Cognitive Detection of Preclinical AD: Validation Using Biomarkers

The current study aims to validate several novel cognitive tasks expected to be sensitive to brain impairment in specific anatomic regions affected in preclinical Alzheimer's disease(pAD). The tasks are validated in 60 cognitively and clinically normal participants ages 60 - 85, inclusive, against reasonably well-established biomarkers of Alzheimer's disease, including 1) simultaneous positron emission tomography (PET) [18F]Flutemetamol amyloid and CT imaging and 2) to the extent data is available from other studies, participants' brain MRI and cerebral spinal fluid (CSF) amyloid and tau.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment

Detailed Description

Biomarkers, such as amyloid deposition, and Hipp volume loss, and low Aβ and high pTau in CSF, are useful for identifying cognitively normal (CN) elderly who are likely have early AD pathology ("preclinical AD"). However, they are invasive and/or expensive. The goal of the current study is to develop and validate cognitive proxies of AD biomarkers by using cognitive tasks that are dependent on brain regions impaired by very early AD pathology. If successful, these tasks will provide a non-invasive and cost-effective way to identify and track change in CN individuals at high risk for progressing to mild cognitive impairment (MCI) and dementia stages of AD and thus will facilitate future prevention trials in pAD.

Subjects will attend three study visits. During the first study visit, subjects will have eligibility criteria confirmed, have a blood sample drawn, and complete about half of the cognitive tasks. The second visit, which will occur within one week of visit one, will involve completion of the remaining cognitive tasks. Subjects will also be asked to have a PET-CT scan during visit three (to occur within 3 months of visits 1 and 2).

• Study Type: Observational
• Enrollment (Actual): 81

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants will be elderly individuals who are participating in ongoing clinical research at the NYU CCN, including at the ADC and the Center for Brain Health (CBH). Participants may also be recruited through community outreach or referrals from other centers. Cognitively normal (CN) participants and participants with amnestic mild cognitive impairment (aMCI) will be enrolled.

Description

Inclusion Criteria:

• Prior enrollment as a participant in the NYU Alzheimer's Disease Center (ADC) and completion of the ADC Clinical Evaluation within the past year.
• Clinical diagnosis of "cognitively normal" or "amnestic mild cognitive impairment" based on recent (within 1 year) consensus meeting cross-referenced with standard neuropsychological scores.
• Normal or corrected-to-normal vision and hearing (able to see images on computer screen and hear auditory events delivered through the computer speaker).

Exclusion Criteria:

• Significant history of mental illness, drug or alcohol abuse; severe trauma preventing normal use of dominant hand (needed to move the mouse cursor); clinical depression (unless medically controlled); other neurologic conditions (i.e. stroke), or learning disability; ophthalmologic/visual problems that prevent viewing a computer screen at a normal distance (such as legal blindness, detached retinas, occlusive cataracts).
• Lack of capacity to give informed consent and no legally authorized representative to provide consent.
• Having pacemakers, aneurysm clips, cochlear implants, or metal/foreign objects in body and therefore, unable to receive MRI.
• Pregnancy, breastfeeding or planning to have a baby.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cognitively Normal; Participants will be deemed cognitively normal based on criteria set forth by the National Alzheimer's Disease Coordinating Center/Alzheimer's Disease Centers (ADCC/ADC).
Amnestic Mild Cognitive Impairment (aMCI); Participants will be deemed aMCI based on criteria set forth by the National Alzheimer's Disease Coordinating Center/Alzheimer's Disease Centers (ADCC/ADC).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of composite score on cognitive tests with biomarkers	The overall score on the cognitive tests will be correlated via a linear regression with biomarker data collected during the study. Each biomarker will be regressed individually. Biomarker data includes: MRI hippocampus (hipp) volume, entorhinal cortex (EC) volume, EC standard uptake value ratios (SUVRs), Hipp SUVR, precuneus (PCu) SUVR, PET-[18F] Flutemetamol SUVR, CSF Aβ and tau levels, levels of diffusion tensor imaging mean diffusivity, and levels of fractional anisotropy.	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Presence of ApoE allele	3 months

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Janssen Scientific Affairs, LLC
• Investigators: Principal Investigator: Martin Sadowski, PhD, NYU Langone Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2016
• Primary Completion (Actual): August 12, 2020
• Study Completion (Actual): August 12, 2020

Study Registration Dates

• First Submitted: November 25, 2015
• First Submitted That Met QC Criteria: November 25, 2015
• First Posted (Estimate): November 30, 2015

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: January 13, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 13-00706

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No