Epilepsy in early onset Alzheimer’s disease

Abstract

Background Epilepsy seems to be an important comorbidity in patients with Alzheimer’s disease (AD), especially in young onset AD (<65 years old). At this time epileptic seizures are still underestimated in this population. However, seizures may interact with AD evolution with possible acceleration of cognitive decline and early institutionalization. Seizures may also be a marker of a more aggressive subtype of AD. This study aims to determine the prevalence of the epileptic comorbidity in patients with early onset AD. Secondly, it will investigate the temporal relationship between AD and epilepsy and extract specific characteristics of AD patients at higher risk of epilepsy. Method All patients diagnosed as early‐onset Alzheimer disease between 2013 and 2019, with abnormal CSF biomarkers for Alzheimer disease, and followed at the University Hospital of Nancy (AD regional center) were selected. Patients with cortical focal lesion or old history of epilepsy were excluded. The usual clinical follow‐up was extended with a prolonged EEG and a specific consultation with an epilepsy expert. Based on this dedicated interrogation and EEG results, patients were then classified as epileptic or non‐epileptic. We collected demographic data and information on epilepsy and AD disorders. Result Among the 22 included patients, 10 were classified as epileptic with a prevalence of 45%. Considering seizure types, patients presented generalized seizures (n=4), typical temporal seizures (n=4), myoclonus (n=1) and extratemporal seizures (n=1). EEG recordings were not useful in our population. Epileptic patients presented a more severe cognitive decline than patients without seizures (MMSE 8.4+/‐6.9 versus MMSE non epileptic 20.9 +/‐ 5.45). 100% of patients with a MMSE <10 had epileptic comorbidity. In our population, epilepsy never occurred before AD diagnosis. Conclusion Epilepsy appears to be a frequent comorbidity in early onset AD patients, with a prevalence of 45% in our study. This comorbidity seems to be a marker for severe AD. The role of the epileptic disorder in the acceleration of cognitive decline as the positive impact of antiepileptic drugs still need to be determined.

Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity—In Vitro and In Vivo Studies

“…Oxidative stress in the hippocampus has been associated with temporal lobe epilepsy, a common form of epilepsy in humans [ 47 ], and it has also been demonstrated to be one of the factors involved in diabetic [ 48 , 49 ] and chemotherapy-induced [ 50 ] neuropathic pain. Importantly, epilepsy and neuropathic pain episodes are regarded as relatively frequent comorbidities in patients with PD and AD [ 51 , 52 , 53 , 54 ].…”

Sleep: The Tip of the Iceberg in the Bidirectional Link Between Alzheimer's Disease and Epilepsy

“…In fact, patients with high cognitive reserves can compensate even for comorbid AD and (subclinical) epilepsy for longer periods, and therefore present only mild symptoms even in more advanced stages of AD in terms of biomarkers. However, once the macro- and microstructural damages reach a level where compensation is no longer possible, the disease seems to progress at an excessive speed, as is the case for AD patients with EA ( Figure 5 ) ( 25 , 130 , 137 ). However, this conclusion might beg the question of what happens to AD patients with EA with more modest cognitive reserve.…”

“…The second point of cross-study consensus is that the progression of AD in patients with a co-occurring epileptic syndrome or epileptiform activities is faster ( 25 , 117 , 130 , 136 ). Moreover, AD patients with EA seem to have worse results on cognitive tests than patients without such aberrant network activities ( 26 , 120 , 121 , 137 ). This correlation does not seem to be merely related to a longer duration of AD or more severe stages of the disease.…”