Screening properties of the German IQCODE with a two-year time frame in MCI and early Alzheimer's disease

Background: The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is a widely used screening tool for dementia. We aimed to determine the ability of the German version of the 16-item IQCODE with a two-year time frame to discriminate healthy mature control participants (NC) from mild cognitive impairment (MCI) and probable early Alzheimer's disease (AD) patients (all with Mini-mental State Examination (MMSE) scores ≥ 24/30) and to optimize diagnostic discriminability by shortening the IQCODE. Methods: 453 NC (49.7% women, age = 69.5 years ± 8.2, education = 12.2 ± 2.9), 172 MCI patients (41.9% women, age = 71.5 years ± 8.8, education = 12.3 ± 3.1) and 208 AD patients (59.1% women, age = 76.0 years ± 6.4, education = 11.4 ± 2.9) participated. Stepwise binary logistic regression analyses (LR) were used to shorten the test. Receiver operating characteristic curves (ROC) determined sensitivities, specificities, and correct classification rates (CCRs) for (a) NC vs. all patients; (b) NC vs. MCI; and (c) NC vs. AD patients. Results: The mean IQCODE was 3.00 for NC, 3.35 for MCI, and 3.73 for AD. CCRs were 85.5% (NC-patient group), 79.9% (NC-MCI), and 90.7% (NC-AD), respectively. The diagnostic discriminability of the shortened 7-item IQCODE (i.e. items 1, 2, 3, 5, 7, 10, 14) was comparable with the longer version (i.e. 7-item CCRs: NC-patient group: 85.3%; NC-MCI: 80.1%, NC-AD: 90.5%). Conclusions: The German 16-item IQCODE with two-year time frame showed excellent screening properties for MCI and early AD patients. An abbreviated 7-item version demonstrated equally high diagnostic discriminability, thus allowing for more economical screenin

Early detection of Alzheimer's disease with a total score of the German CERAD

The goal of the present study was to evaluate the diagnostic discriminability of three different global scores for the German version of the Consortium to Establish a Registry on Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB). The CERAD-NAB was administered to 1100 healthy control participants [NC; Mini-Mental State Examination (MMSE) mean = 28.9] and 352 patients with very mild Alzheimer's disease (AD; MMSE mean = 26.1) at baseline and subsets of participants at follow-up an average of 2.4 (NC) and 1.2 (AD) years later. We calculated the following global scores: Chandler et al.'s (2005) score (summed raw scores), logistic regression on principal components analysis scores (PCA-LR), and logistic regression on demographically corrected CERAD-NAB variables (LR). Correct classification rates (CCR) were compared with areas under the receiver operating characteristics curves (AUC). The CCR of the LR score (AUC = .976) exceeded that of the PCA-LR, while the PCA-LR (AUC = .968) and Chandler (AUC = .968) scores performed comparably. Retest data improved the CCR of the PCA-LR and Chandler (trend) scores. Thus, for the German CERAD-NAB, Chandler et al.'s total score provided an effective global measure of cognitive functioning, whereby the inclusion of retest data tended to improve correct classification of individual cases. (JINS, 2010, 16, 910-920.

Medial perirhinal cortex disambiguates confusable objects

Our brain disambiguates the objects in our cluttered visual world seemingly effortlessly, enabling us to understand their significance and to act appropriately. The role of anteromedial temporal structures in this process, particularly the perirhinal cortex, is highly controversial. In some accounts, the perirhinal cortex is necessary for differentiating between perceptually and semantically confusable objects. Other models claim that the perirhinal cortex neither disambiguates perceptually confusable objects nor plays a unique role in semantic processing. One major hurdle to resolving this central debate is the fact that brain damage in human patients typically encompasses large portions of the anteromedial temporal lobe, such that the identification of individual substructures and precise neuroanatomical locus of the functional impairments has been difficult. We tested these competing accounts in patients with Alzheimer's disease with varying degrees of atrophy in anteromedial structures, including the perirhinal cortex. To assess the functional contribution of each anteromedial temporal region separately, we used a detailed region of interest approach. From each participant, we obtained magnetic resonance imaging scans and behavioural data from a picture naming task that contrasted naming performance with living and non-living things as a way of manipulating perceptual and semantic confusability; living things are more similar to one another than non-living things, which have more distinctive features. We manually traced neuroanatomical regions of interest on native-space cortical surface reconstructions to obtain mean thickness estimates for the lateral and medial perirhinal cortex and entorhinal cortex. Mean cortical thickness in each region of interest, and hippocampal volume, were submitted to regression analyses predicting naming performance. Importantly, atrophy of the medial perirhinal cortex, but not lateral perirhinal cortex, entorhinal cortex or hippocampus, significantly predicted naming performance on living relative to non-living things. These findings indicate that one specific anteromedial temporal lobe region—the medial perirhinal cortex—is necessary for the disambiguation of perceptually and semantically confusable objects. Taken together, these results support a hierarchical account of object processing, whereby the perirhinal cortex at the apex of the ventral object processing system is required to bind properties of not just perceptually, but also semantically confusable objects together, enabling their disambiguation from other similar objects and thus comprehension. Significantly, this model combining a hierarchical object processing architecture with a semantic feature statistic account explains why category-specific semantic impairments for living things are associated with anteromedial temporal lobe damage, and pinpoints the root of this syndrome to perirhinal cortex damag

For debate: substituting placebo controls in long-term Alzheimer's prevention trials

INTRODUCTION: Novel compounds with potential to attenuate or stop the progression of Alzheimer's disease (AD) from its presymptomatic stage to dementia are being tested in man. The study design commonly used is the long-term randomized, placebo-controlled trial (RPCT), meaning that many patients will receive placebo for 18 months or longer. It is ethically problematic to expose presymptomatic AD patients, who by definition are at risk of developing dementia, to prolonged placebo treatment. As an alternative to long-term RPCTs we propose a novel clinical study design, termed the placebo group simulation approach (PGSA), using mathematical models to forecast outcomes of presymptomatic AD patients from their own baseline data. Forecasted outcomes are compared with outcomes observed on candidate drugs, thus replacing a concomitant placebo group. METHODS: First models were constructed using mild cognitive impairment (MCI) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. One outcome is the Alzheimer Disease Assessment Scale - cognitive subscale (ADAScog) score after 24 months, predicted in a linear regression model; the other is the trajectory over 36 months of a composite neuropsychological test score (Neuro-Psychological Battery (NP-Batt)), using a mixed model. Demographics and clinical, biological and neuropsychological baseline values were tested as potential predictors in both models. RESULTS: ADAScog scores after 24 months are predicted from gender, obesity, Functional Assessment Questionnaire (FAQ) and baseline scores of Mini-Mental State Examination, ADAScog and NP-Batt with an R2 of 0.63 and a residual standard deviation of 0.67, allowing reasonably precise estimates of sample means. The model of the NP-Batt trajectory has random intercepts and slopes and fixed effects for body mass index, time, apolipoprotein E4, age, FAQ, baseline scores of ADAScog and NP-Batt, and four interaction terms. Estimates of the residual standard deviation range from 0.3 to 0.5 on a standard normal scale. If novel drug candidates are expected to diminish the negative slope of scores with time, a change of 0.04 per year could be detected in samples of 400 with a power of about 80%. CONCLUSIONS: First PGSA models derived from ADNI MCI data allow prediction of cognitive endpoints and trajectories that correspond well with real observed values. Corroboration of these models with data from other observational studies is ongoing. It is suggested that the PGSA may complement RPCT designs in forthcoming long-term drug studies with presymptomatic AD individuals

Comparison of Verbal Episodic Memory Measures: Consortium to Establish a Registry for Alzheimer's Disease—Neuropsychological Assessment Battery (CERAD-NAB) versus California Verbal Learning Test (CVLT)

Episodic memory is affected early in the course of dementia. Two well-established tests to assess verbal episodic memory functioning are the Word List task from the Consortium to Establish a Registry for Alzheimer's disease Neuropsychological Assessment Battery (CERAD-NAB) and the California Verbal Learning Test (CVLT). In clinical and/or research settings, patients are typically administered either one or the other test, making statistical comparisons difficult. This study aimed to (i) compare the z-scores of these two tests in patients with MCI and different types of dementia and (ii) establish formulae to transform CERAD-NAB scores into CVLT scores and vice versa. Sixty-five patients completed both tests for the first time and within 10 days of each other. Pearson correlation coefficients indicated that the two tests assess similar aspects of episodic memory and that the CVLT is more sensitive to subtle episodic memory impairments. Finally, conversion formulae are provided and their implementation illustrate

The Extension of the German CERAD Neuropsychological Assessment Battery with Tests Assessing Subcortical, Executive and Frontal Functions Improves Accuracy in Dementia Diagnosis

Alzheimer's disease (AD) is the most common form of dementia. Neuropsychological assessment of individuals with AD primarily focuses on tests of cortical functioning. However, in clinical practice, the underlying pathologies of dementia are unknown, and a focus on cortical functioning may neglect other domains of cognition, including subcortical and executive functioning. The current study aimed to improve the diagnostic discrimination ability of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (CERAD-NAB) by adding three tests of executive functioning and mental speed (Trail Making Tests A and B, S-Words).; Logistic regression analyses of 594 normal controls (NC), 326 patients with mild AD and 224 patients with other types of dementia (OD) were carried out, and the area under the curve values were compared to those of CERAD-NAB alone.; All comparisons except AD-OD (65.5%) showed excellent classification rates (NC-AD: 92.7%; NC-OD: 89.0%; NC-all patients: 91.0%) and a superior diagnostic accuracy of the extended version.; Our findings suggest that these three tests provide a sensible addition to the CERAD-NAB and can improve neuropsychological diagnosis of dementia

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

Mid-term changes in cognitive functions in patients with atrial fibrillation: a longitudinal analysis of the Swiss-AF cohort.

BACKGROUND Longitudinal association studies of atrial fibrillation (AF) and cognitive functions have shown an unclear role of AF-type and often differ in methodological aspects. We therefore aim to investigate longitudinal changes in cognitive functions in association with AF-type (non-paroxysmal vs. paroxysmal) and comorbidities in the Swiss-AF cohort. METHODS Seven cognitive measures were administered up to five times between 2014 and 2022. Age-education standardized scores were calculated and association between longitudinal change in scores and baseline AF-type investigated using linear mixed-effects models. Associations between AF-type and time to cognitive drop, an observed score of at least one standard deviation below individual's age-education standardized cognitive scores at baseline, were studied using Cox proportional hazard models of each cognitive test, censoring patients at their last measurement. Models were adjusted for baseline covariates. RESULTS 2,415 AF patients (mean age 73.2 years; 1,080 paroxysmal, 1,335 non-paroxysmal AF) participated in this Swiss multicenter prospective cohort study. Mean cognitive scores increased longitudinally (median follow-up 3.97 years). Non-paroxysmal AF patients showed smaller longitudinal increases in Digit Symbol Substitution Test (DSST), Cognitive Construct Score (CoCo)and Trail Making Test part B (TMT-B) scores vs. paroxysmal AF patients. Diabetes, history of stroke/TIA and depression were associated with worse performance on all cognitive tests. No differences in time to cognitive drop were observed between AF-types in any cognitive test. CONCLUSION This study indicated preserved cognitive functioning in AF patients, best explained by practice effects. Smaller practice effects were found in non-paroxysmal AF patients in the DSST, TMT-B and the CoCo and could indicate a marker of subtle cognitive decline. As diabetes, history of stroke/TIA and depression-but not AF-type-were associated with cognitive drop, more attention should be given to risk factors and underlying mechanisms of AF