Mild Cognitive Impairment Clinical Trials

The primary objective of the study is to evaluate the efficacy of AGB101 on slowing cognitive and functional impairment as measured by reduction in neuronal injury in participants with mild cognitive impairment due to Alzheimer's Disease. Participants will be randomized to receive placebo or AGB101 (220 mg), once daily for 78 weeks. Secondary objectives are to assess the effect of AGB101 compared with placebo on clinical progression as measured by the Clinical Dementia Rating Scale- Sum of Boxes and Memory Box score. Read Less

Therapeutic treatment is yet available for declining memory, which is an impairment affecting the quality of life for many older adults and patients with cognitive impairment. Cognitive training with an immersive video game promises to drive hippocampal-cortical plasticity and associated gains that can restore memory capability or provide therapeutic treatment for memory deficits. Read Less

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. Read Less

In this research study we want to learn more about the effects of non-invasive brain stimulation on memory and brain-network function in cognitively unimpaired older adults and in patients with amnestic mild cognitive impairment (aMCI). This study will use a form of non-invasive brain stimulation called repetitive Transcranial Magnetic Stimulation (rTMS). rTMS will slightly alter activity in an area of your brain that controls memory. Changes resulting from this stimulation will be measured with behavioral tests of memory and general cognition, as well as by taking images of your brain with Magnetic Resonance Imaging (MRI). Participants will come in for one baseline visit followed by 10 days of daily rTMS study visits (Monday through Friday) and an evaluation visit. Then, there will be a 2-week break. After this break, they will return for another baseline visit, an additional 10 days of rTMS, and a final evaluation visit. Read Less

Older adults at risk for dementia show a variety of cognitive deficits, which can be ameliorated by different cognitive training (CT) exercises. The best combination of CT exercises is unknown. The aim is to discover the most efficacious combination of CT exercises as compared to cognitive stimulation (which will serve as a stringent, active control) to modify the functional trajectories of older adults' with MCI, who are at high risk for dementia. The primary objective of the U01 phase was to design and pilot-test an adaptive, randomized clinical trial (RCT) of cognitive training (CT) combinations aimed to enhance performance of instrumental activities of daily living (IADL) among persons with mild cognitive impairment (MCI). In the R01 phase, the objective is to identify the best combination of CT exercises to delay dementia onset among persons with MCI. The longitudinal endpoint goal is reducing incident dementia. The primary aim of the study is to determine which CT combination has the best probability to delay dementia by producing the largest IADL improvements. The study further aims to explore neuroimaging and novel blood-based biomarkers. Read Less

The goal of this clinical study is to investigate the effectiveness of non-invasive stimulation to enhance cognitive control abilities in cognitively healthy adults and older adults diagnosed with mild cognitive disorder (MCI). The main questions it aims to answer are: * whether it is possible to restore various cognitive functions in older adults diagnosed with MCI by delivering theta burst stimulation (TBS), a form of transcranial magnetic stimulation, and * whether closed-loop TBS is able to induce therapeutic benefits that outperform open-loop TBS. Participants play a cognitive video game while a brain-computer interface (BCI) analyzes their electroencephalogram (EEG) signals and decodes the presence or absence of the contingent negative variation (CNV) potential, a marker of cognitive control. The BCI triggers TBS when its outputs indicate that the participant is not engaged properly in the video game. Researchers will compare the effects of sham, closed-loop, and open-loop TBS using the outcome metrics described below to see how much cognitive restorations is achievable with each stimulation modality. Read Less

The aim of this study is to explore the relationship between cortical hyperexcitability, abnormalities of brain network function, and cognitive dysfunction in human patients with AD and whether administration of the antiepileptic medication levetiracetam (LEV) normalizes these measures and improves cognition. Read Less

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. Read Less

Novel blood-based biomarkers of Alzheimer's disease (AD), such as plasma levels of tau phosphorylated at threonine 181 (p-tau181), have shown great promise in detecting early AD pathology. While current studies point to this biomarker as having great clinical utility, one necessary step before clinical implementation is developing safe and effective methods for disclosure of results. Past risk disclosure studies have shown that disclosing risk for AD based on genetics or amyloid status is safe, but these studies have largely focused on cognitively unimpaired individuals. This study seeks to develop comprehensible educational materials to aid risk disclosure and examine the effect of risk disclosure based on plasma p-tau181 results in a group of participants with mild cognitive impairment (MCI) at imminent risk of converting to dementia. First, educational materials will be developed in collaboration with health communication experts and then refined in focus groups made up of individuals with MCI. Educational materials will be analyzed on several key reading and comprehensibility metrics and will include personalized risk estimate based on a well-accepted risk algorithm (Cullen, et al., 2021). Next, these educational materials will be utilized to disclose risk in a randomized controlled trial with an active control arm receiving disclosure based on age, sex, and cognitive status (based on Mini-Mental State Examination), meant to mimic common methods of clinical diagnostic and prognostic decision making, and an intervention arm receiving disclosure based on the above factors plus plasma p-tau181 results. Outcomes will include measures of comprehension and psychological well-being (anxiety, depression, hopelessness, and distress) and will be assessed immediately after risk disclosure and again at six-month follow-up. It is hypothesized that risk disclosure based on plasma p-tau181 is not more psychologically harmful or less comprehensible than disclosure based on demographic factors and MMSE. This pilot study will provide a necessary step towards moving plasma p-tau biomarkers towards safe clinical implementation and will develop educational materials that can be utilized in future studies and clinical practice. Read Less

Eligible older adults with Type 2 Diabetes-Mild Cognitive Impairment (T2D-MCI) will be provided a Continuous Glucose Monitoring (CGM) device and asked to share CGM data with their care partners for daily decision-making for diabetes self-management. After 2 weeks, individual interviews will be conducted in 20 participants (10 dyads). Older adults with T2D-MCI (n=10) and their care partners (n=10) will be interviewed separately to identify key features of the Care Partner-Assisted Intervention through linking continuous glucose monitoring and Mobile Health (CP-CGMH) app. Read Less

The prevalence of dementia will double in the next three decades in the U.S.; effective treatment or prevention for dementia is urgently needed. The current exploratory project aims to evaluate and understand how the brain and cognition may improve after a 12-week intervention that combines brain training and aerobic exercise training to improve brain function, both in those with mild cognitive impairment (some with possible prodromal Alzheimer's disease) and with healthy aging. Findings from this pilot project will guide and refine the development of a future larger clinical trial that aligns with the goals of the National Alzheimer's Plan of Action (NAPA), especially regarding "Prevent and Effectively Treat Alzheimer's Disease (AD) by 2025. Read Less

Studies have determined that compared to cognitively intact older adults (CIOA), older adults with mild cognitive impairment (OAwMCI) exhibit more pronounced balance and gait impairments which lead to an increased risk of falls and mobility decline. Such impairments are evident during dual-tasking (i.e., simultaneous performance of cognitive and motor task) and OAwMCI have demonstrated an increased cognitive-motor interference (deteriorated performance of either or both cognitive/motor task). Furthermore, our preliminary laboratory findings indicate that compared to CIOA, OAwMCI in response to large-magnitude treadmill perturbations exhibits poor reactive responses (first line of defense against balance loss) and are unable to modulate their responses as the magnitude of perturbation increases. Despite that conventional exercise methods offer beneficial effects; they comprise of self-initiated task-specific exercises and may not focus on training reactive responses. Additionally, due to the presence of subtle balance and gait deficits, clinical measures used may not be sensitive enough to determine the risk of fall post-training. Furthermore, these training methods incorporate multiple sessions due to which adherence to exercise training is difficult with only a fraction of the older adults benefiting from it. Therefore, it is essential to incorporate a task-specific strategy that promotes factors associated with falling like balance control, muscular responses, coordination of limbs, and cognition through which OAwMCI may acquire maximum benefits to prevent a balance loss. One feasible method, which harnesses technology that can be used to deliver balance disturbances either while standing or walking in a consistent and controlled manner, is via a custom-based motorized treadmill. The scientific rigor from preliminary studies has reported a successful reduction of falls through a single session exposing CIOA to multiple treadmill-induced perturbations during gait and has shown significant improvement in reactive responses. For that reason, this stage 1 pilot study will examine the feasibility, applicability, and tolerability of a combined cognitive, and perturbation training on biomechanical determinants associated with falls and promote physical activity: kinematic variables, muscular responses, and cognitive function. Read Less