Applied Cognition Benchmarking Study (BRAIN3)

Measuring and Monitoring Brain Health in Older Adults: The Applied Cognition Glymphatic Function Study at The Villages

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Diagnostic test: Device measurements during overnight sleep and morning wake; Diagnostic test: Device measurements during overnight wake and morning sleep

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • The Villages, Florida, United States, 32159
      • UF Health - Precision Health Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participants must have a Montreal Cognitive Assessment (MoCA) score at least 26.
2. Participants must have a Geriatric Depression Scale (GDS) 15-item score of 4 or less.

Exclusion Criteria:

1. 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).
2. Participants with a history of significant neurological disease or history of epilepsy.
3. Participants with cardiovascular disease or cardiovascular risk factors (smoking or hypertension).
4. Participants with diabetes.
5. Participants with traumatic brain injury, or serious mental illness including bipolar disorder, schizophrenia, major depressive disorder or post-traumatic stress disorder.
6. Participants who have taken in the past 30 days prescribed or overthe- counter (OTC) stimulants, sleeping medications, or psychiatric medications including antidepressants.
7. 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.
8. 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.
9. Participants planning travel to alternate time zones within two weeks of study participation
10. Participants with travel plans or conflicts that would prevent them from either Study Visit.
11. Participants who are enrolled in other research studies and are receiving an investigational drug within 30 days of the planned start date.
12. 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.
13. 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.
14. 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
15. Participants who have a pre-planned surgery or medical procedure that would interfere with the conduct of the study.
16. Participants who have an implanted medical device or contraindications that would exclude MRIs
17. Participants with a serious infection requiring medical attention in the past 30 days
18. Participants with a diagnosis of substance use-disorder in the past 2 years.
19. Participants with known acute or chronic kidney disease and/or compromised GFR.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sleep Opportunity-Sleep Deprivation; Participant randomized to overnight sleep period with a morning wake period on first visit of cross-over study.	Diagnostic test: Device measurements during overnight sleep and morning wake; Overnight period and morning period device measurements
Experimental: Sleep Deprivation-Sleep Opportunity; Participant randomized to overnight sleep deprivation period with a morning recovery sleep period on first visit of cross-over study.	Diagnostic test: Device measurements during overnight wake and morning sleep; Overnight period and morning period device measurements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contrast-enhanced MRI	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.	Immediately after the overnight sleep/wake period
Non-invasive MRI - diffusion-based intravoxel incoherent motion	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.).	Immediately before and immediately after each sleep/wake period
Non-invasive MRI - fast functional MRI	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.	Immediately before and immediately after each sleep/wake period
Non-invasive MRI - T1/FLAIR-based assessment	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.).	Immediately before and immediately after each sleep/wake period
Non-invasive MRI - multi-echo arterial spin-labeling	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).	Immediately before and immediately after each sleep/wake period
Non-invasive MRI - phase-contrast	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).	Immediately before and immediately after each sleep/wake period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep EEG	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.	Measurements sampled every 5 to 10 minutes during the overnight sleep period
Blood biomarkers	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	Immediately before and immediately after each sleep/wake period
Cognitive function - trail making tests A&B	Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on Trail Making Tests A&B (time in seconds).	Immediately after the sleep/wake period
Cognitive function - symbol digit modality test	Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on symbol digit modality test (SDMT) (number correct).	Immediately after the sleep/wake period
Cognitive function - psychomotor vigilance test	Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on psychomotor vigilance test (PVT) (mean and standard deviation of reaction time).	Immediately after the sleep/wake period
Cognitive function - digits forward recall	Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on digits forward recall (maximum number of correctly recalled digits).	Immediately after the sleep/wake period

Collaborators and Investigators

• Sponsor: Applied Cognition
• Collaborators: University of Florida Health
• Investigators: Principal Investigator: Carla Vandeweerd, PhD, UF Health

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2022
• Primary Completion (Actual): June 8, 2023
• Study Completion (Actual): June 8, 2023

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: January 12, 2024
• First Posted (Estimated): January 24, 2024

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: AC.2022.02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No