# Lysophosphatidylcholines and Cognition (L-COG) Study

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2020 · $122,813

## Abstract

Adults with type 2 diabetes mellitus (T2DM) are at a higher risk of cognitive decline, vascular dementia, and
Alzheimer’s disease (AD). The biological processes that account for the excess risk of cognitive impairment
and dementia in patients with T2DM are largely unclear. Adults with T2DM have reduced brain volume,
disruptions in white matter connectivity, and an increased burden of vascular lesions compared with controls.
Altered lipid metabolism in the brain occurs in both vascular dementia and AD. Lower concentrations of long-
chain polyunsaturated fatty acids (PUFA) have been described in the frontal cortex, entorhinal cortex, and
hippocampus in the brain in dementia. The brain can synthesize only a few fatty acids, thus, most fatty acids
must enter the brain from the blood. Higher dietary PUFA intake is associated with decreased risk of cognitive
decline and dementia in observational studies, however, PUFA supplementation did not prevent cognitive
decline in clinical trials. Recent animal studies show that long-chain fatty acids such as docosahexaenoic acid
(DHA, 22:6) are transported across the blood-brain barrier (BBB) in the form of lysophosphatidylcholine (LPC)
via a specific LPC receptor, the sodium-dependent LPC symporter 1 (MFSD2A). An insufficient pool of
circulating LPC containing long-chain fatty acids could potentially limit the supply of long-chain fatty acids to
the brain, including PUFA such as DHA, and play a role in the pathobiology of cognitive decline. Human trials
of PUFA supplementation for cognition involved omega-3 PUFA that were not esterified in LPCs. Animal
studies show LPC to be the preferred carrier to transport long-chain PUFA across the BBB via MFSD2A. The
relationship of serum long-chain LPCs with cognitive decline has not been well characterized and remains an
important major gap in knowledge. The specific aim of this project, the Lysophosphatidylcholines and Cognition
(L-COG) Study, is to determine whether diabetic adults with low serum LPC concentrations are at an increased
risk of cognitive decline. To address these aims, we will characterize the relationship of serum LPC
concentrations with cognitive decline in participants in the ACCORDION-MIND Study, a prospective study in
which cognition in adults with T2DM was assessed over an 80 month period. By the end of the study, we will
determine whether low serum LPCs, which comprise a pool of long-chain PUFA for the brain, are an
independent risk factor for cognitive decline in adults with T2DM. The findings from this study have high
translational potential, as low serum LPCs may be a modifiable risk factor for cognitive decline.

## Key facts

- **NIH application ID:** 10040903
- **Project number:** 1R21HL153471-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RICHARD D SEMBA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $122,813
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10040903

## Citation

> US National Institutes of Health, RePORTER application 10040903, Lysophosphatidylcholines and Cognition (L-COG) Study (1R21HL153471-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10040903. Licensed CC0.

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