When left untreated, sleep difficulties are associated with severe adverse consequences, ranging from poor mental health to cardiovascular disease. According to epidemiological studies, sleep difficulties are significantly more common among the elderly, with a prevalence of 36 to 69%. Alzheimer’s disease (AD) accounts for 60 to 70% of all dementia cases, and the accumulation of toxic forms of β-amyloid (Aβ) and tau neurofibrillary tangles in the brain is considered the main pathological mechanism. More than 47 million people worldwide are affected by dementia, and the number is estimated to double every 20 years with the increases in life expectancy. ConclusionsĪctivated neutrophil pathway triggering tau pathology may underline the mechanism of cognitive progression in CSD. Elevated neutrophil-related inflammatory factors were observed in the cognitive progression of CSD and were associated with brain tau burden. High tau burden mediated the influence of neutrophils on cognitive function and exacerbated the CSD-related risk of left hippocampal atrophy. The 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. ResultsĬSD could significantly affect cognitive function. Cognitive progression is defined as the progression from cognitively normal to mild cognitive impairment (MCI)/dementia or from MCI to dementia. We also investigated gene set enrichment analysis (GSEA), Cox proportional hazards model for risk factors, and mediation and interaction effects between indicators. Blood transcriptomics, blood neutrophil, cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD), and neutrophil-related inflammatory factors were measured. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) database was used to assign 784 non-dementia elderly into two groups: a normal sleep group (528 participants) and a CSD group (256 participants) via the Neuropsychiatric Inventory (NPI)-sleep subitem. To investigate the complex connection between chronic sleep disturbance (CSD) and cognitive progression.
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