"Seizure and neurodegeneration": Understanding the nature of seizure in patients with cognitive disorder, A chicken and egg situation

Abstract

AbstractBackgroundThe prevalence of epileptic seizures in dementia is higher than healthy individuals and seizures occur in 10‐22% of individuals with Alzheimer's Disease (AD). This exploratory study investigated the clinicopathological biomarkers and risk factors of individuals with/without active seizures following post‐mortem evaluation.MethodThe study included 1047 subjects with remote and 572 with active seizures. The data was obtained from National Alzheimer’s Coordinating Center(NACC) Dataset. The Chi‐square analysis was performed by using SPSS 26 Package Program with seven variables which consist of 1) major pathological changes (Yes/No/Unknown), 2) Thal phase for amyloid plaques (Phase‐0 to Phase‐5/Unknown), 3) Density of neurocortical plaques (No plaque/Sparse/Moderate/Frequent/Unknown), 4) NIA‐AA AD neuropathological change (No AD/Low‐ADNC/ADNC/Intermediate‐ADNC/High‐ADNC,Unknown), 5)Cerebral amyloid angiopathy (None/Mild/Moderate/Severe/Unknown), 6) AD‐Related genes (Yes/No/Unknown), and 7) Braak stage for neurofibrillary degeneration (Stage‐0 to Stage‐6/Unknown/The presence of tauopathy precludes Braak staging). Post‐hoc comparisons were done by using adjusted residuals.ResultThe chi‐square analysis showed that major pathological changes (χ2=18.107) are more common in patients with active seizures (27.5%) than remote seizures (19.9%). Thal phase for amyloid plaques (χ2=38.771) was significantly different in Stage‐0 and Stage‐1 the percentage of patients with active seizures was higher (5.7%, 4.8%) than remote seizures (1.8%, 1.7%). Braak stage for neurofibrillary degeneration (χ2=81.632) significantly differs among groups. Post‐hoc analysis showed that patients with active seizures (4.4%) had a higher percentage than remote seizures (1.1%) in Stage‐5. Density of neurofibrillary plaques (χ2=36.345) differs in groups showing that frequent plaques are more common in patients with active seizures (11.2%) than remote (6.9%). Cerebral amyloid angiopathy (χ2=51.946) showed a difference indicating mild angiopathy is more common in patients with active seizures (9.6%) than remote (3.9%). (All p<0.001)ConclusionThese results may indicate that seizures are the result of widespread and severe degeneration in the brain or the degeneration is due to these seizures.