured, scheduled activities or personalized content. The primary objective of the LETHE trial is to test the feasibility of a digitally supported multimodal lifestyle program (i.e., retention rate, adherence to intervention), and assess change in dementia risk based on validated risk scores (CAIDE, LIBRA). Other objectives include testing the intervention effects on lifestyle and risk factors, cognition, function, health-related quality of life, health literacy, physical functioning, and dementia-related biomarkers. To this aim, a range of personal, lifestyle, and health-related data will be collected both actively and passively with the help of digital devices. Attitudes towards digital tools and experiences of trial participation will also be explored.

The Influence of Tai Chi Practice on Blood Pressure and Brain Health Among Older Adults With Hypertension (ACTION)

High blood pressure and poor cognitive function are two common health problems among older adults in the United States. They are also closely related because high blood pressure may lead to negative changes in brain structure and function such as poor brain blood flow that can cause poor cognitive function. Executive function is one type of cognitive function that let people plan and perform difficult tasks. It is commonly damaged by high blood pressure. It is also very important for older adults because they need good executive function to live on their own. Tai Chi is a good exercise option for older adults because it is safe, fun, and social. Research studies show that Tai Chi can reduce blood pressure and improve cognitive function, especially executive function. However, researchers do know if these heart and brain health benefits of Tai Chi are connected. In the ACTION study, researchers will first measure how a single session of Tai Chi followed by a 12-week online Tai Chi program with easy movements changes blood pressure and cognitive function, focusing on executive function. Then, researchers will test if these changes in heart and brain health are connected, and if they are connected through the changes in brain structure and function. Both the single session and 12-week online Tai Chi program will be practiced by a group of older adults with high blood pressure and normal cognitive function. They will be new to Tai Chi and not exercising regularly. The hypotheses of the ACTION study are that practicing Tai Chi is good for the heart and brain of older adults with high blood pressure. Specifically, relaxing Tai Chi with gentle movements will reduce blood pressure, and thereby improve cognitive function, particularly executive function.

Cognitive Status After Removal of Skull Base Meningioma

The purpose of this prospectively enrolling trial is to assess long-term cognitive outcomes of patients undergoing surgery for resection of a meningioma associated with the frontal and temporal lobes.

Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly

Over the past ten years, the number of endovascular procedures has increased by 5% per year in Europe with the development of interventional cardiology, such as percutaneous coronary angioplasty, aortic valve replacements (TAVR), and vascular endoprosthesis. The neurological lesions detected on cerebral MRI caused by these endovascular procedures are frequent with an incidence of about 30-70%. These events, although subclinical, have an impact on morbidity and mortality and especially on long-term cognitive decline. TAVR is the reference treatment for symptomatic elderly patients with stenosis of the aortic valve, considered by a multidisciplinary "Heart Team" as at high surgical risk due to comorbidities, age and high perioperative risk scores ( Euroscore 2 and STS scores). Despite the net clinical benefit, an increase of silent neurological events was detected on post-procedural cerebral MRI with an incidence of approximately 70%. The epigenetic involvement in the occurrence of ischemic cerebral lesions is still largely unknown. Epigenetic mechanisms, such as DNA methylation, can be associated with aging processes and modulate the risk of developing cerebrovascular pathologies. They are likely to provide new biomarkers that predict the risk of brain damage. Hypomethylation of leukocyte DNA is directly related to atherosclerosis in humans. This hypomethylation of DNA would represent an easily measurable marker reflecting the presence and progression of atherosclerosis. Because atherosclerotic lesions often precede the clinical manifestation of ischemic cardiovascular disease, such as ischemic heart disease and stroke, DNA hypomethylation could be used to identify individuals at risk for cerebrovascular events. The investigator hypothesize that hypomethylation of leukocyte DNA can predict the risk of developing new ischemic brain lesions especially after a TAVI procedure.

Effects of Turning Based Dual Task Training on Balance and Mild Cognitive Impairment in Diabetic Peripheral Neuropathy

Diabetic Peripheral Neuropathy (DPN) is a common complication of diabetes, characterized by impaired sensory and motor function, often leading to balance dysfunction and an increased risk of falls. Additionally, individuals with DPN are at heightened risk for mild cognitive impairment (MCI), which further compromises functional independence. This study aims to determine the effects of turning-based dual-task training compared to conventional dual-task training on balance, cognitive function, and fall risk in individuals with DPN. Pre- and post-intervention assessments will be conducted using the Berg Balance Scale (BBS), Montreal Cognitive Assessment (MoCA), and Timed Up and Go Test (TUGT) to evaluate balance, cognition, and fall risk respectively.

Minocycline In Neurocognitive Outcomes - Sickle Cell Disease

Sickle cell disease (SCD) is a common, inherited blood disorder that primarily affects people of African Ancestry. It has a lot of complications including neurological complications. The neurological complications of SCD are particularly devastating and lead to cognitive decline even in the absence of overt brain injury. In such cases, it is thought that inflammation in the brain maybe partly responsible for the cognitive decline. The main reasons for this research study are to see 1) how safe and 2) how well minocycline works to try to stop/reverse cognitive decline in people with SCD. People with SCD are at risk for changes in their brain over time that can cause problems with learning, memory, and attention. Part of the reason for this is inflammation within the brain. Minocycline may be able to stop these brain changes by stopping this brain inflammation. Minocycline is a second-generation tetracycline antibiotic that has been shown to both inhibit neuroinflammation and improve cognitive function in a variety of neurodegenerative and psychiatric disorders but has not yet been studied in SCD. We are proposing here, a pilot double-blinded, randomized controlled trial to examine the tolerability and early efficacy of minocycline in adults with SCD at two dosing regimens (200 mg and 300 mg daily) versus placebo over one year. Participants will undergo a neuropsychological exam using the NIH Toolbox Cognition Battery at both study enrollment and exit (after one year) to assess for changes/stability of cognition. Participants will receive monthly phone calls/text messages to assess for adverse events and will be seen every three months for pill counts and routine laboratory monitoring. The primary outcome will be a comparison of adverse events across the two dosing strategies versus placebo. Early evidence for cognitive benefit will also be assessed from the results of the NIH Toolbox.

Community-Based Social Connection Intervention Program to Improve Cardiovascular and Brain Health

This study evaluates the effectiveness of a community-based social connection intervention program (SCIP) designed to reduce social isolation and loneliness and improve cardiovascular and brain health among older adults living in rural Ecuador. Loneliness and social isolation are recognized risk factors for poor cardiovascular outcomes, cognitive decline, depression, and reduced quality of life. However, evidence from low- and middle-income countries, particularly in rural Latin American settings, remains limited. This protocol describes a quasi-experimental, longitudinal study conducted in three rural villages that have been part of a long-standing population-based cohort. The intervention will be implemented in one community and compared with two similar communities that will continue receiving usual community activities. SCIP consists of three components: (1) monthly community activities and educational talks designed to promote social participation; (2) monthly peer-support group sessions facilitated by trained personnel; and (3) individualized home-based coaching delivered twice per month, incorporating principles of Social Cognitive Theory and Cognitive Behavioral Therapy. The program aims to strengthen social networks, enhance coping skills, and promote healthier behaviors. Participants aged 60 years and older will be enrolled and followed for 12 months. Assessments will occur at baseline, 6 months, and 12 months. Primary outcomes include changes in social isolation (Lubben Social Network Scale-6) and loneliness (De Jong Gierveld Scale). Secondary outcomes include cardiovascular health (Life's Essential 8), sleep quality (Pittsburgh Sleep Quality Index), cognitive performance (Montreal Cognitive Assessment), depressive symptoms (DASS-21), and quality of life (SF-36). Exploratory outcomes include incident stroke, cardiovascular events, and mortality, monitored through ongoing community surveillance. This study will generate evidence on the feasibility and impact of a culturally adapted, community-based intervention to promote social connection and healthy aging in a resource-limited rural setting. Findings may inform scalable public health strategies for older adults in similar contexts.

Successful Aging and Age-related Decline

Recent studies have shown promising cognitive and physical interventions aimed at slowing down ageing-related declines in quality of life, but they lack strong ecological validity (brief durations, unrealistic goals, no real-world application) and has yet to show robust evidence that such interventions are stable and suitable in the long-term. The investigators aim to examine whether these interventions can, over four years, significantly slow down the normal rate of ageing-related decline.

Cognitive Changes and Neural Correlates After Rehabilitation of Masticatory Function in Elderly -an Intervention Study

Today in elderly tooth loss and loss of oral function is widespread, but it is an underexplored modifiable risk factor potentially contributing to the development of dementia. In this interventional study a "cause-effect" relationship between mastication and cognition in humans will be investigated. A total of eighty (80) participants, 65-80 years of age, indicated for prosthodontic rehabilitation will be randomly assigned to either the experimental or the control group. Participants will be randomized into two different groups, measurements are going to be conducted before and after prosthetic rehabilitation. The difference between the two groups is that the control group are going to do two measurements before undergoing the rehabilitation, this to control for the test-re-test effect. The aim with this study is to determine if the rehabilitation of chewing function will cause changes in the neurocognitive assessments of episodic memory and learning.

Effect of Hypoxic Conditioning on Cerebrovascular Health in the Elderly

In line with the ever-growing aging of Western populations, the development of preventive strategies to slow down the effects of aging on cardiovascular health represents a major challenge in order to preserve functional capacities and a sufficient quality of life in the elderly. The alteration of vascular function (at the cerebral and systemic level) with aging is an important feature in the clinical picture including a decrease in physical and cognitive capacities. Although physical activity is recognized as an essential means of combating the effects of aging, optimizing its effects by defining the most effective strategies of practice remains a key objective. Offering alternative interventions to exercise training is also necessary for people who are unwilling or unable to engage in a physical activity program. In this context, hypoxic conditioning, alone or in conjunction with rehabilitative exercise training, is a new therapeutic modality with strong preclinical validity, in particular from a cardiovascular standpoint, and used in other pathologies to improve cardiovascular function and exercise performance and quality of life. Our aim is, therefore, to investigate the effect of hypoxic conditioning (alone or in conjunction with exercise training) on cerebrovascular health in the elderly.

Memantine and Exercise to Improve Cognitive Function and Modulate Biological Pathways of Cognitive Decline During Chemotherapy in Breast Cancer

This randomized, placebo-controlled trial aims to assess the feasibility, acceptability, and preliminary efficacy of memantine and the University of Carolina (UNC)'s Get Real \& Heel cancer exercise program (MEM+EX) in addressing cancer-related cognitive impairment (CRCI) and underlying CRCI biomarkers. Ninety stage I-III breast cancer patients during chemotherapy will be randomized into three groups: MEM+EX, memantine, or placebo. The study will evaluate recruitment, retention, adherence, acceptability, cognitive function, brain-derived neurotrophic factor (BDNF), inflammatory markers, and frailty at multiple time points.

A Pivotal Study of Sensory Stimulation in Alzheimer's Disease (HOPE Study)

This is a randomized, double-blind, sham-controlled pivotal study of sensory stimulation in subjects with mild to moderate AD. Up to approximately 670 subjects will be treated with either Active or Sham investigational device, Spectris™ AD, for 60 minutes daily for approximately 12 months. Efficacy will be measured using the Integrated Alzheimer's Disease Mini-Mental State Exam (MMSE) Activities of Daily Living (ADCS-ADL) Rating Scale (iADMARS).

δ in Dementia Clinical Trials

The goal of this clinical trial is to demonstrate potential improvements in clinical trial methods relating to dementia and cognitive decline. The main questions it aims to answer are: * Can an intervention's outcome be better assessed by a latent variable ("δ") integrating cognitive performance with functional status? * Can latent biomarkers of δ guide the selection of an intervention that will modulate dementia severity? * Can a latent variable, derived from information collected remotely from caregivers, preselect subjects most likely to respond to the intervention? * Is the effect of the intervention in fact medicated by changes in the targeted biomarker? In this case, the biomarker will be a latent variable derived from several proteins measured in blood (i.e., so-called "adipokines"). The intervention will be donepezil, a medication approved for the treatment of Alzheimer's Disease, but only recently associated with adipokine changes. Participants with cognitive impairment and their caregivers will be interviewed by telephone and those newly prescribed donepezil by their provider for cognitive impairment will be recruited and enrolled. On the basis of the caregiver's report, the cognitively impaired subjects will be assigned to two groups based on a prediction of their response to donepezil. Researchers will compare those groups to see if dementia severity, as measured by δ, improves in predicted responders, and whether the change in the d-score is mediated by changes in adipokines.

Fortifying Healthy Behaviors, Optimizing Medical Therapies and Enhancing Cognitive Function in Older Adults-pilot Study

The purpose of this research study is to explore ways to improve motor, cognitive and immune functions for aging adults using multiple techniques like lifestyle changes and risk factor management, as well as medications and supplements believed to have a positive effect on health.

A SMART Trial of Adaptive Exercises to Optimize Aerobic-Fitness Responses

The goal of this clinical trial is to test 6 months of aerobic exercise in older adults who are 65 years or older and have mild cognitive impairment (MCI) or probable/possible mild Alzheimer's Disease. The main questions it aims to answer are: * test the effects of aerobic exercise on aerobic fitness, white matter hyperintensity (WMH) volume, and patient-centered outcomes; * identify the best exercise to improve aerobic fitness and reduce non-responses over 6 months; and * examines the mechanisms of aerobic exercise's action on memory in older adults with early AD. Participants will receive 6 months of supervised exercise, undergo cognitive data collection and exercise testing 5 times over a year span, have an MRI brain scan 3 times over a one-year span, and have monthly follow-up discussions on health and wellness.

Measuring and Mapping Cognitive Decline After Brain Radiosurgery

Background Stereotactic Radiosurgery (SRS) is a localised radiotherapy treatment for patients with brain metastases or other benign tumours in the brain, like meningiomas. The Investigators do not currently know if, or how much, SRS affects brain function. Patients with brain tumours do not get tested routinely for their brain function. Understanding short- and long-term side-effects is important for SRS. Brain metastases patients have short life expectancies (6-months to 1-year). However, meningioma patients can live 10 years or more. SRS is used to treat both. The Montreal Cognitive Assessment will be used to test the participants' brain function. Quality-of-life questionnaires QLQ-C30 and BN20 will also be used to assess the participants' physical and mental wellbeing . These are specific for patients with brain cancer. Why is it important This study aims to identify areas in the brain that relate to changes in brain function after SRS. These areas can then have the radiation dose reduced to them in future patients, hoping to minimise side-effects. Research Question Which regions of the brain contribute to a decline in brain function following SRS. Study Design This is a single centre observational study with prospective and retrospective collection of data. This study will look at two groups of patients: Group1: Patients will complete the MoCA and two quality-of-life questionnaires before the treatment and every 3 months for a year. Group2: Patients will complete the MoCA and two quality-of-life questionnaires once. The investigators will use these tests, MRI scans and the SRS treatment plan to identify areas of the brain that are responsible for any problems with the participants' brain function. The participants for Group 1 will be recruited from the SRS Clinics, at City Campus, Nottingham University Hospitals NHS Trust. The participants for Group 2 will be identified through the Mosaiq Oncology Information System. This pilot study is funded by the Midlands Mental Health and Neurosciences Network.

A Clinical Trial to Investigate the Efficacy of the Brain Blossom Supplement to Improve Cognitive Function and Memory

This study evaluates the efficacy of BioNatureHealth's Brain Blossom supplement in improving cognitive function and memory in adults aged 50-70 years. Participants will be randomized to receive either the test product or placebo over 8 weeks, with cognitive battery testing and questionnaires administered at multiple timepoints.

MindWalk Intervention for Older South Asian Caregivers of People With Cognitive Disabilities (CD)

Older South Asian family caregivers experience elevated psychological stress and limited physical activity (PA) due to caregiving responsibilities and additional factors such as lack of access to services, cultural/linguistic barriers, stigma and discrimination. South Asian family caregivers are especially underserved and are a growing ethnic group in the US. Both PA and cognitive training (CT) have shown to improve cognitive function in older adults who experience cognitive function decline because of psychological stress. However, there are no studies using this approach for this population. We propose a randomized control trial pilot study to address this gap. Driven by a Community Advisory Committee (CAC) we will develop this 12-week mindful walking intervention using a participatory methodology in partnership with UIC's Cognition Behavior and Mindfulness Clinic that combines the PA of walking and the CT through mindfulness. We will recruit fifty participants and will randomly and equally assign 25 people to the intervention and 25 people to the control group. The intervention will include: 1) a mindful walking training followed by 2) a prescribed mindful walking regimen, 3) self-reporting of adherence to regimen by the participants using activity logbooks and use of a user-friendly PA tracker (Fitbit) for daily step count, and 4) personalized text messages with reminders and motivational messages for participants to do the mindful walking as prescribed including a weekly check-in call or text message for accountability. The primary aim of the proposed pilot study is to evaluate the feasibility and acceptability of the protocol and intervention implementation. A secondary aim will evaluate the intervention to examine preliminary efficacy in reduction of psychological stress, improvement in cognitive function, increase in physical activity, and increased self-efficacy (self-efficacy for coping with stress, self-efficacy for physical activity, and overall self-efficacy). The findings of this pilot project will provide evidence-based data to support a larger scale study proposal for future funding such as the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) field initiative award, or the National Institute of Health (NIH) Research Project Grant (R21 NIH Exploratory/Developmental Research Grant Award) award, especially National Institute on Aging (NIA) grants.

Brain Health Together: A Live-Streaming Group-Based Digital Program

The purpose of this study is to develop and test a comprehensive Brain Health Together program for older adults living with cognitive decline.

Effects of Blood Pressure on Cognition and Cerebral Hemodynamics in PD

The goal of clinical trial is to learn about how blood pressure fluctuations affect cognitive performance (thinking abilities) and brain blood flow in persons with Parkinson's disease with and without orthostatic hypotension (low blood pressure when standing). The main questions it aims to answer are: * Is there a certain level of blood pressure that correlates with change in cognitive performance while upright? * Is there a certain level of change in brain blood flow that correlates with change in cognitive performance when upright? * How does cognitive performance differ between persons with Parkinson's disease that have orthostatic hypotension and those without orthostatic hypotension? * How does cognitive performance differ between the supine (laying down) and upright positions? * How do blood pressure and brain blood predict changes in cognitive performance over two years? Participants in this study will undergo the following procedures: * Complete a screening visit with questionnaires, medical history, physical exam, and head-up tilt-table test. * Attend one baseline study visit, during which they will undergo a battery of computerized cognitive tests repeated twice: once while laying down and once while upright on a tilt table. Simultaneously, during the experiments we will measure blood pressure using a wrist-worn device and inflatable arm cuff and will measure brain blood flow using functional near-infrared spectroscopy (fNIRS), a non-invasive device that uses light sensors to detect changes in brain blood flow. * Attend one two-year follow-up visit, during which they will repeat a battery of computerized cognitive tests repeated twice: once while laying down and once while upright on a tilt table. During this visit, like before, we will measure blood pressure using a wrist-worn device and inflatable arm cuff and will measure brain blood flow using functional near-infrared spectroscopy (fNIRS). Researchers will compare participants with Parkinson's disease with and without orthostatic hypotension in the laying down and upright positions to see if there are changes in thinking abilities between these groups.

Building a Platform for Precision Anesthesia in the Geriatric Surgical Patient

The research team is creating a foundational infrastructure in order to develop a precision medicine approach for geriatric patients who require surgery with anesthesia. The team plans to build the first of its kind comprehensive database of demographic and risk factor questionnaire responses, biobanked blood specimens, intraoperative electroencephalography (EEG), and inclusive cognitive testing throughout patient interaction starting at the preop appointment until a year later. This will be used to create a predictive model of periooperative neurocognitive disorders.

Culturally Familiar Nostalgic VR Cognitive Training for Older Adults

This randomized controlled trial investigates the effects of a nostalgia-based cognitive training intervention delivered via Virtual Reality (VR) on emotional well-being and cognitive functioning among community-dwelling older adults (≥65 years) in northern Taiwan, specifically targeting those with mild cognitive impairment (MCI) or mild dementia. The study, conducted at National Taiwan Normal University, aims to assess whether engaging older adults in nostalgic VR experiences can enhance nostalgia proneness, life satisfaction, and psychological well-being, while also reducing depressive symptoms and improving cognitive functions. Participants who meet inclusion criteria (aged 65+, capable of communicating in Mandarin or Taiwanese, without severe psychiatric conditions, with sufficient vision/hearing) will be randomly assigned to either the experimental group receiving the "Brain Health Nostalgic VR Program" or a control group engaged in routine weekly activities. Each session, scheduled twice weekly, spans 25-35 minutes in total, including setup, support, and breaks, while the actual VR usage time is 15-25 minutes depending on individual tolerance. Research staff will provide close support and safety monitoring during all sessions. Pre- and post-intervention outcomes will be measured using standardized assessments: Southampton Nostalgia Scale (SNS), Short-Form Life Satisfaction Index (LSI-SF), Geriatric Depression Scale (GDS-15), Short-Form Chinese version of Ryff's Psychological Well-being Scale (PWB-18), and the Montreal Cognitive Assessment Taiwan Version (MoCA-T). The study emphasizes participant safety and data confidentiality throughout its duration. Findings aim to demonstrate VR's potential as a non-invasive, preventive strategy for cognitive decline and mental health enhancement among older populations.