The authors have sufficiently responded to my comments and the comments of the editor and other reviewers. The document is improved as a result and I have no further comments at this stage.

The authors have addressed all the previous points and the new report reads much clearer now. I do not have further suggestions.

The authors plan to investigate whether blood pressure and waste-to-hip ratio influence the progression of cerebral small vessel disease. Overall, the research question and hypothesis are clear and fit into the literature in the field. The analysis plan is generally thorough, and the power analysis is well-described and justifies the planned statistical tests. Below I describe several questions and limitations I found while evaluating the registered report

Intro

-        In the introduction the authors mention that they will replicate findings and extend findings, however, it is unclear which aims, and hypotheses refer to replications versus extensions. It would be useful to make this explicit. What is a replication and what is an extension or novel aim?

Aims and Hypotheses

-        H1, H2, and H3 seem to all be replications of previous research, is that right? If the primary goal of this project is to replicate previous results, then this is fine, but the researchers should make it more explicit in their introduction that the primary goal of this project is replication. However, based on the introduction it seems the researchers have more clear goals to ask novel questions about the influence of gender and Waist to hip ratio on longitudinal white matter lesions. If so, if so, I encourage the authors to explicitly state hypotheses about the waist-to-hip ratio and gender analyses. 

-        Why did the authors select these covariates for their hypotheses? These covariates seem reasonable, but I encourage the authors to justify each covariate and explain why its inclusion is important to each hypothesis/analysis.

Methods

-        The methods are clear and logical. They are sufficiently detailed for replication and to limit analytical flexibility. I appreciate their thorough review of previous literature to justify parameters used in their power analyses

-        How did the authors choose p<.033 for establishing statistical significance? Is this a field convention, or based on another justification?

Statistical Analyses

-        In the abstract and intro, sex/gender stratified analyses are discussed as a central focus of this project and these are included in the statistical models. However, I do not see a clear description of how sex/gender inferences will be made or evaluated from these models. Given the introduction, I encourage the authors to thoroughly describe their plans for evaluating and drawing inferences based on sex/gender. 

Miscellaneous

-       I would highly recommend using fewer acronyms. It is very hard to track what each acronym is, and this makes reading the text burdensome. A few acronyms for the most common and well-known terms are fine, but currently, there is an acronym in nearly every sentence. SBP is not defined as far as I can tell.

In this proposal Beyer et al. have designed a study aimed at assessing the link between blood pressure and progression of white matter hyperintensity load, as well as examining the cognitive implications of white matter hyperintensity progression. Overall, the research questions are pertinent and valid, the methodology is robust, and the transparency of the research plan is satisfactory. I would like to have some clarifications on certain points that are outlined below.

1A. Scientific validity of the research question(s)

This proposal uses a longitudinal design to address the prospective effects of blood pressure and abdominal obesity on the progression of white matter hyperintensities. Additionally, it tests for the functional implication of increases in white matter hyperintensity load, since it also examines its associations with longitudinal decline in executive functions and in general cognition.

The research question is valid and it is clearly defined. The proposal includes both exploratory and hypothesis-based analyses. 

1B. Logic, rationale, and plausibility of the proposed hypotheses

This proposal states three main hypothesis, which are logic and plausible.

1C. Soundness and feasibility of the methodology and analysis pipeline

Methodologically speaking, the current proposal is sound and feasible. The authors have performed a sophisticated statistical power analysis where they take into account previous results from the literature and they simulate their predictive power in their dataset, according to their baseline information.

I was missing some clarification regarding certain aspects of the proposal. Namely:

• Why do the authors focus on systolic blood pressure instead of diastolic blood pressure?
  The longitudinal data has already been collected but the authors do not have access yet. From the information that the authors provide, I assume that the follow-up range should be somewhere between 3 and 10 years. Is this correct? Do the authors happen to have a mode accurate description of this?
• Regarding the confirmatory analyses, the authors will test 3 regression models that are aligned with the hypotheses. The summary provided in Table 7 highlights what predictors are expected to be significant regarding their hypotheses. I am a bit confused regarding the number of predictors and the highlights. The authors state somewhere earlier that the analyses will be divided by sex/gender. Then, why have they included sex as a predictor variable in the regression models? 
• Interactions between variable of interest and age change. Could the authors state a bit clearer what is the rationale for including these interactions?
• Please correct me if I am wrong, in Table 7, M2 and M3 are missing the interaction term hyperintensity load x age change while this is stated in the text. Also, why is it that in M1 the highlighted predictor is the interaction term between systolic blood pressure x age change, while this is not the case for M2 and M3? If I am reading the hypothesis correctly, the predictor of interest in M1 would be systolic blood pressure.
• Regarding the dependent variable specified in models M1-M3, does it reflect the variable collected in the follow-up or is it a change score? Would the authors control for the scores obtained in these very same variables at baseline?

1D. Replicability

The authors have provided detailed methods. I do not have concerns regarding this point.

1E. Consideration of outcome-neutral conditions

This part has been addressed satisfactorily. The authors have detailed the thresholds at which they will consider that a certain variable is invalid for each participant.