Preclinical Alzheimer's Disease, Alzheimer's Disease (AD)
Conditions
Keywords
Preclinical Alzheimer Disease, Alzheimer Disease Biomarkers, Amyloid Beta, Blood-Based Biomarkers, Cognitive Decline, Alzheimer Disease Prevention
Brief summary
The goal of this observational study is to learn how Alzheimer's disease-related blood biomarkers, brain amyloid, and memory and thinking abilities change over time. The study will include up to 3,000 people who previously did not qualify for an anti-amyloid Alzheimer's disease prevention trial based on their amyloid eligibility. Participants may have previously screened for the AHEAD 3-45 Study, A4 Study, or another anti-amyloid Alzheimer's disease prevention trial. The main questions this study aims to answer are: * Can Alzheimer's disease-related blood tests help predict future buildup of amyloid in the brain? * How are changes in Alzheimer's disease-related blood biomarkers related to changes in brain amyloid, memory, thinking, and self-reported cognitive function? * Do these changes differ based on factors such as sex, APOE genetic status, race, ethnicity, socioeconomic status, or social factors? Participants will be followed for about 6 years. They will complete memory and thinking assessments and questionnaires and provide blood samples. Some participants may also be asked to take part in optional activities, including brain imaging with positron emission tomography (PET) or magnetic resonance imaging (MRI), digital cognitive assessments, and questionnaires about habits and social factors.
Interventions
RADIATIONNAV4694
Amyloid PET imaging with NAV4694 injection
Sponsors
University of Southern California
Alzheimer's Clinical Trials Consortium (ACTC)
Alzheimer's Therapeutic Research Institute
Alzheimer's Association
National Institute on Aging (NIA)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. Documentation of the participant's informed consent to study procedures and for the use of protected health information (HIPAA Authorization, or local, regional or country-specific equivalent). Informed consent processes and documentation must adhere to state laws/local requirements, including consent provided by the participant's legally authorized representative (LAR), responsible next of kin, surrogate consent with assent, etc. 2. Previously consented to participate in an anti-amyloid preclinical AD study (e.g., AHEAD 3-45, A4 or other anti-amyloid preclinical AD study). 3. Has screening results that did not meet amyloid eligibility criteria for an anti-amyloid preclinical AD trial (e.g., AHEAD 3-45, A4, or other anti-amyloid preclinical AD study). 4. As assessed by the site PI, participant is likely to be able to comply with the protocol, including completion of all required procedures for the duration of the study, and has adequate vision, hearing (hearing aid permitted), and literacy in English or Spanish sufficient for compliance with required testing procedures. For participants who screen failed from the AHEAD 3-45 Study: 5. Has AHEAD 3-45 screening plasma biomarker results required for determining eligibility to participate in the AHEAD 3-45 Study.
Exclusion criteria
1. Current treatment with an FDA approved medication for Alzheimer's disease, including prior or current treatment with a prohibited medication. 2. Enrollment in another investigational study, or intake of investigational drug, within 30 days prior to screening, or five half-lives of the investigational drug, whichever is longer, unless it can be documented that the participant was in the placebo treatment arm. 3. Screen failed from an anti-amyloid preclinical AD trial (e.g. AHEAD 3-45, A4 or other anti-amyloid preclinical AD trial) due to not meeting basic inclusion criteria (i.e., age requirement; current diagnosis of AD dementia). For participants participating in the optional amyloid PET imaging sub-study: 4. Is pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of change from Baseline through Month 72 in plasma beta-amyloid (Aβ) 40 or 42 ratio | Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72 | Change in plasma Aβ42/Aβ40 ratio over the longitudinal follow-up period will be assessed using repeated blood-based biomarker measurements. |
| Rate of change from Baseline through Month 72 in plasma phosphorylated tau (ptau) 217 | Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72 | Assess longitudinal changes from initial visit in plasma phosphorylated tau (ptau) 217 ratio using a proteomics assay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Change from Baseline through Month 72 as measured by the Preclinical Alzheimer Cognitive Composite 5 (PACC5) | Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72 | The Preclinical Alzheimer Cognitive Composite 5 (PACC5) is a composite measure of episodic memory, timed executive function, semantic memory, and global cognition. It includes: Free and Cued Selective Reminding Test (FCSRT), using the Free + Total Free and Cued Recall score (0-96, higher scores indicate better performance); delayed Paragraph Recall (0-25, higher scores indicate better recall); Digit Symbol Substitution Test (DSST), number correctly completed in 90 seconds (0-91, higher scores indicate better performance); Mini-Mental State Examination (MMSE) (0-30, higher scores indicate better performance); and Category Fluency, number of appropriate words generated, with higher scores indicating better performance. |
| Rate of Change from Baseline through Month 72 as measured Cognitive Function Index (CFI) | Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72 | The participant-reported Cognitive Function Index (CFI) assesses the participant's perceived ability to perform high-level functional tasks in daily life and overall cognitive functional ability. Only the participant-CFI portion will be administered. Participants rate their own abilities using 18 questions. The total participant-CFI score ranges from 0 (minimum) to 18 (maximum), with higher scores indicating greater impairment. The CFI may be self-administered or completed as an interview conducted by clinical site personnel in person or, if necessary, over the phone. |
Countries
United States
Contacts
STUDY_DIRECTORPaul Aisen, MD
University of Southern California (USC) Alzheimer's Therapeutic Research Institute (ATRI)
STUDY_DIRECTORReisa Sperling, MD
Brigham and Women's Hospital and Massachusetts General Hospital
Outcome results
None listed