An international team led by researchers Laura Stankeviciute and Oriol Grau, from the Barcelonaβeta Brain Research Center (BBRC), together with Jonathan Blackman from North Bristol Hospital NHS Trust and the University of Bristol, has demonstrated an association between sleep quality and Alzheimer's-related pathology in people without cognitive impairment.

The results of the analysis, which are part of the European study European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS), have been published in the scientific journal Brain Communications, and indicate that poor sleep quality is related to an increase in Alzheimer's disease pathology. This finding is relevant to help define future therapies, so that they can target the appropriate phase of the disease.

A cross-sectional analysis of sleep quality

The Sleep abnormalities are common in Alzheimer's disease, and sleep quality can be impaired from the preclinical stage of the disease, even when no other symptoms are experienced. Understanding how and when sleep deprivation contributes to the progression of Alzheimer's disease is important for the design and implementation of future therapies.

“The epidemiological and experimental data available to date already indicated that sleep abnormalities contribute to the risk of Alzheimer's disease”, explains Laura Stankeviciute, BBRC predoctoral researcher and one of the study's lead authors. “However, previous studies were limited by the lack of biomarkers for Alzheimer's disease, because they had a non-cross-sectional design, or because of the small size of the sample of participants.”, he clarifies. This is the first study that includes all these factors.

The largest cohort to date for an analysis of sleep quality and efficiency

Thanks to data obtained from the largest cohort to date, the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS), researchers have been able to validate the hypothesis that sleep deprivation is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease in a cross-sectional manner, and that it predicts future increases in pathology in individuals without identifiable symptoms of Alzheimer's disease at baseline.

The BBRC team, in collaboration with researchers from the University of Bristol, has analysed the data from 1,168 adults over 50 years old, including Alzheimer's disease biomarkers in cerebrospinal fluid, cognitive performance and sleep quality. To measure the latter, they used the Pittsburgh Sleep Quality Index (PSQI) questionnaire.

“Through these analyses, we have been able to study associations between the main biomarkers of Alzheimer's disease and different measures of sleep quality, such as its total score, duration, efficiency and alteration.”, specifies the Dr. Oriol Grau, head of the Clinical Research Group and Risk Factors for Neurodegenerative Diseases at the BBRC. By analyzing cerebrospinal fluid samples from 332 participants taken at baseline and after an average period of 1.5 years, researchers were able to assess the effect of baseline sleep quality on changes in Alzheimer's disease biomarkers over time.

Preventive practices to improve sleep quality

Cross-sectional analyses reveal that Poor sleep quality is significantly associated with increased t-tau protein in cerebrospinal fluid. Among other findings, short sleep duration, less than seven hours, was shown to be associated with higher p-tau and t-tau values, key biomarkers for measuring Alzheimer's risk in the preclinical phase of the disease. In addition, longitudinal analyses showed that greater sleep disturbances were associated with a decrease in the Aβ42 biomarker over time.

This study demonstrates that self-reported poor sleep quality is associated with increased Alzheimer's disease-related pathology in individuals without cognitive impairment. “Our results further reinforce the hypothesis that sleep disruption may represent a risk factor for Alzheimer’s disease.”, argues the researcher Laura Stankeviciute. “Future research is therefore needed to test the efficacy of preventative practices designed to improve sleep in the presymptomatic stages of the disease in order to reduce Alzheimer's disease pathology.”, he concludes.

European Prevention of Alzheimer's Dementia (EPAD) is a European collaborative research project to increase knowledge about the preclinical phase of Alzheimer's disease and thus be able to prevent dementia before symptoms appear. The project, in which 38 European institutions participate, is funded by grant n° 115736 from the Innovative Medicines Initiative, a joint initiative of the European Commission's Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA).

Bibliographic reference

Blackman, Jonathan; Stankeviciute, Laura et al. 'Cross-sectional and Longitudinal Association of Sleep and Alzheimer Biomarkers in Cognitively Unimpaired Adults', Brain Communications, https://doi.org/10.1093/braincomms/FCAC257