DPPOS-4: The Diabetes Prevention Program Outcomes Study AD/ADRD Project

Sponsor

Marinella Temprosa (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT05704309

Collaborator

National Institute on Aging (NIA) (NIH)

1,976

Enrollment

Locations

57.7

Anticipated Duration (Months)

73.2

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Alzheimer Disease Dementia, Vascular Dementia PreDiabetes

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1976 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Alzheimer's Disease and Alzheimer's Disease Related Dementias in Prediabetes and Type 2 Diabetes: The Diabetes Prevention Program Outcomes Study AD/ADRD Project

Actual Study Start Date :

Nov 7, 2022

Anticipated Primary Completion Date :

Jan 31, 2027

Anticipated Study Completion Date :

Aug 30, 2027

Outcome Measures

Primary Outcome Measures

Cognitive Diagnoses [Sept 2022 to October 2026]
Classification of normal, mild cognitive impairment or dementia based on NACC UDS

Secondary Outcome Measures

ptau-181 [Sept 2022 to October 2026]
Plasma biomarkers for AD/ADRD
Aβ42/40 ratio [Sept 2022 to October 2026]
Plasma biomarkers for AD/ADRD
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
Amnestic cognitive decline [Sept 2022 to October 2026]
Based on the SEVLT immediate recall (sum of trials 1-3) and delayed recall (trial 4)
Non-amnestic cognitive decline [Sept 2022 to October 2026]
DSST measure
White matter microstructure [March 2023 to October 2026]
Among ppts in the neuromaging subcohort

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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:

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SW American Indian Center - Phoenix	Phoenix	Arizona	United States	85016
2	University of California Los Angeles	Alhambra	California	United States	91801
3	University of California San Diego	San Diego	California	United States	92128
4	University of Colorado	Aurora	Colorado	United States	80045
5	Medstar Health Research Institute	Washington	District of Columbia	United States	20003
6	University of Miami	Miami	Florida	United States	33136
7	University of Hawaii	Honolulu	Hawaii	United States	96813
8	Northwestern University	Chicago	Illinois	United States	60611
9	University of Chicago	Chicago	Illinois	United States	60637
10	Indiana University	Indianapolis	Indiana	United States	46202
11	Pennington Biomedical Center	Baton Rouge	Louisiana	United States	70808
12	Johns Hopkins University	Lutherville	Maryland	United States	21093
13	Biostatistics Center, George Washington University	Rockville	Maryland	United States	20852
14	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
15	Joslin Diabetes Center	Boston	Massachusetts	United States	02215
16	Washington University	Saint Louis	Missouri	United States	63110
17	University of New Mexico	Albuquerque	New Mexico	United States	87131
18	SW American Indian Center - Shiprock	Shiprock	New Mexico	United States	87420
19	SW American Indian Center - Zuni	Zuni	New Mexico	United States	87327
20	Albert Einstein College of Medicine	Bronx	New York	United States	10461
21	Columbia University Medical Center	New York	New York	United States	10032
22	Columbia University	New York	New York	United States	10032
23	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
24	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
25	University of Tennessee	Memphis	Tennessee	United States	38103
26	University of Texas Health Science Center San Antonio	San Antonio	Texas	United States	78229
27	University of Washington, VA Puget Sound Health Care System	Seattle	Washington	United States	98108