Biomarker Exploration in Aging, Cognition and Neurodegeneration (BEACoN)

The BEACoN Study- Biomarker Exploration in Aging, Cognition and Neurodegeneration

The purpose of this research study is to understand the factors that underlie changes in thinking and memory with increasing age. The investigators will test the usefulness of MRI, PET, and cognitive testing in detecting subtle changes in the brain that precede cognitive decline. An addendum to this study includes additional PET scans to examine the relationship between tau protein in the brain and cognitive decline. Tau is a protein that is known to form tangles in the areas of the brain important for memory, and these tau tangles are a hallmark of Alzheimer's disease. This sub-study research aims to look at the tau accumulation in the brain using an investigational drug called MK-6240, which is a radio tracer that gets injected prior to a positron emission tomography (PET) scan.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Impairment; Alzheimer Disease; Cognitive Decline
• Intervention / Treatment: Radiation: Amyloid PET scan; Drug: Tau PET scan using MK-6240; Behavioral: Neurocognitive testing; Other: MRI

Detailed Description

This study investigates the relationship between Alzheimer's disease (AD) pathology, brain structure and function, as well as cognition in non-demented older adults. The goal is to develop a more complete understanding of the factors that lead to cognitive decline in the elderly and progression to AD. The investigators will enroll 200 cognitively intact adults between the ages of 60-85 years old from the UCI Alzheimer's Disease Research Center or directly from the local community. Study procedures will include: 1) PET amyloid scans with Amyvid™ radiotracer (florbetapir-F18) and PET tau scans with [18F]MK6240 radiotracer; 2) High-resolution structural, functional, and diffusion MRI; and 3) Cognitive examinations. The investigators will track cognitive outcomes through longitudinal monitoring. Amyloid imaging will only be conducted once in the study at baseline, and MRI and tau PET imaging will be at baseline and Year 1. The investigators aim to identify the best combination of tests for predicting longitudinal cognitive/clinical decline. The proposed study will significantly inform the understanding of cognitive decline in the aging brain and allow investigators to better define preclinical AD and make recommendations for future intervention trials.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alyssa Harris, BA; Phone Number: 949-824-0904; Email: beacon@uci.edu
• Study Contact Backup: Name: Novelle Meza, BS; Phone Number: 949-824-5049; Email: njmeza@uci.edu

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • Recruiting
      • University of California, Irvine
      • Contact: Alyssa Harris, BA; Phone Number: 949-824-0904; Email: beacon@uci.edu
      • Contact: Novelle Meza, BS; Phone Number: 949-824-5049; Email: njmeza@uci.edu
      • Principal Investigator: Michael A Yassa, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 105 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Aged 60 or older;
2. Speaks fluent English or Spanish;
3. Visual and auditory acuity adequate for neuropsychological and computerized testing;
4. Good general health with no disease(s) expected to interfere with the study;
5. Willing and able to participate for the duration of the study and in all study procedures including MRI and PET;
6. Normal cognition defined as a Clinical Dementia Rating of 0 and a Mini-Mental State Examination score of 25 or higher. FAST Stage 1 or 2.
7. Subjective memory or other cognitive complaints will be included.

Exclusion Criteria:

1. Significant co-morbid neurologic disease such as Parkinson's disease, multiple sclerosis, brain cyst, tumor or aneurysm;
2. Major health conditions, except for Type II diabetes mellitus, hypercholesterolemia, and hypertension, which are NOT exclusionary for this study given their high prevalence in our target populations;
3. Significant psychiatric disorders such as schizophrenia, bipolar disorder, or attention-deficit hyperactivity disorder, except for depression and anxiety, which are NOT exclusionary for this study given their high prevalence in our target populations;
4. Existing diagnosis of dementia or mild cognitive impairment;
5. Alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria);
6. MRI contraindications, e.g. pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body. Females who are pregnant or trying to get pregnant are also excluded;
7. PET contraindications, e.g. significant prior radiation exposure and pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Age 60-65 ApoE e4+; Participants in this cohort are between the ages of 60-65 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.	Radiation: Amyloid PET scan; Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18; Drug: Tau PET scan using MK-6240; Tau Positron Emission Tomography scan using radio tracer MK-6240; Other Names: tau PET; Behavioral: Neurocognitive testing; A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.; Other: MRI; High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.
Experimental: Age 66-70 ApoE e4-; Participants in this cohort are between the ages of 66-70 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.	Radiation: Amyloid PET scan; Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18; Drug: Tau PET scan using MK-6240; Tau Positron Emission Tomography scan using radio tracer MK-6240; Other Names: tau PET; Behavioral: Neurocognitive testing; A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.; Other: MRI; High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.
Experimental: Age 66-70 ApoE e4+; Participants in this cohort are between the ages of 66-70 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.	Radiation: Amyloid PET scan; Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18; Drug: Tau PET scan using MK-6240; Tau Positron Emission Tomography scan using radio tracer MK-6240; Other Names: tau PET; Behavioral: Neurocognitive testing; A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.; Other: MRI; High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.
Experimental: Age 71-75 ApoE e4-; Participants in this cohort are between the ages of 71-75 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.	Radiation: Amyloid PET scan; Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18; Drug: Tau PET scan using MK-6240; Tau Positron Emission Tomography scan using radio tracer MK-6240; Other Names: tau PET; Behavioral: Neurocognitive testing; A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.; Other: MRI; High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.
Experimental: Age 71-75 ApoE e4+; Participants in this cohort are between the ages of 71-75 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.	Radiation: Amyloid PET scan; Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18; Drug: Tau PET scan using MK-6240; Tau Positron Emission Tomography scan using radio tracer MK-6240; Other Names: tau PET; Behavioral: Neurocognitive testing; A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.; Other: MRI; High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.
Experimental: Age 76-80 ApoE e4-; Participants in this cohort are between the ages of 76-80 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.	Radiation: Amyloid PET scan; Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18; Drug: Tau PET scan using MK-6240; Tau Positron Emission Tomography scan using radio tracer MK-6240; Other Names: tau PET; Behavioral: Neurocognitive testing; A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.; Other: MRI; High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.
Experimental: Age 76-80 ApoE e4+; Participants in this cohort are between the ages of 76-80 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.	Radiation: Amyloid PET scan; Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18; Drug: Tau PET scan using MK-6240; Tau Positron Emission Tomography scan using radio tracer MK-6240; Other Names: tau PET; Behavioral: Neurocognitive testing; A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.; Other: MRI; High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.
Experimental: Age 81+ ApoE e4-; Participants in this cohort are between the ages of 81-85 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.	Radiation: Amyloid PET scan; Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18; Drug: Tau PET scan using MK-6240; Tau Positron Emission Tomography scan using radio tracer MK-6240; Other Names: tau PET; Behavioral: Neurocognitive testing; A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.; Other: MRI; High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.
Experimental: Age 81+ ApoE e4+; Participants in this cohort are between the ages of 81-85 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.	Radiation: Amyloid PET scan; Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18; Drug: Tau PET scan using MK-6240; Tau Positron Emission Tomography scan using radio tracer MK-6240; Other Names: tau PET; Behavioral: Neurocognitive testing; A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.; Other: MRI; High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Dementia Rating - Sum of Box Score	A measure of cognitive/clinical decline	Years 4 and 5 of the grant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lure discrimination index - objects	Key measure of performance on the object pattern separation task	Years 4 and 5 of the grant
Change in lure discrimination index - spatial	Key measure of performance on the spatial pattern separation task	Years 4 and 5 of the grant
Change in lure discrimination index - temporal	Key measure of performance on the temporal pattern separation task	Years 4 and 5 of the grant
Change in entorhinal cortical thickness	Key measure of structural decline on MRI scans	Years 4 and 5 of the grant
Change in perforant path integrity	Key measure of structural connectivity decline on MRI scans	Years 4 and 5 of the grant
Change in tau spatial distribution - advancing Braak stage	Key measure of tau spatial spread on tau PET scans	Years 4 and 5 of the grant

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Michael A Yassa, PhD, University of California, Irvine; Study Director: Liv C McMillan, BS, CCRP, University of California, Irvine

Publications and helpful links

Helpful Links

• BEACoN (Biomarker Exploration in Aging, Cognition, and Neurodegeneration) study website

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Estimated): December 22, 2026
• Study Completion (Estimated): December 22, 2027

Study Registration Dates

• First Submitted: February 15, 2019
• First Submitted That Met QC Criteria: February 28, 2019
• First Posted (Actual): March 4, 2019

Study Record Updates

• Last Update Posted (Actual): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: MRI; PET; biomarker; mild cognitive impairment; Alzheimer disease; cognitive impairment
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Nerve Degeneration
• Other Study ID Numbers: 20173832; R01AG053555-02 (U.S. NIH Grant/Contract); 2R01AG053555-06 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No