# Brain blood flow, oxygenation, and cognition in adult onset iron deficiency anemia

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2023 · $680,805

## Abstract

Moderate anemia (hemoglobin < 11 g/dl) occurs 1.5% – 2.0% of the general population. In young and middle-
aged adults, iron deficiency from blood loss represents the dominant mechanism and is heavily over-
represented in women and minority populations. Iron deficiency anemia’s (IDA) negative impact on pediatric
brain function is well established, but its consequences on adult brains are underappreciated. Our preliminary
data demonstrates significant (one standard deviation) deficits in visual and verbal memory, fluid and
visuospatial reasoning, and verbal learning. We also demonstrate decreased cerebral metabolic rate of oxygen
and abnormal blood brain barrier permeability to water that suggest impaired microvascular blood flow
regulation in the brain. The overarching goal for this study is to deeply phenotype the cognitive and
cerebrovascular derangements caused by adult-onset IDA and to determine their reversibility with iron
replacement therapies. We will recruit 96 women ages 14-60 years diagnosed with moderate IDA, and 40
healthy control subjects from four donor centers in the Los Angeles area as well as women recruited from
social media. Most of these subjects will be otherwise entirely healthy but we will exclude individuals with other
mechanisms for their anemia as well as risk factors for small vessel disease including hypertension, sleep
disordered breathing, and diabetes. All anemic and control subjects will undergo comprehensive
cerebrovascular MRI, baseline bloodwork, patient reported outcomes, and neurocognitive testing.
Aims 1 and 2 focus on careful characterization of the cognitive, metabolic, flow, oxygenation, and connectivity
changes in response to IDA. These data will provide new insights into the neuroscientific basis for cognitive
dysfunction in IDA. Aim 3 is interventional; we will restudy all the previously acquired biomarkers after
normalizing hemoglobin level to prove reversibility/irreversibility of the MRI and cognitive deficits.
All patients with confirmed moderate IDA will be randomized to intravenous ferric carboxymaltose versus
standard-of-care therapy (referral to primary care physician for oral iron therapy). The primary endpoint will be
the cerebral metabolic rate by MRI and neurocognition at 12 months. Secondary markers include regional
brain blood flow, cerebrovascular reactivity, tissue oxygenation, blood-brain barrier function, and functional
connectivity. Exploratory markers include brain iron deposition, white matter damage, and brain morphometry.
We will exploit the rapid correction of iron sufficiency in the IV iron treated subjects to uncouple the relative
impacts of iron and anemia. We posit that all subjects who successfully replace their iron stores will normalize
their MRI and cognitive function. However, we anticipate that iron restoration and durability in the standard-of-
care arm will not be as robust as for intravenous iron because of poor compliance, insufficient therapy duration,
and/or lack ...

## Key facts

- **NIH application ID:** 10735765
- **Project number:** 1R01NS117430-01A1
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** JOHN C WOOD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $680,805
- **Award type:** 1
- **Project period:** 2023-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10735765

## Citation

> US National Institutes of Health, RePORTER application 10735765, Brain blood flow, oxygenation, and cognition in adult onset iron deficiency anemia (1R01NS117430-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10735765. Licensed CC0.

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