Alzheimer’s disease and epilepsy: Research hotspots for comorbidity in the era of global aging

•AD pathologies, such as Aβ plaques and hyperphosphorylated tau, may play a role in epilepsy genesis.•Late-onset epilepsy of unknown etiology is associated with increased risk of developing AD dementia.•Sleep disturbances are prevalent in AD and may exacerbate the disease through neuronal hyperactivity.•Animal models are vital for understanding AD and epilepsy links but face challenges in fully replicating human conditions.•Antiepileptic drugs must be carefully managed in AD due to potential exacerbation of cognitive symptoms. Neurological conditions such as Alzheimer’s disease (AD) and epilepsy share a significant clinical overlap, particularly in the elderly, with each disorder potentiating the risk of the other. This interplay is significant amidst an aging global demographic. The review explores the classical pathologies of AD, including amyloid-beta plaques and hyperphosphorylated tau, and their potential role in the genesis of epilepsy. It also delves into the imbalance of glutamate and gamma-amino butyric acid activities, a key mechanism in epilepsy that may be influenced by AD pathology. The impact of age of onset on comorbidity is examined, with early-onset AD and Down syndrome presenting higher risks of epilepsy. The review suggests that epilepsy might precede cognitive symptoms in AD, indicating a complex interaction. Sleep modulation is highlighted as a factor, with sleep disturbances potentially contributing to AD progression. The necessity for cautious medication management is emphasized due to the cognitive effects of certain antiepileptic drugs. Animal models are recognized for their importance in understanding the relationship between AD and epilepsy, though creating fully representative models presents a challenge. The review concludes by noting the efficacy of medications such as lamotrigine, levetiracetam, and memantine in managing both conditions and suggests the ketogenic diet and cannabidiol as emerging treatment options, warranting further investigation for comprehensive patient care strategies.