Insomnia Symptoms and Biomarkers of Alzheimer’s Disease in the Community

Abstract

Background: Insomnia is one of the most common sleep disorders yet its relationship to the biology of Alzheimer’s disease remains equivocal. Objective: We investigated the cross-sectional relationship between insomnia symptom severity and cerebrospinal fluid (CSF) concentrations of Alzheimer’s disease biomarkers in a cognitively unimpaired middle-aged community sample. Methods: A total of 63 participants from the Healthy Brain Project (age = 59±7 years; 67% women) completed a lumbar puncture and two weeks of actigraphy to measure two of insomnia’s core features: difficulty initiating sleep (prolonged sleep onset latency) and difficulty maintaining sleep (wake after sleep onset [WASO] and number of awakenings). Additionally, the Insomnia Severity Index (ISI) was completed by 58 participants. Linear and Tobit regression were used to estimate the associations between each insomnia variable and CSF Aβ42, phosphorylated tau 181 (p-tau181), total-tau, and neurofilament light chain protein (NfL), adjusting for age, sex, and APOE ɛ4 genotype. Results: Higher ISI score was associated with greater average levels of CSF Aβ 42 (per point: 30.7 pg/mL, 95% CI: 4.17–57.3, p = 0.023), as was higher WASO (per 10 min: 136 pg/mL, 95% CI: 48–223, p = 0.002) and more awakenings (per 5:123 pg/mL, 95% CI = 55–192, p < 0.001). Difficulty initiating sleep was not associated with CSF Aβ 42, nor were insomnia features associated with p-tau181, total-tau, or NfL levels. Conclusion: Insomnia symptoms were associated with higher CSF Aβ 42 levels in this relatively young, cognitively unimpaired sample. These findings may reflect increased amyloid production due to acute sleep disruption.

Contribution of Chronic Sleep Deprivation to Age-Related Neurodegeneration in a Mouse Model of Familial Alzheimer’s Disease (5xFAD)

“…Clinical evidence suggests that insomnia as a symptom of AD is highly detrimental, predicting rapid hospitalization and death [ 12 , 24 ]. Recent studies suggest that insomnia, especially at a young age, contributes to the early manifestation of the disease and may act as a triggering factor in the development of early-onset AD [ 3 , 26 ]. Our data showed that 5xFAD mice, which serve as a model for the familiar form of AD, were unable to tolerate prolonged sleep deprivation compared to their non-transgenic littermates (WT).…”