# The Effect of Acylcarnitines on Cognitive Function: A Two‐Sample Mendelian Randomization Study

## TL;DR

This study finds that lower levels of two acylcarnitines are linked to worse cognitive function, suggesting a possible role in early detection of cognitive decline.

## Contribution

The first use of two-sample Mendelian randomization to investigate causal links between 20 acylcarnitines and cognitive outcomes.

## Key findings

- Lower genetically predicted butyrylcarnitine and acetyl-L-carnitine levels are associated with adverse neurocognitive effects.
- Butyrylcarnitine levels show a negative correlation with cognitive function and intelligence.
- No association was found between the acylcarnitines and dementia or brain structure.

## Abstract

Clinical trials investigating the association between acylcarnitines and cognitive function have yielded conflicting results. We conducted a Mendelian randomization (MR) study to examine the causal associations between 20 acylcarnitines and neurocognitive outcomes.

Single‐nucleotide polymorphisms of 20 acylcarnitines were extracted from primary European ancestry‐based genome‐wide association studies. Two‐sample MR (TSMR) was performed to initially screen for acylcarnitines potentially associated with cognitive performance. Further TSMR analysis was conducted to investigate the associations between specific acylcarnitines and other cognitive outcomes, dementia, and brain structure.

Among the 20 acylcarnitines, we observed that lower genetically predicted levels of butyrylcarnitine (β = −0.06, 95% CI: [−0.11 to −0.02], p = 0.003) and acetyl‐L‐carnitine (β = −0.02, 95% CI: [−0.04 to 0], p = 0.04) were associated with adverse neurocognitive effects. Furthermore, we found a negative correlation between low genetically predicted levels of butyrylcarnitine and cognitive function (β = −0.17, 95% CI: [−0.3 to −0.05], p = 0.01) as well as intelligence (β = −0.05, 95% CI: [−0.09 to −0.02], p = 0.003). However, there was no evidence supporting any association between these two acylcarnitines and dementia or brain structure.

Our results suggest a causal association between acetyl‐L‐carnitine and butyrylcarnitine levels and adverse neurocognitive effects. Multicenter, multiregional, and large sample studies are needed to further validate these findings.

This study is the first to employed TSMR to investigate the causal relationship between 20 acylcarnitines and neurocognitive outcomes. The findings indicate that lower genetically predicted levels of acetyl‐L‐carnitine and butyrylcarnitine are associated with diminished cognitive performance, underscoring their potential clinical implications in the early detection of cognitive decline.