Refining Detection of Subclinical Epileptiform Activity in Alzheimer’s Disease: A Case-Control Study and Call for a Consensus
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Objective
Sleep-predominant network hyperexcitability is increasingly recognized as a potential disease-accelerating comorbidity in Alzheimer’s disease (AD). However, its prevalence and risk-factors remain debated, largely due to cohort-specific and methodological differences across studies. In this prospective case-control study, we investigated potential ways of improving detection, from translational approaches focusing on REM-sleep to refined EEG setups and added clinical questionnaires.
Methods
We recruited 30 early-stage AD patients without a history of epilepsy and 30 age-matched controls. Participants underwent overnight polysomnography with video-EEG. Interictal epileptic discharges (IEDs) were identified through a structured three-step review by multiple independent experts using recommended criteria. Neuroanatomical patterns and sleep-related abnormalities were investigated as potential risk factors. Clinical symptoms in favor of epileptic seizures were evaluated through a tailored questionnaire at follow-up.
Results
IEDs were detected in three patients (10%) and one control (3.33%), a difference not reaching statistical significance (p =.612). Most events occurred during NREM sleep. Eight patients (26.67%) reported symptoms compatible with epileptic seizures - one of whom also presented with IEDs. Patients with IEDs or reported symptoms suggestive of potential seizures exhibited more severe sleep-disordered breathing and reduced precuneus volume compared to those without.
Interpretation
Despite efforts to optimize detection accuracy, our findings reveal a lower- than-expected percentage of AD patients with IEDs, yet support previous findings suggesting that sleep-disordered breathing and specific atrophy patterns could flag at-risk patients, guiding screening in clinical settings. Our findings also favour validation efforts of questionnaires to support the diagnostic process. Finally, we highlight methodological issues in IED detection and call for the reevaluation and standardization of diagnostic methods and criteria in this population to improve patient care.
