From comorbidity to continuum: Alzheimer's disease and epilepsy are connected-now what?

Alzheimer's disease (AD) and epilepsy are increasingly recognized not merely as comorbid conditions but as disorders lying along a shared pathophysiological continuum, characterized by overlapping clinical features, network hyperexcitability, and convergent molecular mechanisms. Although bidirectional interactions between AD and epilepsy are now well established, critical questions remain regarding how this knowledge can be translated into improved risk prediction, prevention, and treatment. Classical mechanisms such as amyloid-β and tau pathology, neuroinflammation, and synaptic dysfunction, together with less explored processes including brain insulin resistance, converge on shared downstream effects that promote both neurodegeneration and epileptogenesis. However, marked mechanistic heterogeneity across individuals, limits standardized therapeutic approaches and complicates the prediction of seizure risk in AD and dementia risk in epilepsy. In this review, we synthesize evidence supporting the AD-epilepsy continuum, integrating molecular pathways, genetic and metabolic modifiers, fluid biomarkers, and neuroimaging signatures that may enable earlier identification of vulnerable trajectories. We critically examine pharmacological strategies with dual effects on neuroprotection and seizure control and discuss how targeting shared mechanisms may shift interventions from symptomatic management toward disease modification. Importantly, we highlight current gaps and emerging hypotheses that define the next steps for the field, including patient stratification, early biomarker-guided trial design, and precision-based therapeutic strategies. By moving beyond descriptive associations, this review outlines a framework for translating mechanistic insight into actionable approaches aimed at early detection, personalized intervention, and improved outcomes in individuals at risk across the AD-epilepsy spectrum.