Cholesterol and Alzheimer’s Disease Risk: A Meta-Meta-Analysis
, Alicia Puente-Martínez 2, Silvia Ubillos-Landa 3,*, Joaquín Pacheco-Bonrostro 4 and Javier Santabárbara 5,6Round 1
Reviewer 1 Report
The Manuscript authored by Olalla Sáiz-Vazquez et al, is an interesting meta-meta-analysis related to the link between cholesterol and Alzheimer’s disease risk. The study also emphasize the role of low-density cholesterol (LDL-C) as a risk factor for AD, thus to strength the importance of preventive strategy to reduce the incidence of AD. Here below I reported some criticism and my concerns.
- An extensive English editing is surely needed, in particular in discussion section.
- “senile plates theories” I suppose it should be “senile plaques theories”
- Revise the phrase: “We found that compared with HC, LDL-C levels were higher in AD participants than those in HC, while HDL-C, TC and TG levels were not sensitive hallmarks for AD”, avoiding the repetition about the comparison with HC.
- Correct the use of the acronym Alzheimer’s disease (AD) throughout the manuscript.
- Explicate the acronym EA in the text.
- Modify the sentence: “For instance, Wolozin [49] concluded that the use of statins, including lovastatin and pravastatin, suppressed the development of AD”. This is an erroneous message, since up to know no effective treatment is able to suppress AD.
- In the phrase: “Cholesterol is a modifiable risk factor, so if professionals know the relationship between cholesterol and AD they could help to reduce AD risk”, it is not clear the meaning authors want to give to the sentence.
- use the same style to refer to numbers thus modify the numbers in brackets in the phrase: "with a total of 2289511 participants (N cases = 19,757; N controls = 2,269,754)".
- Authors sometimes refer to the manuscript as “meta-meta-analysis” or “reviews of meta-analysis”, thus mislead the reader since in meta-meta-analysis it is possible to appreciate and understand the analysis performed by the authors, while in reviews of meta-analysis cannot. Thus I suggest to include also in the Abstract that further a meta-meta-analysis has also been performed. I suggest also to modify the title to emphasize the analysis performed. This is an important message that have to be clear to the reader.
Author Response
Response to Reviewer 1 Comments
The Manuscript authored by Olalla Sáiz-Vazquez et al, is an interesting meta-meta-analysis related to the link between cholesterol and Alzheimer’s disease risk. The study also emphasizes the role of low-density cholesterol (LDL-C) as a risk factor for AD, thus to strength the importance of preventive strategy to reduce the incidence of AD. Here below I reported some criticism and my concerns.
- An extensive English editing is surely needed, in particular in discussion section.
Response 1: Even though the first draft was revised by a native-born English speaker, we send it to another expert for new edits.
- “senile plates theories” I suppose it should be “senile plaques theories”
Response 2: Line 291. We apologize for this error. We corrected this mistake using “senile plaques theories”
- Revise the phrase: “We found that compared with HC, LDL-C levels were higher in AD participants than those in HC, while HDL-C, TC and TG levels were not sensitive hallmarks for AD”, avoiding the repetition about the comparison with HC.
Response 3: Line 284. According with the reviewer we checked the phrase and deleted “than those in HC”.
- Correct the use of the acronym Alzheimer’s disease (AD) throughout the manuscript. Explicate the acronym EA in the text.
Response 4: Line 325. We have corrected the use of the acronym Alzheimer’s disease (AD) throughout the manuscript.
- Modify the sentence: “For instance, Wolozin [49] concluded that the use of statins, including lovastatin and pravastatin, suppressed the development of AD”. This is an erroneous message, since up to know no effective treatment is able to suppress AD.
Response 5: Line 340. We agree with the reviewer. Therefore, we changed the phrase using “decrease the risk of AD”.
- In the phrase: “Cholesterol is a modifiable risk factor, so if professionals know the relationship between cholesterol and AD they could help to reduce AD risk”, it is not clear the meaning authors want to give to the sentence.
Response 6: Line 373. Thanks for your comment, we added new information in the text.
- Use the same style to refer to numbers thus modify the numbers in brackets in the phrase: "with a total of 2289511 participants (N cases = 19,757; N controls = 2,269,754)".
Response 7: Line 202. According with the reviewer we modified the numbers in brackets.
- Authors sometimes refer to the manuscript as “meta-meta-analysis” or “reviews of meta-analysis”, thus mislead the reader since in meta-meta-analysis it is possible to appreciate and understand the analysis performed by the authors, while in reviews of meta-analysis cannot. Thus, I suggest to include also in the Abstract that further a meta-meta-analysis has also been performed. I suggest also to modify the title to emphasize the analysis performed. This is an important message that have to be clear to the reader.
Response 8: Lines: 26,81,125, 155, 160, 277, 305, 336, 337, 368, 369, 383, 388. We used meta-meta-analysis to refer to the manuscript as reviewer suggested.
Author Response File: 
Author Response.docx
Reviewer 2 Report
The authors have stated the heading as a review of meta analyses. The manuscript is not written as a review, rather than analysis of the the past reports.
Introduction is confusing, and does not follow any pattern of flow. It has to be organized to make a meaning full paragraph.
The data collection is good, but it not written like a review
The results do not explain what the study means, and why the authors have chosen it. The values are not necessary at all. Rather more focus has to be given on the outcome of the result.
Author Response
Response to Reviewer 2 Comments
- The authors have stated the heading as a review of meta analyses. The manuscript is not written as a review, rather than analysis of the past reports.
Response 1: Thanks for your comment.
This a review of previous meta analyses. The paper is written following the PRISMA guidelines (Preferred Reporting Items for Systematic reviews and Meta-Analyses) (see method section). To clarify this point, we included for the reviewer the checklist of PRISMA statements.
-From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal.pmed1000097
Furthermore, we accepted the suggestion proposed by first reviewer and we use the term meta-meta-analysis to refer the manuscript, not review of meta-analyses.
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
Authors replied to all my corrections and modified accordingly in the manuscript. Thus I suggest the manuscript for a pubblication in the Brain Science Journal.
Reviewer 2 Report
I think the authors have addressed the comments previously made and modified the manuscript accordingly.
