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

> **NIH NIH U19** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $250,000

## Abstract

This U19 proposal 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. We propose 4 interrelated projects that 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, we
will perform 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. We 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 ...

## Key facts

- **NIH application ID:** 11162996
- **Project number:** 3U19AG078558-03S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jose Alejandro Luchsinger
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $250,000
- **Award type:** 3
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11162996

## Citation

> US National Institutes of Health, RePORTER application 11162996, Alzheimer's Disease and Alzheimer's Disease Related Dementias in Prediabetes and Type 2 Diabetes: The Diabetes Prevention Program Outcomes Study AD/ADRD Project (3U19AG078558-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11162996. Licensed CC0.

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