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Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disorder. It is characterized by memory loss and cognition impairment accompanied by personality changes and abnormal behavior. AD is the most common cause of dementia AD dementia accounts for as many as 60 - 70% of senile dementia cases according to the world health organization .
Many factors contribute to AD pathology development including genetics, environment, toxic substances exposure, age, depression, neurotrophic factors deficiency, brain trauma are among these factors. The key neuropathological features of AD include deposition of extracellular amyloid plaque and intracellular neurofibrillary tangles (NFT) starting in hippocampus then spreading to cortical grey mater.
Alzheimer disease can be divided into sporadic Alzheimer disease (SAD) or late onset AD (95% of AD cases) and familial Alzheimer disease (FAD) or early onset AD (1 - 5% of all cases). .
Several factors and mechanisms are involved in its pathogeneses of sporadic AD. Among these factors a well-established mechanism found in sporadic type of AD is insulin signaling dysfunction (insulin resistant brain state). SAD is considered as brain type diabetes (type 3 diabetes).
Insulin receptors (IRs) are well distributed in the central nervous system showing greater abundancy in cerebral cortex and hippocampus. Insulin and insulin signaling molecules play important roles in synapse physiology and plasticity supporting their role in learning and memory.
Other mechanisms involved in SAD include synapse dysfunction, neuro-inflammation, oxidative distress, AB deposition and tau hyperphosphorylation. Streptozotocin (STZ) (a diabetogenic compound commonly used to induce diabetes in animals) has been found to produce similar pathological changes found in SAD.
Alzheimer’s disease is frequently associated with seizures and these can hasten deterioration in cognitive functions. Seizure controlling decision and drug choice in AD patients are challenges we facing. A new research era has been opened with understanding the mechanistic link between AD and epilepsy and their comorbidities. Increased production of amyloid beta peptide, alteration in neuronal structure, neurotransmitters dysfunction and cerebrovascular changes are related to seizures pathophysiology and by targeting those mechanisms AEDS as lacosamide may have a possible role in AD treatment.
Cognition evaluation is an essential domain in tolerability testing of AEDs as cognitive side effects can worse patient quality of life and patient compliance. In addition epigenetics and gene modification considered the new way for various disease future therapy. lacosamide might have potential effect as disease modifying agent considering his Histone deacetylase inhibition activity