Cognitive Decline Risk Stratification in People with Late-Onset Epilepsy of Unknown Etiology: An Electroencephalographic Connectivity and Graph Theory Pilot Study

Abstract

Background: Although people with late onset epilepsy of unknown etiology (LOEU) are at higher risk of cognitive decline compared to the general population, we still lack affordable tools to predict and stratify their risk of dementia. Objective: This pilot-study investigates the potential application of electroencephalography (EEG) network small-world (SW) properties in predicting cognitive decline among patients with LOEU. Methods: People diagnosed with LOEU and normal cognitive examination at the time of epilepsy diagnosis were included. Cerebrospinal fluid biomarkers, brain imaging, and neuropsychological assessment were performed at the time of epilepsy diagnosis. Baseline EEG was analyzed for SW properties. Patients were followed-up over time with neuropsychological testing to define the trajectory of cognitive decline. Results: Over 5.1 years of follow-up, among 24 patients diagnosed with LOEU, 62.5% were female, mean age was 65.3 years, thirteen developed mild cognitive impairment (MCI), and four developed dementia. Patients with LOEU developing MCI had lower values of SW coefficients in the delta (p = 0.03) band and higher SW values in the alpha frequency bands (p = 0.02) compared to patients having normal cognition at last follow-up. The two separate ANOVAs, for low and alpha bands, confirmed an interaction between SW and cognitive decline at follow-up. A similar gradient was confirmed for patients developing dementia compared to those with normal cognitive function as well as to those developing MCI. Conclusion: Baseline EEG analysis through SW is worth investigating as an affordable, widely available tool to stratify LOEU patients for their risk of cognitive decline.

Clinical and Instrumental Characterization of Patients With Late-Onset Epilepsy

“…Moreover, the analysis of pathophysiological markers of amyloidosis, tauopathy and neurodegeneration can identify the predisposition to a subsequent evolution toward a condition as MCI due to AD. Although further confirmation is needed in larger case series, recent scientific evidence shows that LOE patients with an altered CSF profile, in particular low CSF Aβ level, have a greater chance of evolving to dementia in the years following the onset of epilepsy (9)(10)(11)(12)(13). CSF analysis is also important for those patients presenting with rapidly progressive epilepsy, associated with a severe clinical picture.…”

“…Preliminary evidence from small sample studies highlight that cortico-cortical network is already altered at the time of epilepsy diagnosis among those people having the highest risk of dementia. In particular, SW features of people evolving to dementia over a 5-year time were already substantially different from those preserving normal cognitive function over that time (7,13). SW reduction in the theta and delta frequency bands could be considered a potential marker of subtle cortico-cortical disconnection, potentially identifying people with LOE at the highest risk of conversion to dementia in the years following epilepsy diagnosis (7,13).…”

“…In particular, SW features of people evolving to dementia over a 5-year time were already substantially different from those preserving normal cognitive function over that time (7,13). SW reduction in the theta and delta frequency bands could be considered a potential marker of subtle cortico-cortical disconnection, potentially identifying people with LOE at the highest risk of conversion to dementia in the years following epilepsy diagnosis (7,13). Since SW is affordable and available in any setting, SW analysis could be proposed as potential tool to provide a stratification of the risk of dementia, potentially predicting cognitive decline among patients with LOE.…”

“…Recently, EEG connectivity has been investigated also in LOE. By now, only few studies investigated the role of EEG connectivity analysis in LOE patients, with particular regard to LOEU ( 7 , 13 ). Preliminary evidence from small sample studies highlight that cortico-cortical network is already altered at the time of epilepsy diagnosis among those people having the highest risk of dementia.…”

“…While it is well-known that AD patients have an increased risk of epilepsy during the course of the disease (5), recent data show that LOE may represent the first clinical manifestation of AD. In these subjects, the onset of epilepsy may precede the development of cognitive symptoms by years, while the pathophysiological markers of AD are already positive (6)(7)(8)(9)(10)(11)(12)(13).…”