The overlap between epilepsy and Alzheimer’s disease and the consequences for treatment

Intermittent Light Exposures in Humans: A Case for Dual Entrainment in the Treatment of Alzheimer's Disease

“…Moreover, although the 40 Hz flicker is outside the 0.1-30 Hz flicker range that is better known to induce epileptic seizures, at least one study (126) showed the onset of localized seizures at higher frequencies (60-100 Hz), and therefore, those who are known to suffer from epileptic seizures should not use the flickering lights. It has been suggested that AD patients are more prone to seizures (127), and it is not known whether the flickering lights would have a different effect in those with neurodegenerative diseases compared to healthy people. Nevertheless, intermittent flickering light therapy shows a lot of promise due to its affordable price and easy administration.…”

Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer’s disease

“…Glutamate-mediated excitotoxicity has been hypothesized to play a major role in the neurodegeneration that arises with AD and related disorders ( Wang and Reddy, 2017 ; Armada-Moreira et al, 2020 ). In support of this hypothesis, individuals with AD are at greater risk for seizures ( Vossel et al, 2017 ; Asadollahi et al, 2019 ; Gail Canter et al, 2019 ; Powell et al, 2019 ), and many rodent models of AD-like pathology exhibit signs of synaptic hyperexcitability, especially in regions of frank pathology ( Siskova et al, 2014 ; Siwek et al, 2015 ; Tamagnini et al, 2015 ; Maeda et al, 2016 ; Fontana et al, 2017 ; Sompol et al, 2017 ; Hijazi et al, 2019 ). Alleviation of excitotoxicity is thought to underlie the modest clinical efficacy observed in AD patients treated with the weak NMDAR blocker memantine ( Kabir et al, 2019 ).…”

A review of the mechanisms underlying selected comorbidities in Alzheimer’s disease

“…An epileptic seizure is regarded as an important comorbidity of AD, with AD patients demonstrating a greater prevalence of epileptic episodes than non-AD individuals [ 156 ]. However, studies about epilepsy prevalence in AD individuals are not consistent and vary (1.5–64%) [ 157 ] depending on the study nature (prospective/retrospective) [ 158 ]. Epileptic seizures have been observed at the early stage of AD and MCI, but patients with advanced AD are exposed to higher epilepsy risk [ 159 ].…”

“…Among patients with AD, the burden of epilepsy development is significantly higher for those with the inherited form of AD, which is associated with autosomal-dominant mutation of specific genes encoding the APP protein, PSEN1 and PSEN2 [ 158 ]. The prevalence of epilepsy was 60% in patients with APP duplication and 45% for those with PSEN1 mutation.…”

“…Aβ has multidimensional effects on the synapses, neuronal circuits, and neuronal transmission. Several human APP mutant AD mouse models [ 163 , 164 ] indicate that pathological Aβ levels induce neuronal hyperexcitability, manifested by nonconvulsive epileptiform activity in the hippocampus, cortical areas, and abnormal membrane depolarization in cortical pyramidal cells [ 158 , 163 , 164 ]. Moreover, excessive levels of Aβ impair synaptic plasticity and disrupt excitatory synaptic transmission [ 157 ].…”