# Diabetes and brain amyloid in middle aged Hispanics

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $3,234,050

## Abstract

This is a competitive renewal application for grant R01AG050440 (Diabetes and Brain Amyloid in Middle Aged
Hispanics; 09/01/15-05/30/21). The goal of this project is to examine whether type 2 diabetes (referred to as
diabetes from here on) and it’s antecedent, pre-diabetes, are associated with higher brain amyloid ß (Aß) burden,
the main neuropathologic feature of Alzheimer’s disease (AD), compared with persons with normal glucose
tolerance (NGT). We ascertained Aß in vivo using 18F-Florbetaben positron emission tomography (PET) in 350
late middle-aged Hispanics from New York City, aged 64.15 ± 3.34 years of age at the time of recruitment, (72%
female). We also conducted 3T brain magnetic resonance imaging (MRI) to ascertain neurodegeneration and
cerebrovascular disease (CVD), and 18F-MK6240 PET to ascertain tau, allowing to assess the three main
constructs in the 2018 National Institute on Aging (NIA)/Alzheimer’s Association (AA) research framework,
amyloid, tau, and neurodegeneration. We have had two key findings that form the basis for this renewal
application: (1) Pre-diabetes, but not diabetes, is associated with higher brain Aß in cross-sectional, and
longitudinal analyses. The lack of association between diabetes and higher brain Aß as compared with pre-
diabetes is in part explained by diabetes treatment, which was related to lower brain Aß among participants with
elevated glycemia (pre-diabetes and diabetes); (2) Females have higher brain Aß and tau burden as compared
with males in cross-sectional analyses, although females have less neurodegeneration and better verbal memory
compared with males. The cohort is now completing its 2nd wave of assessments (target: 315 participants). We
propose to complete two more waves of brain imaging at intervals of approximately 24 months with an expected
attrition rate of 10% per wave (wave 3: 284 participants; and wave 4: 256 participants), with improved
characterization of diabetes transitions, diabetes medication use, gynecological/obstetrical history in women,
sex hormonal profile, plasma AD biomarkers, and cognitive adjudication. In total, we will have four waves of
ascertainment of Aß, tau, and neurodegeneration in brain imaging and plasma at the end of the project, spanning
the 7th and 8th decades of life. Aim 1 is to compare changes in Aß among persons with NGT, pre-
diabetes/untreated diabetes, and treated diabetes. We will also examine changes in tau, neurodegeneration,
CVD, and cognitive performance as outcomes. We will also examine diabetes category transitions (e.g. NGT to
pre-diabetes) and treatment status as exploratory exposures. We will also explore how sex and APOE-e4 modify
these associations. Aim 2 is to examine the longitudinal association of sex with changes in Aß. We will also
examine changes in tau, neurodegeneration, CVD, and cognitive performance as outcomes. We will explore
whether sex hormonal profile and gynecological and obstetrical history mediate these associations. The ...

## Key facts

- **NIH application ID:** 10301977
- **Project number:** 2R01AG050440-06
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jose Alejandro Luchsinger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,234,050
- **Award type:** 2
- **Project period:** 2015-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10301977

## Citation

> US National Institutes of Health, RePORTER application 10301977, Diabetes and brain amyloid in middle aged Hispanics (2R01AG050440-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10301977. Licensed CC0.

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