Rationale:
Epilepsy is a frequently overlooked comorbidity in neurodegenerative disorders (NDDs) like Alzheimer's (AD), Frontotemporal dementia (FTD), Parkinson's (PD), and Lewy Body Dementia (DLB), where it accelerates cognitive decline and worsens outcomes. Traditionally viewed as distinct conditions, mounting evidence supports common underlying mechanisms necessitating a re-evaluation of diagnostic and therapeutic approaches to mitigate this dual disease burden. Despite its impact, data on prevalence, presentation, and treatment remain limited, and clinical trials on antiseizure therapies are scarce. This scoping review synthesizes current insights, identifies key gaps, and outlines priorities for advancing care in this population.
Methods:
We conducted a scoping review (PubMed, May 2020–May 2025) to evaluate epilepsy in adults ≥65 with PD, AD, FTD, or DLB. Using targeted search terms, we assessed seizure prevalence, diagnostic strategies, ASM use, and key challenges in diagnosis and treatment.
Results:
Of 484 screened articles, 23 met inclusion criteria. AD was the most studied NDD related to epilepsy; data on PD, FTD, and DLB remain limited. Seizure prevalence in AD is noted to range from 10–22% in sporadic forms. In DLB, it is ~3%. Across NDDs, seizures are often subclinical, non-motor, or misattributed to disease progression. There were no identified standardized seizure screening protocols. Long-term EEG and novel modalities such as ear-EEG significantly improve diagnostic accuracy and treatment planning yet underutilized. ASMs such as levetiracetam and lamotrigine have shown promise in controlling seizures while preserving cognition, suggesting dual therapeutic potential. Older ASMs (e.g., phenytoin, valproate) are linked to cognitive decline, metabolic effects, and valproate-induced parkinsonism. Although ASMs are foundational, pharmacoresistance remains a significant challenge. Transcranial magnetic stimulation (TMS) shows promise in both AD and epilepsy separately but its efficacy for epilepsy within the AD population has not been studied. Patients with NDD and recurrent seizures experience worse cognition, greater dependency, and a 1.8-fold increased risk of premature mortality. Polypharmacy, multimorbidity, underrepresentation in clinical trials and a lack of high-quality treatment trials guiding ASM choice in NDDs complicate management in this population.
Conclusions:
Integrated diagnostic and therapeutic approaches are critical to address the burden of epilepsy in NDDs. Future research should prioritize:
(1) implementing standardized seizure screening in NDDs to reduce misattribution of seizures to disease progression,
(2) characterizing the bidirectional influence of epilepsy and neurodegeneration on cognition,
(3) identifying safe and effective ASMs, and
(4) developing disease-modifying therapies addressing shared mechanisms.
Device-based therapies (e.g., vagus nerve stimulation, responsive neurostimulation, deep brain stimulation) and dietary approaches (e.g., ketogenic therapy) also warrant evaluation. A paradigm shift towards integrated neurocognitive and epilepsy care is essential to unlock transformative advances in this field.
Funding: