Memory Impairment

This study is a prospective two-arm, single blind randomized controlled trial design to compare the clinical effectiveness of telemedicine-delivered, 6-session, standardized cognitive behavioral therapy for insomnia (CBT-I) and mindfulness-based treatment for insomnia (MBTI) in treating insomnia symptoms and ameliorating depressive symptoms in persons with mild to moderate TBI and comorbid Post-Traumatic Stress Symptoms (PTSS) and insomnia symptoms in a 360 patients. Participants will undergo assessment (psychosocial questionnaires, neurocognitive testing, sleep monitoring) at baseline, at the end of treatment, and at 2-, 6- and 12-weeks post-treatment. The primary outcome is sleep as measured by the Insomnia Severity Index (ISI).

CORT-X will examine if mitigation of stress-mediated pathogenesis of Alzheimer's disease (AD) is a feasible target for intervention in individuals at risk for this disease. This single-site (Baltimore, Maryland) phase II clinical trial is a 2-week, randomized, placebo-controlled crossover study of the effects of the selective glucocorticoid receptor antagonist, CORT108297, on cognitive test performance in 26 individuals with mild cognitive impairment (MCI) due to AD and in 26 cognitively normal individuals with an increased risk for AD due to family history, genetics, and/or subjective memory complaints. All subjects will participate in a brief stressor (public speaking and mental arithmetic) and provide saliva samples so investigators can measure stress hormone response. Then, following 2 weeks of treatment with placebo or CORT108297, in counterbalanced order, participants will complete cognitive tests assessing memory and executive function. All study participants will receive CORT108297 and placebo over the course of this 10-week trial that requires 6 in-person study visits. The primary aims will compare the effects of CORT108297 to placebo on cognitive test performance in individuals with MCI due to AD and in individuals at risk for AD, and describe the side effects of CORT108297 in study participants. Secondary aims will identify subject characteristics that predict positive response to study drug.

This study is a prospective two-arm, single blind randomized controlled trial design to compare the clinical effectiveness of telemedicine-delivered, 6-session, standardized cognitive behavioral therapy for insomnia (CBT-I) and mindfulness-based treatment for insomnia (MBTI) in treating insomnia symptoms and ameliorating depressive symptoms in persons with mild to moderate TBI and comorbid Post-Traumatic Stress Symptoms (PTSS) and insomnia symptoms in a 360 patients. Participants will undergo assessment (psychosocial questionnaires, neurocognitive testing, sleep monitoring) at baseline, at the end of treatment, and at 2-, 6- and 12-weeks post-treatment. The primary outcome is sleep as measured by the Insomnia Severity Index (ISI).

Cognitive impairment is well established in people with psychosis and is associated with cannabis use. The current study will investigate the neurobiological basis of cognitive change associated with 28-days of cannabis abstinence in people with psychosis and non-psychiatric controls with cannabis use. Participants will be randomized to a cannabis abstinent group or a non-abstinent control group and will undergo magnetic resonance imaging at baseline and following 28-days of abstinence. This study will help characterize the neuropathophysiological processes underlying cognitive dysfunction associated with cannabis use and its recovery which may guide the development of novel interventions for problematic cannabis use.

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.

This phase I clinical trial will examine the safety and efficacy of intermittent hypoxia training (IHT) for up to 12 weeks to treat subjects with mild cognitive impairment (MCI).

Two hallmarks of both healthy aging and age-related disease are 1) memory and navigational deficits, particularly in orienting towards goal locations and planning how to navigate to them, and 2) increased susceptibility to stress and altered regulation of the stress response. However, there are marked individual differences in these age-related changes. The investigators' proposal will help characterize factors that contribute to this variability. Participants will be pseudorandomly assigned to stress-manipulated or control groups. The investigators will give both groups a novel immersive navigation task, validated by the PI in healthy young adults. This paradigm gives participants the opportunity to either (a) flexibly draw on spatial memory in order to plan efficient routes to goal locations, or (b) fall back on inefficient, but cognitively less-demanding, stimulus-response associations (i.e., habits). Using neuroimaging and behavioral measures, the investigators' protocol will test whether experimentally-induced stress leads individuals to bring fewer details about future locations to mind when route planning, and whether such restricted prospective thought ultimately biases participants towards relatively inflexible, habitual actions.

Bio-Hermes-002 is a 120-day cross-sectional study that will result in a blood, CSF, retinal, digital, MRI, and PET brain imaging biomarker database that can be used to determine the primary objective. Digital biomarkers and blood-based biomarkers will be tested to determine whether a meaningful relationship exists between biomarkers alone or in combination with tau or amyloid brain pathology identified through PET images.

The purpose of this study is to assess the ability of the home-based intervention, HOBSCOTCH-CA, to improve the quality of life and cognitive function in Service Members, Veterans and civilians who are survivors of brain cancer or a brain tumor (CA participants). This study will also assess the ability of the HOBSCOTCH-CA program to improve quality of life in caregivers of patients with brain cancer/tumor and to reduce caregiver burden. Enrolling with a Caregiver is optional for CA participants. Investigators will compare two groups of CA participants and their Caregiver (enrolling with a Caregiver is optional): one who receives HOBSCOCTCH-CA immediately (Group 1) and another group that will receive HOBSCOTCH-CA (Group 2) after a 3-month waiting period. Participants will be in the study for about 6 months total. HOBSCOTCH-CA involves 45 to 60 minute one on one virtual sessions with a certified Cognitive Coach including a "pre" program session and 8 weekly sessions thereafter. Participants will learn about problem solving therapy and mindfulness or relaxation training. CA participants are asked to do short homework assignments and keep a brief daily diary on a smart phone app. All participants complete study questionnaires or surveys at enrollment, 3 months later and at 6 months (at the end of the study).

Mental illness is often chronic, severe, and difficult to treat. Though there has been significant progress towards establishing effective and efficient interventions for psychological health problems, many individuals do not gain lasting benefits from these treatments. The Memory Support Intervention (MSI) was developed utilizing existing findings from the cognitive science literature to improve treatment outcomes. In this study, the investigators aim to conduct an open trial that includes individuals 50 years and older to assess if a novel version of the Memory Support Intervention improves sleep and circadian functioning, reduces functional impairment, and improves patient memory for treatment.

The proposed study will evaluate a new approach to cognitive rehabilitation of mTBI using a brain stimulation technique called "Remotely Supervised Transcranial Direct Current Stimulation combined with Cognitive Training" (RS-tDCS+) which has shown promise for improving complex attention in both healthy and clinical populations. RS-tDCS+ is a home-based, low-risk, non-invasive technique that is designed to boost cognitive training by enhancing learning and the brain's ability to reorganize connections. This study will evaluate RS-tDCS+ for improving complex attention in Active Duty Service Members (ADSM) and Veterans with a history of mTBI. Different tests of complex attention and symptom questionnaires will be used to determine the effects of real versus sham (placebo) RS-tDCS+. Second, the investigators will investigate electrical and connectivity changes in the brain associated with RS-tDCS+ using electroencephalogram (EEG) and magnetic resonance imaging (MRI). Third, the investigators will investigate the lasting effects of any observed changes by evaluating participants at 1 and 6 weeks post-treatment. Lastly, the investigators will explore the impact of individual differences (e.g., PTSD, depression, sleep quality, time since injury, baseline impairment, age, sex, ADSM versus Veteran) on treatment outcome.

The purpose of this study is to assess the ability of the home-based intervention, HOBSCOTCH-MS to improve the quality of life and cognitive function in Service Members, Veterans and civilians who have multiple sclerosis with cognitive and memory problems (MS participants). This study will also assess the ability of the HOBSCOTCH-MS program to improve quality of life in caregivers of patients with multiple sclerosis and to reduce caregiver burden. Enrolling with a Caregiver is optional for MS participants. Investigators will compare two groups of MS participants and their Caregiver (enrolling with a Caregiver is optional): one who receives HOBSCOTCH-MS immediately (Group 1) and another group that will receive HOBSCOTCH-MS (Group 2) after a 3-month waiting period. Participants will be in the study for about 6 months total. HOBSCOTCH-MS involves 45 to 60 minute one on one virtual sessions with a certified Cognitive Coach including a "pre" program session and 8 weekly sessions thereafter. Participants will learn about problem solving therapy and mindfulness or relaxation training. MS participants are asked to do short homework assignments and both MS and Caregiver participants are asked to keep a brief daily diary on a smart phone app. All participants complete study questionnaires or surveys at enrollment, 3 months later and at 6 months (at the end of the study). After completing the intervention, MS Participants and their Caregivers may also participate in an optional one-time Key Informant Interview for qualitative analysis in an effort to further adapt and improve the HOBSCOTCH-MS in the future.

Semantic AD

CORT-X will examine if mitigation of stress-mediated pathogenesis of Alzheimer's disease (AD) is a feasible target for intervention in individuals at risk for this disease. This single-site (Baltimore, Maryland) phase II clinical trial is a 2-week, randomized, placebo-controlled crossover study of the effects of the selective glucocorticoid receptor antagonist, CORT108297, on cognitive test performance in 26 individuals with mild cognitive impairment (MCI) due to AD and in 26 cognitively normal individuals with an increased risk for AD due to family history, genetics, and/or subjective memory complaints. All subjects will participate in a brief stressor (public speaking and mental arithmetic) and provide saliva samples so investigators can measure stress hormone response. Then, following 2 weeks of treatment with placebo or CORT108297, in counterbalanced order, participants will complete cognitive tests assessing memory and executive function. All study participants will receive CORT108297 and placebo over the course of this 10-week trial that requires 6 in-person study visits. The primary aims will compare the effects of CORT108297 to placebo on cognitive test performance in individuals with MCI due to AD and in individuals at risk for AD, and describe the side effects of CORT108297 in study participants. Secondary aims will identify subject characteristics that predict positive response to study drug.

The present study is a proof-of-concept clinical trial to test the efficacy of low doses of a repurposed anti-epileptic drug (levetiracetam) in treating memory problems in Parkinson's disease (PD). Neuroimaging techniques will be used to determine the effect of the drug on specific brain regions (hippocampal subfields). Finally, baseline brain activity of PD patients with memory problems will be compared to PD patients without memory problems and healthy older adults to determine if activity in specific brain regions (hippocampal subfields) can be used to predict memory problems in PD. This information will be useful for future clinical trials to target drugs to these brain regions.

The Interventions for Brain Health Virtual Reality Study is a NIH-funded clinical research trial at the University of California San Diego (UCSD) Health under the supervision of the study principal investigator Dr. Judy Pa. The overarching goal of this trial is to use a novel virtual reality (VR) based intervention that simultaneously engages physical and cognitive activity aimed at improving brain health and cognition in older adults. The investigators will compare 3 types of interventions: physical activity, VR cognitive activity, and combined VR physical and cognitive activity over 16 weeks to evaluate physical and brain health changes.

Randomized, placebo-controlled, double-blinded, parallel group clinical trial to investigate if 6 months of oral lithium tablets (S-lithium 0,5-1,0 mmol/l) will prevent cognitive decline after brain radiotherapy in pediatric brain tumor survivors. Primary outcome measure is Processing Speed Index (PSI) 2 years after start of study treatment.

The Alzheimer's disease or related disorders (ADRD) are among the most disabling diseases because of their main features such as cognitive impairment, loss of functional autonomy and behavioural disorders. In absence of current curative treatment, the identification of the predictive risk factors of progression of the disease, evaluated through its main symptoms, represents a major stake of public health. The investigators aimed at developing a database, which includes the patient medical records on a prospective basis, in collaboration with the medical and administrative personal and with the University hospital computer science department. The main objective is to study the predictive factors associated with the change of functional autonomy level, measured every 6 months to 12 months by phone, in a Memory Clinic. The study population would consist in about 1000 patients with ADRD. The length of follow-up of each patient will be 3 years.

Type 1 diabetes mellitus (T1DM), makes its appearance during childhood and youth, but management implications last till late adulthood. Its treatment includes the combination of multiple daily glucose measurements, insulin administration and balanced nutrition. The goals of therapy are to achieve glycemic control (HbA1c \< 7.5%), and minimal glycemic excursions. Furthermore, recent studies imply that keeping HbA1c within target range is not sufficient to prevent complications, attributed mainly to blood glucose level fluctuating from high to low, associated with food intake and adolescents behavior. The current implication of glycemic control on the central nervous system (CNS) includes abnormal electrical brain activity, structural changes in brain's white and grey matter, and cognitive impairment. Still, little is known on the effect of sleep pattern, including circadian rhythm reversal ("biological clock) on asymptomatic glycemic excursions, and on CNS functions. There is no data regarding the association of the biologic clock on CNS functionality among adolescents, nonetheless among T1DM adolescents, for whom behavior and circadian rhythm alterations may have harmful effect. The investigators propose a cross-over designed study by examining adolescents with and without T1DM during 2 weeks of regular sleeping pattern (night sleep), and during 2 weeks of sleeping during the day as happens during summer vacation. The main objective of the proposed study is to offer proof of the clinical and metabolic relevance and cognitive effects of the reversal of the circadian clock in adolescents with and T1DM during summer vacations and weekends. Study is designed to demonstrate a difference among healthy and diabetics during reversed night/day circadian clocks in the time spent within target range of glucose, performance on neuro cognitive tasks, electrical brain activity, and hormonal profile.