# Association Between Rest–Activity Rhythm and 27-Hydroxycholesterol (27-OH) in Patients with Amnestic Mild Cognitive Impairment (aMCI)

## TL;DR

This study found that sleep and circadian rhythm issues in people with early memory problems are linked to changes in cholesterol metabolism, which may contribute to brain degeneration.

## Contribution

The study identifies a novel link between sleep disturbances, circadian rhythm, and cholesterol oxygenation in amnestic mild cognitive impairment.

## Key findings

- aMCI patients had lower 27-OH levels and 27-OH/total cholesterol ratios compared to controls.
- Longer sleep onset latency and lower sleep efficiency in aMCI were associated with higher 27-OH/total cholesterol ratios.
- Higher RAR amplitude was linked to lower 27-OH levels across all participants.

## Abstract

Background/Objectives: Rest–activity rhythm (RAR) disturbances can contribute to aging and dementia via metabolic dysregulation. Hydroxycholesterol (OH) is thought to mediate the link between hypercholesterolemia and neurodegeneration. This study compared sleep and RAR parameters between amnestic mild cognitive impairment (aMCI) patients and normal controls (NCs), and examined their associations with plasma 27-OH levels, reflecting peripheral cholesterol metabolism. Methods: In total, 18 aMCI patients (76.6 ± 6.1 years) and 21 NCs (70.4 ± 6.7 years) underwent five-day actigraphy and dim light melatonin onset assessment. Plasma 27-OH levels were measured via high-performance liquid chromatography-mass spectrometry. Generalized linear models (GLMs) were used to analyze the relationships between sleep, RAR, and 27-OH levels. Results: The aMCI group had significantly lower 27-OH levels and 27-OH/total cholesterol ratios (p < 0.05). GLM revealed that longer sleep onset latency (SOL) was associated with higher 27-OH levels in aMCI, distinguishing them from NCs. Additionally, in aMCI, longer SOL, lower sleep efficiency (SE), and higher fragmentation index (FI) were associated with an increased 27-OH/total cholesterol ratio (p < 0.05). Higher relative amplitude of RAR was linked to lower 27-OH levels across groups (p < 0.01), but RAR parameters showed no significant association with the 27-OH/total cholesterol ratio. Sleep disturbances, including prolonged SOL, reduced SE, and increased FI, were associated with altered peripheral cholesterol oxygenation in aMCI. Conclusions: Greater RAR amplitude correlated with lower 27-OH levels, regardless of cognitive status. These findings suggest that peripheral cholesterol oxygenation in aMCI is related to both sleep disturbances and circadian rhythm dysregulation, highlighting their role in cholesterol metabolism and neurodegeneration.