Reduced overnight memory consolidation and associated alterations in sleep spindles and slow oscillations in early Alzheimer's disease

Annika Hanert; Robby Schönfeld; Frederik D Weber; Alexander Nowak; Juliane Döhring; Sarah Philippen; Oliver Granert; Andrea Burgalossi; Jan Born; Daniela Berg; Robert Göder; Peter Häussermann; Thorsten Bartsch

doi:10.1016/j.nbd.2023.106378

Reduced overnight memory consolidation and associated alterations in sleep spindles and slow oscillations in early Alzheimer's disease

Neurobiol Dis. 2024 Jan:190:106378. doi: 10.1016/j.nbd.2023.106378. Epub 2023 Dec 15.

Authors

Affiliations

¹ Department of Neurology, Memory Disorders and Plasticity Group, University Hospital of Schleswig Holstein, 24105 Kiel, Germany.
² Institute of Psychology, Division of Clinical Psychology, Martin-Luther-University Halle-Wittenberg, 06099 Halle (Saale), Germany.
³ Institute for Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72074 Tübingen, Germany; Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, 6525 EN Nijmegen, the Netherlands; Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, the Netherlands.
⁴ Department of Psychiatry and Psychotherapy, Sleep Laboratory, University Hospital of Schleswig Holstein, 24105 Kiel, Germany.
⁵ Department of Neurology, Memory Disorders and Plasticity Group, University Hospital of Schleswig Holstein, 24105 Kiel, Germany; Institute for General Medicine, University Hospital of Schleswig-Holstein, 24105 Kiel, Germany.
⁶ Institute of Neurobiology, Werner-Reichardt Center for Integrative Neuroscience, University of Tübingen, 72074 Tübingen, Germany.
⁷ Institute for Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72074 Tübingen, Germany.
⁸ Department of Geriatric Psychiatry, LVR Klinik Köln, Academic Teaching Hospital, University of Cologne, Köln, Germany.
⁹ Department of Neurology, Memory Disorders and Plasticity Group, University Hospital of Schleswig Holstein, 24105 Kiel, Germany. Electronic address: t.bartsch@neurologie.uni-kiel.de.

PMID: 38103701
DOI: 10.1016/j.nbd.2023.106378

Abstract

Spatial navigation critically underlies hippocampal-entorhinal circuit function that is early affected in Alzheimer's disease (AD). There is growing evidence that AD pathophysiology dynamically interacts with the sleep/wake cycle impairing hippocampal memory. To elucidate sleep-dependent consolidation in a cohort of symptomatic AD patients (n = 12, 71.25 ± 2.16 years), we tested hippocampal place learning by means of a virtual reality task and verbal memory by a word-pair association task before and after a night of sleep. Our results show an impaired overnight memory retention in AD compared with controls in the verbal task, together with a significant reduction of sleep spindle activity (i.e., lower amplitude of fast sleep spindles, p = 0.016) and increased duration of the slow oscillation (SO; p = 0.019). Higher spindle density, faster down-to-upstate transitions within SOs, and the time delay between SOs and nested spindles predicted better memory performance in healthy controls but not in AD patients. Our results show that mnemonic processing and memory consolidation in AD is slightly impaired as reflected by dysfunctional oscillatory dynamics and spindle-SO coupling during NonREM sleep. In this translational study based on experimental paradigms in animals and extending previous work in healthy aging and preclinical disease stages, our results in symptomatic AD further deepen the understanding of the memory decline within a bidirectional relationship of sleep and AD pathology.

Keywords: Alzheimer's disease; Hippocampal memory; Sleep-dependent memory consolidation; Spatial navigation; Spindles.

MeSH terms

Alzheimer Disease*
Humans
Memory / physiology
Memory Consolidation* / physiology
Memory Disorders / etiology
Polysomnography
Sleep / physiology