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Published

Longitudinal Alterations in Sleep EEG Biomarkers of Memory Consolidation in Middle-Aged and Older Adults

Authors

Destiny E Berisha, Abhishek Dave, Negin Sattari, Miranda G Chappel-Farley, Kate E Sprecher, Jason Bock, Brady A Riedner, Ethan Moran Grover, Erin M Jonaitis, Henrik Zetterberg, Barbara B Bendlin, Bryce A Mander, Ruth M Benca

Abstract

bioRxiv [Preprint]. 2026 May 14:2026.05.11.724419. doi: 10.64898/2026.05.11.724419.

ABSTRACT

The precise coordination of slow oscillations (SO) and sleep spindles during non-rapid eye movement (NREM) sleep supports memory consolidation and may serve as a sensitive marker of cognitive aging. However, longitudinal changes in their oscillatory dynamics in midlife and older age remain poorly understood. Using polysomnography with high-density EEG at two timepoints over ~2.5 years, we examined changes in local NREM slow wave (SW), sleep spindle (occurring in the 11-16 Hz sigma range), and SO-sigma coupling strength in cognitively unimpaired middle-aged to older adults at risk for Alzheimer's disease. Fronto-central SO-sigma power coupling strength significantly declined over time, independent of changes in multiple measures of SW and sleep spindle expression. Local declines in multiple sleep spindle measures were also observed. Greater baseline levels of cerebrospinal fluid (CSF) neurogranin, a postsynaptic protein abundantly expressed in the dendritic spines of the hippocampus and cerebral cortex and implicated in calcium-dependent synaptic plasticity, predicted the magnitude of longitudinal decline in SO-fast sigma coupling strength, which in turn predicted episodic memory performance changes. These findings suggest that longitudinal changes in local sleep oscillatory dynamics are related to decreased synaptic integrity and may serve as an early indicator of memory decline in older adults at risk for Alzheimer's disease.

PMID:42182430 | PMC:PMC13192916 | DOI:10.64898/2026.05.11.724419

UK DRI Authors

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg