Infection, delirium, and risk of dementia in patients with and without white matter disease on previous brain imaging: a population-based study.

BACKGROUND: The increased risk of dementia after delirium and infection might be influenced by cerebral white matter disease (WMD). In patients with transient ischaemic attack (TIA) and minor stroke, we assessed associations between hospital admissions with delirium and 5-year dementia risk and between admissions with infection and dementia risk, stratified by WMD severity (moderate or severe vs absent or mild) on baseline brain imaging. METHODS: We included patients with TIA and minor stroke (National Institutes of Health Stroke Score <3) from the Oxford Vascular Study (OXVASC), a longitudinal population-based study of the incidence and outcomes of acute vascular events in a population of 94 567 individuals, with no age restrictions, attending eight general practices in Oxfordshire, UK. Hospitalisation data were obtained through linkage to the Oxford Cognitive Comorbidity, Frailty, and Ageing Research Database-Electronic Patient Records (ORCHARD-EPR). Brain imaging was done using CT and MRI, and WMD was prospectively graded according to the age-related white matter changes (ARWMC) scale and categorised into absent, mild, moderate, or severe WMD. Delirium and infection were defined by ICD-10 coding supplemented by hand-searching of hospital records. Dementia was diagnosed using clinical or cognitive assessment, medical records, and death certificates. Associations between hospitalisation with delirium and hospitalisation with infection, and post-event dementia were assessed using time-varying Cox analysis with multivariable adjustment, and all models were stratified by WMD severity. FINDINGS: From April 1, 2002, to March 31, 2012, 1369 individuals were prospectively recruited into the study. Of 1369 patients (655 with TIA and 714 with minor stroke, mean age 72 [SD 13] years, 674 female and 695 male, and 364 with moderate or severe WMD), 209 (15%) developed dementia. Hospitalisation during follow-up occurred in 891 (65%) patients of whom 103 (12%) had at least one delirium episode and 236 (26%) had at least one infection episode. Hospitalisation without delirium or infection did not predict subsequent dementia (HR 1·01, 95% CI 0·86-1·20). In contrast, hospitalisation with delirium predicted subsequent dementia independently of infection in patients with and without WMD (2·64, 1·47-4·74; p=0·0013 vs 3·41, 1·91-6·09; p<0·0001) especially in those with unimpaired baseline cognition (cognitive test score above cutoff; 4·01, 2·23-7·19 vs 3·94, 1·95-7·93; both p≤0·0001). However, hospitalisation with infection only predicted dementia in those with moderate or severe WMD (1·75, 1·04-2·94 vs 0·68, 0·39-1·20; pdiff=0·023). INTERPRETATION: The increased risk of dementia after delirium is unrelated to the presence of WMD, whereas infection increases risk only in patients with WMD, suggesting differences in underlying mechanisms and in potential preventive strategies. FUNDING: National Institute for Health and Care Research and Wellcome Trust.

Delirium, confusion, or altered mental status as a risk for abnormal head CT in older adults in the emergency department: A systematic review and meta-analysis.

BACKGROUND: Altered mental status (including delirium) is a common presentations among older adults to the emergency department (ED). We aimed to report the association between altered mental status in older ED patients and acute abnormal findings on head computed tomogram (CT). METHODS: A systematic review was conducted using Ovid Medline, Embase, Clinicaltrials.gov, Web of Science, and Cochrane Central from conception to April 8th, 2021. We included citations if they described patients aged 65 years or older who received head imaging at the time of ED assessment, and reported whether patients had delirium, confusion, or altered mental status. Screening, data extraction, and bias assessment were performed in duplicate. We estimated the odds ratios (OR) for abnormal neuroimaging in patients with altered mental status. RESULTS: The search strategy identified 3031 unique citations, of which two studies reporting on 909 patients with delirium, confusion or altered mental status were included. No identified study formally assessed for delirium. The OR for abnormal head CT findings in patients with delirium, confusion or altered mental status was 0.35 (95% CI 0.031 to 3.97) compared to patients without delirium, confusion or altered mental status. CONCLUSION: We did not find a statistically significant association between delirium, confusion or altered mental status and abnormal head CT findings in older ED patients.

Diagnostic yield of CT head in delirium and altered mental status-A systematic review and meta-analysis.

BACKGROUND: CT head is commonly performed in the setting of delirium and altered mental status (AMS), with variable yield. We aimed to evaluate the yield of CT head in hospitalized patients with delirium and/or AMS across a variety of clinical settings and identify factors associated with abnormal imaging. METHODS: We included studies in adult hospitalized patients, admitted to the emergency department (ED) and inpatient medical unit (grouped together) or the intensive care unit (ICU). Patients had a diagnosis of delirium/AMS and underwent a CT head that was classified as abnormal or not. We searched Medline, Embase and other databases (informed by PRISMA guidelines) from inception until November 11, 2021. Studies that were exclusively performed in patients with trauma or a fall were excluded. A meta-analysis of proportions was performed; the pooled proportion of abnormal CTs was estimated using a random effects model. Heterogeneity was determined via the I2 statistic. Factors associated with an abnormal CT head were summarized qualitatively. RESULTS: Forty-six studies were included for analysis. The overall yield of CT head in the inpatient/ED was 13% (95% CI: 10.2%-15.9%) and in ICU was 17.4% (95% CI: 10%-26.3%), with considerable heterogeneity (I2 96% and 98% respectively). Heterogeneity was partly explained after accounting for study region, publication year, and representativeness of the target population. Yield of CT head diminished after year 2000 (19.8% vs. 11.1%) and varied widely depending on geographical region (8.4%-25.9%). The presence of focal neurological deficits was a consistent factor that increased yield. CONCLUSION: Use of CT head to diagnose the etiology of delirium and AMS varied widely and yield has declined. Guidelines and clinical decision support tools could increase the appropriate use of CT head in the diagnostic etiology of delirium/AMS.

Head computed tomography findings in geriatric emergency department patients with delirium, altered mental status, and confusion: A systematic review.

BACKGROUND: Delirium, altered mental status (AMS), or confusion among older adults are common presentations to the emergency department (ED). We aimed to report the proportion of older ED patients presenting with delirium who have acute abnormal findings on head imaging. We also assessed whether anticoagulation, neurological deficits, trauma, or headache were associated with head imaging abnormalities in these patients. METHODS: A systematic review was performed using Ovid Medline, Embase, Clinicaltrials.gov, Web of Science, and Cochrane Central from conception to April 8, 2021. Citations were included if they described patients aged 65 years or older who received neuroimaging at the time of ED assessment for delirium, confusion, or AMS. Screening, data extraction, and bias assessment were performed in duplicate. The estimated proportion of patients with abnormal neuroimaging and odds ratios (ORs) for each predictor were calculated. RESULTS: The search strategy identified 3014 unique citations, of which six studies reporting on 909 patients with confusion or AMS were included. None of the studies formally diagnosed delirium. Overall, the proportions of older ED patients with AMS or confusion were found to have an abnormal head computed tomography (CT) was 15.6% (95% confidence interval [CI] 7.3%-26.2%). The prevalence of focal neurologic findings was 13.0% (66/506) and for anticoagulation was 9.8% (33/337) among the studies who reported them. The presence of a focal neurological deficit was associated with abnormal head CT (OR 101.8, 95% CI 30.5-340.1). Anticoagulation was not associated with abnormal head CT (OR 1.2, 95% CI 0.4-3.3). No studies reported on the association between headache or trauma and abnormal neuroimaging. CONCLUSIONS: The proportion of abnormal findings on CT neuroimaging in older ED patients with AMS or confusion was 15.6%. The presence of a focal neurological deficit was a strong predictor for the presence of acute abnormality, whereas anticoagulation was not.

Utility of head computed tomography for older adults with suspected delirium in the emergency department: A retrospective observational study.

BACKGROUND: Delirium in older people is associated with significant morbidity and mortality and has life-threatening etiologies making prompt recognition essential. Computed tomography of the head (CT-head) may have a role in determining the cause of delirium; however, inpatient studies suggest it is overused. There is a paucity of emergency department (ED)-based research surrounding the use of CT-head in delirium. This study aims to describe the utility of CT-head in older patients presenting to the ED with symptoms of delirium. METHODS: We conducted a retrospective chart review of patients 65 years and older with symptoms of delirium who visited local EDs over a 3.5-year period (2016-2020). We compared patients who did and did not receive CT-head. Our primary objective was to determine the proportion of acute findings in patients who received CT-head. Our secondary objectives were to describe the proportions of patients who did and did not receive CT-head in terms of their demographics, presenting symptoms, disposition, and indications for and results of CT-head scans. Chi-square tests were utilized for comparisons. RESULTS: A total of 630 encounters were identified through database searching; 526 met inclusion criteria. Thirty-four were excluded for presenting directly to consultants, leaving 492 included encounters. Of those who received a CT-head (n = 279), 13 (4.7%) had acute findings. Of the encounters with acute findings, four (30.77%) had focal neurological deficits (FND), and two (15.38%) had Glasgow Coma Scale (GCS) score < 14. Patients without CT-head (n = 213) were more likely to be discharged (p < 0.01) and less likely to have a FND (p < 0.01). CONCLUSIONS: CT-head is ordered for over half of older ED patients with symptoms of delirium despite infrequent acute findings. Acute findings typically occur in the context of symptoms suggestive of intracranial abnormalities such as FND or GCS < 14. This suggests physicians should be more selective when ordering CT-heads in patients with symptoms of delirium.

Regional cerebral hypometabolism on 18F-FDG PET/CT scan in delirium is independent of acute illness and dementia.

INTRODUCTION: Delirium is associated with new onset dementia and accelerated cognitive decline; however, its pathophysiology remains unknown. Cerebral glucose metabolism previously seen in delirium may have been attributable to acute illness and/or dementia. We aimed to statistically map cerebral glucose metabolism attributable to delirium. METHODS: We assessed cerebral glucose metabolism using 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) in sick, older patients with and without delirium, all without clinical dementia (N = 20). Strict exclusion criteria were adopted to minimize the effect of established confounders on FDG-PET. RESULTS: Patients with delirium demonstrated hypometabolism in the bilateral thalami and right superior frontal, right posterior cingulate, right infero-lateral anterior temporal, and left superior parietal cortices. Regional hypometabolism correlated with delirium severity and performance on neuropsychological testing. DISCUSSION: In patients with acute illness but without clinical dementia, delirium is accompanied by regional cerebral hypometabolism. While some hypometabolic regions may represent preclinical Alzheimer's disease (AD), thalamic hypometabolism is atypical of AD and consistent with the clinical features that are unique to delirium.

Prediction of the development of delirium after transcatheter aortic valve implantation using preoperative brain perfusion SPECT.

OBJECTIVES: Delirium is an important prognostic factor in postoperative patients undergoing cardiovascular surgery and intervention, including transcatheter aortic valve implantation (TAVI). However, delirium after transcatheter aortic valve implantation (DAT) is difficult to predict and its pathophysiology is still unclear. We aimed to investigate whether preoperative cerebral blood flow (CBF) is associated with DAT and, if so, whether CBF measurement is useful for predicting DAT. METHODS: We evaluated CBF in 50 consecutive patients before TAVI (84.7±4.5 yrs., 36 females) using 99mTc ethyl cysteinate dimer single-photon emission computed tomography. Preoperative CBF of the DAT group (N = 12) was compared with that of the non-DAT group (N = 38) using whole brain voxel-wise analysis with SPM12 and region of interest-based analysis with the easy-Z score imaging system. Multivariable logistic regression analysis with the presence of DAT was used to create its prediction model. RESULTS: The whole brain analysis showed that preoperative CBF in the insula was lower in the DAT than in the non-DAT group (P<0.05, family-wise error correction). Decrease extent ratio in the insula of the DAT group (17.6±11.5%) was also greater relative to that of the non-DAT group (7.0±11.3%) in the region of interest-based analysis (P = 0.007). A model that included preoperative CBF in the insula and conventional indicators (frailty index, short physical performance battery and mini-mental state examination) showed the best predictive power for DAT (AUC 0.882). CONCLUSIONS: These results suggest that preoperative CBF in the insula is associated with DAT and may be useful for its prediction.

[Investigation of intracranial pressure in intensive care unit patients with delirium assessed by bedside ultrasound].

OBJECTIVE: To explore the changes of intracranial pressure in intensive care unit (ICU) patients during the occurrence and evolution of delirium by using bedside ultrasound to measure the optic nerve sheath diameter (ONSD) to evaluate intracranial pressure. METHODS: A retrospective observational study was conducted. Adult patients who developed delirium during hospitalization in the general ICU of Beihai People's Hospital from October 2020 to November 2021 were enrolled, and patients who did not have ultrasonographic ONSD records within 24 hours after the diagnosis of delirium were excluded. The ONSD measured before delirium was recorded as ONSD0, the ONSD measured within 24 hours of the onset of delirium recorded as ONSD1, and the ONSD reexamined after ONSD1 recorded as ONSD2. Patients were divided into intracranial hypertension group (ONSD1 > 5 mm) and normal intracranial pressure group (ONSD1 ≤ 5 mm) according to the size of ONSD1. According to the outcome of delirium, the patients were divided into cured, improved, and non-improved groups. The reduction ratio of ONSD2 to ONSD1 in the three groups were calculated and compared. Pearson correlation test was used to analyze the correlation between fluid balance and ONSD changes after delirium. RESULTS: There were 43 patients, including 40 cases in the intracranial hypertension group (the incidence rate was 93.0%), 3 cases in the normal intracranial pressure group, 23 cases were cured, 13 cases were improved, and 7 cases were not improved. In the intracranial hypertension group, 11 cases had ONSD0 and ONSD1 records, and ONSD1 was significantly higher than ONSD0 [mm: 5.88±0.61 vs. 5.34±0.57, 95% confidence interval (95%CI) -0.85 to -0.23, P = 0.003]. The reduction ratio of ONSD2 to ONSD1 in the cured group was significantly higher than that in the improved group and the non-improved group [(12.04±6.20)% vs. (5.68±4.10)%, (0.17±3.96)%; 95%CI were 2.37 to 10.33, 6.41 to 17.31, P values were 0.003 and 0.000, respectively]. The correlation analysis showed that the reduction ratio of ONSD2 to ONSD1 was negatively correlated with fluid balance (r = -0.42, 95%CI was -0.66 to -0.10, P = 0.012). CONCLUSIONS: The incidence of intracranial hypertension in ICU delirium patients is high. A more pronounced decrease in intracranial pressure predicts a better delirium outcome. Dynamic ONSD measurement can provide valuable information for the prevention and treatment of delirium.

Assessment of potential selection bias in neuroimaging studies of postoperative delirium and cognitive decline: lessons from the SAGES study.

Due to cost and participant burden, neuroimaging studies are often performed in relatively small samples of voluntary participants. This may lead to selection bias. It is important to identify factors associated with participation in neuroimaging studies and understand their effect on outcome measures. We investigated the effect of postoperative delirium on long-term (over 48 months) cognitive decline (LTCD) in 560 older surgical patients (≥ 70 years), including a nested MRI cohort (n = 146). We observed a discrepancy in the effect of delirium on cognitive decline as a function of MRI participation. Although overall difference in cognitive decline due to delirium was not greater than what might be expected due to chance (p = .21), in the non-MRI group delirium was associated with a faster pace of LTCD (-0.063, 95% CI -0.094 to -0.032, p < .001); while in the MRI group the effect of delirium was less and not significant (-0.023, 95% CI -0.076, 0.030, p = .39). Since this limits our ability to investigate the neural correlates of delirium and cognitive decline using MRI data, we attempted to mitigate the observed discrepancy using inverse probability weighting for MRI participation. The approach was not successful and the difference of the effect of delirium in slope was essentially unchanged. There was no evidence that the MRI sub-group experienced delirium that differed in severity relative to MRI non-participants. We could not attribute the observed discrepancy to selection bias based on measured factors. It may reflect a power issue due to the smaller MRI subsample or selection bias from unmeasured factors.

A Novel Radiomics-Based Machine Learning Framework for Prediction of Acute Kidney Injury-Related Delirium in Patients Who Underwent Cardiovascular Surgery.

Acute kidney injury (AKI) can be caused by multiple etiologies and is characterized by a sudden and severe decrease in kidney function. Understanding the independent risk factors associated with the development of AKI and its early detection can refine the risk management and clinical decision-making of high-risk patients after cardiovascular surgery. A retrospective analysis was performed in a single teaching hospital between December 1, 2019, and December 31, 2020. The diagnostic performance of novel biomarkers was assessed using random forest, support vector machine, and multivariate logistic regression. The nomogram from multivariate analysis of risk factors associated with AKI indicated that only LVEF, red blood cell input, and ICUmvat contribute to AKI differentiation and that the difference is statistically significant (P < 0.05). Seven radiomics biomarkers were found among 65 patients to be highly correlated with AKI-associated delirium. The importance of the variables was determined using the multilayer perceptron model; fivefold cross-validation was applied to determine the most important delirium risk factors in radiomics of the hippocampus. Finally, we established a radiomics-based machine learning framework to predict AKI-induced delirium in patients who underwent cardiovascular surgery.

Brain Network Dysfunction in Poststroke Delirium and Spatial Neglect: An fMRI Study.

BACKGROUND AND PURPOSE: Delirium, an acute reduction in cognitive functioning, hinders stroke recovery and contributes to cognitive decline. Right-hemisphere stroke is linked with higher delirium incidence, likely, due to the prevalence of spatial neglect (SN), a right-brain disorder of spatial processing. This study tested if symptoms of delirium and SN after right-hemisphere stroke are associated with abnormal function of the right-dominant neural networks specialized for maintaining attention, orientation, and arousal. METHODS: Twenty-nine participants with right-hemisphere ischemic stroke undergoing acute rehabilitation completed delirium and SN assessments and functional neuroimaging scans. Whole-brain functional connectivity of 4 right-hemisphere seed regions in the cortical-subcortical arousal and attention networks was assessed for its relationship to validated SN and delirium severity measures. RESULTS: Of 29 patients, 6 (21%) met the diagnostic criteria for delirium and 16 (55%) for SN. Decreased connectivity of the right basal forebrain to brain stem and basal ganglia predicted more severe SN. Increased connectivity of the arousal and attention network regions with the parietal, frontal, and temporal structures in the unaffected hemisphere was also found in more severe delirium and SN. CONCLUSIONS: Delirium and SN are associated with decreased arousal network activity and an imbalance of cortico-subcortical hemispheric connectivity. Better understanding of neural correlates of poststroke delirium and SN will lead to improved neuroscience-based treatment development for these disorders. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03349411.

The Use of Near-Infrared Spectroscopy and/or Transcranial Doppler as Non-Invasive Markers of Cerebral Perfusion in Adult Sepsis Patients With Delirium: A Systematic Review.

BACKGROUND: Several studies have previously reported the presence of altered cerebral perfusion during sepsis. However, the role of non-invasive neuromonitoring, and the impact of altered cerebral perfusion, in sepsis patients with delirium remains unclear. METHODS: We performed a systematic review of studies that used near-infrared spectroscopy (NIRS) and/or transcranial Doppler (TCD) to assess adults (≥18 years) with sepsis and delirium. From study inception to July 28, 2020, we searched the following databases: Ovid MedLine, Embase, Cochrane Library, and Web of Science. RESULTS: Of 1546 articles identified, 10 met our inclusion criteria. Although NIRS-derived regional cerebral oxygenation was consistently lower, this difference was only statistically significant in one study. TCD-derived cerebral blood flow velocity was inconsistent across studies. Importantly, both impaired cerebral autoregulation during sepsis and increased cerebrovascular resistance were associated with delirium during sepsis. However, the heterogeneity in NIRS and TCD devices, duration of recording (from 10 seconds to 72 hours), and delirium assessment methods (e.g., electronic medical records, confusion assessment method for the intensive care unit), precluded meta-analysis. CONCLUSION: The available literature demonstrates that cerebral perfusion disturbances may be associated with delirium in sepsis. However, future investigations will require consistent definitions of delirium, delirium assessment training, harmonized NIRS and TCD assessments (e.g., consistent measurement site and length of recording), as well as the quantification of secondary and tertiary variables (i.e., Cox, Mxa, MAPOPT), in order to fully assess the relationship between cerebral perfusion and delirium in patients with sepsis.

Utility of white matter disease and atrophy on routinely acquired brain imaging for prediction of long-term delirium risk: population-based cohort study.

BACKGROUND: brain imaging done as part of standard care may have clinical utility beyond its immediate indication. Using delirium as an exemplar, we determined the predictive value of baseline brain imaging variables [white matter changes (WMC) and atrophy] for delirium risk on long-term follow-up after transient ischemic attack (TIA)/stroke in a population-based cohort study. METHODS: surviving TIA/stroke participants in the Oxford Vascular Study (OXVASC) were assessed prospectively for delirium during all hospitalisations over 6 months (2013-14). Using logistic regression, independent associations were determined between baseline OXVASC computed tomography or magnetic resonance brain imaging measures of WMC and cerebral atrophy (none/mild versus moderate/severe) and delirium adjusted for age, sex, baseline stroke severity, depression, illness severity and pre-admission cognition. RESULTS: among 1,565 TIA/stroke survivors with 194 hospital admissions (158 patients, mean/standard deviation age at admission = 79.2/11.5 years), delirium occurred in 59 (37%). WMC and atrophy on baseline imaging were associated with delirium [odds ratio (OR) = 3.41, 1.21-5.85, P = 0.001 and OR = 2.50, 1.23-5.08, P = 0.01 (unadjusted) and OR = 2.67, 1.21-5.85, P = 0.02 and OR = 2.18, 1.00-4.73, P = 0.05 (adjusted age and sex)]. Associations were strengthened when analyses were restricted to patients hospitalised within 5 years of baseline brain imaging [OR = 6.04, 2.39-15.24, P < 0.0001 and OR = 4.64, 1.46-14.82, P = 0.009 (unadjusted)] but only WMC remained significant after adjustment for all covariates including pre-admission cognition (OR = 4.83, 1.29-18.13, P = 0.02 for Mini-Mental State Examination and OR = 5.15, 1.26-21.09, P = 0.02 for Montreal Cognitive Assessment). CONCLUSIONS: WMC and atrophy on brain imaging done up to 5 years earlier predicted delirium and may have clinical utility in risk stratification. Associations with WMC but not atrophy were independent of pre-admission cognitive impairment.

Acute confusional state as a prognostic sign of COVID-19 large-vessel occlusion (LVO).

COVID-19 is well known for its respiratory symptoms, but severe presentations can alter haemostasis, causing acute end-organ damage with poor outcomes. Among its various neurological presentations, cerebrovascular events often present as small-vessel strokes. Although uncommon, in predisposed individuals, large-vessel occlusions (LVOs) can occur as a possible consequence of direct viral action (viral burden or antigenic structure) or virus-induced cytokine storm. Subtle presentations and complicated stroke care pathways continue to exist, delaying timely care. We present a unique case of COVID-19 LVO manifesting as an acute confusional state in an elderly man in April 2020. CT angiography revealed 'de novo' occlusions of the left internal carotid artery and proximal right vertebral artery, effectively blocking anterior and posterior circulations. Delirium can lead to inaccurate stroke scale assessments and prolong initiation of COVID-19 stroke care pathways. Future studies are needed to look into the temporal relationship between confusion and neurological manifestations.

Clinical utility of brain computed tomography in prediction of post-stroke delirium.

Delirium is a common and serious complication of stroke. Early prediction of delirium is important for preventive strategies and close monitoring of high-risk patients. Pre-existing degenerative and vascular changes in the brain could predispose to delirium. We aimed to determine if computed tomography (CT)-based indices could provide additional information about a risk of stroke-associated delirium beyond easiest-to-access clinical predictors. Using semi-quantitative scales (global cortical atrophy, age-related white matter changes, and Scheltens scale), we assessed global and regional brain atrophy and white matter changes in 88 stroke patients with delirium and 142 patients without delirium matched for age and stroke severity. Patients with delirium had greater global and local brain atrophy (the right temporal region, the left parieto-occipital region, the right frontal and occipital horn, and the right and left temporal horn) than patients without delirium. Scores of white matter changes did not differ between groups with exception of greater white matter damage in the right parieto-occipital area in patients with delirium. The discriminatory properties of studied radiological indices were modest (areas under receiver operator curves: 0.58-0.64). CT-based indices of brain atrophy and white matter changes do not provide additional information about a risk of post-stroke delirium beyond the most important clinical predictors.

Brain FDG PET for the Etiological Diagnosis of Clinically Uncertain Cognitive Impairment During Delirium in Remission.

BACKGROUND: Positron emission tomography (PET) of the brain with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) is widely used for the etiological diagnosis of clinically uncertain cognitive impairment (CUCI). Acute full-blown delirium can cause reversible alterations of FDG uptake that mimic neurodegenerative disease. OBJECTIVE: This study tested whether delirium in remission affects the performance of FDG PET for differentiation between neurodegenerative and non-neurodegenerative etiology of CUCI. METHODS: The study included 88 patients (82.0±5.7 y) with newly detected CUCI during hospitalization in a geriatric unit. Twenty-seven (31%) of the patients were diagnosed with delirium during their current hospital stay, which, however, at time of enrollment was in remission so that delirium was not considered the primary cause of the CUCI. Cases were categorized as neurodegenerative or non-neurodegenerative etiology based on visual inspection of FDG PET. The diagnosis at clinical follow-up after ≥12 months served as ground truth to evaluate the diagnostic performance of FDG PET. RESULTS: FDG PET was categorized as neurodegenerative in 51 (58%) of the patients. Follow-up after 16±3 months was obtained in 68 (77%) of the patients. The clinical follow-up diagnosis confirmed the FDG PET-based categorization in 60 patients (88%, 4 false negative and 4 false positive cases with respect to detection of neurodegeneration). The fraction of correct PET-based categorization did not differ between patients with delirium in remission and patients without delirium (86% versus 89%, p = 0.666). CONCLUSION: Brain FDG PET is useful for the etiological diagnosis of CUCI in hospitalized geriatric patients, as well as in patients with delirium in remission.

Association of Renal Clearance with Cerebral White Matter Vascular Disease in Hospitalized Veterans With and Without Delirium.

OBJECTIVES: To assess the relation between renal function and delirium and to assess and compare the relation between cerebral white matter lesion (WML) and renal function as estimated by three formulas for the estimated glomerular filtration rate (eGFR) in older adult hospitalized veterans with and without delirium. METHODS: Commonly used formulas to assess renal function-the four-variable Modification of Diet in Renal Disease (MDRD), the six-variable MDRD, and the Cockcroft-Gault eGFR equations-were used to assess renal function in 100 older adult hospitalized veterans with delirium (delirium group) and 100 hospitalized veterans without delirium (nondelirium group) that were age, sex, and race matched. WML location and volumes were assessed using brain computed tomography imaging for each of the 200 veterans in the study. One radiologist, blinded to the diagnoses of the veterans, examined head computed tomography scans for WML in the cortex, subcortex (frontal, temporal, parietal, occipital lobes), basal ganglia (globus pallidus, caudate, putamen), and internal capsule. WML were graded as not present, <1 cm, 1 to 2 cm, or >2 cm. Exploratory χ2 analyses were used to determine the association between the stage of chronic kidney disease and WML. Simple logistic regression analyses were then used to estimate the strength of association between the stages of kidney disease and WML for particular regions of the brain. RESULTS: The mean age of delirium group and nondelirium group veterans was 66 years. χ2 tests revealed no reliable relation between stages of renal disease and delirium. χ2 exploratory analyses of WML in brain regions by renal disease stages demonstrated significant differences in associations among the MDRD-4, MDRD-6, and Cockcroft-Gault formulas for measuring eGFR. The MDRD-4 formula was least associated with the presence or absence of WML. The Cockcroft-Gault estimation of eGFR was most associated with the presence or absence of WML. Simple logistic regressions showed notable increases in the association between stages of renal failure and WMLs in specific areas of the brain, with the MDRD-4 being the least associative with the fewest specific areas and the Cockcroft-Gault formula being the most associative with the most specific areas. CONCLUSIONS: The association between stages 2 through 5 of chronic kidney disease and WLM support the role of kidney function as a potential risk factor for WML in older adult military veterans. The Cockcroft-Gault formula is an important renal index of suspected WML and renal stages 2 through 5, superior to the MDRD-6 and MDRD-4, respectively, in association with WML in older adult military veterans.

[Diffusion tensor imaging and resting-state functional magnetic resonance imaging in patients with delirium in intensive care unit].

OBJECTIVE: To analyze the brain function of patients with delirium in intensive care unit (ICU) using resting-state functional magnetic resonance imaging (fMRI), further analyze the structural changes in the brain using diffusion tensor imaging (DTI), and explore the correlations of brain function with structural changes in patients with delirium in ICU from a new perspective of functional imaging, provide visual evidence for the diagnosis of delirium. METHODS: Patients with delirium admitted to ICU of the Affiliated Hospital of Zunyi Medical University from January 1st to December 31st in 2017 were enrolled as subjects. During the same period, the healthy volunteers who matched the gender, age and education level of the patients with delirium were enrolled as control group. The intensive care delirium screening checklist (ICDSC) scores within 24 hours after ICU admission were recorded. All the subjects were scanned by fMRI and DTI. The abnormal changes in resting-state brain function of the patients with delirium were evaluated by cerebral regional homogeneity (ReHo) data analysis. The DTI data were processed by the FSL software, and the fractional anisotropy (FA) and mean diffusivity (MD) of the brain were extracted, respectively, to evaluate the damage to brain structure. The values of ReHo, FA and MD were compared between the two groups. The ReHo value of brain region with reduced ReHo value of patients with delirium as compared with the healthy volunteers was extracted for Pearson correlation analysis with ICDSC scores. RESULTS: A total of 22 patients with delirium were included. Seven patients who did not cooperate in the examination, used sedatives or had false images in scanning, were excluded. Finally, 15 patients were enrolled in the delirium group, and 15 healthy volunteers in the healthy control group. (1) No statistically significant difference was found in gender, age or education time between the two groups. ICDSC score of the delirium group was significantly higher than that of the healthy control group (6.07±1.28 vs. 1.07±0.88, P < 0.01). (2) fMRI scanning and analysis results: compared with the healthy control group, the ReHo values of the cerebellum, right hippocampus, striatum, midbrain and pons in the delirium group were significantly increased (all P < 0.05, AlphaSim correction), while the ReHo values of bilateral superior frontal gyrus, bilateral median frontal gyrus, left inferior frontal gyrus, temporal lobe and parietal lobe were significantly lowered (all P < 0.05, AlphaSim correction). Correlation analysis showed that the ReHo value of the left superior frontal gyrus was negatively correlated with ICDSC score in the patients with delirium (r = -0.794, P < 0.05), indicating that the changes in the functional area of the medial frontal gyrus was most closely related to delirium. (3) DTI scanning and analysis results: compared with the healthy control group, the FA values of the left cerebellum, bilateral frontal lobes, left temporal lobe, corpus callosum and left hippocampus in the delirium group were decreased significantly (all P < 0.05, AlphaSim correction), while the MD values of the medial frontal gyrus, right superior temporal gyrus, anterior cingulate gyrus, bilateral insular lobes and left caudate nucleus were enhanced significantly (all P < 0.05, AlphaSim correction), suggesting that the structural and functional damage was found in multiple brain regions in patients with delirium. CONCLUSIONS: Multiple brain regions of patients with delirium present abnormal resting-state brain function. The abnormal resting-state brain function of the left superior frontal gyrus is closely related to the occurrence of delirium. Structural damage is found in multiple brain regions of patients with delirium. The structural changes in the frontal lobe, temporal lobe, corpus callosum, hippocampus and cerebellum and their abnormal functions can be used as preliminary imaging indexes for the diagnosis of delirium.