Sleep Time Estimated by an Actigraphy Watch Correlates With CSF Tau in Cognitively Unimpaired Elders: The Modulatory Role of APOE

Abstract

There is increasing evidence of the relationship between sleep and neurodegeneration, but this knowledge is not incorporated into clinical practice yet. We aimed to test whether a basic sleep parameter, as total sleep estimated by actigraphy for 1 week, was a valid predictor of CSF Alzheimer’s Disease core biomarkers (amyloid-β-42 and –40, phosphorylated-tau-181, and total-tau) in elderly individuals, considering possible confounders and effect modifiers, particularly the APOE ε4 allele. One hundred and twenty-seven cognitively unimpaired volunteers enrolled in the Valdecilla Study for Memory and Brain Aging participated in this study. Seventy percent of the participants were women with a mean age of 65.5 years. After adjustment for covariates, reduced sleep time significantly predicted higher t-tau and p-tau. This association was mainly due to the APOE ε4 carriers. Our findings suggest that total sleep time, estimated by an actigraphy watch, is an early biomarker of tau pathology and that APOE modulates this relationship. The main limitation of this study is the limited validation of the actigraphy technology used. Sleep monitoring with wearables may be a useful and inexpensive screening test to detect early neurodegenerative changes.

Day‐to‐day sleep variability with Alzheimer's biomarkers in at‐risk elderly

“…31,32 Reduced sleep duration was previously associated with higher CSF tau in APOE4 allele carriers only. 33 As we observed associations with CSF ApoE levels and interactions with the APOE4 allele genotype, discrepancies of previous findings in APOE4 allele carriers could be attributed to actual ApoE levels in the brain at a given moment.…”

The relationship between Alzheimer's‐related brain atrophy patterns and sleep macro‐architecture

“…Similar observations were also made in humans, with healthy adults artificially deprived of SWS showing acute increases of cerebrospinal fluid (CSF) Aβ concentrations and reduced SWS being recently associated with reduced cortical and subcortical brain volume and increased white matter hyperintensities 11,12 . Furthermore, cognitively healthy elderly subjects with the apolipoprotein E ( APOE ) ε4 allele, the largest known risk factor for AD, exhibited a reduced objective sleep quality compared to noncarriers, as well as reduced total sleep time (TST), with APOE ε4 status modulating the association between TST and CSF tau levels 13,14 …”

“…11,12 Furthermore, cognitively healthy elderly subjects with the apolipoprotein E (APOE) ε4 allele, the largest known risk factor for AD, exhibited a reduced objective sleep quality compared to noncarriers, as well as reduced total sleep time (TST), with APOE ε4 status modulating the association between TST and CSF tau levels. 13,14 We, therefore, hypothesize that distinct features of polysomnogra- (response rate: 50.1%). 15 All were invited to participate in an MRI or PSG examination and, after excluding all subjects who refused participation in the whole-body MRI or fulfilled an exclusion criterion (e.g., presence of a pacemaker), MRI scans were performed on N = 2159 individuals, and N = 1264 SHIP-Trend participants underwent a PSG assessment.…”

Plasma p-tau231 increases at one-year intervals in cognitively unimpaired subjects

“…We conducted this analysis with volunteers of the 'Valdecilla Cohort for the study of memory and brain aging' from the Memory Unit of the Marqués de Valdecilla University Hospital [10,11]. The Valdecilla cohort is designed to better understand the preclinical phases of AD.…”