Case Report: Longitudinal evaluation of cerebrospinal fluid Alzheimer’s disease core biomarkers in a case of refractory late-onset epilepsy of unknown etiology
- 1Department of Neurology, Kyoto University Graduate School of Medicine , ,
- 2Department of Epilepsy, Movement Disorders, and Physiology, Kyoto University Graduate School of Medicine , ,
- 3Office of Research Acceleration, Kyoto University , ,
Abstract
In recent years, late-onset epilepsy of unknown etiology (LOEU) has increasingly been recognized as a risk factor for Alzheimer's disease (AD) and other forms of dementia. We present a case of refractory LOEU with progressive cognitive decline, longitudinally evaluated over more than 20 years using neuropsychological tests, cerebrospinal fluid (CSF) AD core biomarkers (Aβ42/40 ratio, p-tau), electroencephalography, and neuroimaging. The CSF AD core biomarkers were consistently positive, indicating the presence of both amyloid and tau pathology; however, CSF Aβ levels markedly decreased in parallel with improved seizure control. Notably, the addition of low-dose perampanel (1 mg/day) led to improvement in both cognitive function and seizure control, while ¹⁸F-flutemetamol positron emission tomography remained visually negative despite exceeding the predefined quantitative Centiloid threshold. Two years later, seizure frequency increased again, cognitive function deteriorated, and amyloid PET became visually positive, accompanied by an increase in the quantitative Centiloid value. This longitudinal observation suggests that chronic epileptic activity may modify or confound the interpretation of CSF AD biomarker profiles and contribute to cognitive decline, while concomitant early or slowly progressive AD pathology cannot be excluded. The overall biomarker trajectory, including persistently positive CSF AD biomarkers and progressive amyloid PET findings, is compatible with evolving AD pathology, although the marked decline in absolute CSF Aβ concentrations during improved seizure control suggests that chronic epileptic activity may also influence biomarker dynamics. Careful interpretation of AD biomarkers is therefore essential in patients with LOEU, particularly in the era of anti-amyloid therapies.
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BibTeX
@article{wada2026case,
title = {{Case Report: Longitudinal evaluation of cerebrospinal fluid Alzheimer’s disease core biomarkers in a case of refractory late-onset epilepsy of unknown etiology}},
author = {Takafumi Wada and Akira Kuzuya and Kazuma Koda and Sakiho Ueda and Atsushi Shima and Nobukatsu Sawamoto and Akio Ikeda and Ryosuke Takahashi and Riki Matsumoto},
journal = {Frontiers in aging neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnagi.2026.1807027},
url = {https://europepmc.org/article/PMC/PMC13725761},
note = {CC BY},
}
RIS
TY - JOUR
TI - Case Report: Longitudinal evaluation of cerebrospinal fluid Alzheimer’s disease core biomarkers in a case of refractory late-onset epilepsy of unknown etiology
AU - Takafumi Wada
AU - Akira Kuzuya
AU - Kazuma Koda
AU - Sakiho Ueda
AU - Atsushi Shima
AU - Nobukatsu Sawamoto
AU - Akio Ikeda
AU - Ryosuke Takahashi
AU - Riki Matsumoto
PY - 2026
DA - 2026/10/12
JO - Frontiers in aging neuroscience
DO - 10.3389/fnagi.2026.1807027
UR - https://europepmc.org/article/PMC/PMC13725761
AB - In recent years, late-onset epilepsy of unknown etiology (LOEU) has increasingly been recognized as a risk factor for Alzheimer's disease (AD) and other forms of dementia. We present a case of refractory LOEU with progressive cognitive decline, longitudinally evaluated over more than 20 years using neuropsychological tests, cerebrospinal fluid (CSF) AD core biomarkers (Aβ42/40 ratio, p-tau), electroencephalography, and neuroimaging. The CSF AD core biomarkers were consistently positive, indicating the presence of both amyloid and tau pathology; however, CSF Aβ levels markedly decreased in parallel with improved seizure control. Notably, the addition of low-dose perampanel (1 mg/day) led to improvement in both cognitive function and seizure control, while ¹⁸F-flutemetamol positron emission tomography remained visually negative despite exceeding the predefined quantitative Centiloid threshold. Two years later, seizure frequency increased again, cognitive function deteriorated, and amyloid PET became visually positive, accompanied by an increase in the quantitative Centiloid value. This longitudinal observation suggests that chronic epileptic activity may modify or confound the interpretation of CSF AD biomarker profiles and contribute to cognitive decline, while concomitant early or slowly progressive AD pathology cannot be excluded. The overall biomarker trajectory, including persistently positive CSF AD biomarkers and progressive amyloid PET findings, is compatible with evolving AD pathology, although the marked decline in absolute CSF Aβ concentrations during improved seizure control suggests that chronic epileptic activity may also influence biomarker dynamics. Careful interpretation of AD biomarkers is therefore essential in patients with LOEU, particularly in the era of anti-amyloid therapies.
SN - 1663-4365
ER -