Delirium and frailty in older adults: Clinical overlap and biological underpinnings

Journal of Internal Medicine, Journal Year: 2024, Volume and Issue: 296(5), P. 382 - 398

Published: Oct. 1, 2024

Frailty and delirium are two common geriatric syndromes sharing several clinical characteristics, risk factors, negative outcomes. Understanding their interdependency is crucial to identify shared mechanisms implement initiatives reduce the associated burden. This literature review summarizes scientific evidence on complex interplay between frailty delirium; clinical, epidemiological, pathophysiological commonalities; current knowledge gaps. We conducted a PubMed systematic search in June 2023, which yielded 118 eligible articles out of 991. The synthesis results-carried by content experts-highlights overlapping phenotypes, outcomes explores influence one syndrome onset other. Common identified include inflammation, neurodegeneration, metabolic insufficiency, vascular suggests that factor for delirium, with some support accelerated frailty. proposed unifying framework supports integration measurement both constructs research practice, identifying geroscience approach as potential avenue develop strategies conditions. In conclusion, we suggest might be alternative-sometimes coexisting-manifestations biological aging. Clinically, concepts addressed this can help older adults either or from different perspective. From standpoint, longitudinal studies needed explore hypothesis specific pathways within biology aging may underlie manifestations delirium. Such will pave way future understanding other well.

Language: Английский

---

Mechanisms of perioperative neuronal injury and the search for therapies

British Journal of Anaesthesia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

---

Intranasal Insulin Diminishes Postoperative Delirium and Elevated Osteocalcin and Brain Derived Neurotrophic Factor in Older Patients Undergoing Joint Replacement: A Randomized, Double-Blind, Placebo-Controlled Trial

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 759 - 769

Published: Feb. 1, 2025

Background: Brain energy metabolism disorders, including glucose utilization disorders and abnormal insulin sensitivity, are linked to the pathogenesis of postoperative delirium. Intranasal has shown significant benefits in improving metabolism, sensitivity cognitive function. However, its impact on delirium biomarkers remains unknown. Aim: This randomized, double-blind, placebo-controlled trial was evaluate whether intranasal reduces incidence severity (POD) older patients undergoing joint replacement, effect sensitivity-related biomarkers. Methods: 212 (≥ 65 years) were randomly assigned receive either 40 IU (n=106) or a placebo for 8 days. The primary objective determine POD within 5 days after surgery, estimated using Confusion Assessment Method (CAM) Delirium Rating Scale (DRS)-98. secondary which assessed homeostasis model Insulin Resistance (HOMA-IR) biomarkers, total osteocalcin (tOC), uncarboxylated (ucOC), brain-derived neurotrophic factor (BDNF). Main Results: Compared placebo, significantly reduced surgery (8 [8.33%] vs 23 [23.23%], P = 0.004, odds ratio [OR] 3.33 [95% CI 1.41– 7.88]) (P< 0.001). elevated levels tOC, ucOC, BDNF CSF D 0 (all P< 0.001) tOC plasma , 1 3 It ucOC group but not administration HOMA-IR (P=0.002). Conclusion: notably may be related elevation levels. Trial Registry Numbers: Chinese Clinical (ChiCTR2300068073). Keywords: insulin, osteocalcin, delirium, brain derived factor, patient

Language: Английский

---

Clinical biomarkers of perioperative neurocognitive disorder: initiation and recommendation

Science China Life Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Language: Английский

---

Effect of combination of multiple anti-inflammatory drugs strategy on postoperative delirium among older patients undergoing hip fracture surgery: a pilot randomized controlled trial

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 21, 2025

Abstract Background Postoperative delirium is the most common complication in older patients and associated with surgery-induced inflammation. Although inflammation plays a key role delirium, potential benefits of comprehensive anti-inflammatory approach to managing perioperative systemic remain underexplored. This study evaluated whether bundle strategy, combining dexmedetomidine, glucocorticoids, ulinastatin, nonsteroidal drugs, reduces risk postoperative undergoing hip fracture surgery. Methods dual-center, double-blind, placebo-controlled, parallel-group, pilot was conducted from August 2023 January 2024 at two tertiary university hospitals. A total 132 aged ≥ 65 years an American Society Anesthesiologists physical status 2 or 3 scheduled for elective surgery were screened randomized receive either drug placebo. The primary outcome identified within first three days. blood inflammatory markers acute pain measured mediation analysis. Results Of randomized, 123 (93%) completed trial (mean age, 82 years; 75% women). prevalence significantly lower group (15%, 9/62) compared placebo (44%, 27/61) (risk difference, − 30 percentage points [95% CI, 45 15]; relative [RR], 0.33 0.17 0.64]; P = 0.001). No major adverse events reported group. CRP level (predicted mean difference: 29.4 CI: 46.5, 12.2] mg·L −1 ; adjusted < Mediation analysis showed significant indirect association between through reduced (odds ratio [OR], 0.61 0.26 0.87]). Conclusions demonstrates that surgery, without side effects. Systemic mediates protective effect intervention. These findings provide preliminary evidence supporting paving way large-scale multicenter trials optimize prevention strategies. Trial registration registered Chinese Clinical Registry (ChiCTR2300074303) by Ayixia Nawan on 3, 2023, prior patient enrollment.

Language: Английский

---

Lipid Dysregulation and Delirium in Older Adults: A Review of the Current Evidence and Future Directions

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 224, P. 111299 - 111299

Published: March 12, 2025

Delirium is a complex medical condition marked by acute episodes of cognitive dysfunction and behavioral disturbances, with multifaceted etiology challenging management across various clinical settings. Older adults, particularly in postoperative contexts, are at increased risk developing delirium. Despite extensive research, single underlying pathophysiological mechanism for delirium remains elusive. However, emerging evidence suggests correlation between lipid dysregulation development elderly patients, especially This connection has led to proposed treatments targeting dyslipidemia associated neuroinflammatory effects acute-phase review aims synthesize current literature on the relationship older highlighting need further research into specific neurolipidome constituents age-related profile changes, potentially uncovering novel therapeutic strategies

Language: Английский

---

Delirium in the ICU: Pathophysiology, Diagnosis and Management

Published: Jan. 1, 2025

Language: Английский

---

Association between preoperative persistent hyperglycemia and postoperative delirium in geriatric hip fracture patients

BMC Geriatrics, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 8, 2024

Abstract Background The management of preoperative blood glucose levels in reducing the incidence postoperative delirium (POD) remains controversial. This study aims to investigate impact persistent hyperglycemia on POD geriatric patients with hip fractures. Methods retrospective cohort analyzed medical records who underwent fracture surgery at a tertiary institution between January 2013 and November 2023. Patients were categorized based (hyperglycemia defined as ≥ 6.1mmol/L), clinical classification hyperglycemia, percentile thresholds. Multivariate logistic regression propensity score matching analysis (PSM) employed assess association different POD. Subgroup was conducted explore potential interactions. Results A total 1440 included this study, an rate 19.1% (275/1440). Utilizing multiple analysis, we found that had 1.65-fold increased risk experiencing compared those normal (95% CI: 1.17–2.32). Moreover, significant upward trend discerned both strength predicted probability higher levels. PSM did not alter trend, even after meticulous adjustments for confounding factors. Additionally, when treating continuous variable, observed 6% increase 1-12%) each 1mmol/L elevation Conclusions There exists clear linear dose-response relationship Higher associated greater Clinical trial number NCT06473324.

Language: Английский

---

Persistent delirium is associated with cerebrospinal fluid markers of neuronal injury

Brain Communications, Journal Year: 2024, Volume and Issue: 6(5)

Published: Jan. 1, 2024

Abstract Delirium is associated with the risk of future long-term cognitive impairment, but degree to which markers neuronal injury may be distinct or shared dementia has yet comprehensively described. We investigated CSF biomarkers dementia, astrocytosis and damage in a clinical cohort persistent delirium, comparing them an outpatient memory clinic sample. Our aim was determine if different patterns biomarker changes could implicate specific mechanisms for delirium-related over above that attributable comorbid dementia. recruited 35 participants from Prince Wales Hospital, Sydney, Australia. included inpatients delirium persisting at least 5 days (n = 15, 10 underlying dementia) clinics 20, 17 dementia). assays were as follows: amyloid-β42, amyloid-β40, phosphorylated tau181, neurofilament light chain glial fibrillary acidic protein. used propensity score matching estimate effect sizes each standardized separately (irrespective superimposed delirium). Compared individuals without elevated protein (normalized coefficient per transformed standard deviation, β 0.85; 95% confidence interval: 0.03–1.68) (β 1.1; 0.5–1.6), not tau181. protein, tau181 all increased expected levels cases, former two comparable those seen [glial 1.54; 1.05–2.0) 0.65; 0.24–1.1)]. Persistent linked necessarily These findings support potential direct independent pathophysiology. Whether this involves astrocyte dysfunction axonal are both possibilities. Future work examining acute brain needed.

Language: Английский

---

Role of glia in delirium: proposed mechanisms and translational implications

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 27, 2024

Abstract Delirium is a common acute onset neurological syndrome characterised by transient fluctuations in cognition. It affects over 20% of medical inpatients and 50% those critically ill. associated with morbidity mortality, causes distress to patients carers, has significant socioeconomic costs ageing populations. Despite its clinical significance, the pathophysiology delirium understudied, many underlying cellular mechanisms remain unknown. There are currently no effective pharmacological treatments which directly target disease processes. Although studies focus on neuronal dysfunction delirium, glial cells, primarily astrocytes, microglia, oligodendrocytes, their systems, increasingly implicated pathophysiology. In this review, we discuss current evidence implicates cells including biomarker studies, post-mortem tissue analyses pre-clinical models. particular, how astrocyte pathology, aberrant brain energy metabolism glymphatic dysfunction, reactive blood-brain barrier impairment, white matter changes may contribute pathogenesis delirium. We also outline limitations body work unique challenges faced identifying causative Finally, established neuroimaging single-cell techniques provide further mechanistic insight at levels.

Language: Английский

---