Analyzing of Alzheimer’s Disease Based on Biomedical and Socio-Economic Approach Using Molecular Communication, Artificial Neural Network, and Random Forest Models

Round 1

Reviewer 1 Report

The study Biomedical and Socio-economic based Analysis of Alzhemer's 2 Disease: The Case of Turkey is dealing with an important topic. However, I suggest clarifying the design of the study and the methods.

Overall, the study needs a thorough review for grammar and mispellings. Also, please, structure the study with sections in accordance with a scientific report.

Introduction

-It is well conducted and referenced, but you failed to state your research gap and the aim of your study.

Methods

-I miss a methods section to report what has been done. You state that a random forest plot was conducted, but how, which variables did you take into account?

-Also, is this a consequence of a systematic review of the literature?

Results

-There is no results´section but only figures and tables with data of unknown origin. 

Discussion

-There is no limitation section to acknowledge your weak points. This is critical to report. 

Author Response

We appreciate the valuable feedback. We believe that the quality of the manuscript has improved significantly after addressing these critical comments.

We present a reply to every each of your comments and made necessary corrections and/or adjustments throughout the manuscript. The new whole manuscript and changes/corrections can be also tracked through bold-faced format and responses to the comments are shown in blue.

We would like to thank you for your time and efforts in the reviewing process of our paper.

Author Response File: Author Response.pdf

Reviewer 2 Report

17 June 2022

Regarding the review of manuscript ‘BIOMEDICAL AND SOCIO-ECONOMIC BASED ANALYSIS OF ALZHEIMER'S DISEASE: THE CASE OF TURKEY’ by Bayraktar Y et al., submitted to Sustainability

Manuscript ID: sustainability-1783953

Dear Authors, 

In the present article entitled ‘Biomedical and Socio-economic based Analysis of Alzheimer's Disease: The Case of Turkey’, authors aimed to investigate how biological engineering can be applied to produce solutions to various diseases such as Alzheimer's due to problems in the molecule or cell communication. Here, firstly authors proposed a molecular communication model that could be used in the diagnosis of Alzheimer's disease, and its results were analyzed with an artificial neural network. Secondly, the ratio of people suffering from Alzheimer's disease to the total population, educational statute, income inequality, poverty threshold, and the number of the poor taken into consideration, and detailed distribution according to Turkey was examined by using the Random Forest model. Results showed that the higher income level was causally associated with a lower risk of Alzheimer's disease.

The main strength of this manuscript is that it addresses an interesting and timely question, providing a captivating interpretation and investigating rate of 65+ age in Turkey population, and how this increase also affects the Alzheimer’s people. In general, I think the idea of this manuscript is really interesting and the authors’ fascinating observations on this timely topic may be of interest to the readers of Sustainability. However, some comments, as well as some crucial evidence that should be included to support the authors’ argumentation, needed to be addressed to improve the quality of the manuscript, its adequacy, and its readability prior to the publication in the present form, in particular reshaping parts of the Introduction and Results sections by adding more evidence. 

Please consider the following comments:

1.      Title: The title is rather vague. I recommend pinpointing it to help a reader grasp the content of this manuscript, including prevalence or something else.

2.      Abstract: According to the Journal’s guidelines, authors should have provided an abstract of about 200 words maximum. Indeed, the current one includes 225 words. Please correct it and present the background, methods, results, and conclusion proportionally.

3.      Keywords: Please list ten keywords.

4.      A Graphical Abstract is highly recommended

5.      In general, I recommend authors to use more evidence to back their claims, especially in the Introduction of the paper, which I believe is currently lacking. Thus, I recommend the authors to attempt to deepen the subject of their manuscript, as the bibliography is too concise: nonetheless, in my opinion, less than 50 articles for a research article are too low. Indeed, currently authors cite only 40 papers, and they are too low. Therefore, I suggest the authors to focus their efforts on researching more relevant literature: I believe that adding more studies and reviews will help them to provide better and more accurate background to this study.

6.      The objectives of this study are generally clear and to the point; however, I believe that there are some ambiguous points that require clarification or refining. I believe that the authors should be explicit on how they assessed the role of molecular communication-based models in AD’s diagnosis.

7.      Introduction: The ‘Introduction’ section is well-written and nicely presented, with a good balance of information about pathophysiology and neurological signs associated with Alzheimer’s disease. Nevertheless, I believe that more information on risk factors, pathogenesis, and structural and functional changes associated with neurodegeneration in AD will provide a better and more accurate background. (https://doi.org/10.3390/toxics10040191; https://doi.org/10.3390/ijms22168726; https://doi.org/10.17219/acem/149897; https://doi.org/10.1186/s41983-022-00455-z; https://doi.org/10.3390/ijms21249338; https://doi.org/10.3390/microorganisms9112281; https://doi.org/10.3390/ijms222212442). Thus, I suggest the authors to make such effort to provide a brief overview of the pertinent published on neurobiological signs of AD, because as it stands, this information is not highlighted in the text. In this regard, I would recommend citing a recent review that examined pathophysiological basis and biomarkers of AD pathology and investigated molecular signs of neuroinflammation in neurodegenerative diseases, in particular Alzheimer’s disease (https://doi.org/10.3390/biomedicines10030544; https://doi.org/10.3390/ijms21072431). Importantly, I also recommend a relevant study in which author investigated age-related impairments in the ability to process contextual information and in the regulation of responses to threat, addressing that structural and physiological alterations in the prefrontal cortex and medial temporal lobe determine cognitive changes in advanced aging, that can eventually cause patterns of cognitive dysfunctions observed in patients with AD/MCI (https://doi.org/10.1038/s41598-018-31000-9). I firmly believe that these improvements will help to provide a more coherent and defined background.

8.      Introduction: In according with the previous point raised, when authors stated that ‘Alzheimer's disease (AD) is estimated to be a disease caused by incorrect communication or failure of cells. Aβ peptides are formed by the breakdown of amyloid precursor proteins (app), known as the first type membrane protein, by β-secretase and γ-secretase enzymes as shown in Figure 1’, I would suggest adding some studies that discussed amyloid-β (Aβ) pathology in AD and related effect on cognitive abilities, highlighting the combined effect of forms of Aβ and tau protein to drive healthy neurons into the diseased state. Aβ peptide and tau protein consistently accumulate in the frontal and/or parietal lobes, and cause alterations of frontal lobe that impact memory and error-driven learning in individuals who have a high risk of dementia: a novel manuscript provides an overview of the anatomical–functional interplay between the prefrontal cortex and heart-related dynamics in human emotional conditioning (learning) and proposes a theoretical model to conceptualize these psychophysiological processes, the neurovisceral integration model of fear (NVI-f) that can be impaired in the context of psychiatric disorder (https://doi.org/10.1016/j.tins.2022.04.003), while another recent study demonstrated, on a neurophysiological level, the role of PFC in fear conditioning (https://doi.org/10.1111/psyp.14122). Secondary, authors also might to consider some studies that have focused on this topic (https://doi.org/10.1007/978-3-319-56015-1_444-1; https://doi.org/10.3390/biomedicines10010076). I believe that adding information from these studies may improve the theoretical background of the present article and its argumentation by highlighting how cognitive alterations caused by frontal dysfunction are fundamental as neurodegenerative biomarkers of AD.

9.      Results: In my opinion, this section is well organized, but it illustrates findings in an excessively broad way, without really providing full statistical details, to ensure in-depth understanding and replicability of the findings. Specifically, provide more detail about Aβ ratio increases, because it appears unclear and hard to grasp how to interpret these findings. Also, in my opinion, it is necessary for the authors to present their findings using summary tables.

10.  In my opinion, I think the ‘Conclusions’ paragraph would benefit from some thoughtful as well as in-depth considerations by the authors, because as it stands, it is very descriptive but not enough theoretical as a discussion should be. Authors should make an effort, trying to explain the theoretical implication as well as the translational application of their research.

11.  In according to the previous comment, I would ask the authors to include a ‘Limitations and future directions’ section before the end of the manuscript, in which authors can describe in detail and report all the technical issues brought to the surface.

12.  References: Authors should consider revising the bibliography, as there are several incorrect citations. Indeed, according to the Journal’s guidelines, they should provide the abbreviated journal name in italics, the year of publication in bold, the volume number in italics for all the references. 

Overall, the manuscript contains six figures, two tables and 40 references. The number of references is too low for a research paper, and this prevents the possibility of publishing it in this form – in my opinion. This manuscript might carry important value providing a captivating interpretation and investigating rate of 65+ age in Turkey population, and how this increase also affects the Alzheimer’s people. 

I hope that, after these careful revisions, the manuscript can meet the Journal’s high standards for publication. I am available for a new round of revision of this article.

I declare no conflict of interest regarding this manuscript.

 

Best regards,

 

 

Reviewer 

Author Response

We appreciate the valuable feedback. We believe that the quality of the manuscript has improved significantly after addressing these critical comments.

We present a reply to every each of your comments and made necessary corrections and/or adjustments throughout the manuscript. The new whole manuscript and changes/corrections can be also tracked through bold-faced format and responses to the comments are shown in blue.

We would like to thank you for your time and efforts in the reviewing process of our paper.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The authors addressed well my comments. 

Author Response

Minor corrections have been done. We truly appreciate your time and guidance you've done 

Reviewer 2 Report

23 June 2022 

Regarding the review of manuscript ‘BIOMEDICAL AND SOCIO-ECONOMIC BASED ANALYSIS OF ALZHEIMER'S DISEASE: THE CASE OF TURKEY’ by Bayraktar Y et al., submitted to Sustainability

Manuscript ID: sustainability-1783953 

Dear Authors, 

In this research article entitled ‘Analysis of Alzhemer's Disease using Molecular Communication, Artificial Neural Network and Random Forest Models: The Case of Turkey’, authors proposed a molecular communication model that could be used in the diagnosis of Alzheimer's disease, and its results were analyzed with an artificial neural network.

I only have one last suggestion to do, to further improve the theoretical background of the present paper and its argumentation: in this regard, I would recommend deepening the information about Aβ peptide and tau protein accumulation in the frontal and/or parietal lobes, by adding evidence of alterations of frontal lobe that impact memory and error-driven learning in individuals who have a high risk of dementia (https://doi.org/10.1111/psyp.14122).

Overall, this is a timely and needed study, and I look forward to seeing further studies on this issue by these authors in the future.

I am always available for other revisions of such as interesting and important reviews.

Thank You for your work.

I declare no conflict of interest regarding this manuscript.

 

Best regards,

 

 Reviewer

Author Response

We present a reply to each comment and made necessary corrections and/or adjustments throughout the manuscript. To achieve an undemanding perceivable text, the adjusted text is made in regard to the comments presented with track follow. While reviewers’ comments were presented in a bold-faced format, responses to the comments were shown in blue. We would like to thank you for your time and efforts in the reviewing process of our paper

Author Response File: Author Response.pdf