CSF in Epileptic Prodromal Alzheimer's Disease: No Diagnostic Contribution but a Pathophysiological One

Abstract

Objective: To study whether cerebrospinal fluid (CSF) analysis may serve as a diagnostic test for the screening of epilepsy in sporadic prodromal Alzheimer's disease (AD).Methods: A total of 29 patients with epileptic prodromal sporadic AD patients (epADs) were included and were retrospectively compared with 38 non-epileptic prodromal AD patients (nepADs) for demographics, clinical features, Mini-Mental Status Examination (MMSE) results, CSF biomarkers, and electro-radiological features.Results: Our study did not show any significant differences in CSF biomarkers regarding neurodegeneration, albumin levels, and inflammation between epADs and nepADs. The epADs were significantly older at diagnosis (p = 0.001), more hypertensive (p = 0.01), and displayed larger white matter hyperintensities on brain magnetic resonance imaging (MRI; p = 0.05). There was a significant correlation between the CSF Aβ-42 and Aβ-40 levels with interictal epileptiform discharges and delta slowing on EEGs recordings, respectively (p = 0.03).Conclusions: Our study suggests that CSF may not serve as a surrogate marker of epilepsy in prodromal AD and cannot circumvent the operator-dependent and time-consuming interpretation of EEG recordings. In humans, AD-related epileptogenesis appears to involve the Aβ peptides but likely also additional non-amyloid factors such as small-vessel disease (i.e., white matter hyperintensities).

The Association Between Alzheimer's Disease and Epilepsy: A Narrative Review

“…This is further supported by other studies that have shown an increase in the epileptiform activity in AD patients with seizures during sleep EEG recordings [5,24]. But, it should also be noted that a normal EEG can be expected in 85% of epileptic patients with AD [25]. Therefore it can be concluded that the prevalence of epileptiform discharges is probably more than observed and also highlights the need for better biomarkers to detect seizures in AD.…”

“…They also found a significant correlation between the presence of CSF amyloid proteins and epileptic patterns on EEG. However, the authors concluded that CSF analysis could not serve as a substitute biomarker since there can be other causative factors apart from an amyloid-centric pathology, thus making this diagnostic modality inferior to others [25].…”

Molecular Biomarkers of Neuronal Injury in Epilepsy Shared with Neurodegenerative Diseases

“…In the same study, levels of p-tau and t-tau in CSF were enhanced by epileptic activity in AD patients [ 63 ]. To investigate if alterations in neuronal proteins of CSF can differentiate prodromal late-onset AD with and without seizures, their variations were quantified and compared [ 64 ]. Although the results of this analysis showed no difference, there was a significant correlation of the dynamics of Aβ1-42 and Aβ1-40 in CSF with interictal epileptiform discharges and EEG delta activity.…”