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.

Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer’s Disease

“…In recent years, acetylcholine esterase (AChE) inhibitors mostly approved by drug administration to treat AD, which rises the acetylcholine (ACh) availability to some extent alleviating this neurotransmitter insufficiency in AD patients, or they are non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, which blocks the NMDA-associated ion channel consequently lower calcium influx and restrain excitotoxicity ( Kabir et al., 2019b ; Kabir et al., 2019a ; Kabir et al., 2020b ). Surprisingly, particular cannabinoid molecules play a role in the same target compared to contemporary medicaments, resulting in analogous or increased favorable effects.…”

Mechanism, Diagnosis, Medication, Care Guidance, and Health Promotion in Alzheimer’s Disease

“…What is more, studies show that a combination of ChEI and Memantine has the additional ameliorating ability on neurobehavioral symptoms. Therefore, combination therapy using Namzaric was approved by FDA [34].The limitation of single-target ChEIs and NMDA antagonists prompts researches for multifunctional CTs and medications aiming at the origin of AD pathogenesis.…”

“…Each medication in CT has a therapeutic effect on different pathogeneses of AD including amyloid pathology, tau pathology, neurotrophic deficits, excitotoxicity, metabolic alterations and oxidative stress. According to the detailed review from [34], Table 6 for currently researched CTs with its effect and progress is concluded.…”

Revisiting the Amyloid Cascade Hypothesis: From Anti-Aβ Therapeutics to Auspicious New Ways for Alzheimer’s Disease

“…Indeed, AD can exactly be identified only after death via relating clinical measures with an investigation of brain tissues upon autopsy. Currently, available therapies are mainly symptomatic and ineffective against the development of the disease [15]. Now, cholinesterase inhibitors [16] and the N-methyl-d-aspartate (NMDA) receptor antagonist memantine [17] merely represent the receivable options.…”