Measuring Brain Amyloid Plaque Load in Older Adults Using BAY 94-9172

BAY 94-9172 PET/CT in Cognitively Normal Older Adults, Older Adults With Mild Cognitive Impairment, and Older Adults With Alzheimer's Disease

The overall goal of this project is to establish and validate biomarkers associated with the risk and progression of late onset Alzheimer's disease, mild cognitive impairment and cognitive decline. The investigators will use baseline and longitudinal measurements of plasma amyloid beta-40 and amyloid beta-42 to investigate the risk of developing mild cognitive impairment and late onset Alzheimer's disease, as well as the rates of cognitive decline and Alzheimer's disease progression. The driving hypothesis of the study is that amyloid beta in the brain as measured by positron emission tomography positivity is associated with the onset of cognitive decline associated with late onset Alzheimer's disease.

Study Overview

• Status: Completed
• Conditions: Late Onset Alzheimer Disease
• Intervention / Treatment: Drug: BAY 94-9172 (Florbetaben)

Detailed Description

This project is a sub-study of the Washington Heights-Inwood Community Aging Project, which is a multidisciplinary, epidemiological study of Alzheimer's disease and related neurodegenerative disorders. We will obtain positron emission tomography scans and simultaneous x-ray computed tomography scans using Florbetaben from Bayer on a selection of ongoing participants who will be selected on the basis of change in plasma levels of amyloid beta over time. Approximately 200 participants will receive scans beginning in 2009 and in the 2010-2012 assessment wave and then again in a 2014-2015 assessment wave. Our intention is to examine whether uptake of Florbetaben in the brain is associated with decline in cognition over the 10 years prior to the PET scan.

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Current Washington Heights-Inwood Community Aging Project (WHICAP) participant Age 65 or older Residing in the community of Washington-Heights/Inwood/Hamilton Heights
• Is able to provide informed consent, understand the information provided on the purpose and conduct of the trial and exhibits adequate visual, auditory and communication capabilities to enable compliance with study procedures. This includes performing the psychometric testing and being able to lie down flat in the Positron Emission Tomography (PET) scanner
• Possesses a general health that permits adequate compliance with all study procedures.
• Informed consent has been signed and dated (with time) by the subject and/or the subject's caregiver (for probable Alzheimer's Disease (AD) patients)

Exclusion Criteria:

• Has any contraindication to PET, such as claustrophobia, or inability to lie flat for half an hour as determined by the onsite radiologist performing the scan
• Current, past, or anticipated exposure to radiation, which may include being badged for radiation exposure in the workplace or participation in nuclear medicine procedures, including research protocols in the last year
• Significant active physical illness particularly those that may affect the brain including blood dyscrasias, lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease, low hemoglobin and malignancy
• Scheduled for surgery and/or another invasive procedure within the time period of up to 24 hours following scan
• Allergic to the tracer or any of its constituents and/or has a history of severe allergic reactions to drugs or allergens (e.g. patients with allergic asthma)
• Critically ill and/or medically unstable and whose clinical course within the observation period is unpredictable, e.g. participants with 14 days of myocardial infarction or stroke, unstable participants with previous surgery (within 7 days), participants with advanced heart insufficiency (New York Heart Association (NYHA) stage IV), or participants with acute renal failure.
• Has received any contrast material (X-ray, Magnetic Resonance Imaging (MRI)), or radiopharmaceuticals within 48 hours prior to the application of the Investigational Medicinal Product (IMP) or for whom application of such a substance is planned for 24 hours following IMP administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY 94-9172; BAY 94-9172 PET/CT	Drug: BAY 94-9172 (Florbetaben); Measure of brain amyloid load using BAY 94-9172 PET/CT; Other Names: Florbetaben; Bay 91-9172

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship Between Cognitive Change Over Time and Amyloid (Aβ) Deposition	We used PET imaging to measure presence of amyloid. The outcomes are cognitive z-scores, which had mean of zero and SD of 1, with no units. There are four cognitive domains (language, memory, processing speed, and visuospatial ability). Individual neuropsychological test Z-scores within each domain were averaged to get the mean domain z-scores. Finally, the four cognitive domain-specific Z-scores were then averaged into a global cognitive Z-score. A larger Z-score represents better cognitive performance. Latent growth curve model was used to test for the association between Aβ and cognitive change over time. The Beta weight is a coefficient from the model that indicates the difference in cognitive change between people with and without amyloid. A positive Beta weight indicates that Aβ deposition is associated with less decline in cognitive scores, a negative Beta weight indicates greater decline. The Beta weight is unitless, and it does not have a range.	up to 3 years and 10 months

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: Bayer; National Institute on Aging (NIA)
• Investigators: Principal Investigator: Richard Mayeux, BS, MD, MSc, Columbia University; Study Chair: Yaakov Stern, BA, PhD, Columbia University

Publications and helpful links

General Publications

• Cosentino SA, Stern Y, Sokolov E, Scarmeas N, Manly JJ, Tang MX, Schupf N, Mayeux RP. Plasma ss-amyloid and cognitive decline. Arch Neurol. 2010 Dec;67(12):1485-90. doi: 10.1001/archneurol.2010.189. Epub 2010 Aug 9.
• Forsberg A, Almkvist O, Engler H, Wall A, Langstrom B, Nordberg A. High PIB retention in Alzheimer's disease is an early event with complex relationship with CSF biomarkers and functional parameters. Curr Alzheimer Res. 2010 Feb;7(1):56-66. doi: 10.2174/156720510790274446.
• Gu Y, Razlighi QR, Zahodne LB, Janicki SC, Ichise M, Manly JJ, Devanand DP, Brickman AM, Schupf N, Mayeux R, Stern Y. Brain Amyloid Deposition and Longitudinal Cognitive Decline in Nondemented Older Subjects: Results from a Multi-Ethnic Population. PLoS One. 2015 Jul 29;10(7):e0123743. doi: 10.1371/journal.pone.0123743. eCollection 2015.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2010
• Primary Completion (Actual): October 22, 2014
• Study Completion (Actual): October 22, 2014

Study Registration Dates

• First Submitted: October 14, 2010
• First Submitted That Met QC Criteria: October 15, 2010
• First Posted (Estimated): October 18, 2010

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Biomarker; Alzheimer's disease; Positron emission tomography; Brain amyloid plaque load
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 6045/7130R (Bayer); IND 78868 (Other Identifier: U.S. Food and Drug Administration); R01AG037212-01 (U.S. NIH Grant/Contract)