Biomarker Exploration in Aging, Cognition and Neurodegeneration

NCT ID: NCT03860857

Last Updated: 2026-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-01

Study Completion Date

2027-12-22

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Alzheimer Disease Cognitive Impairment Cognitive Decline

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

All participants will complete the same study procedures, including the tau PET scans with investigational radio tracer 18F-MK6240. The arms define the age range and APOE status of the participants, with each having their own enrollment target.
Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Amyloid PET scan

Intervention Type RADIATION

Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Tau PET scan using MK-6240

Intervention Type DRUG

Tau Positron Emission Tomography scan using radio tracer MK-6240

Neurocognitive testing

Intervention Type BEHAVIORAL

A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.

MRI

Intervention Type OTHER

High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

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.

Group Type EXPERIMENTAL

Amyloid PET scan

Intervention Type RADIATION

Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Tau PET scan using MK-6240

Intervention Type DRUG

Tau Positron Emission Tomography scan using radio tracer MK-6240

Neurocognitive testing

Intervention Type BEHAVIORAL

A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.

MRI

Intervention Type OTHER

High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

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.

Group Type EXPERIMENTAL

Amyloid PET scan

Intervention Type RADIATION

Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Tau PET scan using MK-6240

Intervention Type DRUG

Tau Positron Emission Tomography scan using radio tracer MK-6240

Neurocognitive testing

Intervention Type BEHAVIORAL

A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.

MRI

Intervention Type OTHER

High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

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.

Group Type EXPERIMENTAL

Amyloid PET scan

Intervention Type RADIATION

Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Tau PET scan using MK-6240

Intervention Type DRUG

Tau Positron Emission Tomography scan using radio tracer MK-6240

Neurocognitive testing

Intervention Type BEHAVIORAL

A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.

MRI

Intervention Type OTHER

High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

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.

Group Type EXPERIMENTAL

Amyloid PET scan

Intervention Type RADIATION

Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Tau PET scan using MK-6240

Intervention Type DRUG

Tau Positron Emission Tomography scan using radio tracer MK-6240

Neurocognitive testing

Intervention Type BEHAVIORAL

A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.

MRI

Intervention Type OTHER

High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

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.

Group Type EXPERIMENTAL

Amyloid PET scan

Intervention Type RADIATION

Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Tau PET scan using MK-6240

Intervention Type DRUG

Tau Positron Emission Tomography scan using radio tracer MK-6240

Neurocognitive testing

Intervention Type BEHAVIORAL

A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.

MRI

Intervention Type OTHER

High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

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.

Group Type EXPERIMENTAL

Amyloid PET scan

Intervention Type RADIATION

Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Tau PET scan using MK-6240

Intervention Type DRUG

Tau Positron Emission Tomography scan using radio tracer MK-6240

Neurocognitive testing

Intervention Type BEHAVIORAL

A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.

MRI

Intervention Type OTHER

High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

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.

Group Type EXPERIMENTAL

Amyloid PET scan

Intervention Type RADIATION

Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Tau PET scan using MK-6240

Intervention Type DRUG

Tau Positron Emission Tomography scan using radio tracer MK-6240

Neurocognitive testing

Intervention Type BEHAVIORAL

A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.

MRI

Intervention Type OTHER

High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

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.

Group Type EXPERIMENTAL

Amyloid PET scan

Intervention Type RADIATION

Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Tau PET scan using MK-6240

Intervention Type DRUG

Tau Positron Emission Tomography scan using radio tracer MK-6240

Neurocognitive testing

Intervention Type BEHAVIORAL

A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.

MRI

Intervention Type OTHER

High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

Interventions

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Amyloid PET scan

Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Intervention Type RADIATION

Tau PET scan using MK-6240

Tau Positron Emission Tomography scan using radio tracer MK-6240

Intervention Type DRUG

Neurocognitive testing

A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.

Intervention Type BEHAVIORAL

MRI

High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

Intervention Type OTHER

Other Intervention Names

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tau PET

Eligibility Criteria

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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.
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

University of California, Irvine

OTHER

Sponsor Role lead

Responsible Party

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Michael Yassa

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael A Yassa, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Irvine

Liv C McMillan, BS, CCRP

Role: STUDY_DIRECTOR

University of California, Irvine

Locations

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University of California, Irvine

Irvine, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Evelyn Chang, BA

Role: CONTACT

949-824-0904

Novelle Meza, BS

Role: CONTACT

949-824-5049

Facility Contacts

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Evelyn Chang, BA

Role: primary

949-824-0904

Novelle Meza, BS

Role: backup

949-824-5049

References

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Stevenson RF, Reagh ZM, Chun AP, Murray EA, Yassa MA. Pattern Separation and Source Memory Engage Distinct Hippocampal and Neocortical Regions during Retrieval. J Neurosci. 2020 Jan 22;40(4):843-851. doi: 10.1523/JNEUROSCI.0564-19.2019. Epub 2019 Nov 20.

Reference Type RESULT
PMID: 31748377 (View on PubMed)

Holbrook AJ, Tustison NJ, Marquez F, Roberts J, Yassa MA, Gillen DL; Alzheimer's Disease Neuroimaging Initiative section sign. Anterolateral entorhinal cortex thickness as a new biomarker for early detection of Alzheimer's disease. Alzheimers Dement (Amst). 2020 Aug 25;12(1):e12068. doi: 10.1002/dad2.12068. eCollection 2020.

Reference Type RESULT
PMID: 32875052 (View on PubMed)

Chappel-Farley MG, Mander BA, Neikrug AB, Stehli A, Nan B, Grill JD, Yassa MA, Benca RM. Symptoms of obstructive sleep apnea are associated with less frequent exercise and worse subjective cognitive function across adulthood. Sleep. 2022 Mar 14;45(3):zsab240. doi: 10.1093/sleep/zsab240.

Reference Type RESULT
PMID: 34604910 (View on PubMed)

Adams JN, Kim S, Rizvi B, Sathishkumar M, Taylor L, Harris AL, Mikhail A, Keator DB, McMillan L, Yassa MA. Entorhinal-Hippocampal Circuit Integrity Is Related to Mnemonic Discrimination and Amyloid-beta Pathology in Older Adults. J Neurosci. 2022 Nov 16;42(46):8742-8753. doi: 10.1523/JNEUROSCI.1165-22.2022. Epub 2022 Oct 27.

Reference Type RESULT
PMID: 36302636 (View on PubMed)

Adams JN, Marquez F, Larson MS, Janecek JT, Miranda BA, Noche JA, Taylor L, Hollearn MK, McMillan L, Keator DB, Head E, Rissman RA, Yassa MA. Differential involvement of hippocampal subfields in the relationship between Alzheimer's pathology and memory interference in older adults. Alzheimers Dement (Amst). 2023 Apr 5;15(2):e12419. doi: 10.1002/dad2.12419. eCollection 2023 Apr-Jun.

Reference Type RESULT
PMID: 37035460 (View on PubMed)

Related Links

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https://beacon.bio.uci.edu

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

Other Identifiers

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R01AG053555

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20173832

Identifier Type: -

Identifier Source: org_study_id

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