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Neuroscience Bulletin Dec 2018Alzheimer's disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD... (Review)
Review
Alzheimer's disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD. In this review, we summarize the latest achievements, including diagnostic biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials targeting amyloid-beta (Aβ), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.
Topics: Alzheimer Disease; Animals; Biomarkers; Biomedical Research; Disease Progression; Humans; Magnetic Resonance Imaging
PubMed: 29956105
DOI: 10.1007/s12264-018-0249-z -
Alzheimer's & Dementia : the Journal of... Sep 2018Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's... (Review)
Review
INTRODUCTION
Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, sex and gender have not yet been adequately integrated into many of these approaches.
METHODS
The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD.
RESULTS
The current review is a result of this Network's efforts and aims to: (1) highlight the current state-of-the-science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research.
DISCUSSION
The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes.
Topics: Alzheimer Disease; Animals; Gender Identity; Humans; Sex Characteristics
PubMed: 29907423
DOI: 10.1016/j.jalz.2018.04.008 -
Neurologic Clinics May 2017Early-onset Alzheimer disease (EOAD), with onset in individuals younger than 65 years, although overshadowed by the more common late-onset AD (LOAD), differs... (Review)
Review
Early-onset Alzheimer disease (EOAD), with onset in individuals younger than 65 years, although overshadowed by the more common late-onset AD (LOAD), differs significantly from LOAD. EOAD comprises approximately 5% of AD and is associated with delays in diagnosis, aggressive course, and age-related psychosocial needs. One source of confusion is that a substantial percentage of EOAD are phenotypic variants that differ from the usual memory-disordered presentation of typical AD. The management of EOAD is similar to that for LOAD, but special emphasis should be placed on targeting the specific cognitive areas involved and more age-appropriate psychosocial support and education.
Topics: Age of Onset; Alzheimer Disease; Disease Progression; Humans
PubMed: 28410659
DOI: 10.1016/j.ncl.2017.01.005 -
Seminars in Neurology Apr 2019Alzheimer's disease (AD) is the commonest neurodegenerative disease and the most frequent cause of dementia. It affects 30 million people worldwide. Current research... (Review)
Review
Alzheimer's disease (AD) is the commonest neurodegenerative disease and the most frequent cause of dementia. It affects 30 million people worldwide. Current research criteria focus on biomarkers' status for amyloid and tau using positron emission tomography and cerebrospinal fluid analysis, independent of clinical status. Current epidemiological data, which mostly rely on biomarker-undetermined AD cases, have highlighted ApoE4 and age as the main risk factors. Rare autosomal dominant mutations also account for a small fraction of early-onset AD. The main clinical phenotype at presentation is the amnestic phenotype targeting episodic memory. This is followed by rarer phenotypes such as posterior cortical atrophy, logopenic variant of primary progressive aphasia, frontal variant AD, corticobasal syndrome, and other even rarer presentations mimicking language variants of frontotemporal dementia. Main differential diagnoses include hippocampal sclerosis with TDP-43, primary age-related tauopathy, argyrophilic grain disease, frontotemporal lobar degeneration, Lewy body disease, chronic traumatic encephalopathy as well as nondegenerative disorders such as cerebrovascular disease, chronic alcohol consumption, limbic encephalitis, medial temporal lobe epilepsy, and others. Co-occurrence of AD pathology with other neurodegenerative and vascular diseases is common and increases with age. This presents a challenge in current clinical practice due to a lack of reliable biomarkers for non-AD neurodegenerative diseases.
Topics: Alzheimer Disease; Humans
PubMed: 30925614
DOI: 10.1055/s-0039-1681041 -
Alzheimer's & Dementia : the Journal of... Mar 2016During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker... (Review)
Review
During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.
Topics: Alzheimer Disease; Animals; Brain; Disease Progression; Humans
PubMed: 27012484
DOI: 10.1016/j.jalz.2016.02.002 -
Biochemical Pharmacology May 2023Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases that affect millions of people worldwide, with both prevalence and incidence increasing... (Review)
Review
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases that affect millions of people worldwide, with both prevalence and incidence increasing with age. It is characterized by cognitive decline associated, specifically, with degeneration of cholinergic neurons. The problem of this disease is even more fundamental as the available therapies remain fairly limited and mainly focused on symptoms' relief. Although the aetiology of the disease remains elusive, two main pathological hallmarks are described: i) presence of neurofibrillary tangles formed by unfolded protein aggregates (hyperphosphorylated Tau protein) and ii) presence of extracellular aggregates of amyloid-beta peptide. Given the complexity surrounding the pathogenesis of the disease, several potential targets have been highlighted and interrelated upon its progression, such as oxidative stress and the accumulation of metal ions. Thus, advances have been made on the development of innovative multitarget therapeutical compounds to delay the disease progression and restore cell function. This review focuses the ongoing research on new insights and emerging disease-modifying drugs for AD treatment. Furthermore, classical and novel potential biomarkers for early diagnosis of the disease, and their role in assisting on the improvement of targeted therapies will also be approached.
Topics: Humans; Alzheimer Disease; tau Proteins; Amyloid beta-Peptides; Oxidative Stress
PubMed: 36996971
DOI: 10.1016/j.bcp.2023.115522 -
Molecular Biology Reports Jul 2021Alzheimer's disease (AD) is a neurodegenerative old age disease that is complex, multifactorial, unalterable, and progressive in nature. The currently approved therapy... (Review)
Review
Alzheimer's disease (AD) is a neurodegenerative old age disease that is complex, multifactorial, unalterable, and progressive in nature. The currently approved therapy includes cholinesterase inhibitors, NMDA-receptor antagonists and their combination therapy provides only temporary symptomatic relief. Sincere efforts have been made by the researchers globally to identify new targets, discover, and develop novel therapeutic agents for the treatment of AD. This brief review article is intended to cover the recent advances in drug development and emerging therapeutic agents for AD acting at different targets. The article is compiled using various scientific online databases and by referring to clinicaltrials.gov and ALZFORUM (alzforum.org) websites. The upcoming therapies act on one or more targets including amyloids (secretases, Aβ production, amyloid deposition, and immunotherapy), tau proteins (tau phosphorylation/aggregation and immunotherapy) and neuroinflammation in addition to other miscellaneous targets. Despite the tremendous improvement in our understanding of the underlying pathophysiology of AD, only aducanumab was approved by FDA for the treatment of AD in 18 years i.e., since 2003. Hence, it is concluded that novel therapeutic strategies are required to discover and develop therapeutic agents to fight against the century old AD.
Topics: Alzheimer Disease; Animals; Biomarkers; Clinical Trials as Topic; Disease Management; Disease Susceptibility; Drug Development; Humans; Molecular Targeted Therapy; Treatment Outcome
PubMed: 34181171
DOI: 10.1007/s11033-021-06512-9 -
International Journal of Molecular... Jan 2023There is a paucity of empirical research on the use of non-pharmacological interventions to both treat and curb the spread of Alzheimer's disease (AD) across the globe.... (Review)
Review
There is a paucity of empirical research on the use of non-pharmacological interventions to both treat and curb the spread of Alzheimer's disease (AD) across the globe. This paper examines the biochemical and clinical outlook and the social implications of the condition in relation to psychological aspects that may indicate a direction for further interventions. There is a scarcity of research on the effectiveness of using various psychological aspects of AD, a disease characterized by a process of transition from health and independence to a dependent state with a progressive loss of memory and functional skills. The paper investigates the biochemical and psychological aspects of AD and their significance for improving quality of life for patients with this disease. Psychological interventions based on, among other factors, biochemical studies, are conducted to improve the emotional wellbeing of AD patients and may assist in slowing down the progression of the disease. To date, however, no effective methods of AD treatment have been established.
Topics: Humans; Alzheimer Disease; Quality of Life
PubMed: 36674580
DOI: 10.3390/ijms24021059 -
Molecular Neurobiology Dec 2020Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term... (Review)
Review
Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term "microbiota-gut-brain axis" from "gut-brain axis" underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. Alterations in the composition of gut microbiota are associated with multiple neuropsychiatric disorders. Although a causal relationship between gut dysbiosis and neural dysfunction remains elusive, emerging evidence indicates that gut dysbiosis may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, and insulin resistance in the pathogenesis of Alzheimer's disease (AD). Illustration of the mechanisms underlying the regulation by gut microbiota may pave the way for developing novel therapeutic strategies for AD. In this narrative review, we provide an overview of gut microbiota and their dysregulation in the pathogenesis of AD. Novel insights into the modification of gut microbiota composition as a preventive or therapeutic approach for AD are highlighted.
Topics: Alzheimer Disease; Animals; Brain; Dysbiosis; Gastrointestinal Microbiome; Humans; Insulin Resistance; Oxidative Stress
PubMed: 32829453
DOI: 10.1007/s12035-020-02073-3 -
The American Journal of Managed Care Aug 2020Alzheimer disease is the most common cause of dementia and the fifth leading cause of death in adults older than 65 years. The estimated total healthcare costs for the...
Alzheimer disease is the most common cause of dementia and the fifth leading cause of death in adults older than 65 years. The estimated total healthcare costs for the treatment of Alzheimer disease in 2020 is estimated at $305 billion, with the cost expected to increase to more than $1 trillion as the population ages. Most of the direct costs of care for Alzheimer disease are attributed to skilled nursing care, home healthcare, and hospice care. Indirect costs of care, including quality of life and informal caregiving, are likely underestimated and are associated with significant negative societal and personal burden. Managed care organizations are in a unique position to develop utilization strategies that would positively impact early diagnosis and treatment to lead to better outcomes and lower costs for patients, caregivers, and the healthcare system. Additionally, the recent inclusion of Alzheimer disease diagnoses into risk corridor calculations by the Centers for Medicare & Medicaid Services may encourage Medicare Advantage organizations to invest in programs that aid in its early detection and diagnosis.
Topics: Aged; Alzheimer Disease; Caregivers; Cost of Illness; Health Care Costs; Humans; Managed Care Programs; Medicare; Quality of Life; United States
PubMed: 32840331
DOI: 10.37765/ajmc.2020.88482