Abstract
BackgroundBased on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ42, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals.MethodsOne-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF Aβ42, P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time.ResultsSpindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF Aβ42, P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD.ConclusionsReduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline.
Highlights
Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of Cerebrospinal fluid (CSF) Aβ42, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals
CSF measures of tau do not correlate with measures of sleep quality or habitual sleep duration In order to ascertain that the influence of tau is specific to spindles, we investigated potential relationships between T-tau and P-tau and sleep quality variables measured with PSG, including sleep efficiency, wake after sleep onset (WASO), AHI4% and Apnea-Hypopnea Index (AHI)-all, as well as variables measured with actigraphy, including habitual sleep duration (TST)
In addition to total spindle density, we found evidence that spindle duration and fast spindle density during NREM stage 2 (N2) sleep are significantly associated with CSF T-tau
Summary
Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ42, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals. Cerebrospinal fluid (CSF) Aβ and tau concentrations have been used extensively as biomarkers of AD pathology and found to correlate with plaques and tangles at post-mortem [5,6,7,8]. Low NREM stage 3 (N3) slow wave activity (SWA) is associated, in healthy midlife and young-old, with trait-markers of high cerebrospinal fluid (CSF) Aβ [11, 12], while active disruption of slow wave sleep (SWS) results in state-dependent CSF Aβ peptide increases within subjects [13]. Unlike Aβ, associations between poor SWS and CSF tau have not been reported [12, 13], suggesting that disruption in other sleep oscillations could be linked to tau pathology
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