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Advances in Alzheimer’s Disease: Prevention, Diagnosis and Treatment
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Advances in Alzheimer’s Disease: Prevention, Diagnosis and Treatment

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 (15 May 2024) | Viewed by 12797

Special Issue Editors

Prof. Dr. Félix P. Bermejo-Pareja

E-Mail Website
Guest Editor
1. Research Institute (Imas12), University Hospital "12 de Octubre", Madrid, Spain
2. Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Carlos III Institute of Health, Madrid, Spain
Interests: Alzheimer’s disease; neurological diseases; neurodegenerative diseases; neurodegeneration; neuroimaging; brain diseases; neurobiology; clinical neurology; mild cognitive impairment; molecular neuroscience
Dr. Teodoro Del-Ser

E-Mail Website
Guest Editor
Alzheimer’s Centre Reina Sofia—CIEN Foundation, Madrid, Spain
Interests: clinical neuropsychology; neuropsychological assessment memory; neurological diseases; behavioral neuroscience; neurodegeneration neuroscience; Alzheimer’s disease; pharmaceutical development; neurology
Prof. Dr. Israel Contador Castillo

E-Mail Website
Guest Editor
Deptartment of Basic Psychology, Psychobiology and Methodology of Behavioral Sciences, Faculty of Psychology, University of Salamanca, 37005 Salamanca, Spain
Interests: aging; dementia; mild cognitive impairment; memory; neuropsychology; Alzheimer’s disease; gerontology; health psychology; cognition disorders; clinical neuropsychology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alzheimer’s disease (AD) and other related progressive dementias result in significant medical, social and economic impact and are of great concern to the elderly population and their families. In the medical field, this concern is rightly justified. After more than 50 years of expensive research, the early identification of AD and even its nosological definition still presents difficulties, and the main therapeutic investments dedicated to removing beta-amyloid or tau deposits in the brain have been discouraging. The good news is that  controlling the environmental risk factors for dementia (lifestyle, lowering blood pressure, physical exercise, and others) can decrease the incidence of dementia and AD in developed countries.

In this Special Issue, we aim to present a state-of-the art revision of several aspects of dementia and AD: nosological concept, clinical diagnosis (AD and mild cognitive impairment) with psychological, biomarkers, and neuroimaging aids, and main neuropathological data. AD therapy and prevention will also be updated.  

We invite the readers of JCM to send articles on hot controversies about this subject, e.g., aging, immunity, diabetes, gut microbiome, nutrition, potential infectious agents, informal therapies, and chronic family and institutional care, in contributing toward providing a valuable update on this cumbersome disorder.

Prof. Dr. Félix P. Bermejo-Pareja
Dr. Teodoro Del-Ser
Prof. Dr. Israel Contador Castillo
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.

Keywords

  • Alzheimer’s disease
  • dementia, neurological diseases
  • neurodegenerative diseases
  • brain diseases
  • neurobiology
  • clinical neurology
  • mild cognitive impairment
  • molecular neuroscience
  • aged

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Published Papers (6 papers)

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Research

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16 pages, 3261 KiB  
Article
Neuropathological Heterogeneity of Dementia Due to Combined Pathology in Aged Patients: Clinicopathological Findings in the Vallecas Alzheimer’s Reina Sofía Cohort
by Iván Burgueño-García, María José López-Martínez, Alicia Uceda-Heras, Lucía García-Carracedo, María Ascensión Zea-Sevilla, Héctor Rodrigo-Lara, Iago Rego-García, Laura Saiz-Aúz, Paloma Ruiz-Valderrey, Francisco J. López-González, Virginia Guerra-Martín and Alberto Rábano
J. Clin. Med. 2024, 13(22), 6755; https://doi.org/10.3390/jcm13226755 - 10 Nov 2024
Viewed by 554
Abstract
Background/Objectives: Clinicopathological research in late-life dementia has focused recently on combined neurodegenerative and vascular conditions underlying the high phenotypic heterogeneity of patients. The Vallecas Alzheimer’s Reina Sofía (VARS) cohort (n > 550), and particularly the series of associated brain donations (VARSpath cohort) [...] Read more.
Background/Objectives: Clinicopathological research in late-life dementia has focused recently on combined neurodegenerative and vascular conditions underlying the high phenotypic heterogeneity of patients. The Vallecas Alzheimer’s Reina Sofía (VARS) cohort (n > 550), and particularly the series of associated brain donations (VARSpath cohort) are presented here. The aim of this study is to contribute to research in dementia with a well-characterized cohort from a single center. Methods: A total of 167 patients with complete neuropathological work-ups were analyzed here. The cohort is characterized by a high female predominance (79%), advanced age at death (88 yrs.), and a high frequency of ApoE-e4 haplotype (43%). Results: The main neuropathological diagnosis was Alzheimer’s disease (79.6%), followed by vascular dementia (10.2%) and Lewy body dementia (6%). Overall, intermediate-to-high cerebrovascular disease was observed in 38.9%, Lewy body pathology in 57.5%, LATE (TDP-43 pathology) in 70.7%, ARTAG in 53%, and argyrophilic grain disease in 12% of the patients. More than one pathology with a clinically relevant burden of disease was present in 71.1% of the brains, and a selection of premortem neuropsychological and functional scores showed significant correlation with the number of co-pathologies identified in postmortem brains. Conclusions: The VARS cohort, with thorough clinical follow-up, regular blood sampling, 3-Tesla MR, and a high rate of postmortem brain donation, can provide essential multidisciplinary data in the rising age of modifying therapies and biomarkers for Alzheimer’s disease and related dementias. Full article
(This article belongs to the Special Issue Advances in Alzheimer’s Disease: Prevention, Diagnosis and Treatment)
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14 pages, 2215 KiB  
Article
Alterations in Gut Microbiota and Their Correlation with Brain Beta-Amyloid Burden Measured by 18F-Florbetaben PET in Mild Cognitive Impairment Due to Alzheimer’s Disease
by Geon Ha Kim, Bori R. Kim, Hai-Jeon Yoon and Jee Hyang Jeong
J. Clin. Med. 2024, 13(7), 1944; https://doi.org/10.3390/jcm13071944 - 27 Mar 2024
Cited by 1 | Viewed by 1478
Abstract
(1) Background: This study investigated changes in the gut microbial composition of individuals with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and their relationship with positron emission tomography (PET) amyloid accumulation. (2) Methods: In total, 17 cognitively normal individuals without amyloid-beta (Aβ) [...] Read more.
(1) Background: This study investigated changes in the gut microbial composition of individuals with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and their relationship with positron emission tomography (PET) amyloid accumulation. (2) Methods: In total, 17 cognitively normal individuals without amyloid-beta (Aβ) accumulation (Aβ−NC) and 24 with Aβ-positive mild cognitive impairment (Aβ+MCI) who underwent 18F-florbetaben PET and fecal bacterial 16S ribosomal RNA gene sequencing were enrolled. The taxonomic compositions of the Aβ−NC and Aβ+MCI groups were compared. The abundance of taxa was correlated with the standardized uptake value ratio (SUVR), using generalized linear models. (3) Results: There were significant differences in microbiome richness (ACE, p = 0.034 and Chao1, p = 0.024), alpha diversity (Shannon, p = 0.039), and beta diversity (Bray–Curtis, p = 0.018 and Generalized UniFrac, p = 0.034) between the Aβ−NC and Aβ+MCI groups. The global SUVR was positively correlated with the genus Intestinibacter (q = 0.006) and negatively correlated with the genera Roseburia (q = 0.008) and Agathobaculum (q = 0.029). (4) Conclusions: In this study, we identified significant changes in the gut microbiota composition that occur in individuals with MCI due to AD. In particular, the correlation analysis results between PET amyloid burden and gut microbial abundance showed that amyloid deposition is associated with a reduction in specific taxa involved in butyrate production. Full article
(This article belongs to the Special Issue Advances in Alzheimer’s Disease: Prevention, Diagnosis and Treatment)
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14 pages, 828 KiB  
Article
The Levels of Leptin, Cystatin C, Neuropilin-1 and Tau Protein in Relation to Dietary Habits in Patients with Alzheimer’s Disease
by Sylwia Bogdan, Anna Puścion-Jakubik, Katarzyna Klimiuk, Katarzyna Socha, Jan Kochanowicz and Ewa Gorodkiewicz
J. Clin. Med. 2023, 12(21), 6855; https://doi.org/10.3390/jcm12216855 - 30 Oct 2023
Viewed by 1114
Abstract
Alzheimer’s disease (AD) is the most common form of dementia in older people. Its prevalence is expected to increase, and therefore it poses a serious challenge to the healthcare system. The aim of the study was to assess the concentration of leptin, cystatin [...] Read more.
Alzheimer’s disease (AD) is the most common form of dementia in older people. Its prevalence is expected to increase, and therefore it poses a serious challenge to the healthcare system. The aim of the study was to assess the concentration of leptin, cystatin C, neuropilin-1 and tau protein, as well as the influence of dietary habits on these parameters, in a group of AD patients (n = 110) compared to 60 healthy people (n = 60). It has been shown that AD patients, compared to healthy people, are characterized by significantly higher median concentrations of leptin (9.97 vs. 3.08), cystatin c (1.53 vs. 0.56) and tau protein (8.46 vs. 4.19), but significantly lower median neuropilin-1 (69.94 vs. 167.28). Multiple regression analyses showed that leptin levels could be explained by dietary habits in 27%, cystatin C in 51%, neuropilin-1 in 41% and tau protein in 25% of cases. Modification of eating habits may contribute to improving the values of the discussed parameters. Full article
(This article belongs to the Special Issue Advances in Alzheimer’s Disease: Prevention, Diagnosis and Treatment)
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Review

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45 pages, 5992 KiB  
Review
Controversial Past, Splendid Present, Unpredictable Future: A Brief Review of Alzheimer Disease History
by Félix Bermejo-Pareja and Teodoro del Ser
J. Clin. Med. 2024, 13(2), 536; https://doi.org/10.3390/jcm13020536 - 17 Jan 2024
Cited by 6 | Viewed by 3825
Abstract
Background: The concept of Alzheimer disease (AD)—since its histological discovery by Alzheimer to the present day—has undergone substantial modifications. Methods: We conducted a classical narrative review of this field with a bibliography selection (giving preference to Medline best match). Results: The following subjects [...] Read more.
Background: The concept of Alzheimer disease (AD)—since its histological discovery by Alzheimer to the present day—has undergone substantial modifications. Methods: We conducted a classical narrative review of this field with a bibliography selection (giving preference to Medline best match). Results: The following subjects are reviewed and discussed: Alzheimer’s discovery, Kraepelin’s creation of a new disease that was a rare condition until the 1970′s, the growing interest and investment in AD as a major killer in a society with a large elderly population in the second half of the 20th century, the consolidation of the AD clinicopathological model, and the modern AD nosology based on the dominant amyloid hypothesis among many others. In the 21st century, the development of AD biomarkers has supported a novel biological definition of AD, although the proposed therapies have failed to cure this disease. The incidence of dementia/AD has shown a decrease in affluent countries (possibly due to control of risk factors), and mixed dementia has been established as the most frequent etiology in the oldest old. Conclusions: The current concept of AD lacks unanimity. Many hypotheses attempt to explain its complex physiopathology entwined with aging, and the dominant amyloid cascade has yielded poor therapeutic results. The reduction in the incidence of dementia/AD appears promising but it should be confirmed in the future. A reevaluation of the AD concept is also necessary. Full article
(This article belongs to the Special Issue Advances in Alzheimer’s Disease: Prevention, Diagnosis and Treatment)
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Other

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16 pages, 556 KiB  
Systematic Review
Radiomics and Artificial Intelligence for the Diagnosis and Monitoring of Alzheimer’s Disease: A Systematic Review of Studies in the Field
by Roberta Bevilacqua, Federico Barbarossa, Lorenzo Fantechi, Daniela Fornarelli, Enrico Paci, Silvia Bolognini, Cinzia Giammarchi, Fabrizia Lattanzio, Lucia Paciaroni, Giovanni Renato Riccardi, Giuseppe Pelliccioni, Leonardo Biscetti and Elvira Maranesi
J. Clin. Med. 2023, 12(16), 5432; https://doi.org/10.3390/jcm12165432 - 21 Aug 2023
Cited by 7 | Viewed by 2135
Abstract
The use of radiomics and artificial intelligence applied for the diagnosis and monitoring of Alzheimer’s disease has developed in recent years. However, this approach is not yet completely applicable in clinical practice. The aim of this paper is to provide a systematic analysis [...] Read more.
The use of radiomics and artificial intelligence applied for the diagnosis and monitoring of Alzheimer’s disease has developed in recent years. However, this approach is not yet completely applicable in clinical practice. The aim of this paper is to provide a systematic analysis of the studies that have included the use of radiomics from different imaging techniques and artificial intelligence for the diagnosis and monitoring of Alzheimer’s disease in order to improve the clinical outcomes and quality of life of older patients. A systematic review of the literature was conducted in February 2023, analyzing manuscripts and articles of the last 5 years from the PubMed, Scopus and Embase databases. All studies concerning discrimination among Alzheimer’s disease, Mild Cognitive Impairment and healthy older people performing radiomics analysis through machine and deep learning were included. A total of 15 papers were included. The results showed a very good performance of this approach in the differentiating Alzheimer’s disease patients—both at the dementia and pre-dementia phases of the disease—from healthy older people. In summary, radiomics and AI can be valuable tools for diagnosing and monitoring the progression of Alzheimer’s disease, potentially leading to earlier and more accurate diagnosis and treatment. However, the results reported by this review should be read with great caution, keeping in mind that imaging alone is not enough to identify dementia due to Alzheimer’s. Full article
(This article belongs to the Special Issue Advances in Alzheimer’s Disease: Prevention, Diagnosis and Treatment)
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12 pages, 433 KiB  
Study Protocol
The Effects of Methylfolate on Cognitive Decline and Dementia: A Protocol for Systematic Review and Meta-Analysis
by Leícia Iris de Assunção Prado, Ana Lúcia Junger, Leonardo Ferreira Caixeta, Matias Noll, Cesar de Oliveira and Érika Aparecida Silveira
J. Clin. Med. 2023, 12(9), 3075; https://doi.org/10.3390/jcm12093075 - 24 Apr 2023
Cited by 2 | Viewed by 3057
Abstract
Introduction: Dementia and cognitive decline are highly prevalent in later life and are growing public health concerns worldwide due to the increasing aging population. Individuals diagnosed with dementia have reduced mental function, resulting in social and cognitive skill deficits, increased dependence, and reduced [...] Read more.
Introduction: Dementia and cognitive decline are highly prevalent in later life and are growing public health concerns worldwide due to the increasing aging population. Individuals diagnosed with dementia have reduced mental function, resulting in social and cognitive skill deficits, increased dependence, and reduced autonomy—all of which are conditions associated with higher mortality rates. This systematic review aims to assess the effectiveness of treating dementia and cognitive decline with methylfolate. The main outcomes analyzed will be dementia and changes in cognitive function measured by different instruments in older adults treated with methylfolate. Secondary outcomes, such as inflammatory markers, plasma folic-acid levels, and total homocysteine, will also be assessed. Methods and Analysis: This study will be carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This protocol is registered in the International Prospective Registry of Systematic Reviews, under the code CRD42021275755. We will include clinical trials conducted with older adults diagnosed with dementia or cognitive decline and treated with folic acid. The searches will be conducted on the PubMed, Scopus, and Embase databases, and the articles will be selected by reading their titles and abstracts first, followed by the full text. The quality of the selected studies will be assessed using GRADE and the risk of bias will be assessed using the Downs-and-Black method. Ethics and Dissemination: The results will be presented at scientific conferences and disseminated by publishing a scientific article in an international English-language journal. We hope to find robust and significant evidence regarding the effectiveness of methylfolate supplementation in improving dementia symptoms and cognitive decline among older adults. By systematizing this evidence and possibly performing a meta-analysis study, we expect to significantly contribute to the treatment of this health problem, reduce mortality, and improve the quality of life and health of this population, boosting the development of medical protocols capable of reducing the financial effects of public health. Full article
(This article belongs to the Special Issue Advances in Alzheimer’s Disease: Prevention, Diagnosis and Treatment)
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