MRI and PET Biomarkers for Cognitive Decline in Older Adults

Sponsor

University of California, Irvine (Other)

Overall Status

Recruiting

CT.gov ID

NCT03860857

Collaborator

National Institute on Aging (NIA) (NIH)

200

Enrollment

Location

Arms

79.7

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease Cognitive Impairment Cognitive Decline	Radiation: Amyloid PET scan Drug: Tau PET scan using MK-6240 Behavioral: Neurocognitive testing Other: MRI	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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)

Primary Purpose:

Health Services Research

Official Title:

MRI and PET Biomarkers for Cognitive Decline in Older Adults

Actual Study Start Date :

May 1, 2018

Anticipated Primary Completion Date :

Dec 22, 2023

Anticipated Study Completion Date :

Dec 22, 2024

Arms and Interventions

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 81-85 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 81-85 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.

Outcome Measures

Primary Outcome Measures

Change in Clinical Dementia Rating - Sum of Box Score [Years 4 and 5 of the grant]
A measure of cognitive/clinical decline

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Between the ages of 60 and 85;
Speaks fluent English;
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.