Neutrophil activation may trigger tau burden contributing to cognitive progression of chronic sleep disturbance in elderly individuals not living with dementia

BMC Medicine, 2023 · DOI: https://doi.org/10.1186/s12916-023-02910-x · Published: May 25, 2023

Simple Explanation

This study investigates the link between chronic sleep disturbance (CSD) and cognitive decline in elderly individuals without dementia, using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The research explores how sleep problems might affect the brain and contribute to conditions like Alzheimer's disease, focusing on the role of inflammation and specific proteins in the brain. The study suggests that sleep disturbances can activate certain pathways in the immune system, potentially leading to brain damage and cognitive issues.

Study Duration

Up to 168 months (14 years)

Participants

784 non-dementia elderly

Evidence Level

Longitudinal analysis

Key Findings

1
CSD could significantly affect cognitive function.
2
Activated neutrophil pathways for cognitive progression in CSD were identified by transcriptomics GSEA, which was reflected by increased blood neutrophil level and its correlation with cognitive progression in CSD.
3
High tau burden mediated the influence of neutrophils on cognitive function and exacerbated the CSD-related risk of left hippocampal atrophy.

Research Summary

This study investigates the complex connection between chronic sleep disturbance (CSD) and cognitive progression in non-dementia elderly individuals using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The research identifies activated neutrophil pathways in cognitively progressive subjects with CSD and highlights the role of tau burden in mediating the impact of neutrophils on cognitive function and hippocampal atrophy. The findings suggest that activated neutrophil pathways triggering tau pathology may underlie the mechanism of cognitive progression in CSD, offering potential targets for dementia prevention.

Practical Implications

Potential Therapeutic Targets

The identification of neutrophil activation and tau pathology as key pathways in cognitive decline associated with CSD suggests potential therapeutic targets for dementia prevention.

Clinical Monitoring

Monitoring blood neutrophil levels in elderly individuals with CSD could help identify those at higher risk of cognitive progression.

Lifestyle Interventions

Interventions aimed at improving sleep quality and reducing inflammation may help mitigate the risk of cognitive decline in elderly individuals with CSD.

Study Limitations

1
Lack of follow-up data on blood neutrophils.
2
Absence of tau PET imaging to investigate regional tau pathology in CSD.
3
Inclusion of both cognitively normal and MCI subjects at baseline, which may have affected the population heterogeneity bias.

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