Associations between sleep quality and biomarkers for neurodegeneration - A longitudinal one-year case-control study of patients with bipolar disorder and healthy control individuals

Disturbed sleep during affective episodes may impact levels of cerebrospinal fluid (CSF)-amyloid-beta (Aβ)42 and other biomarkers of neurodegeneration in patients with bipolar disorder (BD). The study aimed to investigate the correlations between sleep and biomarkers for Alzheimer's disease (AD) and neurodegeneration in BD and healthy controls (HC). We present a prospective, longitudinal case-control study of euthymic patients with BD (N ​= ​86) and HC (N ​= ​44). All participants were evaluated with clinical assessments at baseline, and after a year. The patients’ affective states were recorded weekly as euthymic, subthreshold level, major depression, or (hypo)mania. Patients were re-assessed during and after an episode if it occurred during follow-up. Total sleep scores based on three Hamilton-17 Depression Scale items were analyzed in relation to concentrations of CSF-Aβ42, CSF-Aβ40, CSF-Aβ38, CSF-Aβ42/40 and 42/38 ratios, CSF-soluble amyloid-precursor proteins α+β, plasma-Aβ42, plasma-Aβ40, CSF-phosphorylated-tau, CSF-total-tau, plasma-total-tau, CSF-neurofilament-light, plasma-neurofilament-light, CSF-neurogranin, serum-S100B, CSF-8-oxo-7,8-dihydro-guanosine, CSF-8-oxo-7,8-dihydro-2′-deoxyguanosine, urine-8-oxo-7,8-dihydro-guanosine, and urine-8-oxo-7,8-dihydro-2′-deoxyguanosine. The primary outcome was the association between total sleep scores and levels of CSF-Aβ42 at baseline and follow-up estimated by the regression coefficient in a linear mixed model. We found no statistically significant associations between sleep and CSF-Aβ42 (−2.307 ​pg/ml (95% CI: -9.525–4.911; p ​= ​0.523)) or any other biomarkers. However, higher sleep scores appeared to be associated with higher CSF-Aβ42/40 and CSF-Aβ42/38 ratios, and lower CSF-total-tau concentration, but were not statistically significant after correction for multiple testing. In conclusion attenuated sleep during an affective episode was not associated with changes in biomarkers for AD and neurodegeneration in BD, but larger prospective studies are needed.