Treatment Combinations for Alzheimer’s Disease: Current and Future Pharmacotherapy Options

Abstract

Although Alzheimer’s disease (AD) is the world’s leading cause of dementia and the population of patients with AD continues to grow, no new therapies have been approved in more than a decade. Many clinical trials of single-agent therapies have failed to affect disease progression or symptoms compared with placebo. The complex pathophysiology of AD may necessitate combination treatments rather than monotherapy. The goal of this narrative literature review is to describe types of combination therapy, review the current clinical evidence for combination therapy regimens (both symptomatic and disease-modifying) in the treatment of AD, describe innovative clinical trial study designs that may be effective in testing combination therapy, and discuss the regulatory and drug development landscape for combination therapy. Successful combination therapies in other complex disorders, such as human immunodeficiency virus, may provide useful examples of a potential path forward for AD treatment.

Associations between handgrip strength and mild cognitive impairment in middle‐aged and older adults in six low‐ and middle‐income countries

“…1 Specifically, the proportion of those with dementia residing in LMICs is expected to rise from 58% in 2015 to 68% in 2050. 3 As there are at present no effective treatments for dementia, 4,5 there is an increasing emphasis on intervening in the precursory stage of dementia such as mild cognitive impairment (MCI). The identification of modifiable risk factors for cognitive decline among people with MCI can serve as a target for prevention of later onset dementia.…”

Physical activity correlates in people with mild cognitive impairment: findings from six low- and middle-income countries

“…There are at the moment no proven treatments available to cure dementia or to alter its clinical course 7,8 . Therefore, primary prevention and public health initiatives in the precursory stages of dementia is essential.…”

Recycling old drugs: cardiac glycosides as therapeutics to target barrier inflammation of the vasculature, meninges and choroid plexus

“…As such, the identification of therapeutic compounds that effectively attenuate neuroinflammation has the potential to be beneficial in a diverse range of neurodegenerative diseases, neuropsychiatric disorders, and acute brain injuries. Unfortunately, compounds that were beneficial in preclinical models of neurological disease, including anti-inflammatory therapies, have largely failed to effectively translate to clinical use ( 64, 65 ). Whilst the failure of anti-inflammatory interventions may be a function of inappropriate timing in the treatment regime, the lack of translational therapeutics could be equally attributed to the frequent use of rodent models in neurological drug discovery, in which responses may poorly reflect those observed in humans.…”