Galantamine-memantine combination superior to donepezil-memantine combination in Alzheimer’s disease: critical dissection with an emphasis on kynurenic acid and mismatch negativity
Journal Title: Journal of Geriatric Care and Research - Year 2018, Vol 5, Issue 2
Abstract
Background: The donepezil-memantine combination is a US Food and Drug Administration (FDA)–approved medication to treat Alzheimer’s disease (AD). Galantamine is superior to donepezil because it is a positive allosteric modulator of the alpha-7 nicotinic acetylcholine receptor (α7nAChR). Although galantamine and memantine are both FDA approved for the treatment of AD, the combination is still underutilized in clinical practice. Aim: The objective of this review was to critically examine the mechanisms by which the galantamine-memantine combination may be superior to the donepezil-memantine combination in AD by targeting the cholinergic-nicotinic and glutamatergic systems concurrently. Method: PubMed and Google Scholar were searched using the keywords Alzheimer’s disease, cholinergic, glutamatergic, α7nAChR, N-methyl-D-aspartate (NMDA) receptors, donepezil, galantamine, memantine, clinical trials, and biomarkers. Results: AD is associated with several biomarkers such as kynurenine pathway (KP) metabolites, mismatch negativity (MMN), brain-derived neurotrophic factor (BDNF), and oxidative stress. In several preclinical studies, cognitive impairments significantly improved with the galantamine-memantine combination compared to either medication alone. Synergistic benefits were also seen with the combination. In a randomized controlled trial (RCT) in prodrome AD, cognition significantly improved with the galantamine-memantine combination compared to galantamine alone; cognition declined after galantamine was discontinued. However, in an RCT in AD, cognition did not significantly improve with the galantamine-memantine combination compared to galantamine alone. In a retrospective study in AD, the galantamine-memantine combination significantly improved cognition compared to the donepezil-memantine combination. Galantamine and memantine via the α7nACh and NMDA receptors can counteract the effects of kynurenic acid and enhance MMN and BDNF. Conclusion: Future studies with the galantamine-memantine combination with KP metabolites, MMN, and BDNF as biomarkers are warranted. Positive RCTs in AD may lead to FDA approval of the combination, resulting in greater utilization in clinical practice. In the meantime, clinicians may continue to use the galantamine-memantine combination to treat patients with AD.
Authors and Affiliations
Maju Mathew Koola, Agnieszka Nikiforuk, Anilkumar Pillai, Ajay K. Parsaik
Keywords
Related Articles
- EP ID EP552295
- DOI -
- Views 69
- Downloads 0
Proposal for the empowerment of interdependent self management support for people with dementia
The concept of ‘living well’ varies among individuals, and such diversity should be valued. However, maintaining co-beneficial relationships is critical for all the persons with dementia to live well with dementia, since...
Clash between traditions and economy in geriatric care in India: observations from a tertiary care hospital
India is the second most populous country in the world, with an ever-increasing percentage of elderly people (geriatric age group). This population is expected to increase to 300 million by 2050.1 During a research proje...
Physician assisted death in the UK: decision making on a debatable issue
The majority of the British public support medically assisted suicide. However, it remains illegal under British criminal law despite several attempts to legalize it. The uncertainty of medical opinion has impacted on th...
Covert administration of medications in old age psychiatry: a reflection
Covert administration of medications is often observed as a controversial practice, which is used in psychiatry over the years, particularly for the management of challenging behaviours of patients without mental capacit...
Edentulism in elderly: a review of current clinical concerns in India
Background: Edentulism is one of the public health burdens for elderly people; as about 30% of the elderly population aged over 65 years is edentulous across the globe. There is a significant rise in the demographic grow...