Current practices in studies applying the target trial emulation framework: a protocol for a systematic review.

INTRODUCTION: Observational studies represent an alternative to estimate real-world causal effects in the absence of available randomised controlled trials (RCTs). Target trial emulation is a framework for the application of RCT design principles to emulate a hypothetical open-label RCT (the hypothetical target trial) using existing observational data as the primary data source as opposed to the prospective recruitment and measurement of randomised units. The aim of this systematic review is to investigate the practices of studies applying the target trial emulation framework to evaluate the effectiveness of interventions. METHODS AND ANALYSIS: We will systematically search in Medline (via Ovid), Embase (via Ovid, entries from medRxiv are included), PsycINFO (via Ovid), SCOPUS, Web of Science, Cochrane Library, the ISRCTN registry and ClinicalTrials.gov for all study reports and protocols which used the trial emulation framework (without time restriction). We will extract information concerning study design, data source, analysis, results, interpretation and dissemination. Two reviewers will perform study selection, data extraction and quality assessment. Disagreements between reviewers will be resolved by a third reviewer. A narrative approach will be used to synthesise and report qualitative and quantitative data. Reporting of the review will be informed by Preferred Reporting Items for Systematic Review and Meta-Analysis guidance (PRISMA). ETHICS AND DISSEMINATION: Ethical approval is not required as it is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations.

Neuropsychiatric Inventory domains cluster into neuropsychiatric syndromes in Alzheimer's disease: A systematic review and meta-analysis.

BACKGROUND: Studies of patients with Alzheimer's disease (AD) have observed that neuropsychiatric symptoms (NPS) tend to co-occur as neuropsychiatric syndromes and have generally shown mixed results regarding the number and composition of syndromes. We systematically reviewed how neuropsychiatric syndromes in AD have been defined and compared the different published definitions in a pooled sample of AD patients using meta-analytic structural equation modeling (MASEM). METHODS: Studies examining the factor structure of the Neuropsychiatric Inventory (NPI) and published from 1994 to 2021 were included. We contacted the corresponding authors of eligible studies for correlation coefficients between NPI items. We pooled correlations under a random effects MASEM model and fitted and compared measurement models from published studies to identify a best-fitting model. RESULTS: Twenty-five studies were included in the systematic review, and correlations were obtained from seven studies for MASEM. For the NPI-10 (seven studies, n = 5185), a five-factor structure was found to have a good fit to the data. For the NPI-12 (four studies, n = 2397), we were unable to identify a factor structure that displayed a good model fit. CONCLUSION: This systematic review and meta-analysis contribute to the development of a theoretical model of neuropsychiatric syndromes in AD and reveals the barriers that accompany MASEM methodology.

Low Accuracy of Brief Cognitive Tests in Tracking Longitudinal Cognitive Decline in an Asian Elderly Cohort.

BACKGROUND: Researchers have questioned the utility of brief cognitive tests such as the Mini-Mental Status Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in serial administration and suggested that brief cognitive tests may not accurately track changes in Global Cognition. OBJECTIVE: To examine the accuracy of longitudinal changes on brief cognitive tests in reflecting progression in Global Cognition measured using comprehensive neuropsychological assessments. METHODS: Two hundred and seven participants were assessed with the MMSE, MoCA, and a validated comprehensive neuropsychological battery. Global z-scores on the battery were derived and used to assess overall and significant (≥0.5 standard deviation) decline on Global Cognition. Different patterns of decline on MMSE/MoCA were classified. Accuracy was examined using receiver operating characteristic curve, and sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were reported. RESULTS: The overall ability of MMSE/MoCA change scores to discriminate participants who did and did not decline on Global Cognition was fair-to-moderate (AUC [95% CI] = 0.71 [0.64-0.78] & 0.73 [0.66-0.80] for overall decline; 0.78 [0.70-0.85] & 0.80 [0.73-0.86] for significant decline, respectively). Changes in MMSE/MoCA had low accuracy in identifying significant Global Cognitive Decline (PPV = 0.41 & 0.46, respectively) but high accuracy in ruling out significant decline and identifying cognitively stable participants (NPV = 0.89 & 0.88, respectively). CONCLUSION: There is limited utility in brief cognitive tests for tracking cognitive decline. Instead, they should be used for identifying participants who remain cognitively stable on follow up. These results accentuate the importance of acknowledging the limitations of brief cognitive tests when assessing cognitive change.