Investigating Sleep Disturbances in Mild Cognitive Impairment—Implications for Alzheimer’s and Parkinson’s Diseases: A Research Protocol

Abstract

Introduction: Sleep disturbances are recognized as both an early symptom and contributor to neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Disrupted sleep impairs the brain's ability to clear toxic proteins, leading to cognitive decline and the accumulation of biomarkers such as amyloid-beta and alpha-synuclein. Despite evidence linking poor sleep to neurodegeneration, the impact of varying sleep disturbance severities on disease progression in mild cognitive impairment remains unclear.

Methods: A longitudinal cohort of 300 participants aged 60 and older, diagnosed with mild cognitive impairment, will be stratified by sleep disturbance severity (normal, mild, severe) using validated measures, including the Pittsburgh Sleep Quality Index, and actigraphy. Annual neuropsychological assessments will measure cognitive decline, while biomarkers such as amyloid-beta and alpha-synuclein will be tracked through cerebrospinal fluid and blood samples. Statistical models, including linear mixed-effects and Kaplan-Meier survival analyses, will assess relationships between sleep disturbances, cognitive outcomes, and biomarker progression.

Anticipated Results: Recruitment will conclude in 1 year, with baseline assessments commencing shortly after. Initial results will establish correlations between sleep disturbance severity, cognitive status, and biomarkers. Longitudinal data is expected to reveal accelerated cognitive decline in participants with severe sleep disturbances, potentially 25-35% faster than those with normal sleep patterns. Biomarker analysis is anticipated to show progressive reductions in CSF amyloid-beta levels and changes in alpha-synuclein concentrations, possibly correlating with sleep disturbance severity.

Discussion: Preliminary findings will likely confirm that severe sleep disturbances result in a 25–30% faster cognitive decline compared to mild or no disturbances. Biomarker analysis projects a 30% increase in amyloid-beta levels for severe disturbances. These results underscore sleep as a modifiable risk factor, supporting interventions to delay cognitive decline and improve outcomes.

Conclusion: This study highlights the novel focus on how varying severities of sleep disturbances influence neurodegeneration, addressing a critical gap in research. By identifying sleep as a modifiable risk factor, it provides insights for targeted interventions to delay cognitive decline and disease progression.