Applied Cognition Benchmarking Study
- Conditions
- Healthy
- Registration Number
- NCT06222385
- Lead Sponsor
- Applied Cognition
- Brief Summary
This is a cross-over randomized study to validate the Sponsor investigational medical device against measurements of glymphatic function from MRI-based neuroimaging, EEG, blood biomarkers and cognitive tests in healthy older volunteers.
- Detailed Description
The study population will consist of healthy individuals, ages 55 to 65, that are cognitively normal and do not have a medical history of neurological or sleep disorder, cardiovascular disease, hypertension, or diabetes. The objectives of this study are to define whether sleep- and wake-associated device measurements (i) faithfully reflect glymphatic function measured by gold-standard contrast enhanced MRI and non-invasive MRI-based measures of glymphatic function; (ii) replicate pre-clinical findings between sleep EEG power bands and glymphatic flow; (iii) predict plasma levels of Alzheimer's disease (AD)-related biomarkers; and (iv) predict morning cognitive performance.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 34
- Participants must have a Montreal Cognitive Assessment (MoCA) score at least 26.
- Participants must have a Geriatric Depression Scale (GDS) 15-item score of 4 or less.
- Participants with a formal diagnosis of any sleep disorder (e.g., sleep apnea on positive-airway-pressure (PAP) therapy, insomnia, restless leg syndrome, circadian rhythm sleep disorder, parasomnia).
- Participants with a history of significant neurological disease or history of epilepsy.
- Participants with cardiovascular disease or cardiovascular risk factors (smoking or hypertension).
- Participants with diabetes.
- Participants with traumatic brain injury, or serious mental illness including bipolar disorder, schizophrenia, major depressive disorder or post-traumatic stress disorder.
- Participants who have taken in the past 30 days prescribed or overthe- counter (OTC) stimulants, sleeping medications, or psychiatric medications including antidepressants.
- Participants who consume more than 400 mg/day of caffeine. Participants will be required to not consume caffeine beginning 12pm on the day-of the sleep study.
- Female Participants who consume more than 3 alcoholic drinks on any day or more than 7 drinks per week. Male participants who consume more than 4 alcoholic drinks on any day or more than 14 drinks per week.
- Participants planning travel to alternate time zones within two weeks of study participation
- Participants with travel plans or conflicts that would prevent them from either Study Visit.
- Participants who are enrolled in other research studies and are receiving an investigational drug within 30 days of the planned start date.
- Participants who have any condition that, in the opinion of the Sponsor Principal Investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements.
- Participants with absolute or relative contraindications to MRI imaging based on current up-to-date screening questionnaires including claustrophobia, inability to lie still on their back for 30-45 minutes or require sedation prior to the MRI.
- Participants with a head circumference greater than 60 cm that would prevent use of a high-resolution 64 channel MRI head coil required for this study
- Participants who have a pre-planned surgery or medical procedure that would interfere with the conduct of the study.
- Participants who have an implanted medical device or contraindications that would exclude MRIs
- Participants with a serious infection requiring medical attention in the past 30 days
- Participants with a diagnosis of substance use-disorder in the past 2 years.
- Participants with known acute or chronic kidney disease and/or compromised GFR.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Primary Outcome Measures
Name Time Method Non-invasive MRI - fast functional MRI Immediately before and immediately after each sleep/wake period Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by non-invasive MRI measures of glymphatic function using fast functional MRI (f-MRI) low-frequency vasomotor oscillations, Hz.
Non-invasive MRI - multi-echo arterial spin-labeling Immediately before and immediately after each sleep/wake period Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by non-invasive MRI measures of glymphatic function using multi-echo arterial spin-labeling (ME-ASL)-MRI (glial-vascular water transport) (flow in ml/sec).
Non-invasive MRI - diffusion-based intravoxel incoherent motion Immediately before and immediately after each sleep/wake period Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by non-invasive MRI measures of glymphatic function using diffusion-based intravoxel incoherent motion (IVIM)-MRI (long-distance water transport) (diffusion signal, a.u.).
Contrast-enhanced MRI Immediately after the overnight sleep/wake period Overnight sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by ROI parenchymal signal intensity using gold-standard contrast-enhanced MRI for gray and white matter ROI.
Non-invasive MRI - T1/FLAIR-based assessment Immediately before and immediately after each sleep/wake period Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by non-invasive MRI measures of glymphatic function using T1/FLAIR-based assessment of MRI-visible perivascular spaces (MVPVS) that are structural indicators of perivascular impairment, (a.u.).
Non-invasive MRI - phase-contrast Immediately before and immediately after each sleep/wake period Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by non-invasive MRI measures of glymphatic function using phase-contrast (PC)-MRI (aqueductal cerebral spinal fluid (CSF) flow) (flow in ml/sec).
- Secondary Outcome Measures
Name Time Method Cognitive function - symbol digit modality test Immediately after the sleep/wake period Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on symbol digit modality test (SDMT) (number correct).
Sleep EEG Measurements sampled every 5 to 10 minutes during the overnight sleep period Device overnight sleep measurements (impedances in milli-ohms) correlations with overnight recorded sleep EEG power bands (relative delta, theta, alpha and beta power in %) and heart rate replicate pre-clinical correlations of glymphatic flow (measured using 2-photon microscopy in a.u.) with EEG power bands (relative delta, theta, alpha and beta power in %) and heart rate.
Cognitive function - psychomotor vigilance test Immediately after the sleep/wake period Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on psychomotor vigilance test (PVT) (mean and standard deviation of reaction time).
Blood biomarkers Immediately before and immediately after each sleep/wake period Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic clearance measured by amyloid beta40, beta42, n-tau 181, n-tau 217, p-tau 181, p-tau 217 blood biomarkers
Cognitive function - trail making tests A&B Immediately after the sleep/wake period Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on Trail Making Tests A\&B (time in seconds).
Cognitive function - digits forward recall Immediately after the sleep/wake period Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on digits forward recall (maximum number of correctly recalled digits).
Trial Locations
- Locations (1)
UF Health - Precision Health Research Center
🇺🇸The Villages, Florida, United States
UF Health - Precision Health Research Center🇺🇸The Villages, Florida, United States