A Review of Biomarkers in Delirium Superimposed on Dementia (DSD) and Their Clinical Application to Personalized Treatment and Management

Abstract

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.

Alterations in Neurotrophins in Alcohol-Addicted Patients during Alcohol Withdrawal

“…Malewska et al indicated higher BDNF levels after the presence of AWS with DTs than before AWS [ 28 ]. The findings suggest that BDNF might be a candidate for personalized medicine-based detection of delirium [ 118 ]. Moreover, Huang et al suggested that chronic drinking leads to decreased BDNF levels, and patients with more deficient BDNF expression are prone to the development of DTs [ 119 ].…”

Causal relationships between delirium and Alzheimer's disease: a bidirectional two-sample Mendelian randomization study

“…In our study, the effect estimate of IVW (OR 1.32, 95% CI 1.13–1.54) demonstrates that AD is indeed a risk factor for delirium, which aligns with previous research demonstrating that dementia and recognition decline are independent risk factors for delirium [ 31 , 32 ]. Although the exact mechanisms of delirium are not completely understood, it is believed to be a multifactorial process that can result in brain dysfunction, often involving abnormal nerve transmission and neuroinflammation [ 10 , 33 , 34 ]. Patients with dementia and pre-existing neurodegeneration may be more prone to neuroinflammatory cytokines, and trigger greater oxidative stress during surgery, pain or other stressful situations, potentially increasing the risk of delirium.…”

Early postoperative cognitive decline—are there any preventive strategies for surgical patients in the emergency setting?

“…In order to early recognize vulnerable patients with high risk for postoperative delirium development, a brief evaluation of the cardiopulmonary status, prescribed and overthe-counter medication review, as well as nutrition status and bad habits are recommended, if at all possible [66]. Several studies pointed out the utility of biomarkers for preoperative risk prediction in developing postoperative cognitive impairments [67,68]. While there is no strong evidence to promote measuring of an extensive panel of inflammatory markers to predict early or long-term cognitive disorders, there is reasonable data recommending the utility of preoperatively CRP (C-reactive protein) levels in patients' risk stratification to develop postoperative delirium [69][70][71].…”