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Abstract
Objective: To determine the relationship between sleep quality and CSF markers of Alzheimer disease (AD) pathology in late midlife.
Methods: We investigated the relationship between sleep quality and CSF AD biomarkers in a cohort enriched for parental history of sporadic AD, the Wisconsin Registry for Alzheimer's Prevention. A total of 101 participants (mean age 62.9 ± 6.2 years, 65.3% female) completed sleep assessments and CSF collection and were cognitively normal. Sleep quality was measured with the Medical Outcomes Study Sleep Scale. CSF was assayed for biomarkers of amyloid metabolism and plaques (β-amyloid 42 [Aβ42]), tau pathology (phosphorylated tau [p-tau] 181), neuronal/axonal degeneration (total tau [t-tau], neurofilament light [NFL]), neuroinflammation/astroglial activation (monocyte chemoattractant protein–1 [MCP-1], chitinase-3-like protein 1 [YKL-40]), and synaptic dysfunction/degeneration (neurogranin). To adjust for individual differences in total amyloid production, Aβ42 was expressed relative to Aβ40. To assess cumulative pathology, CSF biomarkers were expressed in ratio to Aβ42. Relationships among sleep scores and CSF biomarkers were assessed with multiple regression, controlling for age, sex, time between sleep and CSF measurements, and CSF assay batch.
Results: Worse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater AD pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42. There were no significant associations between sleep and NFL or neurogranin.
Conclusions: Self-report of poor sleep was associated with greater AD-related pathology in cognitively healthy adults at risk for AD. Effective strategies exist for improving sleep; therefore sleep health may be a tractable target for early intervention to attenuate AD pathogenesis.
GLOSSARY
- Aβ42=
- β-amyloid 42;
- AD=
- Alzheimer disease;
- BMI=
- body mass index;
- ESS=
- Epworth Sleepiness Scale;
- MCP-1=
- monocyte chemoattractant protein–1;
- MOS=
- Medical Outcomes Study;
- NFL=
- neurofilament light;
- OSA=
- obstructive sleep apnea;
- p-tau=
- phosphorylated tau;
- PiB=
- Pittsburgh compound B;
- t-tau=
- total tau;
- WRAP=
- Wisconsin Registry for Alzheimer's Prevention;
- YKL-40=
- chitinase-3-like protein 1
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
Editorial, page 419
- Received August 28, 2016.
- Accepted in final form April 14, 2017.
- © 2017 American Academy of Neurology
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