Instrumental variables in real-world clinical studies of dementia and neurodegenerative disease: Systematic review of the subject-matter argumentation, falsification test, and study design strategies to justify a valid instrument.

"CONFLICT OF INTEREST STATEMENT All authors declare no conflicts of interest."

"SH (Pre‐Doctoral Fellowship, NIHR302746) is funded by the National Institute for Health and Care Research (NIHR) for this research project. JH and JPT are supported by the NIHR Newcastle Biomedical Research Centre. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, National Health Service (NHS), or the UK Department of Health and Social Care."

"The review protocol was registered on PROSPERO (CRD42023392589). We amended our study to exclude MR studies to focus on IV analysis in clinical settings. We also relaxed the inclusion criteria to include outcome measures of dementia symptom staging or dementia risk score; these outcomes were deemed clinically relevant and their inclusion would allow us to cover studies that may not have access to or collected diagnosis data. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines (Page et al., )."