# Systemic and dietary advanced glycation end products in type 2 diabetes-related cognitive decline and incident dementia: effects on Alzheimer's pathology and cerebrovascular disease

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $860,421

## Abstract

ABSTRACT
Treatments for Alzheimer's disease (AD) and cognitive decline is a health priority in our aging population and
especially in elderly with type 2 diabetes (T2D) who are at high risk of developing these conditions. Compelling
small scale studies suggest that high dietary and serum levels of Advanced Glycation End products (AGEs), a
group of glucose-derived compounds, chronically elevated in T2D, contribute to cognitive impairment and
increased AD and vascular brain pathology in old age. However, there is scarcity of large scale longitudinal
studies of well-characterized older adults with T2D making it difficult to obtain evidence linking dietary and
serum AGEs with impaired cognition in T2D elderly and whether serum AGEs mediate the associations of
dietary AGEs with cognition. These gaps in knowledge impede the development of treatments based on AGEs
to decrease the growing burden of AD and cognitive decline.
To fill these gaps, the overall goal of this proposal is to test the hypothesis that dietary and circulating AGEs
are related to impaired cognition in T2D elderly through an association with AD-related and cerebrovascular
neuropathologies. To achieve these aims, we will enroll 921 non-demented community-dwelling T2D older
adults from the Israel Diabetes and Cognitive Decline Study (IDCD; R01 AG034087) who undergo annual
cognitive testing. This study proposes a comprehensive assessment of dietary and serum AGEs levels. In 255
IDCD participants we will quantify blood brain barrier (BBB) dysfunction (using novel contrast-enhanced MRI),
cerebral blood flow (CBF; via ASL-MRI), cerebrovascular reactivity (with Transcranial Doppler), carotid plaque
volume burden (via 3D ultrasound), and amyloid (via PET). This comprehensive large-scale study will 1)
provide evidence that dietary and serum AGEs levels are related to incident dementia and cognitive decline in
older adults with T2D, 2) identify the key neuropathological indices linking dietary and serum AGEs with
cognition and 3) test if serum AGEs mediate the association of dietary AGEs with cognition and
neuropathology. These data are crucial for developing treatments targeting AGEs for late-life T2D-related
cognitive impairment. Thus, these data have the potential to decrease the growing burden of cognitive
impairment and affect the brain health of millions in our aging population.

## Key facts

- **NIH application ID:** 10064989
- **Project number:** 5R01AG061093-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Michal Schnaider Beeri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $860,421
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064989

## Citation

> US National Institutes of Health, RePORTER application 10064989, Systemic and dietary advanced glycation end products in type 2 diabetes-related cognitive decline and incident dementia: effects on Alzheimer's pathology and cerebrovascular disease (5R01AG061093-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10064989. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*