The Diabetes Prevention Program Outcomes Study AD/ADRD Project
- Conditions
- DiabetesAlzheimer DiseaseDementia, VascularDementiaPreDiabetes
- Registration Number
- NCT05704309
- Lead Sponsor
- Marinella Temprosa
- 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.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 1976
- 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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Cognitive Diagnoses Sept 2022 to October 2026 Classification of normal, mild cognitive impairment or dementia based on NACC UDS
- Secondary Outcome Measures
Name Time Method White matter microstructure March 2023 to October 2026 Among ppts in the neuromaging subcohort
ptau-181 Sept 2022 to October 2026 Plasma biomarkers for AD/ADRD
Amnestic cognitive decline Sept 2022 to October 2026 Based on the SEVLT immediate recall (sum of trials 1-3) and delayed recall (trial 4)
Aβ42/40 ratio Sept 2022 to October 2026 Plasma biomarkers for AD/ADRD
Non-amnestic cognitive decline Sept 2022 to October 2026 DSST measure
Neurofilament Light Chain (NfL) Sept 2022 to October 2026 Plasma biomarkers for AD/ADRD
Glial fibrillary acidic protein (GFAP) Sept 2022 to October 2026 Plasma biomarkers for AD/ADRD
Trial Locations
- Locations (27)
University of Chicago
🇺🇸Chicago, Illinois, United States
Joslin Diabetes Center
🇺🇸Boston, Massachusetts, United States
University of Washington, VA Puget Sound Health Care System
🇺🇸Seattle, Washington, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of California Los Angeles
🇺🇸Alhambra, California, United States
SW American Indian Center - Zuni
🇺🇸Zuni, New Mexico, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
SW American Indian Center - Shiprock
🇺🇸Shiprock, New Mexico, United States
University of Tennessee
🇺🇸Memphis, Tennessee, United States
Medstar Health Research Institute
🇺🇸Washington, District of Columbia, United States
University of Miami
🇺🇸Miami, Florida, United States
Johns Hopkins University
🇺🇸Lutherville, Maryland, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
SW American Indian Center - Phoenix
🇺🇸Phoenix, Arizona, United States
University of Hawaii
🇺🇸Honolulu, Hawaii, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of California San Diego
🇺🇸San Diego, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Biostatistics Center, George Washington University
🇺🇸Rockville, Maryland, United States
Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
Pennington Biomedical Center
🇺🇸Baton Rouge, Louisiana, United States
University of Texas Health Science Center San Antonio
🇺🇸San Antonio, Texas, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Columbia University
🇺🇸New York, New York, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States