Higher Plasma p-tau217 Correlates with Worse Cognition and Sleep Microarchitecture Integrity in Late Onset Unexplained Epilepsy
Abstract number :
1.099
Submission category :
11. Behavior/Neuropsychology/Language / 11A. Adult
Year :
2024
Submission ID :
879
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Rani Sarkis, MD, MSC – Brigham and Women's Hospital, Harvard Medical School
Lei Liu, MD, PhD – Brigham and Women's Hospital
Janet Orozco, BS – Brigham and Women's Hospital
Alexis Hankerson, MPH – Brigham and Women's Hospital
Shean Purcell, PhD – Brigham and Women's Hospital
Senthil Palanivelu, PhD – Brigham and Women's Hospital
Nataliia Kozhemiako, PhD – Brigham and Women's Hospital
Rebecca Amariglio, PhD – Brigham and Women's Hospital
Page Pennell, MD – University of Pittsburgh
Gad Marshall, MD – Brigham and Women's Hospital
Rationale: Late-onset unexplained epilepsy (LOUE) has been linked to accelerated cognitive decline and a higher risk of dementia. Plasma p-tau217, a novel plasma biomarker, correlates with tau pathology and amyloid PET findings in Alzheimer’s disease and shows elevated levels with worsening cognitive status. Consequently, it holds promise as a potential screening tool for use in epilepsy clinics. Additionally, research has established a connection between sleep microarchitecture and cognitive status in elderly individuals, thus impairment in the integrity of sleep microarchitecture is one potential mechanism whereby neurodegenerative proteins exert their influence. The study aimed to investigate the association of plasma p-tau217 with cognitive performance in LOUE and its correlation with measures of sleep microarchitecture and hippocampal volume.
Methods: 63 participants were prospectively recruited from Brigham and Women’s Hospital and affiliated hospitals. Inclusion criteria: new-onset seizures within 5 years, age ≥55 y/o, absence of cortical lesions on MRI and provoking factors. Participants underwent a neuropsychological battery which included the Preclinical Alzheimer Cognitive Composite (PACC-5), Z scores were generated from a control population from the Harvard Aging Brain Study with a similar age range. A delayed verbal recall (DVR) Z score was extracted by combining the two memory tests from the PACC.
A 24-hour EEG was obtained within 1 year of cognitive assessment. Sleep was manually scored, and sleep spindle features were then extracted using Luna software at the F3,C3 electrodes. Measures of interest for the 11 and 15 Hz frequencies included slow oscillation (SO) coupled spindle density (per minute), magnitude of spindle-SO coupling, and number of spindles overlapping a SO. Additionally, a volumetric MRI was obtained within 1 year of testing and processed to extract hippocampal volume (HV) using Freesurfer software. Plasma p-tau217 was drawn on the day of cognitive testing.
Results: A total of 63 participants were recruited mean age 70.4 ± 7.0 years, 51% female. The average PACC Z score was -0.48 ± 0.92, and DVR Z score -0.73 ± 1.22. When controlling for age, sex, and years of education, plasma p-tau217 negatively correlated with DVR (β=-0.09, p =0.0073) and showed a trend for negative correlation with the PACC (β=-0.05, p=0.06).
When controlling for age and sex, plasma p-tau217 was negatively correlated with measures of 11Hz spindle-SO coupling at F3, and measures of 11Hz and 15Hz spindle-SO coupling at C3 (Table 1). There was also no association between p-tau217 levels and HV (β=-0.000001, p=0.63)
Conclusions: In LOUE, plasma ptau217 negatively correlates with measures of verbal memory and sleep microarchitecture but not hippocampal volume. These findings suggest the utility of plasma ptau217 as a biomarker in this patient population, and emphasize the close link between neurodegenerative proteins, sleep integrity, and cognition in older adults with epilepsy.
Funding: American Epilepsy Society Junior Investigator Award, NIH K23NS119798 (RAS)
Behavior