Anti-Dementia Medications and Anti-Alzheimer’s Disease Drugs: Side Effects, Contraindications, and Interactions

Abstract

Dementia affects an increasingly large proportion of the older population and is most frequently caused by Alzheimer’s disease, followed by vascular and mixed etiologies and rarer neurodegenerative conditions, such as frontotemporal dementia. Early-stage Alzheimer’s disease is characterized by memory-dominant cognitive deterioration, followed by a deterioration of normal daily activities and behavioral symptoms such as apathy, depression, agitation, and delusions. Until recently, only symptomatic treatment options for dementia were available, including cholinesterase inhibitors and memantine, offering some retardation of symptom progression, but without any disease-modifying effects. While those drugs are generally well tolerated, with common side effects including nausea, diarrhea, and vertigo, more effective drugs are needed, targeting the underlying neurobiological changes. The pathological hallmarks of Alzheimer’s disease include intracellular neurofibrillary tangles and extracellular amyloid-β fibrils and plaques, and different approaches targeting those changes are currently under scrutiny in clinical trials. Recently the first disease-modifying drug Aducanumab, a passive immunization against fibrillar amyloid-β, was approved in the USA by the Food and Drug Administration. However, the fast-track approval has attracted some criticism because of the uncertain clinical benefits of the drug, and further research is warranted to develop effective treatments offering a sufficiently large clinical benefit. Phase III trials are ongoing exploring the effectiveness and tolerability of several promising monoclonal antibodies against amyloid-β, including donanemab, gantenerumab, solanezumab, and crenezumab.