Mild Cognitive Impairment Clinical Trials

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

The investigators aim to use the new PET radioligand, 18F-MK-6240, to detect tau pathology in cognitive healthy and mild cognitive impairment (MCI) elders. The investigators will then examine the interactions between differential tau burden and performance on cognitive tasks, functional magnetic resonance imaging (fMRI) neural activation patterns, and other cognitive and behavioral measures. By investigating these relationships, the investigators hope to understand the cognitive and behavioral outcomes of tau deposition found in specific brain regions in cognitively normal/mildly cognitively impaired adults. Furthermore, the study aims to examine how the presence of tau may contribute to the risk of subsequent cognitive decline, neurodegeneration, and dementia. Read Less

The goal of this study is to investigate whether Low Intensity Focused Ultrasound Pulsation (LIFUP) targeting a part of the brain involved in memory will have an affect on brain activity and whether it may improve memory in people with Mild Cognitive Impairment and Mild Alzheimer's Disease. The main questions the study seeks to answer are: Can LIFUP increase brain activity in the targeted area? Can LIFUP improve memory in people with MCI and mild AD? Can LIFUP improve connectivity of memory networks in the brain? Participants in this study will complete MRIs and memory testing, and receive Low Intensity Focused Ultrasound to a part of their brain involved in memory (the entorhinal cortex). Read Less

The goal of this study is to objectively test one's sense of smell, called olfaction, in participants with Subjective Cognitive Concerns (SCC), Mild Cognitive Impairment, Mild Behavioral Impairment (MBI), and age-matched controls. The main question it aims to answer is whether the AROMHA Brain Health Test could serve as a predictive biomarker of neurodegenerative disorders. This understanding will aid in the development of a noninvasive, cost-effective diagnostic tool that reliably and specifically distinguishes disease and normal aging populations. Participants will take the approximately 45-minute AROMHA Brain Health Smell Test where they will peel and sniff labels on the physical smell cards and answer questions on the web-based app relating to what they smelled. Participants will undergo tests for odor intensity, odor identification, odor discrimination, and episodic olfactory memory, but will not be provided the results of these tests. Read Less

This is a pilot study of non-invasive transcranial magnetic stimulation (TMS) to improve memory in healthy adults. It will also examine treating memory deficits in older adults with amnestic mild cognitive impairment (aMCI), a condition that frequently precedes Alzheimer's disease (AD. The study will test whether a form of non-invasive brain stimulation repetitive transcranial magnetic stimulation (rTMS) can improve memory abilities in healthy young adults, healthy older adults, and older adults with aMCI by retuning memory-related brain networks. This study is a key first step which will support the long-term goal of treating memory deficits in neurological patients. It is expected that rTMS will improve memory abilities in all participants, and that the improvements in memory will be attributable to changes in the connectivity of memory-related brain networks. Read Less

This single-center, double-blind, placebo-controlled study will recruit in total 39 participants with either Mild Cognitive Impairment due to Alzheimer's disease (MCI) or Mild Alzheimer's disease dementia (mild AD). There will be 3 Dose levels. An initial cohort of 13 subjects will be randomized to a Dose level 1 (0.1 mg/kg vs. placebo) lasting 8 weeks. An additional 13 subjects will be recruited and randomized into Dose level 2 (0.25 mg/kg vs. placebo) for 8 weeks and 13 subjects for the last Dose level 3 (0.5 mg/kg vs. placebo) for 8 weeks. The primary objective will be to assess safety and tolerability of CpG 1018. Read Less

The objective of this study is to test the effects of caffeine on neurocognitive and clinical recovery after major surgery. Specifically, this trial tests the primary hypothesis that caffeine will reduce the incidence of postoperative delirium. Read Less

The current study is a double-blind, placebo-control randomized clinical trial examining the efficacy of memory retraining in individuals with Mild Cognitive Impairment (MCI). Impairment in higher level cognitive processing, such as new learning and memory, is one of the most common deficits in individuals with MCI and such deficits have been shown to exert significant negative impact on multiple aspects of everyday life, including occupational and social functioning. Despite these findings, few studies have attempted to treat these cognitive deficits in order to improve the everyday functioning of individuals with MCI. Through a small randomized clinical trial, the investigators found that individuals with MCI with documented cognitive impairment show a significant improvement in their memory performance following a treatment protocol designed to facilitate learning. The current proposal will replicate this finding and further evaluate (a) the impact of the treatment on everyday functioning, (b) the long term efficacy of the treatment and (c) the utility of booster sessions in facilitating long-term treatment effects. We will randomly assign older individuals who meet criteria for a diagnosis of amnestic MCI to a memory retraining group or a placebo control group. Both groups will undergo baseline, immediate and long-term follow-up assessment consisting of: (1) a traditional neuropsychological battery, (2) an assessment of global functioning examining the impact of the treatment on daily activities, and (3) functional neuroimaging. This design will allow the investigators to evaluate the efficacy of this particular memory retraining technique in an aMCI population through the assessment of cognitive function via a standard evaluation. In addition, the investigators will be able to draw conclusions regarding the impact of this particular memory remediation program on everyday life from questionnaires completed by the participant and a significant other. Optional enrollment in pre- post neuroimaging will also allow the investigators to look at changes in the brain. Read Less

The proposed research will test a novel network-based neurostimulation approach using MRI-derived measures of brain connectivity to establish target sites for neurostimulation and test for the enhancement of memory function beyond a sham stimulation condition. This will be tested in cohort of MCI adults using network-based transcranial magnetic stimulation (TMS) to assess for behavioral improvement due to the controlled intervention. This study will provide important evidence towards the efficacy of neuromodulatory treatments for memory decline and will accelerate the discovery of potent non-invasive treatments to remediate cognitive decline in cognitively impaired older adults. 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

This multi-site study will be the first to evaluate the dose-dependent effects of t-PBM in amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer's Disease (AD) (CDR of 0.5-1, FAST 1-4; age 65-85) in a randomized clinical trial of 8 weeks of t-PBM vs. sham. At baseline, all subjects will complete initial neuropsychological testing. To elucidate mechanisms of action of t-PBM, prior to treatment, subjects will undergo neuroimaging related to critical features of AD: tau 18F MK-6240 load (PET), measures of brain bioenergetics (31P-MRS), and functional connectivity (rs-fMRI). After undergoing target engagement testing (t-PBM session performed during fMRI to detect BOLD changes with active t-PBM), subjects will then be randomized to t-PBM/sham and complete 24 t-PBM/sham treatments, ~11 min per day, 3 days per week, for 8 weeks. t-PBM will be administered via continuous, 808 nm wavelength laser delivery to the forehead bilaterally (at standard EEG electrode positions F4, F3). Read Less

This is a 2-arm intervention pilot study with the objective to examine if an in-person and a remote multi-component intervention program can improve chronic stress, vascular measures, and executive function among African American and White patients with Mild Cognitive Impairment. Researchers plan to enroll 60 participants with over-recruitment of African American patients. 30 participants will be recruited from the Cognitive Empowerment Program to participate in PRogram to Improve Stress-levels and Enhance Memory (PRISEM) Cognitive Empowerment Program (CEP) (i.e., in-person lifestyle intervention program) and 30 participants will be recruited from Emory primary care clinics to participate in PRISEM Remote (i.e., remote lifestyle intervention program). The participants in both intervention arms will be asked to participate in group-based and/or individual activities that focus on improving health education, nutrition, physical activity, cognitive health, stress levels, and overall well-being. The duration of the study for all participants will be 9 months with 3 study visits. At each study visit, the following measures will be assessed: psychosocial, behavioral, vascular/physical, and executive function. Read Less