Introduction Delirium is associated with future dementia progression. Yet whether this occurs subclinically over months and years, or persistent delirium merges into worsened dementia is not understood. Our objective was to estimate the prevalence of persistent delirium and understand variation in its duration. Methods We adopted an identical search strategy to a previous systematic review, only including studies using a recognised diagnostic framework for ascertaining delirium at follow-up (persistent delirium). Studies included hospitalised older patients outside critical and palliative care settings. We searched MEDLINE, EMBASE, PsycINFO and the Cochrane Database of Systematic Reviews on 11th January 2022. We applied risk of bias assessments based on Standards of Reporting of Neurological Disorders criteria and assessed strength of recommendations using the grading of recommendation, assessment, development and evaluation (GRADE) approach. Estimates were pooled across studies using random-effects meta-analysis, and we estimated associations with follow-up duration using robust error meta-regression. Results We identified 13 new cohorts, which we added to 10 from the previous systematic review (23 relevant studies, with 39 reports of persistent delirium at 7 time-points in 3186 individuals admitted to hospital care (mean age 82 years and 41% dementia prevalence). Studies were mainly at moderate risk of bias. Pooled delirium prevalence estimates at discharge were 36% (95% CI 22% to 51%, 13 studies). Robust error meta-regression did not show variation in prevalence of persistent delirium over time (-1.6% per month, 95% CI -4.8 to 1.6, p=0.08). Margins estimates for this model indicate a prevalence of persistent delirium of 16% (95% CI 6% to 25%) at 12 months. Conclusions This systematic review emphasises the importance of delirium as a persistent and extensive problem (GRADE certainty = moderate), raising questions on chronic delirium as a clinical entity and how it might evolve into dementia. Addressing persistent delirium will require a whole-system, integrated approach to detect, follow-up and implement opportunities for recovery across all healthcare settings.

SummaryThe anaesthetic and analgesic properties ojalcohol haw been known for sereral thousand years, but thrrr is little eridence that surgeons were employing it .fseqirently jor these purposes in the days before the discowry ojreliable inhalation anaesthesia. Its main use was as a stimulant for resuscitation. Attempts to introduce its use into anaesthetic practice in this century hare not been successful.

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Background: Delirium is a common post-operative complication, particularly in older adults undergoing major or emergency procedures. It is associated with increased length of intensive care and hospital stay, post-operative mortality and subsequent dementia risk. Current methods of predicting delirium incidence, duration and severity have limitations. Investigation of blood and cerebrospinal fluid (CSF) biomarkers linked to delirium may improve understanding of the underlying pathophysiology, particularly with regard to the extent this is shared or distinct with underlying dementia. Together, these have the potential for development of better risk stratification tools and perioperative interventions. Methods: 200 patients over the age of 70 scheduled for surgery with routine spinal anaesthetic will be recruited from UK hospitals. Their cognitive and functional baseline status will be assessed pre-operatively by telephone. Time-matched CSF and blood samples will be taken at the time of surgery and analysed for known biomarkers of neurodegeneration and neuroinflammation. Patients will be assessed daily for delirium until hospital discharge and will have regular cognitive follow-up for two years. Primary outcomes will be change in modified Telephone Interview for Cognitive Status (TICS-m) score at 12 months and rate of change of TICS-m score. Delirium severity, duration and biomarker levels will be treated as exposures in a random effects linear regression models. PRIMED Risk has received regulatory approvals from Health Research Authority and London – South East Research Ethics Committee. Discussion: The main anticipated output from this study will be the quantification of biomarkers of acute and chronic contributors to cognitive impairment after surgery. In addition, we aim to develop better risk prediction models for adverse cognitive outcomes.