Anti-Dementia Medications: Classification, Indications, and Differential Indications

Abstract

Dementia is a progressive condition with loss of cognitive and functional abilities, which usually occurs in later life, extends over several years, leads to the need for full-time care, and is associated with reduced life expectancy. The most common cause of dementia is Alzheimer’s disease (AD). Other dementia types include vascular dementia, dementia associated with Parkinson’s disease (PDD) and Lewy body disease (LBD), frontotemporal dementia, and mixed forms. There is no causal treatment available for any of these dementia types. Licensed symptomatic treatments for mild to moderate AD are the acetylcholinesterase inhibitors (AchE-I) Donepezil, Galantamine, and Rivastigmine (also licensed for mild to moderate PDD). For moderate to severe AD, the N-Methyl-D-Aspartat (NMDA) receptor channel antagonist Memantine is licensed. For the other dementia types, there is no specific symptomatic medication available. AchE-I and Memantine both are superior to placebo with regard to cognition and functional abilities with a modest effect size. The differential indications mainly follow tolerability, route of administration, and specific contraindications. Strong efforts are underway to develop more effective treatments for dementia, which so far, however, have not shown sufficiently large effects on clinical progression to become licensed in Europe. At present, the anti-amyloid antibody Aducanumab has received accelerated approval in the United States for mild cognitive impairment and mild dementia due to AD based on evidence for amyloid reduction with the requirement of another study to establish clinical efficacy.