PMID- 38059250 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231208 IS - 0976-3147 (Print) IS - 0976-3155 (Electronic) IS - 0976-3155 (Linking) VI - 14 IP - 4 DP - 2023 Oct-Dec TI - Guidelines for pharmacotherapy in Alzheimer's disease - A primer on FDA-approved drugs. PG - 566-573 LID - 10.25259/JNRP_356_2023 [doi] AB - The growing prevalence of dementia makes it important for us to better understand its pathophysiology and treatment modalities, to improve the quality of life of patients and caregivers. Alzheimer's disease (AD), a neurodegenerative disease, is the most common form of amnestic dementia in the geriatric population. Pathophysiology of AD is widely attributed to aggregation of amyloid-beta (Abeta) plaques and hyperphosphorylation of tau proteins. Initial treatment modalities aimed to increase brain perfusion in a non-specific manner. Subsequent therapy focused on rectifying neurotransmitter imbalance in the brain. Newer drugs modify the progression of the disease by acting against aggregated Abeta plaques. However, not all drugs used in therapy of AD have been granted approval by the United States Food and Drug Administration (FDA). This review categorizes and summarizes the FDA-approved drugs in the treatment of AD in a manner that would make it a convenient reference for researchers and practicing physicians alike. Drugs that mitigate symptoms of dementia may be categorized into mitigators of Behavioral and Psychological Symptoms of Dementia (BPSD), and mitigators of cognitive decline. BPSD mitigators include brexpiprazole, an atypical antipsychotic with a once-daily dosage suited to treat agitation in dementia patients, and suvorexant, an orexin receptor antagonist used to treat sleep disturbances. Cognitive decline mitigators include cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine and glutamate inhibitors such as memantine. Donepezil is the most commonly prescribed drug. It is cheap, well-tolerated, and may be prescribed orally once daily, or as a transdermal patch once weekly. It increases ACh levels, enhances oligodendrocyte differentiation and also protects against Abeta toxicity. However, regular cardiac monitoring is required due to reports of cardiac conduction side effects. Rivastigmine requires a twice-daily oral dosage or once-daily replacement of transdermal patch. It has fewer cardiac side effects than donepezil, but local application-site reactions have been noted. Galantamine, in addition to improving cognitive symptoms in a short span of time, also delays the development of BPSDs and has minimal drug-drug interactions by virtue of having multiple metabolic pathways. However, cardiac conduction disturbances must be closely monitored for. Memantine, a glutamate regulator, acts as an anti-Parkinsonian agent and an antidepressant, in addition to improving cognition and neuroprotection, and requires a once-daily dosage in the form of immediate-release or sustained-release oral tablets. Disease-modifying drugs such as aducanumab and lecanemab reduce the Abeta burden. Both act by binding with fibrillary conformations of Abeta plaques in the brain. These drugs have a risk of causing amyloid-related imaging abnormalities, especially in persons with ApoE4 gene. Aducanumab is administered once every 4 weeks and lecanemab once every 2 weeks. The decision on the choice of the drug must be made after considering the availability of drug, compliance of patient (once-daily vs. multiple doses daily), cost, specific comorbidities, and the risk-benefit ratio for the particular patient. Other non-pharmacological treatment modalities must also be adopted to have a holistic approach toward the treatment of AD. CI - (c) 2023 Published by Scientific Scholar on behalf of Journal of Neurosciences in Rural Practice. FAU - Varadharajan, Ashvin AU - Varadharajan A AD - Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka, India. FAU - Davis, Aarjith Damian AU - Davis AD AUID- ORCID: 0000-0001-9270-3798 AD - Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka, India. FAU - Ghosh, Aishwarya AU - Ghosh A AD - Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka, India. FAU - Jagtap, Tejaswini AU - Jagtap T AUID- ORCID: 0009-0005-7469-3078 AD - Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka, India. FAU - Xavier, Anjo AU - Xavier A AUID- ORCID: 0009-0003-2485-6743 AD - Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka, India. FAU - Menon, Anjana Jayakumar AU - Menon AJ AD - Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka, India. FAU - Roy, Dwaiti AU - Roy D AD - Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka, India. FAU - Gandhi, Sandhya AU - Gandhi S AD - Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka, India. FAU - Gregor, Thomas AU - Gregor T AUID- ORCID: 0000-0003-3148-3466 AD - Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka, India. LA - eng PT - Journal Article PT - Review DEP - 20231007 PL - United States TA - J Neurosci Rural Pract JT - Journal of neurosciences in rural practice JID - 101533710 PMC - PMC10696336 OTO - NOTNLM OT - Alzheimer's disease treatment OT - Brexpiprazole OT - Dementia OT - Lecanemab OT - United States Food and Drug Administration COIS- There are no conflicts of interest. EDAT- 2023/12/07 06:42 MHDA- 2023/12/07 06:43 PMCR- 2023/11/10 CRDT- 2023/12/07 04:17 PHST- 2023/07/03 00:00 [received] PHST- 2023/09/06 00:00 [accepted] PHST- 2023/12/07 06:43 [medline] PHST- 2023/12/07 06:42 [pubmed] PHST- 2023/12/07 04:17 [entrez] PHST- 2023/11/10 00:00 [pmc-release] AID - 10.25259/JNRP_356_2023 [pii] AID - 10.25259/JNRP_356_2023 [doi] PST - ppublish SO - J Neurosci Rural Pract. 2023 Oct-Dec;14(4):566-573. doi: 10.25259/JNRP_356_2023. Epub 2023 Oct 7.