Combination Drug Therapy for the Management of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Even though the number of AD patients is rapidly growing, there is no effective treatment for this neurodegenerative disorder. At present, implementation of effective treatment approaches for AD is vital to meet clinical needs. In AD research, priorities concern the development of disease-modifying therapeutic agents to be used in the early phases of AD and the optimization of the symptomatic treatments predominantly dedicated to the more advanced AD stages. Until now, available therapeutic agents for AD treatment only provide symptomatic treatment. Since AD pathogenesis is multifactorial, use of a multimodal therapeutic intervention addressing several molecular targets of AD-related pathological processes seems to be the most practical approach to modify the course of AD progression. It has been demonstrated through numerous studies, that the clinical efficacy of combination therapy (CT) is higher than that of monotherapy. In case of AD, CT is more effective, mostly when started early, at slowing the rate of cognitive impairment. In this review, we have covered the major studies regarding CT to combat AD pathogenesis. Moreover, we have also highlighted the safety, tolerability, and efficacy of CT in the treatment of AD.

Keywords: Alzheimer’s disease; combination therapy; dementia; multi-target-directed ligands.

Figure 1

Chemical structure of one heterodimer of galantamine and memantine.

Figure 2

The linking of memantine and nitroglycerin leads to a new drug nitromemantine.

Figure 3

Chemical structure of one heterodimer of donepezil and clioquinol.

Figure 4

The linking of rivastigmine and rasagiline leads to a new drug ladostigil.

Figure 5

The linking of VK-28 and propargylamine leads to a new drug M-30.