Informant-based tools for assessment and monitoring of cognition, behavior, and function in neurocognitive disorders: Systematic review and report from a CCCDTD5 Working Group.

OBJECTIVE: As part of the fifth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, we assessed the literature on informant-based tools for assessment and monitoring of cognition, behavior, and function in neurocognitive disorders (NCDs) to provide evidence-based recommendations for clinicians and researchers. METHODS: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards guidelines. Publications that validated the informant-based tools or described their key properties were reviewed. Quality of the studies was assessed using the modified Quality Assessment tool for Diagnostic Accuracy Studies. RESULTS: Out of 386 publications identified through systematic search, 34 that described 19 informant-based tools were included in the final review. Most of these tools are backed by good-quality studies and are appropriate to use in clinical care or research. The tools vary in their psychometric properties, domains covered, comprehensiveness, completion time, and ability to detect longitudinal change. Based on these properties, we identify different tools that may be appropriate for primary care, specialized memory clinic, or research settings. We also identify barriers to use of these tools in routine clinical practice. CONCLUSION: There are several good-quality tools available to collect informant-report for assessment and monitoring of cognition, behavior, or function in patients with NCDs. Clinicians and researchers may choose a particular tool based on their specific needs such as domains of interest, desired psychometric properties, and feasibility. Further work is needed to make the tools more user-friendly and to adopt them into routine clinical care.

CSF biomarker variability in the Alzheimer's Association quality control program.

BACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. METHODS: Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. RESULTS: A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1-42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). CONCLUSIONS: The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians.