# Cerebral arterial compliance, blood flow, and cognition in Veterans with diabetes

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2022 · —

## Abstract

Type 2 diabetes mellitus (T2DM), which is highly prevalent among Veterans, increases the risk of cognitive
impairment and dementia, including Alzheimer’s disease (AD). We have shown that T2DM—even during
midlife—is associated with steeper cognitive decline, reduced cerebral blood flow (CBF) in regions that are
predilection sites for AD pathology, and greater neuropathologic changes at autopsy (Bangen et al., 2013;
Bangen et al., 2016; Bangen et al., in prep). Identifying individuals who are most likely to decline prior to the
occurrence of significant brain changes is essential, so that interventions can be applied before extensive
cerebrovascular lesions and cognitive changes develop. Accordingly, studies investigating incipient cognitive
and neuroimaging changes in middle age when neuropathologic changes are already occurring are critical to
optimize brain health and improve outcomes in T2DM and other high-risk populations.
 Most previous neuroimaging studies of brain changes underlying cognitive impairment 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 hyperintensities (WMH) and
infarcts. However, recent advances in MRI have allowed for the development of sensitive, sophisticated
methods for the non-invasive measurement of cerebral blood flow (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 the mechanisms that precede the development of irreversible
parenchymal/structural damage and may also yield important markers of risk for cognitive decline in at-risk
populations. 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 the context of
T2DM.
 We therefore propose to advance the field by assessing neuropsychological functioning, macrovascular AC
and microvascular CBF, and established MR markers of AD and cerebrovascular disease in a sample of 120
middle-aged Veterans with and without a diagnosis of T2DM (aged 45-60). Participants will undergo
comprehensive neuropsychological assessment; laboratory testing to assess blood-based markers related to
glycemia, inflammation, and endothelial function; CSF measurement of amyloid and tau; and neuroimaging
exams including high resolution structural imaging and highly novel arterial spin labeling (ASL) MRI methods
that estimate cerebral arterial compliance and blood flow. The goals of this project are to investigate whether
early changes in cerebrovascular functioning (i.e., reduced AC and CBF) relate to MRI markers of CVD
lesions, AD markers, and cognition in T2DM. We will also investigate whether potentially modifiable factors
such as inflammation and endothelial dysfunction alter associations betwe...

## Key facts

- **NIH application ID:** 10295158
- **Project number:** 5I01CX001842-03
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Katherine Bangen
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10295158

## Citation

> US National Institutes of Health, RePORTER application 10295158, Cerebral arterial compliance, blood flow, and cognition in Veterans with diabetes (5I01CX001842-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10295158. Licensed CC0.

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