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MRI and PET Biomarkers for Cognitive Decline in Older Adults

Primary Purpose

Alzheimer Disease, Cognitive Impairment, Cognitive Decline

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Amyloid PET scan
Tau PET scan using MK-6240
Neurocognitive testing
MRI
Sponsored by
University of California, Irvine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for Alzheimer Disease focused on measuring Alzheimer disease, cognitive impairment, mild cognitive impairment, biomarker, MRI, PET

Eligibility Criteria

60 Years - 105 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Aged 60 and above;
  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 27 or higher.

Exclusion Criteria:

  1. Significant co-morbid neurologic disease such as Parkinson's disease, multiple sclerosis, brain cyst, tumor or aneurysm;
  2. Major health conditions such as uncontrolled diabetes mellitus, uncontrolled hypertension, nutritional deficiency or uncontrolled thyroid disease;
  3. Significant psychiatric disorders such as schizophrenia, bipolar disorder, anxiety disorder, major depressive disorder, or attention-deficit hyperactivity disorder;
  4. ADRC consensus diagnosis of dementia or mild cognitive impairment;
  5. Cognitive impairment when tested at baseline (defined as a score on any neuropsychological test of 1.5 SDs or more outside the age norm);
  6. Alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria);
  7. 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;
  8. PET contraindications, e.g. significant prior radiation exposure and pregnancy.

Sites / Locations

  • University of California, IrvineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Age 60-65 ApoE e4+

Age 66-70 ApoE e4-

Age 66-70 ApoE e4+

Age 71-75 ApoE e4-

Age 71-75 ApoE e4+

Age 76-80 ApoE e4-

Age 76-80 ApoE e4+

Age 81+ ApoE e4-

Age 81+ ApoE e4+

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Change in Clinical Dementia Rating - Sum of Box Score
A measure of cognitive/clinical decline

Secondary Outcome Measures

Change in lure discrimination index - objects
Key measure of performance on the object pattern separation task
Change in lure discrimination index - spatial
Key measure of performance on the spatial pattern separation task
Change in lure discrimination index - temporal
Key measure of performance on the temporal pattern separation task
Change in entorhinal cortical thickness
Key measure of structural decline on MRI scans
Change in perforant path integrity
Key measure of structural connectivity decline on MRI scans
Change in tau spatial distribution - advancing Braak stage
Key measure of tau spatial spread on tau PET scans

Full Information

First Posted
February 15, 2019
Last Updated
October 18, 2022
Sponsor
University of California, Irvine
Collaborators
National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT03860857
Brief Title
MRI and PET Biomarkers for Cognitive Decline in Older Adults
Official Title
MRI and PET Biomarkers for Cognitive Decline in Older Adults
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2018 (Actual)
Primary Completion Date
December 22, 2023 (Anticipated)
Study Completion Date
December 22, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Irvine
Collaborators
National Institute on Aging (NIA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Cognitive Impairment, Cognitive Decline
Keywords
Alzheimer disease, cognitive impairment, mild cognitive impairment, biomarker, MRI, PET

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Age 60-65 ApoE e4+
Arm Type
Experimental
Arm Description
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.
Arm Title
Age 66-70 ApoE e4-
Arm Type
Experimental
Arm Description
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.
Arm Title
Age 66-70 ApoE e4+
Arm Type
Experimental
Arm Description
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.
Arm Title
Age 71-75 ApoE e4-
Arm Type
Experimental
Arm Description
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.
Arm Title
Age 71-75 ApoE e4+
Arm Type
Experimental
Arm Description
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.
Arm Title
Age 76-80 ApoE e4-
Arm Type
Experimental
Arm Description
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.
Arm Title
Age 76-80 ApoE e4+
Arm Type
Experimental
Arm Description
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.
Arm Title
Age 81+ ApoE e4-
Arm Type
Experimental
Arm Description
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.
Arm Title
Age 81+ ApoE e4+
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Amyloid PET scan
Intervention Description
Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18
Intervention Type
Drug
Intervention Name(s)
Tau PET scan using MK-6240
Other Intervention Name(s)
tau PET
Intervention Description
Tau Positron Emission Tomography scan using radio tracer MK-6240
Intervention Type
Behavioral
Intervention Name(s)
Neurocognitive testing
Intervention Description
A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.
Intervention Type
Other
Intervention Name(s)
MRI
Intervention Description
High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.
Primary Outcome Measure Information:
Title
Change in Clinical Dementia Rating - Sum of Box Score
Description
A measure of cognitive/clinical decline
Time Frame
Years 4 and 5 of the grant
Secondary Outcome Measure Information:
Title
Change in lure discrimination index - objects
Description
Key measure of performance on the object pattern separation task
Time Frame
Years 4 and 5 of the grant
Title
Change in lure discrimination index - spatial
Description
Key measure of performance on the spatial pattern separation task
Time Frame
Years 4 and 5 of the grant
Title
Change in lure discrimination index - temporal
Description
Key measure of performance on the temporal pattern separation task
Time Frame
Years 4 and 5 of the grant
Title
Change in entorhinal cortical thickness
Description
Key measure of structural decline on MRI scans
Time Frame
Years 4 and 5 of the grant
Title
Change in perforant path integrity
Description
Key measure of structural connectivity decline on MRI scans
Time Frame
Years 4 and 5 of the grant
Title
Change in tau spatial distribution - advancing Braak stage
Description
Key measure of tau spatial spread on tau PET scans
Time Frame
Years 4 and 5 of the grant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
105 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Aged 60 and above; Speaks fluent English or Spanish; Visual and auditory acuity adequate for neuropsychological and computerized testing; Good general health with no disease(s) expected to interfere with the study; Willing and able to participate for the duration of the study and in all study procedures including MRI and PET; Normal cognition defined as a Clinical Dementia Rating of 0 and a Mini-Mental State Examination score of 27 or higher. Exclusion Criteria: Significant co-morbid neurologic disease such as Parkinson's disease, multiple sclerosis, brain cyst, tumor or aneurysm; Major health conditions such as uncontrolled diabetes mellitus, uncontrolled hypertension, nutritional deficiency or uncontrolled thyroid disease; Significant psychiatric disorders such as schizophrenia, bipolar disorder, anxiety disorder, major depressive disorder, or attention-deficit hyperactivity disorder; ADRC consensus diagnosis of dementia or mild cognitive impairment; Cognitive impairment when tested at baseline (defined as a score on any neuropsychological test of 1.5 SDs or more outside the age norm); Alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria); 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; PET contraindications, e.g. significant prior radiation exposure and pregnancy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alyssa Harris, BA
Phone
949-824-0904
Email
beacon@uci.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Novelle Meza, BS
Phone
949-824-5049
Email
njmeza@uci.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael A Yassa, PhD
Organizational Affiliation
University of California, Irvine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Liv C McMillan, BS, CCRP
Organizational Affiliation
University of California, Irvine
Official's Role
Study Director
Facility Information:
Facility Name
University of California, Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alyssa Harris, BA
Phone
949-824-0904
Email
beacon@uci.edu
First Name & Middle Initial & Last Name & Degree
Novelle Meza, BS
Phone
949-824-5049
Email
njmeza@uci.edu
First Name & Middle Initial & Last Name & Degree
Michael A Yassa, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://beacon.bio.uci.edu
Description
BEACoN (Biomarker Exploration in Aging, Cognition, and Neurodegeneration) study website

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MRI and PET Biomarkers for Cognitive Decline in Older Adults

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