William J. Jagust

Human in vivo tau pathology, impaired NREM sleep oscillations and memory decline in aging

Abstract:

Aging disrupts sleep. Moreover, these sleep impairments are exaggerated in Alzheimer’s disease, and are proposed to contribute to cognitive decline. Recent human studies have linked β-amyloid with non-rapid eye-movement (NREM) sleep disruption. However, the impact of tau pathology on human sleep oscillations and cognition remains uninvestigated. Here, we tested the hypothesis that tau burden within medial temporal lobe (MTL) impairs the coupled relationship between the two key NREM sleep oscillations—sleep spindles and slow waves, and their known support of hippocampal memory.




Authors:

  • Joseph R. Winer

  • Bryce A. Mander

  • Randolph F. Helfrich

  • Anne Maass

  • Theresa M. Harrison

  • Suzanne L. Baker

  • Robert T. Knight

  • William J. Jagust

  • Matthew P. Walker

Date: 2018

DOI: 10.1016/j.jalz.2018.06.2344

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Old brains come uncoupled in sleep: slow wave-spindle synchrony, brain atrophy, and forgetting

ABSTRACT

The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults. Directional cross-frequency coupling analyses demonstrated that the slow wave governs a precise temporal coordination of sleep spindles, the quality of which predicts overnight memory retention. Moreover, selective atrophy within the medial frontal cortex in older adults predicted a temporal dispersion of this slow wave-spindle coupling, impairing overnight memory consolidation and leading to forgetting. Prefrontal-dependent deficits in the spatiotemporal coordination of NREM sleep oscillations therefore represent one pathway explaining age-related memory decline.





AUTHORS

  • Randolph F. Helfrich

  • Bryce A. Mander

  • William J. Jagust

  • Robert T. Knight

  • Matthew P. Walker

Date: 2018

DOI: 10.1016/j.neuron.2017.11.020

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