Independent External Validation of a Preoperative Prediction Model for Delirium After Cardiac Surgery: A Prospective Observational Cohort Study

Objective: This investigation provided independent external validation of an existing preoperative risk prediction model. Design: A prospective observational cohort study of patients undergoing cardiac surgery covering the period between April 16, 2018 and January 18, 2022. Setting: Two academic hospitals in Switzerland. Participants: Adult patients (≥60 years of age) who underwent elective cardiac surgery, including coronary artery bypass graft, mitral or aortic valve replacement or repair, and combined procedures. Interventions: None. Measurements and main results: The primary outcome measure was the incidence of postoperative delirium (POD) in the intensive or intermediate care unit, diagnosed using the Intensive Care Delirium Screening Checklist. The prediction model contained 4 preoperative risk factors to which the following points were assigned: Mini-Mental State Examination (MMSE) score ≤23 received 2 points; MMSE 24-27, Geriatric Depression Scale (GDS) >4, prior stroke and/or transient ischemic attack (TIA), and abnormal serum albumin (≤3.5 or ≥4.5 g/dL) received 1 point each. The missing data were handled using multiple imputation. In total, 348 patients were included in the study. Sixty patients (17.4%) developed POD. For point levels in the prediction model of 0, 1, 2, and ≥3, the cumulative incidence of POD was 12.6%, 22.8%, 25.8%, and 35%, respectively. The validation resulted in a pooled area under the receiver operating characteristics curve of 0.60 (median CI, 0.525-0.679). Conclusions: The evaluated predictive model for delirium after cardiac surgery in this patient cohort showed only poor discriminative capacity but fair calibration. Keywords: External validation; cardiac surgery; delirium; predictio

Conversion between the Montreal Cognitive Assessment and the Mini-Mental Status Examination.

BACKGROUND Early and accurate detection of cognitive changes using simple tools is essential for an appropriate referral to a more detailed neurocognitive assessment and for the implementation of therapeutic strategies. The Mini-Mental Status Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are two commonly used psychometric tests for cognitive screening. Both tests have different strengths and weaknesses. Preferences regarding test selection may therefore differ among clinicians. The aim of this retrospective observational cohort study was to define corresponding scores for the MMSE and the MoCA. METHODS We examined the relationship between the cognitive screening tests in 803 German-speaking Memory Clinic outpatients, encompassing a wide range of neurocognitive disorders. We produced a conversion table using the equipercentile equating method with log-linear smoothing. In addition, we conducted a systematic review of existing MMSE-MoCA conversions to create a table allowing for the conversion of MoCA scores into MMSE scores and vice versa using the weighted mean method. RESULTS The Memory Clinic sample showed that the prediction of MMSE to MoCA was overall less accurate compared to the conversion from MoCA to MMSE. The 19 studies included after thorough literature search showed that MoCA scores were consistently lower than MMSE scores. Eleven of 19 conversion studies had addressed the conversion of the MoCA to the MMSE, while two studies converted MMSE to MoCA scores. Another six studies applied bi-directional conversions. We provide an easy-to-use table covering the entire range of scores and taking into account all currently existing conversion formulas. CONCLUSION The comprehensive MMSE-MoCA conversion table enables a direct comparison of cognitive test scores at screening examinations and over the course of disease in patients with neurocognitive disorders

Identifying a cut‐off point for normal mobility: a comparison of the timed ‘up and go' test in community‐dwelling and institutionalised elderly women

Background: physical mobility testing is an essential component of the geriatric assessment. The timed up and go test measures basic mobility skills including a sequence of functional manoeuvres used in everyday life. Objectives: to create a practical cut‐off value to indicate normal versus below normal timed up and go test performance by comparing test performance of community‐dwelling and institutionalised elderly women. Setting and participants: 413 community‐dwelling and 78 institutionalised mobile elderly women (age range 65-85 years) were enrolled in a cross‐sectional study. Measurements: timed up and go test duration, residential and mobility status, age, height, weight and body mass index were documented. Results: 92% of community‐dwelling elderly women performed the timed up and go test in less than 12 seconds and all community‐dwelling women had times below 20 seconds. In contrast only 9% of institutionalised elderly women performed the timed up and go test in less than 12 seconds, 42% were below 20 seconds, 32% had results between 20 and 30 seconds and 26% were above 30 seconds. The 10th-90th percentiles for timed up and go test performance were 6.0-11.2 seconds for community‐dwelling and 12.7-50.1 seconds for institutionalised elderly women. When stratifying participants according to mobility status, the timed up and go test duration increased significantly with decreasing mobility (Kruskall‐Wallis‐test: p<0.0001). Linear regression modelling identified residential status (p<0.0001) and physical mobility status (p<0.0001) as significant predictors of timed up and go performance. This model predicted 54% of total variation of timed up and go test performance. Conclusion: residential and mobility status were identified as the strongest predictors of timed up and go test performance. We recommend the timed up and go test as a screening tool to determine whether an in‐depth mobility assessment and early intervention, such as prescription of a walking aid, home visit or physiotherapy, is necessary. Community‐dwelling elderly women between 65 and 85 years of age should be able to perform the timed up and go test in 12 seconds or les

Use it or lose it! Cognitive activity as a protec-tive factor for cognitive decline associated with Alzheimer's disease.

Because of the worldwide aging of populations, Alzheimer's disease and other dementias constitute a devastating experience for patients and families as well as a major social and economic burden for both healthcare systems and society. Multiple potentially modifiable cardiovascular and lifestyle risk factors have been associated with this disease. Thus, modifying these risk factors and identifying protective factors represent important strategies to prevent and delay disease onset and to decrease the social burden. Based on the cognitive reserve hypothesis, evidence from epidemiological studies shows that low education and cognitive inactivity constitute major risk factors for dementia. This indicates that a cognitively active lifestyle may protect against cognitive decline or delay the onset of dementia. We describe a newly developed preventive programme, based on this evidence, to stimulate and increase cognitive activity in older adults at risk for cognitive decline. This programme, called "BrainCoach", includes the technique of "motivational interviewing" to foster behaviour change. If the planned feasibility study is successful, we propose to add BrainCoach as a module to the already existing "Health Coaching" programme, a Swiss preventive programme to address multiple risk factors in primary care

Le Registre suisse pour la santé du cerveau - Une infrastructure nationale pour la recherche sur la maladie d’Alzheimer [The Swiss Brain Health Registry : a national infrastructure for Alzheimer's research]

The Memory Centres of several Swiss hospitals have set up a national online registry for Alzheimer's research, called www.BHR-suisse.org. This type of registry already exists in the United States (www.brainhealthregistry.org/) and the Netherlands (https://hersenonderzoek.nl/). It contributes, as do these initiating sites, to the creation of a global database of research partners &lt;sup&gt;b&lt;/sup&gt; who wish to contribute by participating in studies on neurodegenerative diseases and more particularly on Alzheimer's disease. By registering, they provide a certain amount of information and become potential research partners. Researchers can then select a panel of volunteers according to the selection and exclusion criteria of their studies, contact them and include them in their studies

Serum neurofilament light in atrial fibrillation: clinical, neuroimaging and cognitive correlates

Emerging evidence suggests that atrial fibrillation is associated with cognitive dysfunction independently of stroke, but the underlying mechanisms remain unclear. In this cross-sectional analysis from the Swiss-atrial fibrillation Study (NCT02105844), we investigated the association of serum neurofilament light protein, a neuronal injury biomarker, with (i) the CHA; 2; DS; 2; -VASc score (congestive heart failure, hypertension, age 65-74 or >75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, sex), clinical and neuroimaging parameters and (ii) cognitive measures in atrial fibrillation patients. We measured neurofilament light in serum using an ultrasensitive single-molecule array assay in a sample of 1379 atrial fibrillation patients (mean age, 72 years; female, 27%). Ischaemic infarcts, small vessel disease markers and normalized brain volume were assessed on brain MRI. Cognitive testing included the Montreal cognitive assessment, trail-making test, semantic verbal fluency and digit symbol substitution test, which were summarized using principal component analysis. Results were analysed using univariable and multivariable linear regression. Neurofilament light was associated with the CHA; 2; DS; 2; -VASc score, with an average 19.2% [95% confidence interval (17.2%, 21.3%)] higher neurofilament per unit CHA; 2; DS; 2; -VASc increase. This association persisted after adjustment for age and MRI characteristics. In multivariable analyses, clinical parameters associated with neurofilament light were higher age [32.5% (27.2%, 38%) neurofilament increase per 10 years], diabetes mellitus, heart failure and peripheral artery disease [26.8% (16.8%, 37.6%), 15.7% (8.1%, 23.9%) and 19.5% (6.8%, 33.7%) higher neurofilament, respectively]. Mean arterial pressure showed a curvilinear association with neurofilament, with evidence for both an inverse linear and a U-shaped association. MRI characteristics associated with neurofilament were white matter lesion volume and volume of large non-cortical or cortical infarcts [4.3% (1.8%, 6.8%) and 5.5% (2.5%, 8.7%) neurofilament increase per unit increase in log-volume of the respective lesion], as well as normalized brain volume [4.9% (1.7%, 8.1%) higher neurofilament per 100 cm; 3; smaller brain volume]. Neurofilament light was inversely associated with all cognitive measures in univariable analyses. The effect sizes diminished after adjusting for clinical and MRI variables, but the association with the first principal component was still evident. Our results suggest that in atrial fibrillation patients, neuronal loss measured by serum neurofilament light is associated with age, diabetes mellitus, heart failure, blood pressure and vascular brain lesions, and inversely correlates with normalized brain volume and cognitive function

Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases

Neuronal damage is the morphological substrate of persisting neurological disability. Neurofilaments (Nf) are cytoskeletal proteins of neurons and their release into cerebrospinal fluid has shown encouraging results as a biomarker for neurodegeneration. This study aimed to validate the quantification of the Nf light chain (NfL) in blood samples, as a biofluid source easily accessible for longitudinal studies. Methods We developed and applied a highly sensitive electrochemiluminescence (ECL) based immunoassay for quantification of NfL in blood and CSF. Results Patients with Alzheimer’s disease (AD) (30.8 pg/ml, n=20), Guillain-Barré-syndrome (GBS) (79.4 pg/ml, n=19) or amyotrophic lateral sclerosis (ALS) (95.4 pg/ml, n=46) had higher serum NfL values than a control group of neurological patients without evidence of structural CNS damage (control patients, CP) (4.4 pg/ml, n=68, p<0.0001 for each comparison, p=0.002 for AD patients) and healthy controls (HC) (3.3 pg/ml, n=67, p<0.0001). Similar differences were seen in corresponding CSF samples. CSF and serum levels correlated in AD (r=0.48, p=0.033), GBS (r=0.79, p<0.0001) and ALS (r=0.70, p<0.0001), but not in CP (r=0.11, p=0.3739). The sensitivity and specificity of serum NfL for separating ALS from healthy controls was 91.3% and 91.0%. Conclusions We developed and validated a novel ECL based sandwich immunoassay for the NfL protein in serum (NfLUmea47:3); levels in ALS were more than 20-fold higher than in controls. Our data supports further longitudinal studies of serum NfL in neurodegenerative diseases as a potential biomarker of on-going disease progression, and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials