Associations of blood cell indices and anemia with risk of incident dementia

We thank Dr Zhang and Dr Zhou for their thoughtful comments to our work and appreciate the opportunity to address the two important issues they raised. First, Dr Zhang and Dr Zhou pointed out that our study, while accounting for the history of stroke, might not have adequately addressed other chronic brain disorders that could potentially influence brain structure and function. However, given the vast array of chronic brain disorders, including but not limited to traumatic brain injuries, neurodegenerative diseases, and brain tumors, it is quite a challenge to adjust for all potential confounding factors. Each of these disorders may have differential effects on brain morphology and could influence the outcome in distinct ways. In large-scale cohort studies, there's an inherent balance between comprehensiveness and feasibility. Addressing every potential chronic brain disorder would significantly complicate the analysis and might introduce new sources of error or bias.1 Meanwhile, many high-quality studies utilizing UK Biobank imaging data, which we've referenced, do not typically adjust for these factors.2-5 Second, Dr Zhang and Dr Zhou raised the question that the exact location of the head and the radio-frequency receive coil in the scanner can introduce variability. They suggested that these factors could affect the quality and interpretation of MRI data. Acknowledging this potential variability, we adjusted our MRI analysis to incorporate these elements as covariates. The derived results were consistent with our primary findings. Specifically, our observations suggesting significant associations between blood cell indicators and the volume of various brain regions, as well as a majority of white matter tracts, remained unchanged. The results also affirmed the associations we identified previously between blood cell indicators and vascular-rich brain regions. For those interested in a deeper insight, the results are available in the Supplementary Tables. In conclusion, while both raised concerns have potential implications, their impact on MRI analysis, based on our findings and referenced literature, appears limited. We appreciate the detailed feedback from Zhang and Zhou. Scientific research is a continuous endeavor, and such inputs play a pivotal role in enhancing the quality of future research. The authors have nothing to report. The author declares no conflicts of interest. Author disclosures are available in the supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.