Commemorative Issue Celebrating the 20th Anniversary of the Alzheimer’s Foundation of America: Understanding and Treating Alzheimer’s Disease

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Neurology".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 32458

Special Issue Editors


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Guest Editor
NYU Long Island School of Medicine, Mineola, NY 11501, USA
Interests: Alzheimer’s disease; neurodegenerative disorder; rheumatoid arthritis
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Departments of Psychiatry and Medicine, NYU Long Island School of Medicine, Mineola, NY 11501, USA
Interests: dementia; delirium; geriatric psychiatry; psychosomatic medicine; psychopharmacology

Special Issue Information

Dear Colleagues, 

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by acognitive decline affecting memory, planning, problem-solving, language, and activities of daily living. Hallmarks of the disease are the accumulation of amyloid-β peptide and hyperphosphorylated tau protein in the brain. Unfortunately, immune-based therapies targeting these proteins have been disappointing, and there is no cure. The principal risk factor for AD is age, and as the population grows older, the global prevalence will increase dramatically. AD is, therefore, an urgent public health problem.

In this Special Issue, we encourage the submission of manuscripts on any aspect of AD diagnosis, pathogenesis and treatment. We welcome original studies, reviews, and opinion articles. This Special Issue will focus on hot topics related to AD, bring in experts in the field to discuss current therapeutic approaches, as well as novel treatments under development. The diagnosis, predictive tools and molecular mechanisms of disease pathophysiology are also of great interest. The importance of lifestyle factors such as diet and physical activity is also recognized. This Special Issue in honor of the 20th Anniversary of the Alzheimer’s Foundation of America will provide a state-of-the-art overview of this subject, which will serve as a valued point of reference for geriatricians, neurologists, internal medicine physicians, psychiatrists, neuroscientists, molecular biologists and healthcare workers.

Dr. Allison B. Reiss
Dr. Aaron Pinkhasov
Guest Editors

Manuscript Submission Information

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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. Medicina is an international peer-reviewed open access monthly 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 1800 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
  • tau
  • amyloid
  • mitochondria
  • treatment
  • neuron
  • dementia
  • pathophysiology
  • neuroimaging
  • neuroplasticity

Published Papers (10 papers)

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Research

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12 pages, 333 KiB  
Article
Relationship between Depressive Symptoms, Caregiver Strain, and Social Support with Dementia Grief in Family Caregivers
by Miriam Sánchez-Alcón, Almudena Garrido-Fernández, José María Cano-Rojas, José Luis Sánchez-Ramos and Juan Diego Ramos-Pichardo
Medicina 2024, 60(4), 643; https://doi.org/10.3390/medicina60040643 - 17 Apr 2024
Viewed by 323
Abstract
Background and Objectives: Dementia grief in family caregivers of people with dementia refers to grieving prior to the death of the care recipient. It is related to psychosocial risk factors that may have a negative impact on the health of these family [...] Read more.
Background and Objectives: Dementia grief in family caregivers of people with dementia refers to grieving prior to the death of the care recipient. It is related to psychosocial risk factors that may have a negative impact on the health of these family caregivers. This study aimed to describe the relationship between depressive symptoms, caregiver strain, and social support with dementia grief in family caregivers of people with dementia. Materials and Methods: A descriptive correlational cross-sectional study was conducted. A total of 250 family caregivers of people with dementia participated. Dementia grief was the main variable, and depressive symptoms, caregiver strain, and social support were assessed. Additionally, socio-demographic data were collected. Descriptive statistics were calculated, and a bivariate correlation analysis and a multiple linear regression analysis were performed for dementia grief. Results: Higher scores for dementia grief were found in women, in family caregivers of patients at advanced stages of dementia, and in family caregivers with a low level of education. High levels of depressive symptoms and caregiver strain and low levels of social support indicated greater intensity of dementia grief. Depressive symptomatology was the variable with the greatest influence on dementia grief. Caregiver strain and social support also related to dementia grief, but to a lesser extent. Conclusions: In family caregivers, depressive symptoms, caregiver strain, and social support are related to the intensity of dementia grief, with a greater influence of depressive symptoms. Moreover, being female, having a low level of education, and caring for a care recipient at an advanced stage of dementia are factors associated with increased dementia grief. Concerning study limitations, the sample was restricted, belonging to a specific region of Spain and to a Provincial Federation of associations. It is necessary to exercise caution in generalizing results due to the sociodemographic and geographical characteristics of the sample. Full article
10 pages, 1921 KiB  
Article
The Relationships between Caregiver Burden, Physical Frailty, Race, Behavioral and Psychological Symptoms (BPSD), and Other Associated Variables: An Exploratory Study
by Carl I. Cohen, Saeed Hashem, Kay Thwe Kyaw, Sharon A. Brangman, Suzanne Fields, Bruce R. Troen and Michael Reinhardt
Medicina 2024, 60(3), 426; https://doi.org/10.3390/medicina60030426 - 01 Mar 2024
Viewed by 894
Abstract
Background and Objectives: For persons with dementia, the relationships between caregiver burden, physical frailty, race, behavioral and psychological symptoms (BPSD), and other associated variables are poorly understood. Only one prior study examined the relationships among these variables but did not include race, which [...] Read more.
Background and Objectives: For persons with dementia, the relationships between caregiver burden, physical frailty, race, behavioral and psychological symptoms (BPSD), and other associated variables are poorly understood. Only one prior study examined the relationships among these variables but did not include race, which is an important social determinant of health outcomes in the United States. To examine these interactions, we conducted a cross-sectional exploratory study based on a model by Sugimoto and colleagues. Materials and Methods: The sample comprised 85 patient–caregiver dyads (58% White) seen in four centers in diverse regions of New York State. All patients met DSM5 criteria for a major neurocognitive disorder, had a Clinical Dementia Rating sum score of ≥3, and Mini-Mental State Examination (MMSE) score of 10 to 26. Other measures included the SHARE-Frailty Instrument(FI), the Neuropsychiatric Inventory (NPI) to assess BPSD, Zarit’s Caregiver Burden Interview (CBI), Lawton’s Activities of Daily Living (ADL) Scale, the MMSE, the Cumulative Illness Rating Scale for Geriatrics (CIRSG), age, and gender. Results: In our sample, 59% met the criteria for prefrail/subsyndromal or frail/syndromal (SSF) on the SHARE-FI. SSF had significant direct effects on the NPI and significant indirect effects on the CBI mediated through the NPI; the NPI had significant direct effects on the CBI. Race (White) had significant direct effects on the CBI (higher) and SSF (lower) but did not have significant indirect effects on the CBI. MMSE, ADL, and CIRSG were not significantly associated with the NPI or the CBI. Conclusions: Our analysis demonstrated that frailty, race, BPSD, and caregiver burden may directly or indirectly influence one another, and therefore should be considered essential elements of dementia assessment, care, and research. These results must be viewed as provisional and should be replicated longitudinally with larger samples. Full article
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21 pages, 3056 KiB  
Article
Evaluating the Diagnostic Value of Electrovestibulography (EVestG) in Alzheimer’s Patients with Mixed Pathology: A Pilot Study
by Zeinab A. Dastgheib, Brian J. Lithgow and Zahra K. Moussavi
Medicina 2023, 59(12), 2091; https://doi.org/10.3390/medicina59122091 - 28 Nov 2023
Viewed by 1093
Abstract
Background and Objectives: Diagnosis of dementia subtypes caused by different brain pathophysiologies, particularly Alzheimer’s disease (AD) from AD mixed with levels of cerebrovascular disease (CVD) symptomology (AD-CVD), is challenging due to overlapping symptoms. In this pilot study, the potential of Electrovestibulography (EVestG) [...] Read more.
Background and Objectives: Diagnosis of dementia subtypes caused by different brain pathophysiologies, particularly Alzheimer’s disease (AD) from AD mixed with levels of cerebrovascular disease (CVD) symptomology (AD-CVD), is challenging due to overlapping symptoms. In this pilot study, the potential of Electrovestibulography (EVestG) for identifying AD, AD-CVD, and healthy control populations was investigated. Materials and Methods: A novel hierarchical multiclass diagnostic algorithm based on the outcomes of its lower levels of binary classifications was developed using data of 16 patients with AD, 13 with AD-CVD, and 24 healthy age-matched controls, and then evaluated on a blind testing dataset made up of a new population of 12 patients diagnosed with AD, 9 with AD-CVD, and 8 healthy controls. Multivariate analysis was run to test the between population differences while controlling for sex and age covariates. Results: The accuracies of the multiclass diagnostic algorithm were found to be 85.7% and 79.6% for the training and blind testing datasets, respectively. While a statistically significant difference was found between the populations after accounting for sex and age, no significant effect was found for sex or age covariates. The best characteristic EVestG features were extracted from the upright sitting and supine up/down stimulus responses. Conclusions: Two EVestG movements (stimuli) and their most informative features that are best selective of the above-populations’ separations were identified, and a hierarchy diagnostic algorithm was developed for three-way classification. Given that the two stimuli predominantly stimulate the otholithic organs, physiological and experimental evidence supportive of the results are presented. Disruptions of inhibition associated with GABAergic activity might be responsible for the changes in the EVestG features. Full article
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12 pages, 348 KiB  
Article
A Perspective: Challenges in Dementia Research
by Mark Stecker
Medicina 2022, 58(10), 1368; https://doi.org/10.3390/medicina58101368 - 28 Sep 2022
Viewed by 2399
Abstract
Although dementia is a common and devastating disease that has been studied intensely for more than 100 years, no effective disease modifying treatment has been found. At this impasse, new approaches are important. The purpose of this paper is to provide, in the [...] Read more.
Although dementia is a common and devastating disease that has been studied intensely for more than 100 years, no effective disease modifying treatment has been found. At this impasse, new approaches are important. The purpose of this paper is to provide, in the context of current research, one clinician’s perspective regarding important challenges in the field in the form of specific challenges. These challenges not only illustrate the scope of the problems inherent in finding treatments for dementia, but can also be specific targets to foster discussion, criticism and new research. One common theme is the need to transform research activities from small projects in individual laboratories/clinics to larger multinational projects, in which each clinician and researcher works as an integral part. This transformation will require collaboration between researchers, large corporations, regulatory/governmental authorities and the general population, as well as significant financial investments. However, the costs of transforming the approach are small in comparison with the cost of dementia. Full article

Review

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32 pages, 1351 KiB  
Review
Alzheimer’s Disease Treatment: The Search for a Breakthrough
by Allison B. Reiss, Dalia Muhieddine, Berlin Jacob, Michael Mesbah, Aaron Pinkhasov, Irving H. Gomolin, Mark M. Stecker, Thomas Wisniewski and Joshua De Leon
Medicina 2023, 59(6), 1084; https://doi.org/10.3390/medicina59061084 - 04 Jun 2023
Cited by 6 | Viewed by 4319
Abstract
As the search for modalities to cure Alzheimer’s disease (AD) has made slow progress, research has now turned to innovative pathways involving neural and peripheral inflammation and neuro-regeneration. Widely used AD treatments provide only symptomatic relief without changing the disease course. The recently [...] Read more.
As the search for modalities to cure Alzheimer’s disease (AD) has made slow progress, research has now turned to innovative pathways involving neural and peripheral inflammation and neuro-regeneration. Widely used AD treatments provide only symptomatic relief without changing the disease course. The recently FDA-approved anti-amyloid drugs, aducanumab and lecanemab, have demonstrated unclear real-world efficacy with a substantial side effect profile. Interest is growing in targeting the early stages of AD before irreversible pathologic changes so that cognitive function and neuronal viability can be preserved. Neuroinflammation is a fundamental feature of AD that involves complex relationships among cerebral immune cells and pro-inflammatory cytokines, which could be altered pharmacologically by AD therapy. Here, we provide an overview of the manipulations attempted in pre-clinical experiments. These include inhibition of microglial receptors, attenuation of inflammation and enhancement of toxin-clearing autophagy. In addition, modulation of the microbiome-brain-gut axis, dietary changes, and increased mental and physical exercise are under evaluation as ways to optimize brain health. As the scientific and medical communities work together, new solutions may be on the horizon to slow or halt AD progression. Full article
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15 pages, 656 KiB  
Review
Informal Caregiving and Alzheimer’s Disease: The Psychological Effect
by Emily Hellis and Elizabeta B. Mukaetova-Ladinska
Medicina 2023, 59(1), 48; https://doi.org/10.3390/medicina59010048 - 27 Dec 2022
Cited by 7 | Viewed by 4188
Abstract
Background and Objectives: People with Alzheimer’s disease and dementia in general benefit from home-based care as demonstrated via their better quality of life, increased lifespan, and delayed disease progression. Since currently nearly half of the dementia care is being provided by informal [...] Read more.
Background and Objectives: People with Alzheimer’s disease and dementia in general benefit from home-based care as demonstrated via their better quality of life, increased lifespan, and delayed disease progression. Since currently nearly half of the dementia care is being provided by informal and unpaid caregiving, the health, wellbeing and quality of life of informal dementia caregivers is extremely important. Materials and Methods: We used a systematic review process with searches based upon the six elements from the “Quality of Life Scale for Informal Carers of Older Adults” with additional items on traditional and non-traditional caregiving ideologies, as well as caregivers’ experiences. Results: We identified 19 studies with primary data. Informal caregivers of older adults with Alzheimer’s Disease experience significant emotional strain, documented through increased levels of anxiety and depression, as well as increased caregiver burden and poorer quality of life, primarily due to caregiving ideologies, financial strain and a lack of support. Conclusions: Our findings suggest that caregiving should be a normative component of adult education to better prepare individuals with the mental and physical skills required for undertaking informal caregiving. They should also help inform policy makers to develop novel programs and services to both assist and reduce informal caregivers’ strain, whilst considering their different social and cultural contexts. Full article
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29 pages, 741 KiB  
Review
How Telemedicine Can Improve the Quality of Care for Patients with Alzheimer’s Disease and Related Dementias? A Narrative Review
by Efthalia Angelopoulou, Nikolaos Papachristou, Anastasia Bougea, Evangelia Stanitsa, Dionysia Kontaxopoulou, Stella Fragkiadaki, Dimosthenis Pavlou, Christos Koros, Yıldız Değirmenci, John Papatriantafyllou, Eleftherios Thireos, Antonios Politis, Agis Tsouros, Panagiotis Bamidis, Leonidas Stefanis and Sokratis Papageorgiou
Medicina 2022, 58(12), 1705; https://doi.org/10.3390/medicina58121705 - 22 Nov 2022
Cited by 13 | Viewed by 4811
Abstract
Background and Objectives: Dementia affects more than 55 million patients worldwide, with a significant societal, economic, and psychological impact. However, many patients with Alzheimer’s disease (AD) and other related dementias have limited access to effective and individualized treatment. Care provision for dementia [...] Read more.
Background and Objectives: Dementia affects more than 55 million patients worldwide, with a significant societal, economic, and psychological impact. However, many patients with Alzheimer’s disease (AD) and other related dementias have limited access to effective and individualized treatment. Care provision for dementia is often unequal, fragmented, and inefficient. The COVID-19 pandemic accelerated telemedicine use, which holds promising potential for addressing this important gap. In this narrative review, we aim to analyze and discuss how telemedicine can improve the quality of healthcare for AD and related dementias in a structured manner, based on the seven dimensions of healthcare quality defined by the World Health Organization (WHO), 2018: effectiveness, safety, people-centeredness, timeliness, equitability, integrated care, and efficiency. Materials and Methods: MEDLINE and Scopus databases were searched for peer-reviewed articles investigating the role of telemedicine in the quality of care for patients with dementia. A narrative synthesis was based on the seven WHO dimensions. Results: Most studies indicate that telemedicine is a valuable tool for AD and related dementias: it can improve effectiveness (better access to specialized care, accurate diagnosis, evidence-based treatment, avoidance of preventable hospitalizations), timeliness (reduction of waiting times and unnecessary transportation), patient-centeredness (personalized care for needs and values), safety (appropriate treatment, reduction of infection risk),integrated care (interdisciplinary approach through several dementia-related services), efficiency (mainly cost-effectiveness) and equitability (overcoming geographical barriers, cultural diversities). However, digital illiteracy, legal and organizational issues, as well as limited awareness, are significant potential barriers. Conclusions: Telemedicine may significantly improve all aspects of the quality of care for patients with dementia. However, future longitudinal studies with control groups including participants of a wide educational level spectrum will aid in our deeper understanding of the real impact of telemedicine in quality care for this population. Full article
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22 pages, 466 KiB  
Review
Plants, Plants, and More Plants: Plant-Derived Nutrients and Their Protective Roles in Cognitive Function, Alzheimer’s Disease, and Other Dementias
by Helen Ding, Allison B. Reiss, Aaron Pinkhasov and Lora J. Kasselman
Medicina 2022, 58(8), 1025; https://doi.org/10.3390/medicina58081025 - 30 Jul 2022
Cited by 8 | Viewed by 3798
Abstract
Background and Objectives: Alzheimer’s disease (AD) is the most common form of dementia, with the risk of developing it attributed to non-modifiable and modifiable factors. Currently, there is no cure for AD. A plant-based diet may protect against cognitive decline, due to the [...] Read more.
Background and Objectives: Alzheimer’s disease (AD) is the most common form of dementia, with the risk of developing it attributed to non-modifiable and modifiable factors. Currently, there is no cure for AD. A plant-based diet may protect against cognitive decline, due to the effects of plant-based nutrients such as vitamins, antioxidants, and fiber. The aim of the review is to summarize current literature on plant-based nutrients and their impact on cognition. Materials and Methods: A search was conducted on PubMed for clinical and murine studies, using combinations of the following words: “Alzheimer’s disease”, “dementia”, “cognition”, “plant-based diet”, “mild cognitive impairment”, “vitamin B”, “vitamin C”, “vitamin E, “beta carotene”, “antioxidants”, “fiber”, “vitamin K”, “Mediterranean diet”, “vitamin D”, and “mushrooms”. Results and Conclusions: A diet rich in vitamin B and antioxidants can benefit the cognitive functions of individuals as shown in randomized clinical trials. Vitamin K is associated with improved cognition, although large randomized controlled trials need to be done. Fiber has been shown to prevent cognitive decline in animal studies. Vitamin D may contribute to cognitive health via anti-inflammatory processes. Several medical organizations have recommended a plant-based diet for optimizing cognitive health and potentially helping to prevent dementia. Full article
21 pages, 1388 KiB  
Review
Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation
by Jeffrey Cummings and Jefferson Kinney
Medicina 2022, 58(7), 952; https://doi.org/10.3390/medicina58070952 - 19 Jul 2022
Cited by 15 | Viewed by 5274
Abstract
Background and Objectives: The US Food and Drug Administration (FDA) defines a biomarker as a characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention. Biomarkers may be used in clinical care [...] Read more.
Background and Objectives: The US Food and Drug Administration (FDA) defines a biomarker as a characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention. Biomarkers may be used in clinical care or as drug development tools (DDTs) in clinical trials. The goal of this review and perspective is to provide insight into the regulatory guidance for the use of biomarkers in clinical trials and clinical care. Materials and Methods: We reviewed FDA guidances relevant to biomarker use in clinical trials and their transition to use in clinical care. We identified instructive examples of these biomarkers in Alzheimer’s disease (AD) drug development and their application in clinical practice. Results: For use in clinical trials, biomarkers must have a defined context of use (COU) as a risk/susceptibility, diagnostic, monitoring, predictive, prognostic, pharmacodynamic, or safety biomarker. A four-stage process defines the pathway to establish the regulatory acceptance of the COU for a biomarker including submission of a letter of intent, description of the qualification plan, submission of a full qualification package, and acceptance through a qualification recommendation. Biomarkers used in clinical care may be companion biomarkers, in vitro diagnostic devices (IVDs), or laboratory developed tests (LDTs). A five-phase biomarker development process has been proposed to structure the biomarker development process. Conclusions: Biomarkers are increasingly important in drug development and clinical care. Adherence to regulatory guidance for biomarkers used in clinical trials and patient care is required to advance these important drug development and clinical tools. Full article
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9 pages, 608 KiB  
Review
The Knowledge and Attitudes of Primary Care and the Barriers to Early Detection and Diagnosis of Alzheimer’s Disease
by Donna de Levante Raphael
Medicina 2022, 58(7), 906; https://doi.org/10.3390/medicina58070906 - 07 Jul 2022
Cited by 10 | Viewed by 3939
Abstract
Primary care physicians play a vital role in the clinical care of their patients, early identification of dementia, and disease advocacy. It is essential to assess the knowledge and attitudes of physicians in the diagnosis of Alzheimer’s disease and other dementias. In primary [...] Read more.
Primary care physicians play a vital role in the clinical care of their patients, early identification of dementia, and disease advocacy. It is essential to assess the knowledge and attitudes of physicians in the diagnosis of Alzheimer’s disease and other dementias. In primary care, the diagnosis of Alzheimer’s disease is often missed or delayed. With the increased prevalence of Alzheimer’s disease and the growing impact of dementia on health care resources, early detection by primary care physicians (PCP) is essential. Thus, their knowledge and attitudes about early detection and diagnosis are crucial. To examine the knowledge and attitudes of primary care physicians regarding early detection and diagnosis of Alzheimer’s disease and how barriers may contribute to missed and delayed detection and diagnosis. An interpretive scope review was used to synthesize and analyze a body of literature published over the past decade. The study population are physicians in the United States. The current health systems experience challenges in providing early, safe, accurate, and comprehensive Alzheimer’s diagnosis and care by a primary care physician trained or knowledgeable in diagnosing the various forms of dementia. This article identifies several interrelated obstacles to early detection and diagnosis in primary dementia care, including gaps in knowledge, attitudes, skills, and resources for person with dementia (PWD)/caregivers and their primary care providers and systematic and structural barriers that negatively impact dementia care. Research shows that Alzheimer’s disease has gone underdiagnosed and undertreated. Delays in detection, diagnosis, and resource utilization may have social and clinical implications for individuals affected by Alzheimer’s disease and their families, including challenges in obtaining an accurate diagnosis. Until the issues of missed and delayed Alzheimer’s screening become more compelling, efforts to promote early detection and diagnosis should focus on the education of physicians and removing the barriers to diagnosis. Full article
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