Mild Cognitive Impairment

Researchers are conducting the 100-Year Human Aging Study, an observational trial designed to follow participants over their lifespans to investigate which health measurements can predict mortality, serious diseases, and functional disability. The study aims to validate many longevity measures that currently lack prospective evidence by tracking physiological, cognitive, social, and environmental factors that change with aging. This research will generate important data to improve understanding of aging and longevity medicine. Participants undergo comprehensive multi-system clinical screenings including tests like cardiopulmonary exercise testing, body composition assessment by DEXA, echocardiography, electrocardiography, spirometry, neurocognitive testing, sensory assessments, metabolic testing, and detailed medical and social histories. The study allows for different levels of participation, from single tests to full two-visit screening batteries, and encourages repeat testing to capture health changes over time. During the study, participants receive individualized reports including investigational estimates of biological age and predicted cause of death. Researchers collect data on mortality, serious health events, chronic diseases, functional ability, and lifestyle changes through periodic follow-up over many years, potentially up to 100 years. This extensive data collection helps evaluate how well these measurements predict aging outcomes. All data are stored in raw form for future analysis and participants are supported with ongoing contact and opportunities for repeat assessments.

Cognitive impairment related to dementia is often missed in primary care, especially among older adults from minority and socio-economically disadvantaged populations. Researchers are evaluating the 5-Cog brief cognitive assessment, a quick, simple, and standardized tool that takes less than 5 minutes and addresses cultural and logistical barriers. This pragmatic cluster-randomized trial aims to test whether the 5-Cog paradigm improves detection of new cases of cognitive impairment and dementia care in older adults with cognitive concerns. The study involves 22 primary care clinics in Bronx and Indiana, enrolling about 6,600 patients aged 65 and older who report cognitive concerns. Participants receive either the 5-Cog battery combined with a clinical decision-making tool or enhanced usual care, which includes cognitive concern screening. The 5-Cog battery includes tests like Picture Memory Impairment Screen, Motoric Cognitive Risk Syndrome diagnosis, and Symbol Match. Primary care physicians receive results and decision support but use their clinical judgment in care decisions. Participants undergo cognitive concern screening before their appointments. Researchers will review new cognitive impairment diagnoses and improvements in dementia care within 90 days after the primary care visit using electronic medical records. Additional evaluations include tests for reversible causes, medication changes, specialist referrals, and social support. The study also examines the 5-Cog paradigm's implementation and cost-effectiveness, focusing on populations facing health disparities. Total participation duration varies by patient and clinic schedule.

Researchers are investigating how the antidepressant citalopram affects the brain's response to emotional information, focusing on the amygdala, a key brain area involved in depression. This study explores how different parts of the amygdala react to positive and negative emotional stimuli, using advanced brain scanning technology to understand the underlying brain mechanisms. Participants will receive a single oral dose of either 20 mg citalopram or a placebo in a randomized, double-blind design. After dosing, participants will undergo high-strength 7T fMRI brain scans while viewing emotional faces. This precise imaging allows researchers to observe how citalopram influences specific subfields of the amygdala during emotional processing. Participants will be screened for medical and psychiatric health before joining. During the study, brain activity and behavioral responses such as accuracy and reaction time during a gender discrimination task will be measured about three hours after dosing. The study includes safety monitoring and lasts for a few hours on the study day, focusing on neural and behavioral outcomes related to emotional processing.

Researchers are studying the brain's action observation network (AON), which is involved in understanding and imitating movements, especially focusing on subcortical areas and the cerebellum. The study aims to explore how this network functions in healthy individuals and in people with Cerebral Palsy (CP) who have early brain injuries. This research seeks to understand differences in brain activation patterns and their relation to clinical features in CP patients using advanced imaging techniques. Participants will undergo a 7 Tesla MRI scan using a high-resolution functional and anatomical protocol. The MRI will capture detailed images of brain structures including the cerebral cortex, subcortical nuclei, and cerebellum. Visual tasks involving observation of hand movements and tool use will be presented during the scan. CP patients will also receive a full clinical assessment before the MRI. The study includes both healthy volunteers and CP patients, with careful monitoring of participant compliance to avoid motion artifacts. During the study, researchers will evaluate brain activation and connectivity maps of the AON from the 7T MRI data. Participants' motor functions and clinical characteristics will be assessed for correlation with imaging results. The study involves observation during MRI scanning, clinical assessments, and monitoring of participants' responses to visual stimuli. This trial is expected to provide detailed insights into brain network organization and its changes in CP. The total participation includes MRI scanning and clinical evaluations around a single visit.

Researchers are evaluating the use of [18F]-MFBG PET scans to assess heart nerve activity in people with Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), and Alzheimer's disease (AD). The study compares this method with the current standard [123I]-MIBG SPECT scans, focusing on distinguishing between PD and MSA as well as DLB and AD. This is a prospective study conducted at two centers, aiming to validate the accuracy and feasibility of [18F]-MFBG PET for these neurological conditions. Participants will undergo several imaging tests including dynamic cardiac [18F]-MFBG PET, [123I]-MIBG SPECT, and cerebral [18F]-PE2I PET scans. Healthy volunteers and patients with confirmed diagnoses will be included, with groups divided by age and disease duration. A dosimetry study will also be conducted for healthy volunteers to measure radiation exposure from [18F]-MFBG. Multiple visits to the hospital are required for scans and assessments. During the study, participants will have thorough neurological assessments, brain MRI scans, and blood sampling alongside PET and SPECT imaging. Researchers will evaluate diagnostic accuracy, effect size of tracer uptake changes, and relationships between heart nerve imaging and brain dopamine transporter changes and autonomic dysfunction. The study includes monitoring for safety and will analyze regional heart uptake patterns. Participants can expect 3 to 4 hospital visits with detailed imaging and clinical evaluations over the study period.

Researchers are investigating the early brain regions involved in Alzheimer's disease and its precursors using novel molecular probes [18F]AV45 (Ab2) and [18F]AV1451 (Tau) with PET/CT imaging. This study aims to understand the distribution of positive brain lesions affecting mental state tests like the simple mental state examination and the Montreal Cognitive Assessment Scale in Alzheimer's patients. The goal is to provide molecular imaging information that may help study Alzheimer's disease mechanisms and establish objective diagnostic criteria for early detection. The study uses new imaging agents Ab2 and Tau PET/CT, which can detect pathological changes at the molecular level before symptoms appear. These molecular probes offer earlier and more visual detection of Alzheimer's disease-related changes, helping to define positive diagnostic criteria for early Alzheimer's disease. Participants include groups with mild cognitive impairment, Alzheimer's disease, and healthy volunteers. Participants will be assessed through PET/CT imaging using these molecular probes to observe brain pathology. Researchers will evaluate the diagnostic criteria for Ab2 and Tau imaging within two months. The study includes cognitive tests and clinical dementia rating scales. This observational study involves healthy volunteers and patients with mild cognitive impairment or Alzheimer's disease, aiming to improve early diagnosis through imaging techniques.

Researchers are evaluating the use of PET imaging with the radioligand [18F]PI-2620 to detect tau protein deposits in people with Alzheimer's disease and healthy controls. This open-label, multi-center, non-randomized Phase 3 study aims to compare PET imaging results during life with brain tissue analysis after death to better understand tau pathology in Alzheimer's. The study is sponsored by Lantheus Biosciences Ltd. and focuses on diagnostic accuracy and safety of this imaging technique. Participants receive an intravenous injection of [18F]PI-2620 at a dose of 185 MBq ± 20%. The study involves a PET scan procedure that participants must tolerate, including lying still in the scanner. There are no randomized groups or placebo controls as this is an open-label study. The research compares the PET imaging findings with post-mortem brain autopsy results to evaluate the ability of this imaging to detect tau deposits accurately. During the study, participants undergo PET imaging and are monitored for their ability to tolerate the scan. Brain donation consent is required for post-mortem histopathological comparison. Researchers assess the diagnostic performance of the PET scan in correctly identifying tau-related pathology and Alzheimer's disease changes. The primary outcome focuses on the accuracy of visual assessment of PET images compared to autopsy findings, with follow-up continuing until study completion and an average of one year after death.

Researchers are evaluating MK-2214, a study treatment designed to slow certain brain changes in people with early Alzheimer's disease (AD), a condition that causes memory loss, speech difficulties, and problems with decision-making. The study aims to find out if MK-2214 can slow the spread of tau protein in the brain compared to a placebo and to assess the treatment's safety and tolerability. Tau is a protein that builds up in AD and damages brain cells, impacting daily functioning. Participants will be randomly assigned to receive either MK-2214 or a placebo through intravenous (IV) infusions every 4 weeks during the study period. The study uses a quadruple-blind design, meaning that participants, care providers, researchers, and those assessing outcomes will not know which treatment is given. This phase 2 trial is planned to last up to approximately 23 months for treatment and assessment. During the study, participants will undergo brain scans including tau PET imaging and assessments of cognitive and daily living abilities at regular intervals. Researchers will monitor changes in tau protein levels, cognitive scores such as the Clinical Dementia Rating-Sum of Boxes (CDR-SB), and safety outcomes including adverse events and treatment discontinuations. The total study duration includes up to about 26 months of follow-up to evaluate safety and effectiveness.

Researchers are evaluating a gene therapy called AAV2-BDNF in people aged 50 to 80 years diagnosed with early Alzheimer's Disease or Mild Cognitive Impairment. This first-in-human Phase I trial aims to test whether the brain-delivered protein Brain-Derived Neurotrophic Factor (BDNF) can slow or prevent brain cell loss and activate healthy brain cells. The study uses a harmless virus to deliver the BDNF gene directly to brain cells, as BDNF cannot cross into the brain through the bloodstream. Participants will receive a single gene transfer procedure of AAV2-BDNF, an engineered virus designed to produce BDNF in the brain. The trial involves 12 participants, 6 with early Alzheimer's Disease and 6 with Mild Cognitive Impairment. No repeat dosing or daily medications are expected. The treatment is open-label, meaning all participants receive the gene therapy. During the 24-month study, participants will undergo evaluations including memory tests like the Ray Auditory Verbal Learning Task, Benson Complex Figure Draw, Mini-Mental State Exam, and Alzheimer's Disease Assessment Scale. Brain imaging with MRI and PET scans will monitor safety and biological effects. Biomarkers in cerebrospinal fluid will also be measured. Caregivers will assist by observing for adverse events and attending clinic visits. Safety and memory changes are the main outcomes assessed throughout the study.

Researchers are evaluating the effects of a cognitive nutritional supplement on attention and focus in adults aged 25 to 65 years. This 12-week, double-blind, randomized study compares the supplement to a placebo in a general population of men and women in the United States, aiming to assess changes in cognitive functions related to attention and focus. Participants will take either pills of the cognitive nutritional supplement or matching placebo pills daily for 12 weeks. The study is conducted in a parallel design with two groups, where neither participants nor researchers know which treatment is given. Key assessments occur at the start, midpoint (week 6), and end (week 12) of the study. During the study, participants will use a study-provided iPad to complete various cognitive tests measuring attention and focus, including the Feature Match test and other related assessments at weeks 0, 6, and 12. Dietary intake and nutrient consumption are also monitored through food frequency questionnaires. Safety and adherence are tracked throughout the study period, with participants following specific guidelines on diet, physical activity, and substance use to ensure consistent testing conditions.