Management of financial conflicts of interests in clinical practice guidelines in Germany: results from the public database GuidelineWatch.

BACKGROUND: The reliability of clinical practice guidelines has been disputed because guideline panel members are often burdened with financial conflicts of interest (COI). Current recommendations for COI regulation advise not only detailed declaration but also active management of conflicts. To continuously assess COI declaration and management in German guidelines we established the public database LeitlinienWatch (GuidelineWatch). METHODS: We analyzed all German guidelines at the highest methodological level (S3) that included recommendations for pharmacological therapy (n = 67) according to five criteria: declaration and assessment of COI, composition of the guideline development group, independence of the coordinators and lead authors, imposed abstentions because of COI and public external review. Each criterion was assessed using predefined outcome categories. RESULTS: Most guidelines (76%) contained a detailed declaration of COI. However, none of the guidelines provided full transparency of COI assessment results. The guideline group was composed of a majority of participants with COI in 55% of the guidelines, no guideline was free of participants with COI. Only 9% of guidelines had coordinators and lead authors without any financial COI. Most guidelines (70%) did not provide a rule for abstentions for participants with COI. In 21% of guidelines there was a rule, but abstentions were either not practiced or not documented, whereas in 7% partial abstentions and in 2% complete abstentions were documented. Two thirds of the guideline drafts (67%) were not externally reviewed via a public website. CONCLUSIONS: COI are usually documented in detail in German guidelines of the highest methodological level. However, considerable improvement is needed regarding active management of COI, including recruitment of independent experts for guideline projects, abstention from voting for participants with COI and external review of the guideline draft. We assume that the publicly available ratings on GuidelineWatch will improve the handling of conflicts of interest in guideline development.

Cognitive Reserve in Alzheimer's Dementia: Diagnostic Accuracy of a Testing-the-Limits Paradigm.

Individuals with higher cognitive reserve are more able to cope with pathological brain alterations, potentially due to the application of more efficient cognitive strategies. The extent to which an individual's cognitive performance can be increased by advantageous conditions differs substantially between patients with Alzheimer's dementia (AD) and healthy older adults and can be assessed with the Testing-the-Limits (TtL) approach. Thus, TtL has been proposed as a tool for the early diagnosis of AD. Here, we report the diagnostic accuracy of a memory TtL paradigm to discriminate between AD patients and controls. The TtL paradigm was administered to 57 patients with clinically diagnosed AD and 94 controls. It consisted of a pre-test condition, representing baseline cognitive performance, the presentation of an encoding strategy, and two subsequent post-test conditions, representing learning potential. Receiver operating characteristic (ROC) curves were analyzed for each condition in order to receive optimal cutoff points along with their sensitivity and specificity and to compare the diagnostic accuracy of the conditions. Differentiation between AD patients and controls, indicated by the area under the ROC curve, increased significantly for the TtL post-test and total error scores compared to the pre-test score. The combined error score in the two post-tests could differentiate between AD patients and controls with a sensitivity of 0.93 and a specificity of 0.80. The presented approach can be carried out in 25 minutes and thus constitutes a time- and cost-effective way to diagnose AD with high accuracy.

Amyloid beta 1-42 in cerebrospinal fluid is associated with cognitive plasticity.

Cerebrospinal fluid (CSF) total tau-protein (t-tau) and amyloid-beta 1-42 (Abeta(1-42)) have been increasingly included in the diagnostic process of Alzheimer's disease (AD). We aimed to analyze whether these CSF biomarkers correlate with cognitive plasticity as measured by a dynamic recognition test strategy. We assessed 29 elderly individuals (15 with incipient and 14 without AD) from an outpatient memory clinic at a university hospital by a Testing-the-Limits (TtL) based recognition paradigm consisting of a pre-test (baseline) and two post-test conditions with an interposed encoding instruction. We identified a negative association between Abeta(1-42) and the two post-test failure rates, but not with that of the pre-test. Also, none of the standard tests correlates with Abeta 42-1 level. T-tau does not correlate with recognition performance. Our results suggest that Abeta(1-42) could be useful as a state marker for cognitive plasticity.

Reduced benefit from mnemonic strategies in early-stage Alzheimer's disease: a brief testing-the-limits paradigm for clinical practice.

Discriminating incipient Alzheimer's disease (AD) from major depression (MD) and age related memory decline is a challenge in clinical practice. Since AD is characterized by an early loss of neuronal and functional plasticity, a dynamic test strategy, such as the testing-the-limits (TtL) approach, that measures learning capacity can be a helpful diagnostic tool. To evaluate this, a short recognition paradigm consisting of a pre-test (baseline) and two post-test conditions with an interposed encoding instruction was developed and administered to individuals with incipient AD (n = 19; Mini Mental Status Examination (MMSE) 26.5), patients with depressive disorders (n = 11; MMSE 30), and healthy controls (n = 11; MMSE 30). In addition, participants completed a set of traditional neuropsychological tests that focused on the subjects' cognitive baseline performance. Intergroup comparisons (Kruskal-Wallis, U test) revealed significantly higher post-test failure rates in AD patients. Pre-test performance of MD and AD patients did not differ. Intra-group comparisons (Friedman, Wilcoxon test) showed that all three subject samples benefit from intervention in post-test 1. In contrast to MD and healthy individuals, who revealed significantly lower failure rates in post-test 2 compared to the pre-test, AD patients did not improve. Out of the 15 traditional test scores obtained, only two discriminated simultaneously between AD and each of the other groups. Our data confirm the finding of an impaired cognitive plasticity already present in very early stages of AD and illustrate the efficiency of a dynamic test approach in identifying incipient dementia.