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Systematic Review: Electrophysiological Markers of Language in Neurodegenerative Diseases
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Poster E118 in Poster Session E, Thursday, October 26, 10:15 am - 12:00 pm CEST, Espace Vieux-Port
Stéphanie De Keulenaer1, Sara Van Mossevelde1,2, Tobi Van den Bossche1,2, David Crossiers1,2, Patrick Cras1,2,3, Tommas Ellender1, Rose Bruffaerts1,2; 1UAntwerp, 2University hospital of Antwerp, 3IBB-Neurobiobank Antwerp
An early and accurate diagnosis enables optimal care of patients with neurodegenerative diseases. Electroencephalography (EEG) shows advantages in terms of availability, comfort, cost and time-effectiveness compared to routinely used diagnostic tools such as e.g. neuropsychological testing or the collection of cerebrospinal fluid. This systematic review aims to evaluate the diagnostic utility of electrophysiological markers in Alzheimer's disease (AD), Frontotemporal Dementia (FTD) including Primary Progressive Aphasia (PPA), and Lewy Body Dementia (LBD). Considering the variable prevalence of language deficits in the three populations, we opted to scope the literature related to semantic processing separately. The review was registered with PROSPERO (ID: CRD42023392253). We systematically searched databases Pubmed, Cochrane, Web of Science, and Scopus for articles published from 2000 to January 2023. Our complete search string defined a total of 12010 studies, 714 papers were eligible for full-text screening after removal of duplicates and screening of the abstracts by 2 blinded reviewers. Additionally, three eligible articles were added. For the language sub-review, only articles including a semantic event-related (ERP) paradigm were selected. Sixteen articles were selected for full-text screening, of which 12 were included. Regarding participant characteristics, eight studies included individuals diagnosed with AD, while four studies studied differences in PPA subtypes. Interestingly, one study compared AD to semantic variant PPA (svPPA). Notably, no study included LBD participants. Our findings highlight the N400 component, elicited by a semantically unexpected stimulus, as the most prominent ERP-marker across populations. Alterations in amplitude, latency or topography of the N400 were reported in all included studies. In AD, the N400 amplitude was consistently reduced (less negative) in seven out of eight studies. Furthermore, one study comparing individuals with symptomatic AD, presymptomatic AD and familial non-carriers of the E280A presenilin 1 mutation causative of AD, suggested that topographic disruptions in N400 generators precede a decrease in N400 amplitude. Similarly, PPA patients exhibited significant alterations in the N400 response to semantic violations compared to healthy controls. More specifically, N400 responses were hardly detectable in semantic PPA (svPPA), delayed in logopenic (lvPPA), and showed mixed results in nonfluent PPA (nfvPPA). Moreover, alterations in N400 topography showed prominent disturbances in svPPA. Additionally, one paper argued that not only the N400 but also the P600 holds potential for discriminating nfvPPA from lvPPA. Likewise, one AD study stated that combining the N400 and P600 increases diagnostic accuracy in mild AD. In conclusion, our review supports the diagnostic and differential diagnostic value of electrophysiological markers, and in particular the N400. Nonetheless, alterations in this component were not limited to PPA and AD, but were also observed in healthy elderly controls in all three studies including younger and older healthy controls. Therefore, further comprehensive research should include larger study populations and direct comparisons between neurodegenerative diseases and healthy controls as similar effects in healthy ageing and interindividual differences complicate interpretation. Additionally, standardization of used paradigms, stimuli, modalities and outcome measures could increase the value of reported results.
Topic Areas: Methods,