# Intracranial arterial compliance, cerebral blood flow, and dementia risk in older adults with type 2 diabetes

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $42,376

## Abstract

Type 2 diabetes mellitus (T2DM), which is rising in prevalence, increases risk of cognitive impairment and
dementia, including Alzheimer’s disease (AD). In our prior work we have shown that T2DM is associated with
steeper cognitive decline and reduced cerebral blood flow (CBF) in regions that are predilection sites for AD
pathology. Identifying individuals who are likely to decline prior to the occurrence of brain changes is essential
so that interventions can be applied before extensive cerebrovascular lesions and cognitive changes develop.
 Most previous neuroimaging studies of brain changes underlying cognitive dysfunction in T2DM have
applied conventional structural magnetic resonance imaging (MRI) to detect end-stage macrostructural
changes associated with cerebrovascular disease (CVD) such as white matter lesions (WML). However, recent
advances in MRI have allowed for the development of sensitive methods for the non-invasive measurement of
CBF and cerebral arterial compliance (AC), or the ability of vessels to distend or increase in volume in
response to changes in blood pressure. Such methods may help elucidate mechanisms that precede the
development of irreversible parenchymal/structural damage and may yield important markers of risk for
cognitive decline. Although T2DM has been associated with peripheral arterial stiffening using carotid-femoral
pulse wave velocity, no studies have examined intracranial arterial stiffening (i.e., decreased AC) in T2DM.
 We propose to assess cognition, AC and CBF, and established MRI markers CVD in a sample of 100 older
adults with T2DM and 50 non-diabetic control participants. Participants will undergo laboratory testing to
assess blood-based markers related to glycemia and cardiometabolic health and neuroimaging including novel
arterial spin labeling (ASL) MRI protocols that estimate cerebral arterial compliance and blood flow at baseline,
12-month follow up, and 24-month follow up. Our goals are to investigate whether early changes in
cerebrovascular functioning (i.e., reduced AC and CBF) relate to MRI markers of CVD lesions and cognition.
 The current proposal for a research supplement to promote diversity in health-related research would
provide funding for Einat Brenner to complete a postdoctoral fellowship in my lab. Through this diversity
supplement, she is proposing to extend the parent R01 to obtain serum measures of brain-derived
neurotrophic factor (BDNF). Her aims examine whether (1) reduced serum BDNF levels relate to lower
cerebral blood flow/arterial compliance and BDNF levels moderate associations between cerebral blood
flow/arterial compliance and MRI markers of cerebrovascular disease and (2) reduced serum BDNF levels
relate to poorer memory and executive functioning and BDNF levels moderate the associations between
cerebral blood flow/arterial compliance and cognition. Her training goals include learning new imaging
techniques (e.g., arterial spin labeling to measure cerebral blood flo...

## Key facts

- **NIH application ID:** 10402683
- **Project number:** 3R01AG063782-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Katherine Bangen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $42,376
- **Award type:** 3
- **Project period:** 2020-05-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402683

## Citation

> US National Institutes of Health, RePORTER application 10402683, Intracranial arterial compliance, cerebral blood flow, and dementia risk in older adults with type 2 diabetes (3R01AG063782-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10402683. Licensed CC0.

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