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Prevention of Alzheimer's Disease: The Impact of Modifiable Risk Factors
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Prevention of Alzheimer's Disease: The Impact of Modifiable Risk Factors

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (25 April 2022) | Viewed by 8455

Special Issue Editors

Dr. Beatriz Olaya

E-Mail Website
Guest Editor
1. Research, Innovation and Teaching Unit, Parc Sanitari Sant Joan de Déu, Sant Boi de Llogregat, Spain
2. Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
Interests: epidemiology; aging; mental health; cognitive function; lifetime perspective; depression; anxiety
Special Issues, Collections and Topics in MDPI journals
Dr. Javier Santabárbara

E-Mail Website
Guest Editor
1. Department of Microbiology, Pediatrics, Radiology and Public Health, Universidad de Zaragoza, Zaragoza, Spain
2. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain
3. Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain
Interests: epidemiology; biostatistics; aging; mental health; dementia; anxiety; depression
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Dementia, with Alzheimer's disease (AD) as its most common late-life form, has devastating effects on patients, families and society in general. As life expectancy has constantly increased in recent decades, the prevalence of dementia has continued to rise in parallel. In 2018, around 50 million people suffered from dementia, and this number is estimated to be three times higher in 2050. This figure will probably be higher in low- and middle-income countries, where around two-thirds of people are estimated to have dementia. With no current effective treatments, the main focus has been on understanding the role of potential modifiable risk factors. The evidence to date indicates that risk factors such as low education, smoking, depression, and physical inactivity could, together, account for around 40% of dementias globally. This brings hope for establishing early delivered strategies to prevent or delay the onset of dementias. 

Despite the increasing evidence of potential modifiable risk factors for AD, there is a need for understanding new modifiable risk factors for AD and other dementias, since the causes of 60% of dementia remain unknown. There is also a lack of evidence through randomized control trials with interventions specifically designed to reduce or modify risk factors for AD and dementia. This Special Issue is thus devoted to collecting further evidence on modifiable risk factors and exploring potential new therapies for dementia and AD, with a special focus on preventive programs delivered early in life.

Authors and research groups are welcome to contribute to this Special Issue by submitting manuscripts in any format (original articles, systematic reviews and state-of-the-art reviews).

Dr. Beatriz Olaya
Dr. Javier Santabárbara
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (4 papers)

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Research

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13 pages, 1321 KiB  
Article
The Risk of Developing Alzheimer’s Disease and Parkinson’s Disease in Patients with Inflammatory Bowel Disease: A Meta-Analysis
by Marta Szandruk-Bender, Benita Wiatrak and Adam Szeląg
J. Clin. Med. 2022, 11(13), 3704; https://doi.org/10.3390/jcm11133704 - 27 Jun 2022
Cited by 22 | Viewed by 3127
Abstract
Recently, a growing body of research has linked gut microbiota dysbiosis to central nervous system diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and has suggested that AD and PD pathology may take its origin from chronic inflammation in the gastrointestinal [...] Read more.
Recently, a growing body of research has linked gut microbiota dysbiosis to central nervous system diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and has suggested that AD and PD pathology may take its origin from chronic inflammation in the gastrointestinal tract. Thus, this study aimed to elucidate whether inflammatory bowel disease (IBD) is associated with a higher risk of developing AD and PD as compared to the non-IBD population by conducting a meta-analysis. A thorough search of Pubmed and Embase databases was performed to identify all relevant articles. The quality of included studies was assessed using the Newcastle-Ottawa Scale. The odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed using a fixed-effect model. To assess publication bias and heterogeneity among the studies, Egger’s test and L’Abbé plots were used, respectively. A total of eight eligible studies were included in this meta-analysis. No significant heterogeneity or significant publication bias was detected. The risk of developing AD in IBD patients was higher than in non-IBD patients (OR = 0.37; 95% CI = 0.14–1.00; p = 0.05), and there was a relationship between the occurrence of AD and Crohn’s disease or ulcerative colitis (OR = 0.11; 95% CI = 0.04–0.30; p < 0.0001, OR = 0.14; 95% CI = 0.04–0.49; p = 0.0024, respectively). The risk of developing both of the most common neurodegenerative diseases, AD and PD, was also significantly higher in patients diagnosed with Crohn’s disease or ulcerative colitis (OR = 0.21; 95% CI = 0.09–0.49; p = 0.0003, OR = 0.25; 95% CI = 0.13–0.51; p = 0.0001, respectively). This meta-analysis revealed a higher risk of AD and PD among CD and UC patients compared to the general population. It may suggest a key role for the gut microbiota in the pathogenesis of not only Crohn’s disease and ulcerative colitis but also AD and PD. The identification of this potential risk may provide earlier preventive measures to be implemented to reduce comorbidity and mortality rate. Full article
(This article belongs to the Special Issue Prevention of Alzheimer's Disease: The Impact of Modifiable Risk Factors)
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11 pages, 1702 KiB  
Article
Ovocystatin Induced Changes in Expression of Alzheimer’s Disease Relevant Proteins in APP/PS1 Transgenic Mice
by Bartlomiej Stanczykiewicz, Jakub Gburek, Maria Rutkowska, Marta Lemieszewska, Krzysztof Gołąb, Katarzyna Juszczyńska, Aleksandra Piotrowska, Tadeusz Trziszka, Piotr Dzięgiel, Marzenna Podhorska-Okołów, Agnieszka Zabłocka and Joanna Rymaszewska
J. Clin. Med. 2022, 11(9), 2372; https://doi.org/10.3390/jcm11092372 - 23 Apr 2022
Cited by 3 | Viewed by 2148
Abstract
Background: Ovocystatin is marked by structural and biological similarities to human cystatin C, which plays an important role in the course of neurodegenerative diseases. Recently, it has been shown that ovocystatin might prevent aging-related cognitive impairment in rats and reduce memory decline in [...] Read more.
Background: Ovocystatin is marked by structural and biological similarities to human cystatin C, which plays an important role in the course of neurodegenerative diseases. Recently, it has been shown that ovocystatin might prevent aging-related cognitive impairment in rats and reduce memory decline in an APP/PS1 mice model. Thus, this study aimed to assess the effect of ovocystatin on histopathological changes in APP/PS1 mice. Materials and methods: Ovocystatin was administered intraperitoneally for four weeks (40 μg/mouse) to 35-weeks-old transgenic (AD, n = 14) and wild type (NCAR, n = 15) mice (stock B6C3-Tg(APPswe, PSEN1dE9)85Dbo/Mmjax). A histopathological evaluation comprised antibodies directed against β-amyloid (1:400, SIG-39320-1000, Covance) and Tau (1:4000, AHB0042, Invitrogen). Three regions of the hippocampus— the dentate gyrus (DG) and the cornu ammonis (CA1 and CA3)—were analyzed by immunohistochemistry in each animal. All differences are expressed as percentage relative to the control group. Results: The main results showed that the percentage of immunoreactive area of β-amyloid, tau protein deposits in APP/PS1+ovCYS was decreased in DG, CA1, and CA3 regions compared with the APP/PS1 control, respectively (p < 0.05). Conclusions: Ovocystatin caused significant changes in the expression pattern of all investigated proteins in hippocampal tissues both in APP/PS1 and NCAR mice. Full article
(This article belongs to the Special Issue Prevention of Alzheimer's Disease: The Impact of Modifiable Risk Factors)
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Review

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16 pages, 785 KiB  
Review
The Role of Human Herpesvirus 6 Infection in Alzheimer’s Disease Pathogenicity—A Theoretical Mosaic
by Constantin Romanescu, Thomas Gabriel Schreiner and Ilya Mukovozov
J. Clin. Med. 2022, 11(11), 3061; https://doi.org/10.3390/jcm11113061 - 29 May 2022
Cited by 11 | Viewed by 2197
Abstract
Alzheimer’s disease (AD), a neurodegenerative disorder generally affecting older adults, is the most common form of dementia worldwide. The disease is marked by severe cognitive and psychiatric decline and has dramatic personal and social consequences. Considerable time and resources are dedicated to the [...] Read more.
Alzheimer’s disease (AD), a neurodegenerative disorder generally affecting older adults, is the most common form of dementia worldwide. The disease is marked by severe cognitive and psychiatric decline and has dramatic personal and social consequences. Considerable time and resources are dedicated to the pursuit of a better understanding of disease mechanisms; however, the ultimate goal of obtaining a viable treatment option remains elusive. Neurodegenerative disease as an outcome of gene–environment interaction is a notion widely accepted today; a clear understanding of how external factors are involved in disease pathogenesis is missing, however. In the case of AD, significant effort has been invested in the study of viral pathogens and their role in disease mechanisms. The current scoping review focuses on the purported role HHV-6 plays in AD pathogenesis. First, early studies demonstrating evidence of HHV-6 cantonment in either post-mortem AD brain specimens or in peripheral blood samples of living AD patients are reviewed. Next, selected examples of possible mechanisms whereby viral infection can directly or indirectly contribute to AD pathogenesis are presented, such as autophagy dysregulation, the interaction between miR155 and HHV-6, and amyloid-beta as an antimicrobial peptide. Finally, closely related topics such as HHV-6 penetration in the CNS, HHV-6 involvement in neuroinflammation, and a brief discussion on HHV-6 epigenetics are examined. Full article
(This article belongs to the Special Issue Prevention of Alzheimer's Disease: The Impact of Modifiable Risk Factors)
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16 pages, 842 KiB  
Review
Depression as a Risk Factor for Alzheimer’s Disease: A Systematic Review of Longitudinal Meta-Analyses
by Olalla Sáiz-Vázquez, Patricia Gracia-García, Silvia Ubillos-Landa, Alicia Puente-Martínez, Silvia Casado-Yusta, Beatriz Olaya and Javier Santabárbara
J. Clin. Med. 2021, 10(9), 1809; https://doi.org/10.3390/jcm10091809 - 21 Apr 2021
Cited by 66 | Viewed by 5549
Abstract
Alzheimer’s disease (AD) is the most frequent cause of dementia, linked to morbidity and mortality among elderly patients. Recently, several clinical studies suggested that depression is a potential risk factor for cognitive decline and AD. A review of meta-analyses was performed, calculating pooled [...] Read more.
Alzheimer’s disease (AD) is the most frequent cause of dementia, linked to morbidity and mortality among elderly patients. Recently, several clinical studies suggested that depression is a potential risk factor for cognitive decline and AD. A review of meta-analyses was performed, calculating pooled odds ratios to estimate the risk of AD in people with a prior diagnosis (or clinically significant symptoms) of depression. A total of six meta-analyses which represented 28 individual studies were analyzed. A significant association between depression and AD was found (OR = 1.54, 95% CI [1.02–2.31]; p = 0.038). The results showed that heterogeneity across studies was substantial. We found a significant positive effect size for clinical measures of depression, but not for symptomatic rating scales, in the association of depression with risk of AD. The type of rating scale used to assess depression and the cut-off criteria selected also moderated the relationship between depression and AD risk. We found that studies that used clinically significant criteria for diagnosis of depression had more consistent and significant results than studies that used symptomatic scales. Full article
(This article belongs to the Special Issue Prevention of Alzheimer's Disease: The Impact of Modifiable Risk Factors)
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