Hippocampal Tau Deposition as a Key Indicator of Sleep and Memory Impairment in Drug-resistant Focal Epilepsy
Abstract number :
1.321
Submission category :
4. Clinical Epilepsy / 4B. Clinical Diagnosis
Year :
2024
Submission ID :
886
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Thaera Arafat, MD – Montreal Neurological Institute and Hospital, McGill University
Nicolás von Ellenrieder, PhD – Montreal Neurological Hospital and Institute
Jordan DeKraker, PhD – McGill University
Jessica Royer, PsyD – McGill University
Raul Rodriguez-Cruces, PhD – McGill University
Judy Chen, BS – McGill University
Zhengchen Cai, PHD – Montreal Neurological Institute and Hospital, McGill University
Andrea Bernasconi, MD – McGill University
Neda Bernasconi, MD,PHD – McGill University
Jean Gotman, PhD – Montreal Neurological Hospital and Institute
Boris Bernhardt, PhD – McGill University
Rationale: Tau aggregates in positron emission tomography (PET) imaging are considered as a biomarker for the early stages of neurodegenerative disorders and network hyperexcitability, which can cause seizures and subclinical epileptic activity in 60% of Alzheimer’s disease patients (Lam AD et al., 2020). Evidence suggests that sleep impairment is linked to cognitive decline in both tauopathy and focal drug-resistant epilepsy (DRE), particularly in cases of hippocampal sclerosis temporal epilepsy (TLE) (Kim RT et al., 2024, Spanò G et al., 2020).
Pathological tau has been detected in drug-resistant focal epilepsy through various studies examining post-mortem and surgically resected tissue (Smith KM et al., 2019).
However, the role of tau PET imaging and its correlation with sleep and memory impairment in focal DRE remains unexplored. This study aims to investigate the relationship between sleep spindles and tau deposition in the hippocampus in focal DRE, particularly in TLE. We hypothesize a negative correlation between spindle rates and ipsilateral hippocampal tau deposits.
Methods: We included 20 focal DRE patients (12 male; 33.9 ± 12.0 y, 18 TLE) who underwent scalp EEG recordings with 29 channels in the epilepsy monitoring unit and F18-MK6240 PET with 3T MRI. Scalp EEG recordings were sleep-scored according to AASM criteria, and N2 epochs were selected. Sleep spindles (10-16 Hz, 0.5-3 seconds) were automatically detected using a common average montage. F18-MK6240 PET uptake was aligned with T1-weighted MRI, then volume-corrected and normalized to the cerebellum to obtain a standardized uptake value ratio (SUVR). In all patients, we automatically segmented the hippocampus based on the HippUnfold algorithm (DeKraker J et al.,2022), and measured tau uptake across the entire hippocampal extent. We investigated the correlation between ipsilateral hippocampal tau, age and spindle rates, adjusting for age, as well as the relationship between spindle rates and age.
Results: Spindle rates per minute during N2 sleep were negatively correlated with the SUVR of tau deposits in the ipsilateral hippocampus (r = -0.45, p = 0.05, Figure 1a). Additionally, age showed a negative correlation with spindle rates (r = -0.66, p = 0.001, Figure 1b) and a positive correlation with tau deposits (r = 0.46, p = 0.04, Figure 1c). After adjusting for age, a moderate negative correlation between spindle rates and tau deposits remained (r = -0.26, p = 0.35).
Conclusions: There is a negative correlation between spindle rates and tau deposits, potentially associated with cognitive dysfunction in TLE patients. However, a direct association between spindles and tau deposits, independent of the age effect, needs to be clarified in a larger population.
Funding: This study was supported by a project grant of the Canadian Institutes of Health Research to BCB (PJT-174995, FDN-143208).
Clinical Epilepsy