Sleep Biomarkers for Predicting Cognitive Decline and Alzheimer's Disease: A Systematic Review of Longitudinal Studies

Background: Sleep disturbances are considered a hallmark of dementia, and strong evidence supports the association between alterations in sleep parameters and cognitive decline in patients with mild cognitive impairment and Alzheimer's disease (AD). Objective: This systematic review aims to summarize the existing evidence on the longitudinal association between sleep parameters and cognitive decline, with the goal of identifying potential sleep biomarkers of AD-related neurodegeneration. Methods: Literature search was conducted in PubMed, Web of Science, and Scopus databases from inception to 28 March 2023. Longitudinal studies investigating the association between baseline objectively-measured sleep parameters and cognitive decline were assessed for eligibility. Results: Seventeen studies were included in the qualitative synthesis. Sleep fragmentation, reduced sleep efficiency, reduced REM sleep, increased light sleep, and sleep-disordered breathing were identified as predictors of cognitive decline. Sleep duration exhibited a U-shaped relation with subsequent neurodegeneration. Additionally, several sleep microstructural parameters were associated with cognitive decline, although inconsistencies were observed across studies. Conclusions: These findings suggest that sleep alterations hold promise as early biomarker of cognitive decline, but the current evidence is limited due to substantial methodological heterogeneity among studies. Further research is necessary to identify the most reliable sleep parameters for predicting cognitive impairment and AD, and to investigate interventions targeting sleep that can assist clinicians in the early recognition and treatment of cognitive decline. Standardized procedures for longitudinal studies evaluating sleep and cognition should be developed and the use of continuous sleep monitoring techniques, such as actigraphy or EEG headband, might be encouraged.