Super-Fast, Super-Early: High-Frequency Oscillations May Be a Prelude to Alzheimer's Dementia in Down Syndrome

High-Frequency Oscillations >250 Hz in People with Down Syndrome and Associated Alzheimer's Disease Dementia Lisgaras CP, Giménez S, Carmona-Iragui M, Maure-Blesa L, Blessing E, Fortea J, Osorio RS. Alzheimers Dement . 2025;21(7):e70386. https://doi.org/10.1002/alz.70386 Introduction: Alzheimer's disease (AD) dementia has near full penetrance in adults with Down syndrome (DS) and is strongly linked to late-onset myoclonic epilepsy in Down syndrome (LOMEDS). However, promising biomarkers of epileptogenicity, such as high-frequency oscillations (HFOs >250 Hz), have not been studied. This study is the first to use wideband polysomnography in DS to investigate if HFOs occurred and preceded AD dementia and LOMEDS. Methods: Wideband (0.1 to 500 Hz, 2048 Hz) polysomnography was performed using the international 10–20 system. HFOs were automatically detected during slow-wave sleep, followed by manual review. Results: Fourteen individuals with DS and five age-matched euploid controls were studied, with all DS cases showing HFOs. HFOs emerged before AD dementia and LOMEDS and showed hemispheric lateralization in asymptomatic but not symptomatic AD dementia cases. A trend toward increasing HFO rates with age in DS warrants further confirmation. Discussion: HFOs are promising biomarkers that may predict symptomatic AD dementia in adults with DS.