The Diabetes Prevention Program Outcomes Study AD/ADRD Project

NCT ID: NCT05704309

Last Updated: 2025-08-26

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 1976 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-11-07
• Study Completion Date: 2027-08-30

Brief Summary

The DPPOS AD/ADRD project will address the overarching question: What are the determinants and the nature of cognitive impairment among persons with pre-diabetes (PreD) and type 2 diabetes (T2D), who are a high-risk group for cognitive impairment and represent a large fraction of the United States (US) population? This U19 proposal addresses the National Alzheimer's Project Act goal to "prevent, halt, or reverse AD" in the high-risk group of persons with pre-diabetes and type 2 diabetes, who represent over half of the population aged 60 years and older in the US.

Detailed Description

DPPOS AD/ADRD focuses on one of the most important, complex questions in Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRD) research: What are the determinants and the nature of cognitive impairment among persons with pre-diabetes (PreD) and type 2 diabetes (T2D), who are a high-risk group for cognitive impairment and represent a large fraction of the United States (US) population? Despite knowledge that persons with PreD and T2D are a high-risk group for cognitive decline, mild cognitive impairment (MCI), and dementia, the risk factors, mechanisms, and neuropathology of cognitive impairment in persons with PreD and T2D remain unclear. Gaps in knowledge on cognitive impairment in PreD and T2D include: (a) the role of AD and/or non-AD neuropathology beyond vascular contributions to cognitive impairment and dementia (VCID); (b) the role of glycemia, related metabolic factors such as hyperinsulinemia, and traditional micro and macrovascular complications of PreD/T2D; (c) the role of glucose-lowering medications, primarily metformin; and (d) the role of physical activity, physical function, and frailty, key in PreD and T2D. The 4 interrelated projects will address these gaps, leveraging the Diabetes Prevention Program (DPP) Outcomes Study (DPPOS) cohort and its detailed PreD/T2D phenotyping, adding state of the art AD/ADRD phenotyping. The DPPOS cohort currently has a mean age of 72 years, with 76% over the age of 65. Thus, the cohort is in a period of the lifespan when the development of cognitive decline, MCI, and dementia accelerates. This extensively phenotyped cohort represents an estimated 50 million Americans. To address this proposal's complex interrelated questions, the study has two waves of state-of-the-art AD/ADRD phenotyping during the proposed 5-year funding period, including comprehensive cognitive assessments and syndrome adjudication and plasma and brain imaging biomarkers of AD/ADRD. The study will address the complex overarching question of our project through the following aims: (1) To establish 5 cores to support the 4 integrated scientific projects: An Administrative Core, a Clinical Operations and Procedures Core, a Cognitive Assessment and Adjudication Core, a Neuroimaging and Plasma Biomarkers Core, and A Biostatistics and Data Infrastructure Core: (2) To conduct 4 integrated projects focused on key aspects of the central question of this proposal: Project 1 will examine the association of cognitive decline, MCI, and dementia in the DPPOS cohort with biomarkers of neuropathology and brain insulin signaling, and with sociodemographic and behavioral factors; Project 2 will examine the associations of cumulative glycemia, related metabolic factors, and microvascular and macrovascular complications, with cognitive syndromes and biomarkers of neuropathology; Project 3 will examine the association of cumulative exposure to metformin and other T2D medications with cognitive syndromes and biomarkers of neuropathology; Project 4 will evaluate the association of trajectories of physical activity, physical function and frailty with cognitive syndromes and biomarkers of neuropathology.

Conditions

Diabetes; Alzheimer Disease; Dementia, Vascular; Dementia; PreDiabetes

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• All surviving participants originally randomized in the Diabetes Prevention Program
• For Brain Imaging subcohort, only participants aged 55 years and older and those without contraindication to MRI will be included. Contraindications to MRI include the inability to lie flat, claustrophobia, and the presence of indwelling metallic objects, medical or non-medical, that are not 3T MRI compatible.

Exclusion Criteria

-

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Marinella Temprosa

OTHER

Sponsor Role: lead

Responsible Party

Marinella Temprosa

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jose Luchsinger

Role: PRINCIPAL_INVESTIGATOR

Columbia University

David Nathan

Role: STUDY_CHAIR

Massachusetts General Hospital

Marinell Temprosa

Role: PRINCIPAL_INVESTIGATOR

George Washington University

Locations

SW American Indian Center - Phoenix

Phoenix, Arizona, United States

University of California Los Angeles

Alhambra, California, United States

University of California San Diego

San Diego, California, United States

University of Colorado

Aurora, Colorado, United States

Medstar Health Research Institute

Washington D.C., District of Columbia, United States

University of Miami

Miami, Florida, United States

University of Hawaii

Honolulu, Hawaii, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

Pennington Biomedical Center

Baton Rouge, Louisiana, United States

Johns Hopkins University

Lutherville, Maryland, United States

Biostatistics Center, George Washington University

Rockville, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Joslin Diabetes Center

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

University of New Mexico

Albuquerque, New Mexico, United States

SW American Indian Center - Shiprock

Shiprock, New Mexico, United States

SW American Indian Center - Zuni

Zuni, New Mexico, United States

Columbia University Medical Center

New York, New York, United States

Columbia University

New York, New York, United States

Albert Einstein College of Medicine

The Bronx, New York, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Tennessee

Memphis, Tennessee, United States

University of Texas Health Science Center San Antonio

San Antonio, Texas, United States

University of Washington, VA Puget Sound Health Care System

Seattle, Washington, United States

Countries

United States

Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Individual Participant Data Set

will be available in 2025

View Document

Related Links

http://www.dppos.org

Study website

Other Identifiers

1U19AG078558

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DPPOS AD/ADRD

Identifier Type: -

Identifier Source: org_study_id