Present Algorithms and Future Treatments for Alzheimer’s Disease

Abstract

An estimated 47 million people live with Alzheimer’s disease (AD) and other forms of dementia worldwide. Although no disease-modifying treatments are currently available for AD, earlier diagnosis and proper management of the disease could have considerable impact on patient and caregiver quality of life and functioning. Drugs currently approved for AD treat the cognitive, behavioral, and functional symptoms of the disease and consist of three cholinesterase inhibitors (ChEIs) and the N-methyl-D-aspartate receptor antagonist memantine. Treatment of patients with mild to moderate AD is generally initiated with a ChEI. Patients who show progression of symptoms while on ChEI monotherapy may be switched to another ChEI and/or memantine can be added to the treatment regimen. In recent years, putative disease-modifying therapies have emerged that aim to slow the progression of AD instead of only addressing its symptoms. However, many therapies have failed in clinical trials in patients with established AD, suggesting that, once developed, disease-modifying agents may need to be deployed earlier in the course of illness. The goal of this narrative literature review is to discuss present treatment algorithms and potential future therapies in AD.

Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism

“…New drug candidates under clinical trials are targeting Aβ, cholinergic neurotransmission, NMDARs, tau proteins, neurovasculation, inflammation, or virus [93]. Memantine belongs to the NMDAR modulators, which is one of only two classes of medications so far approved for the treatment of AD [94]. Thus, it is worth exploring new lead compounds among NMDAR antagonists.…”

Clinical Pharmacists in Chronic Care

“…Patients with AD particularly susceptible to risk of anticholinergic side effects with certain medications and should be assisted by a pharmacist in selecting safe formulation such as OTC product. Pharmacists can also counsel patients and their caregivers on the safe use of alternative medicines that high majority of caregivers had requested relaxing plants and vitamins from the pharmacy for anxiety and insomnia [242]. As AD is a progressive condition, in its early stages, individuals may present with MCI and some 40% of individuals with MCI deteriorated to dementia (estimated out-of-pocket caregiver costs more than 10 billion in 2016 in Canada alone).…”

“…Treatment algorithm for Alzheimer's disease based on severity of symptoms[242]. Abbreviations: AD, Alzheimer's disease; ChEI, cholinesterase inhibitor; ER, extended release; XR, extended release.…”

Novel Acetylcholinesterase Inhibitors Based on Uracil Moiety for Possible Treatment of Alzheimer Disease

“…The reduction of Aβ production and increased clearance of pathogenic Aβ forms are some of the key targets in the development of oncoming therapeutic agents for AD treatment. Currently, the primary therapeutic treatment for AD is a cholinergic replacement strategy using acetylcholinesterase (AChE) inhibitors, namely donepezil, rivastigmine, and galantamine [ 14 ]. These drugs, able to improve memory and cognitive dysfunctions, are unfortunately unable to slow down neurodegeneration [ 15 , 16 ].…”