Update on the pharmacological management of neurodegenerative diseases: Alzheimer’s disease

Abstract

Neurodegenerative diseases (NDDs) are the most common causes of morbidity and cognitive impairment, particularly among the elderly population worldwide. Due to increasing life expectancy, there has been an increase in the prevalence of NDDs. One of the most common NDDs is Alzheimer’s disease (AD), which is characterised by a complex, multifactorial irreversible aetiology, including the progressive loss of neurons. It is also the most common cause of dementia. Pathologically, AD is associated with the presence of amyloid plaques and intracellular neurofibrillary tangles. The management of AD focuses mainly on establishing an early, accurate clinical diagnosis, early drug administration, treatment of comorbidities and dementia-related complications, as well as treatment of behavioural and psychological symptoms. There is currently no cure for AD, and the currently United States Food and Drug Administration (US-FDA) approved drugs only offer symptomatic relief aiming to improve cognitive and behavioural symptoms; however, they do not target the underlying AD pathology or prevent neuronal degeneration. The current US-FDA approved drugs used for the management of AD include acetylcholinesterase inhibitors (donepezil, galantamine, and rivastigmine), N-methyl-D-aspartate (NMDA) receptor antagonist (memantine), and monoclonal antibody against Aβ (Lecanemab). It should be noted that all these approved drugs only assist in the management of symptoms; however, they do not prevent neuronal loss, brain atrophy, and progressive deterioration of cognition associated with AD. To curb the increasing prevalence of AD, new therapeutic strategies are required, including the development of gene therapy, drugs targeting Aβ, and drugs targeting neuronal hyperexcitability among others.