Delirium In Individuals Research Articles

The Relationship between Delirium and Dementia.

Delirium and dementia are common causes of cognitive impairment in older adults. They are distinct but interrelated. Delirium, an acute confusional state, has been linked to the chronic and progressive loss of cognitive ability seen in dementia. Individuals with dementia are at higher risk for delirium, and delirium itself is a risk factor for incident dementia. Additionally, delirium in individuals with dementia can hasten underlying cognitive decline. In this review, we summarize recent literature linking these conditions, including epidemiological, clinicopathological, neuroimaging, biomarker, and experimental evidence supporting the intersection between these conditions. Strategies for evaluation and diagnosis that focus on distinguishing delirium from dementia in clinical settings and recommendations for delirium prevention interventions for patients with dementia are presented. We also discuss studies that provide evidence that delirium may be a modifiable risk factor for dementia and consider the impact of delirium prevention interventions on long-term outcomes.

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

BackgroundPrevious observational studies have suggested a notably elevated prevalence of delirium in individuals diagnosed with Parkinson’s disease (PD), thereby implying a potential increased susceptibility to delirium among PD patients. However, it is imperative to acknowledge that observational studies inherently possess limitations, rendering it arduous to establish a definitive causal or reverse causal association between delirium and PD.MethodsTo explore the relationship between delirium and PD, a bidirectional two-sample Mendelian randomization (MR) was conducted using summary statistics obtained from genome-wide association studies. The main analysis was performed using the inverse-variance weighted (IVW) method, with further analyses conducted using MR Egger, weighted median, and weighted mode to ensure accuracy of findings. Additionally, Cochran’s Q statistics and MR Egger intercept were utilized to assess heterogeneity and horizontal pleiotropy, respectively.ResultsAccording to the results obtained from the IVW model, no compelling evidence was found to support a potential causal association between delirium and PD (IVW: odds ratio [OR]: 0.996, 95% confidence interval CI 0.949–1.043, P = 0.845). Additionally, in the reverse direction, based on the results obtained from the IVW model, no significant evidence was found to support a causal association between PD and delirium (IVW: OR: 1.078, 95%CI 0.960–1.204, P = 0.225). A sensitivity analysis verified the reliability of the results.ConclusionAccording to the MR findings, a bidirectional causal relationship between delirium and PD is not observed. It is crucial to conduct further research in clinical practice to investigate the association between delirium and the risk of PD.

Triglyceride-glucose index as a valuable predictor for aged 65-years and above in critical delirium patients: evidence from a multi-center study

BackgroundThe triglyceride-glucose index (TyG), an established indicator of insulin resistance, is closely correlated with the prognosis of several metabolic disorders. This study aims to investigate the association between the TyG index and the incidence of critical delirium in patients aged 65 years and older.MethodsWe focused on evaluating patients aged 65 years and older diagnosed with critical delirium. Data were obtained from the Medical Information Database for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Multivariate logistic regression and restricted cubic spline (RCS) regression were used to determine the relationship between the TyG index and the risk of delirium.ResultsParticipants aged 65 years and older were identified from the MIMIC-IV (n = 4,649) and eICU-CRD (n = 1,844) databases. Based on optimal thresholds derived from RCS regression, participants were divided into two cohorts: Q1 (< 8.912), Q2 (≥ 8.912). The logistic regression analysis showed a direct correlation between the TyG index and an increased risk of critical delirium among ICU patients aged 65 and older. These findings were validated in the eICU-CRD dataset, and sensitivity analysis further strengthened our conclusions. In addition, the subgroup analysis revealed certain differences.ConclusionThis study highlights a clear, independent relationship between the TyG index and the risk of critical delirium in individuals aged 65 years and older, suggesting the importance of the TyG index as a reliable cardio-cerebrovascular metabolic marker for risk assessment and intervention.

Association of Delirium with Long‐term Cognitive Decline: An Update

AbstractBackgroundDelirium has been associated with a variety of unfavorable outcomes, including increasing length of stay in the hospital, poor functioning, and death. We compiled the literature and conducted a meta‐analysis (Goldberg et al, JAMA Neurol, 2021) in order to determine if delirium was also associated with long term cognitive decline. Twenty‐three studies that included over 3500 delirium and 6900 control patients were included in the meta‐analysis. Cognitive assessments were conducted on average at 2.3 years after the episode of delirium. We found that the overall effect size G was .45 (P&lt;.001) indicating that patients who experienced delirium performed significantly worse than controls who did not experience delirium.MethodWe will search the literature on cognitive changes after delirium from Jan 1, 2019 onward. We will include all relevant studies with the same inclusion criteria as our prior study (namely an episode of delirium, cognitive assessment 3 or more months after the episode, and a control group). We will then compute the effect size G for each individual study in order to determine if the values are consistent with our previous findings. We will also examine if delirium meets Bradford Hill criteria for playing a causal role in cognitive decline in association studies.Second, we will review the literature on cognitive changes after delirium in individuals experiencing SARS‐CoV‐2 infection, given the many reports of patients experiencing delirium in the ICU while ventilated. We will derive G for these studies, so long as they incorporate a control group that adjusts for disease severity and virus positivity.ResultWe will present results of this new review in terms of G for individual studies, overall G when these are added to the original meta‐analysis, and a Bradford Hill criteria checklist. For delirium after SARS‐Cov‐2 infection we will rely on a narrative description.ConclusionFirst, we will examine trends in reports of the magnitude cognitive changes after delirium over the past three years, as well as examine if newer or more comprehensive methodologies are being deployed. Second, we will examine the extent of cognitive changes after delirium in the context of severe COVID‐19.

The inter-relationship between delirium and dementia: the importance of delirium prevention.

Delirium and dementia are two frequent causes of cognitive impairment among older adults and have a distinct, complex and interconnected relationship. Delirium is an acute confusional state characterized by inattention, cognitive dysfunction and an altered level of consciousness, whereas dementia is an insidious, chronic and progressive loss of a previously acquired cognitive ability. People with dementia have a higher risk of developing delirium than the general population, and the occurrence of delirium is an independent risk factor for subsequent development of dementia. Furthermore, delirium in individuals with dementia can accelerate the trajectory of the underlying cognitive decline. Delirium prevention strategies can reduce the incidence of delirium and associated adverse outcomes, including falls and functional decline. Therefore, delirium might represent a modifiable risk factor for dementia, and interventions that prevent or minimize delirium might also reduce or prevent long-term cognitive impairment. Additionally, understanding the pathophysiology of delirium and the connection between delirium and dementia might ultimately lead to additional treatments for both conditions. In this Review, we explore mechanisms that might be common to both delirium and dementia by reviewing evidence on shared biomarkers, and we discuss the importance of delirium recognition and prevention in people with dementia.

Preoperative MRI brain phenotypes are related to postoperative delirium in older individuals

The underlying structural correlates of predisposition to postoperative delirium remain largely unknown. A combined analysis of preoperative brain magnetic resonance imaging (MRI) markers could improve our understanding of the pathophysiology of delirium. Therefore, we aimed to identify different MRI brain phenotypes in older patients scheduled for major elective surgery, and to assess the relation between these phenotypes and postoperative delirium. Markers of neurodegenerative and neurovascular brain changes were determined from MRI brain scans in older patients (n = 161, mean age 71, standard deviation 5 years), of whom 24 (15%) developed delirium. A hierarchical cluster analysis was performed. We found six distinct groups of patients with different MRI brain phenotypes. Logistic regression analysis showed a higher odds of developing postoperative delirium in individuals with multi-burden pathology (n = 15 (9%), odds ratio (95% confidence interval): 3.8 (1.1–13.0)). In conclusion, these results indicate that different MRI brain phenotypes are related to a different risk of developing delirium after major elective surgery. MRI brain phenotypes could assist in an improved understanding of the structural correlates of predisposition to postoperative delirium.

Incidence and risk factors of delirium after percutaneous coronary intervention in individuals hospitalised for acute myocardial infarction: protocol for a systematic review and meta-analysis

IntroductionDelirium in the postoperative period is a wide-reaching problem that affects important clinical outcomes. The incidence and risk factors of delirium in individuals with acute myocardial infarction (AMI) after primary...

The Healthy Heart-Mind Trial: Randomized Controlled Trial of Melatonin for Prevention of Delirium.

Delirium is a serious medical condition with increased incidence in at-risk surgical populations. We sought to determine if melatonin use reduces the incidence of delirium in individuals undergoing major cardiac surgery. Randomized double-blind placebo-controlled clinical trial (two arms, 1:1 allocation, parallel design). The trial took place in two metropolitan hospitals (public tertiary and private) in Perth, Western Australia. We recruited 210 adults aged 50 years or older who were due to undergo coronary artery bypass grafting or valve replacement surgery. Participants were randomly assigned (1:1) to 7 days of treatment with melatonin 3 mg at night or matching placebo, starting 2 days before the surgery. The primary outcome of interest was incident delirium within 7 days of surgery as assessed via daily clinical assessment that included the Confusion Assessment Method. Secondary outcomes of interest included duration and severity of delirium, length of hospital stay, cognitive function, and mood and anxiety symptoms at discharge and 3 months after the surgery. The groups were well balanced for demographic and clinical parameters. Forty-two participants developed delirium, but it was evenly distributed between the groups (melatonin 21/98, 21.4%; placebo 21/104, 20.2%; adjusted odds ratio [OR] = .78; 95% confidence interval [CI] = .35-1.75). The median duration of delirium was 3 (interquartile range [IQR] = 2-4) and 2 (IQR = 1-3) days for people treated with melatonin and placebo, respectively (z = -1.03; P = .304). A similar proportion of participants experienced severe episodes of delirium in each group (melatonin 9/21, 42.9% vs placebo 6/21, 28.6%; χ2 = .93; P = .334; adjusted OR = 1.98; 95% CI = .40-9.78). The groups did not differ in terms of length of stay, mood, anxiety, and cognitive performance. The findings of this randomized double-blind placebo-controlled trial do not support the prophylactic use of melatonin to prevent delirium after major cardiac surgery. J Am Geriatr Soc 68:112-119, 2019.

Association between preoperative nutritional status and postoperative delirium in individuals with coronary artery bypass graft surgery: A prospective cohort study.

The prevalence of delirium and undernutrition are both relatively high subsequent to coronary artery bypass graft (CABG) surgery. The aim of this study was to evaluate the association between preoperative malnutrition and the occurrence of delirium after CABG surgery. In this prospective cohort study, body mass index, mid-upper arm circumference, triceps skinfold, and adductor pollicis muscle thickness of 398 adult patients before CABG surgery were measured by a single trained dietitian. Also, Nutritional Risk Screening 2002 (NRS-2002) and subjective global assessment (SGA) were obtained from patients. Delirium was defined by the confusion assessment method for the intensive care unit. SPSS software was used for performing the statistical analyses. Logistic regression analysis was applied to examine the effect of various factors on the development of delirium. Postoperative delirium was detected in 17% of patients (n = 68). Multivariate regression analysis adjusted by other risk factors indicated that risk for delirium was 1.56-fold higher in patients with NRS-2002 >3 (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.20-3.24; P = 0.001). Severe undernutrition at admission as assessed by SGA was independently associated with the occurrence of delirium (OR, 2.58; 95% CI, 1.02-3.48; P = 0.005). Risk for delirium was 1.26-fold higher in patients with adductor pollicis muscle thickness <15 mm (OR, 1.26; 95% CI, 1.02-3.14; P = 0.02). Since the prevalence of delirium is relatively high in CABG surgery and undernutrition is related to postoperative delirium, considering nutrition status with NRS-2002, SGA, or adductor pollicis muscle thickness before surgery could decrease the risk for postoperative delirium.

Preventing Postoperative Delirium After Major Noncardiac Thoracic Surgery-A Randomized Clinical Trial.

To assess the efficacy of haloperidol in reducing postoperative delirium in individuals undergoing thoracic surgery. Randomized double-blind placebo-controlled trial. Surgical intensive care unit (ICU) of tertiary care center. Individuals undergoing thoracic surgery (N=135). Low-dose intravenous haloperidol (0.5 mg three times daily for a total of 11 doses) administered postoperatively. The primary outcome was delirium incidence during hospitalization. Secondary outcomes were time to delirium, delirium duration, delirium severity, and ICU and hospital length of stay. Delirium was assessed using the Confusion Assessment Method for the ICU and delirium severity using the Delirium Rating Scale-Revised. Sixty-eight participants were randomized to receive haloperidol and 67 placebo. No significant differences were observed between those receiving haloperidol and those receiving placebo in incident delirium (n=15 (22.1%) vs n=19 (28.4%); p = .43), time to delirium (p = .43), delirium duration (median 1 day, interquartile range (IQR) 1-2 days vs median 1 day, IQR 1-2 days; p = .71), delirium severity, ICU length of stay (median 2.2 days, IQR 1-3.3 days vs median 2.3 days, IQR 1-4 days; p = .29), or hospital length of stay (median 10 days, IQR 8-11.5 days vs median 10 days, IQR 8-12 days; p = .41). In the esophagectomy subgroup (n = 84), the haloperidol group was less likely to experience incident delirium (n=10 (23.8%) vs n=17 (40.5%); p = .16). There were no differences in time to delirium (p = .14), delirium duration (median 1 day, IQR 1-2 days vs median 1 day, IQR 1-2 days; p = .71), delirium severity, or hospital length of stay (median 11 days, IQR 10-12 days vs median days 11, IQR 10-15 days; p = .26). ICU length of stay was significantly shorter in the haloperidol group (median 2.8 days, IQR 1.1-3.8 days vs median 3.1 days, IQR 2.1-5.1 days; p = .03). Safety events were comparable between the groups. Low-dose postoperative haloperidol did not reduce delirium in individuals undergoing thoracic surgery but may be efficacious in those undergoing esophagectomy. J Am Geriatr Soc 66:2289-2297, 2018.

The incidence of delirium after cardiac surgery in the elderly: protocol for a systematic review and meta-analysis

IntroductionDelirium is one of the most common complications after cardiac surgery in the elderly. Future studies aimed at preventing postoperative delirium will need an accurate estimate of incidence. However, there...

Sex Differences in Hip Fracture Surgery: Preoperative Risk Factors for Delirium and Postoperative Outcomes.

To describe the differences observed in risk factors for delirium and outcomes between men and women undergoing hip fracture repair surgery. Prospective cohort study. Academic medical center. Individuals with acute hip fracture admitted to an academic medical center (N = 431). Information on preoperative demographic characteristics, medical history, laboratory results, and postoperative outcomes was obtained according to history and chart review. Delirium was assessed using the Confusion Assessment Method. The overall incidence of postoperative delirium was 34%, with men more likely to experience postoperative delirium (44.8%) than women (30.2%) (P = .004). Male sex was associated with postoperative delirium in individuals with hip fracture, even after adjusting for other preoperative risk factors. Other significant preoperative risk factors included age, dementia, Parkinson's disease, and American Society of Anesthesiologists classification. Men were also more likely to experience other postoperative complications and have longer hospital length of stay. Men are at higher risk of postoperative delirium after hip fracture repair than women and have more postoperative surgical complications. Their higher risk of postoperative delirium may be due to their underlying preoperative disease severity.

Associations Between Delirium and Preoperative Cerebrospinal Fluid C-Reactive Protein, Interleukin-6, and Interleukin-6 Receptor in Individuals with Acute Hip Fracture.

To examine whether delirium in individuals with hip fracture is associated with high C-reactive protein (CRP), interleukin-6 (IL-6), and soluble IL-6 receptor (sIL-6R) levels in the cerebrospinal fluid (CSF). Prospective cohort study. Two university hospitals in Oslo, Norway, and Edinburgh, United Kingdom. Individuals admitted with acute hip fracture (N = 151). Participants were assessed for delirium pre- and postoperatively using the Confusion Assessment Method. Prefracture cognitive impairment was detected using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Serum was collected preoperatively and CSF just before the onset of spinal anesthesia. Cytokine levels in serum and CSF samples were determined using an enzyme-linked immunosorbent assay. Student t-tests or Mann-Whitney U-tests were used for between-group comparisons. Spearman rho was used for correlations. Sixty participants had prior cognitive impairment (IQCODE score ≥3.44). Delirium was diagnosed in 46 participants (77%) with prior cognitive impairment and 25 (29%) without. In participants without prior cognitive impairment, CSF CRP levels were higher in participants with delirium (median 0.05 μg/mL, interquartile range (IQR) 0.02-0.12 μg/mL) than in those without delirium (median 0.01 μg/mL, IQR 0.00-0.06 μg/mL) (P = .01); there were no differences in participants with prior cognitive impairment. In secondary analyses, in participants with prior cognitive impairment, the concentration of CSF sIL-6R was higher in those participants who developed delirium than in the other subgroups, but this difference was not statistically significant. Serum levels of CRP, IL-6, and sIL-6R were not different according to delirium in participants with or without prefracture cognitive impairment. High CSF levels of CRP and sIL-6R may be associated with delirium. Different pathophysiological mechanisms may operate in different subgroups, notably in relation to the presence of prior cognitive impairment.

Impaired olfaction and risk of delirium or cognitive decline after cardiac surgery.

To determine the prevalence of impaired olfaction in individuals presenting for cardiac surgery and the independent association between impaired olfaction and postoperative delirium and cognitive decline. Nested prospective cohort study. Academic hospital. Individuals undergoing coronary artery bypass, valve surgery, or both (n = 165). Olfaction was measured using the Brief Smell Identification Test, with impaired olfaction defined as an olfactory score below the fifth percentile of normative data. Delirium was assessed using a validated chart review method. Cognitive performance was assessed using a neuropsychological testing battery at baseline and 4 to 6 weeks after surgery. Impaired olfaction was identified in 54 of 165 participants (33%) before surgery. Impaired olfaction was associated with greater adjusted risk of postoperative delirium (relative risk = 1.90, 95% confidence interval = 1.17-3.09, P = .009). There was no association between impaired olfaction and change in composite cognitive score in the overall study population. Impaired olfaction is prevalent in individuals undergoing cardiac surgery and is associated with greater adjusted risk of postoperative delirium but not cognitive decline. Impaired olfaction may identify unrecognized vulnerability to postoperative delirium in individuals undergoing cardiac surgery.

Preoperative risk factors for postoperative delirium following hip fracture repair: a systematic review.

Systematically identify preoperative clinical risk factors for incident postoperative delirium in individuals undergoing hip fracture repair in order to guide clinicians in identifying high risk patients at admission. This is a systematic review of prospective observational studies with estimation of association between preoperative risk factors and incident postoperative delirium in multivariate models. Electronic searches were conducted in PubMed, Embase, PsycINFO, CINAHL, Cochrane Library, Proquest Dissertations and Theses, and WorldCatDissertations. Hand searches were conducted in selected journals and their supplements. Search yielded 6380 titles and abstracts from electronic databases and 72 titles from hand searches, and 10 studies met inclusion criteria. The following risk factors were significant in bivariate models: cognitive impairment, age, gender, institutionalization, functional impairment, body mass index (BMI), albumin, comorbidities, American Society of Anesthesiologist classification, acute medical conditions, polypharmacy, and vision impairment. Among all of these risk factors, cognitive impairment most consistently remained statistically significant after adjusting for other risk factors in multivariate models, followed by BMI/albumin and multiple comorbidities. In our systematic review, cognitive impairment was one of the strongest preoperative risk factors for postoperative delirium after hip fracture surgery. Preoperative cognitive assessment may be one of the most useful methods of identifying those who are at high risk for postoperative delirium and prioritizing delivery of delirium prevention measures.

Melatonin and melatonin agonist for delirium in the elderly patients.

The objective of this review is to summarize the available data on the use of melatonin and melatonin agonist for the prevention and management of delirium in the elderly patients from randomized controlled trials (RCTs). A systematic search of 5 major databases PubMed, MEDLINE, PsychINFO, Embase, and Cochrane Library was conducted. This search yielded a total of 2 RCTs for melatonin. One study compared melatonin to midazolam, clonidine, and control groups for the prevention and management of delirium in individuals who were pre- and posthip post-hip arthroplasty. The other study compared melatonin to placebo for the prevention of delirium in older adults admitted to an inpatient internal medicine service. Data from these 2 studies indicate that melatonin may have some benefit in the prevention and management of delirium in older adults. However, there is no evidence that melatonin reduces the severity of delirium or has any effect on behaviors or functions in these individuals. Melatonin was well tolerated in these 2 studies. The search for a melatonin agonist for delirium in the elderly patients yielded 1 study of ramelteon. In this study, ramelteon was found to be beneficial in preventing delirium in medically ill individuals when compared to placebo. Ramelteon was well tolerated in this study.

A tale of two methods: chart and interview methods for identifying delirium.

To compare chart- and interview-based methods for identification of delirium. Prospective cohort study. Two academic medical centers. Individuals aged 70 and older undergoing major elective surgery (N = 300) (majority orthopedic surgery). Participants were interviewed daily during hospitalization for delirium using the Confusion Assessment Method (CAM; interview-based method), and their medical charts were reviewed for delirium using a validated chart-review method (chart-based method). Rate of agreement of the two methods and characteristics of those identified using each approach were examined. Predictive validity for clinical outcomes (length of stay, postoperative complications, discharge disposition) was compared. In the absence of a criterion standard, predictive value could not be calculated. The cumulative incidence of delirium was 23% (n = 68) according to the interview-based method, 12% (n = 35) according to the chart-based method, and 27% (n = 82) according to the combined approach. Overall agreement was 80%; kappa was 0.30. The methods differed in detection of psychomotor features and time of onset. The chart-based method missed delirium in individuals that the CAM identified who were lacking features of psychomotor agitation or inappropriate behavior. The CAM-based method missed chart-identified cases occurring during the night shift. The combined method had high predictive validity for all clinical outcomes. Interview- and chart-based methods have specific strengths for identification of delirium. A combined approach captures the largest number and broadest range of delirium cases.

Anticholinergic Activity in Cerebrospinal Fluid and Serum in Individuals with Hip Fracture with and without Delirium

To examine whether anticholinergic activity (AA) in cerebrospinal fluid (CSF) and serum is associated with risk of delirium in individuals with hip fracture. Prospective cohort study. Two university hospitals in Oslo, Norway, and Edinburgh, UK. Individuals admitted with acute hip fracture (N = 151). Participants were assessed daily for delirium using the Confusion Assessment Method (preoperatively and postoperative days 1-5 (all) or until discharge (participants with delirium)). Prefracture cognitive function was assessed using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Serum was collected preoperatively and CSF at the onset of spinal anesthesia. AA in serum (SAA) and CSF samples was determined according to a muscarinic radio receptor bioassay. The association between AA measures and delirium was evaluated using logistic multivariate analyses. Fifty-two (54%) of the participants in Oslo and 20 (39%) in Edinburgh developed delirium. There was no statistically significant difference in AA between participants with and without delirium in Oslo (serum: 7.02 vs 6.08 pmol/mL, P = .54; CSF: 0.39 vs 0.48 pmol/mL, P = .26) or in Edinburgh (serum: 1.35 vs 1.62 pmol/mL, P = .76; CSF: 0.36 vs 0.31 pmol/mL, P = .93). Nor was there any difference in SAA (Oslo, P = .74; Edinburgh, P = .51) or CSF AA (Oslo, P = .21; Edinburgh, P = .93) when participants were subdivided into prevalent, incident, subsyndromal, and never delirium. Stratifying participants according to prefracture cognitive status (IQCODE) gave the same results. This is the first study of AA in CSF of individuals with and without delirium. The study does not support the hypothesis that central (CSF) or peripheral (serum) AA is an important mechanism of delirium in individuals with hip fracture.

Delirium Superimposed on Dementia: Accuracy of Nurse Documentation

Delirium is an acute, fluctuating confusional state that results in poor outcomes for older adults. Dementia causes a more convoluted course when coexisting with delirium. This study examined 128 days of documentation to describe what nurses document when caring for patients with dementia who experience delirium. Nurses did not document that they recognized delirium. Common descriptive terms included words and phrases indicating fluctuating mental status, lethargy, confusion, negative behavior, delusions, and restlessness. Delirium is a medical emergency. Nurses are in need of education coupled with clinical and decisional support to facilitate recognition and treatment of underlying causes of delirium in individuals with dementia.

Delirium in Early-Stage Alzheimer's Disease: Enhancing Cognitive Reserve as a Possible Preventive Measure

Delirium is a disorder of acute onset with fluctuating symptoms and is character ized by inattention, disorganized thinking and altered levels of consciousness. The risk for delirium is greatest in individual with dementia, and the incidence of both is increasing worldwide because of the aging of our population. Although s clinical trials have tested interventions f delirium prevention in individuals without dementia, little is known about the m anisms for the prevention of delirium i early-stage Alzheimer's disease (AD). Th purpose of this article is to explore ways o preventing delirium and slowing the ra of cognitive decline in early-stage AD enhancing cognitive reserve. An agenda for future research on interventions to prevent delirium in individuals with early-stage AD is also presented.