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).

Keywords: Alzheimer's disease; cerebrospinal fluid; late onset epilepsy; mild cognitive impairment; small vessel disease.

Figure 1

Study flow chart. ASMs, antiseizure medications; CSF, cerebrospinal fluid; EOAD, early onset Alzheimer's disease; LOAD, late onset Alzheimer's disease.

Figure 2

CSF compounds in epADs and nepADs.

Figure 3

EEG features of prodromal AD patients. (A) Distributions of non-epileptiform activity on EEG recordings; (B) distributions of epileptiform activity on EEG recordings; Δ delta slowing; θ, theta slowing; BI-F, bi-frontal; BI-FT, bi-fronto-temporal; BI-H, bi-hemispheric; BIL-F, bilateral frontal; BI-T, bi-temporal; BI-T/T+, bitemporal or bitemporal with extension to the frontal, central or posterior electrodes; L-H, left hemispheric; L-POST, left posterior (parieto-occipital); L-T, left temporal; L-T/T+, left temporal or left temporal with extension to the frontal, central or posterior electrodes; R-FT, right fronto-temporal; R-T, right temporal; R-T/T+, right temporal or right temporal with extension to the frontal, central or posterior electrodes; R-POST, right posterior (parieto-occipital).

Figure 4

Correlations between EEG features and CSF amyloid peptides. IEDs, interictal epileptiform discharges.