Jahangir Saira, Allala Manoj, Khan Armughan S, Muyolema Arce Veronica E, Patel Anandkumar, Soni Karsh, Sharafshah Alireza
Neurology, Dow University of Health Sciences, Civil Hospital Karachi, Karachi, PAK.
Internal Medicine, Mediciti Institute of Medical Sciences, Medchal, IND.
Cureus. 2023 May 6;15(5):e38627. doi: 10.7759/cureus.38627. eCollection 2023 May.
Delirium superimposed on dementia (DSD) occurs when patients with pre-existing dementia develop delirium. This complication causes patients to become impaired, posing safety concerns for both hospital staff and patients. Furthermore, there is an increased risk of worsening functional disability and death. Despite medical advances, DSD provides both diagnostic and therapeutic challenges to providers. Identifying at-risk patients and providing personalized medicine and patient care can decrease disease burden in a time-efficient manner. This review delves into bioinformatics-based studies of DSD in order to design and implement a personalized medicine-based approach. Our findings suggest alternative medical treatment methods based on gene-gene interactions, gene-microRNA (miRNA) interactions, gene-drug interactions, and pharmacogenetic variants involved in dementia and psychiatric disorders. We identify 17 genes commonly associated with both dementia and delirium including apolipoprotein E (ApoE), brain-derived neurotrophic factor (BDNF), catechol-O-methyltransferase (COMT), butyrylcholinesterase (BChE), acetylcholinesterase (AChE), DNA methyltransferase 1 (DNMT1), prion protein (PrP), tumor necrosis factor (TNF), serine palmitoyltransferase long chain base subunit 1 (SPTLC1), microtubule-associated protein tau (MAPT), alpha-synuclein (αS), superoxide dismutase 1 (SOD1), amyloid beta precursor protein (APP), neurofilament light (NFL), neurofilament heavy, 5-hydroxytryptamine receptor 2A (HTR2A), and serpin family A member 3 (ERAP3). In addition, we identify six main genes that form an inner concentric model, as well as their associated miRNA. The FDA-approved medications that were found to be effective against the six main genes were identified. Furthermore, the PharmGKB database was used to identify variants of these six genes in order to suggest future treatment options. We also looked at previous research and evidence on biomarkers that could be used to detect DSD. According to research, there are three types of biomarkers that can be used depending on the stage of delirium. The pathological mechanisms underlying delirium are also discussed. This review will identify treatment and diagnostic options for personalized DSD management.
痴呆叠加谵妄(DSD)是指患有痴呆症的患者出现谵妄。这种并发症会导致患者功能受损,给医院工作人员和患者都带来安全隐患。此外,功能残疾恶化和死亡的风险也会增加。尽管医学不断进步,但DSD给医疗人员带来了诊断和治疗方面的挑战。识别高危患者并提供个性化医疗和患者护理可以高效减轻疾病负担。本综述深入探讨基于生物信息学的DSD研究,以设计和实施基于个性化医疗的方法。我们的研究结果表明,可以根据基因-基因相互作用、基因-微小RNA(miRNA)相互作用、基因-药物相互作用以及痴呆和精神疾病中涉及的药物遗传学变异来选择替代医学治疗方法。我们确定了17个通常与痴呆和谵妄相关的基因,包括载脂蛋白E(ApoE)、脑源性神经营养因子(BDNF)、儿茶酚-O-甲基转移酶(COMT)、丁酰胆碱酯酶(BChE)、乙酰胆碱酯酶(AChE)、DNA甲基转移酶1(DNMT1)、朊蛋白(PrP)、肿瘤坏死因子(TNF)、丝氨酸棕榈酰转移酶长链碱基亚基1(SPTLC1)、微管相关蛋白tau(MAPT)、α-突触核蛋白(αS)、超氧化物歧化酶1(SOD1)、淀粉样前体蛋白(APP)、神经丝轻链(NFL)、神经丝重链、5-羟色胺受体2A(HTR2A)和丝氨酸蛋白酶抑制剂家族A成员3(ERAP3)。此外,我们确定了形成内部同心模型的六个主要基因及其相关的miRNA。我们还确定了被发现对这六个主要基因有效的FDA批准药物。此外,利用药物基因组知识库(PharmGKB)数据库确定这六个基因的变异,以提出未来的治疗选择。我们还研究了以往关于可用于检测DSD的生物标志物的研究和证据。根据研究,根据谵妄的阶段可以使用三种类型的生物标志物。文中还讨论了谵妄的病理机制。本综述将确定个性化DSD管理的治疗和诊断选择。