Drug treatments in Alzheimer's disease

Abstract

Despite the significant public health issue that it poses, only five medical treatments have been approved for Alzheimer's disease (AD) and these act to control symptoms rather than alter the course of the disease. Studies of potential disease-modifying therapy have generally been undertaken in patients with clinically detectable disease, yet evidence suggests that the pathological changes associated with AD begin several years before this. It is possible that pharmacological therapy may be beneficial in this pre-clinical stage before the neurodegenerative process is established. Techniques providing earlier diagnosis, such as cerebrospinal fluid biomarkers and amyloid positron emission tomography neuroimaging, are key to testing this theory in clinical trials. Recent results from trials of agents such as aducanumab are encouraging but must also be interpreted with caution. Such medicines could potentially delay the onset of dementia and would therefore markedly reduce its prevalence. However, we currently remain a good distance away from clinically available disease-modifying therapy.

Keywords: Alzheimer’s disease; amyloid; pharmacological therapy.

Fig 1.

Aetiology of Alzheimer's disease with therapeutic targets. A – secretase enzyme inhibitors; B – NMDA receptor modulators, eg memantine; C – immunotherapy, including immunisation and direct anti-amyloid therapy, including monoclonal antibodies; D – anti-tau therapy; E – anti-inflammatory treatments, including NSAIDs; F – anticholinesterase inhibitors, eg donepezil. APP = amyloid precursor protein; NFTs = neurofibrillary tangles; NMDA = N-methyl-D-aspartate; NSAIDs = non-steroidal anti-inflammatory drugs.