Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT05704309 |
| Other study ID # |
DPPOS AD/ADRD |
| Secondary ID |
1U19AG078558 |
| Status |
Enrolling by invitation |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 7, 2022 |
| Est. completion date |
August 30, 2027 |
Study information
| Verified date |
February 2024 |
| Source |
George Washington University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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.
