High-frequency oscillations >250 Hz in people with Down syndrome and associated Alzheimer's disease dementia

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.

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.

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.

HFOs are promising biomarkers that may predict symptomatic AD dementia in adults with DS.

Wideband polysomnography reveals a new electrical abnormality in DS. HFOs precede AD dementia in DS. The occurrence of HFOs in DS is independent of an epilepsy diagnosis. HFOs showed hemispheric lateralization in asymptomatic DS cases. A trend of increased HFO rate with advancing age warrants further investigation.