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Alzheimer's & Dementia : the Journal of... Apr 2023This article describes the public health impact of Alzheimer's disease, including prevalence and incidence, mortality and morbidity, use and costs of care, and the...
This article describes the public health impact of Alzheimer's disease, including prevalence and incidence, mortality and morbidity, use and costs of care, and the overall impact on family caregivers, the dementia workforce and society. The Special Report examines the patient journey from awareness of cognitive changes to potential treatment with drugs that change the underlying biology of Alzheimer's. An estimated 6.7 million Americans age 65 and older are living with Alzheimer's dementia today. This number could grow to 13.8 million by 2060 barring the development of medical breakthroughs to prevent, slow or cure AD. Official death certificates recorded 121,499 deaths from AD in 2019, and Alzheimer's disease was officially listed as the sixth-leading cause of death in the United States. In 2020 and 2021, when COVID-19 entered the ranks of the top ten causes of death, Alzheimer's was the seventh-leading cause of death. Alzheimer's remains the fifth-leading cause of death among Americans age 65 and older. Between 2000 and 2019, deaths from stroke, heart disease and HIV decreased, whereas reported deaths from AD increased more than 145%. This trajectory of deaths from AD was likely exacerbated by the COVID-19 pandemic in 2020 and 2021. More than 11 million family members and other unpaid caregivers provided an estimated 18 billion hours of care to people with Alzheimer's or other dementias in 2022. These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver. Unpaid dementia caregiving was valued at $339.5 billion in 2022. Its costs, however, extend to family caregivers' increased risk for emotional distress and negative mental and physical health outcomes - costs that have been aggravated by COVID-19. Members of the paid health care workforce are involved in diagnosing, treating and caring for people with dementia. In recent years, however, a shortage of such workers has developed in the United States. This shortage - brought about, in part, by COVID-19 - has occurred at a time when more members of the dementia care workforce are needed. Therefore, programs will be needed to attract workers and better train health care teams. Average per-person Medicare payments for services to beneficiaries age 65 and older with AD or other dementias are almost three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 22 times as great. Total payments in 2023 for health care, long-term care and hospice services for people age 65 and older with dementia are estimated to be $345 billion. The Special Report examines whether there will be sufficient numbers of physician specialists to provide Alzheimer's care and treatment now that two drugs are available that change the underlying biology of Alzheimer's disease.
Topics: Humans; Aged; United States; Alzheimer Disease; Pandemics; Health Care Costs; COVID-19; Medicare; Caregivers
PubMed: 36918389
DOI: 10.1002/alz.13016 -
Current Neuropharmacology 2020The only conclusive way to diagnose Alzheimer's is to carry out brain autopsy of the patient's brain tissue and ascertain whether the subject had Alzheimer's or any... (Review)
Review
BACKGROUND
The only conclusive way to diagnose Alzheimer's is to carry out brain autopsy of the patient's brain tissue and ascertain whether the subject had Alzheimer's or any other form of dementia. However, due to the non-feasibility of such methods, to diagnose and conclude the conditions, medical practitioners use tests that examine a patient's mental ability.
OBJECTIVE
Accurate diagnosis at an early stage is the need of the hour for initiation of therapy. The cause for most Alzheimer's cases still remains unknown except where genetic distinctions have been observed. Thus, a standard drug regimen ensues in every Alzheimer's patient, irrespective of the cause, which may not always be beneficial in halting or reversing the disease progression. To provide a better life to such patients by suppressing existing symptoms, early diagnosis, curative therapy, site-specific delivery of drugs, and application of hyphenated methods like artificial intelligence need to be brought into the main field of Alzheimer's therapeutics.
METHODS
In this review, we have compiled existing hypotheses to explain the cause of the disease, and highlighted gene therapy, immunotherapy, peptidomimetics, metal chelators, probiotics and quantum dots as advancements in the existing strategies to manage Alzheimer's.
CONCLUSION
Biomarkers, brain-imaging, and theranostics, along with artificial intelligence, are understood to be the future of the management of Alzheimer's.
Topics: Alzheimer Disease; Animals; Biomarkers; Brain; Disease Progression; Early Diagnosis; Humans; Neuroimaging
PubMed: 32484110
DOI: 10.2174/1570159X18666200528142429 -
Alzheimer's & Dementia : the Journal of... Apr 2018In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and... (Review)
Review
In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a "research framework" because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.
Topics: Alzheimer Disease; Animals; Biomarkers; Brain; Humans; National Institute on Aging (U.S.); United States
PubMed: 29653606
DOI: 10.1016/j.jalz.2018.02.018 -
The Journal of Prevention of... 2021Mild Alzheimer's disease is the leading cause of dementia, accounting for 50-70% of cases. Alzheimer's disease is an irreversible neurodegenerative disease, which... (Review)
Review
Mild Alzheimer's disease is the leading cause of dementia, accounting for 50-70% of cases. Alzheimer's disease is an irreversible neurodegenerative disease, which affects daily life activities and social functioning. As life expectancy increases and demographic ageing occurs, the global prevalence of Alzheimer's disease is expected to continue to rise especially in developing countries, leading to a costly burden of disease. Alzheimer's disease is a complex and multifactorial disorder that is determined by the interaction of genetic susceptibility and environmental factors across the life course. Epidemiological studies have identified potential modifiable risk and protective factors for Alzheimer's disease prevention. Moreover, Alzheimer's disease is considered to start decades earlier before clinical symptoms occur, thus interventions targeting several risk factors in non-demented elderly people even middle-aged population might prevent or delay Alzheimer's disease onset. Here, we provide an overview of current epidemiological advances related to Alzheimer's disease modifiable risk factors, highlighting the concept of early prevention.
Topics: Alzheimer Disease; Cardiovascular Diseases; Exercise; Humans; Life Style; Prevalence; Protective Factors; Risk Factors
PubMed: 34101789
DOI: 10.14283/jpad.2021.15 -
Journal of Alzheimer's Disease : JAD 2019Population-based clinic-pathological studies have established that the most common pathological substrate of dementia in community-dwelling elderly people is mixed,... (Review)
Review
Population-based clinic-pathological studies have established that the most common pathological substrate of dementia in community-dwelling elderly people is mixed, especially Alzheimer's disease (AD) and cerebrovascular ischemic disease (CVID), rather than pure AD. While these could be just two frequent unrelated comorbidities in the elderly, epidemiological research has reinforced the idea that mid-life (age <65 years) vascular risk factors increase the risk of late-onset (age ≥ 65 years) dementia, and specifically AD. By contrast, healthy lifestyle choices such as leisure activities, physical exercise, and Mediterranean diet are considered protective against AD. Remarkably, several large population-based longitudinal epidemiological studies have recently indicated that the incidence and prevalence of dementia might be decreasing in Western countries. Although it remains unclear whether these positive trends are attributable to neuropathologically definite AD versus CVID, based on these epidemiological data it has been estimated that a sizable proportion of AD cases could be preventable. In this review, we discuss the current evidence about modifiable risk factors for AD derived from epidemiological, preclinical, and interventional studies, and analyze the opportunities for therapeutic and preventative interventions.
Topics: Alzheimer Disease; Genetic Predisposition to Disease; Humans; Prevalence; Risk Factors
PubMed: 30776012
DOI: 10.3233/JAD181028 -
Journal of Alzheimer's Disease : JAD 2017The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various... (Review)
Review
The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-β peptides (Aβ). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways. Studies in germ-free animals and in animals exposed to pathogenic microbial infections, antibiotics, probiotics, or fecal microbiota transplantation suggest a role for the gut microbiota in host cognition or AD-related pathogenesis. The increased permeability of the gut and blood-brain barrier induced by microbiota dysbiosis may mediate or affect AD pathogenesis and other neurodegenerative disorders, especially those associated with aging. In addition, bacteria populating the gut microbiota can secrete large amounts of amyloids and lipopolysaccharides, which might contribute to the modulation of signaling pathways and the production of proinflammatory cytokines associated with the pathogenesis of AD. Moreover, imbalances in the gut microbiota can induce inflammation that is associated with the pathogenesis of obesity, type 2 diabetes mellitus, and AD. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of the gut microbiota in the development of AD. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for AD.
Topics: Alzheimer Disease; Brain; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans
PubMed: 28372330
DOI: 10.3233/JAD-161141 -
Current Alzheimer Research 2019Alzheimer´s disease (AD) and related forms of dementia are increasingly affecting the aging population throughout the world, at an alarming rate. The World Alzheimer´s... (Review)
Review
Alzheimer´s disease (AD) and related forms of dementia are increasingly affecting the aging population throughout the world, at an alarming rate. The World Alzheimer´s Report indicates a prevalence of 46.8 million people affected by AD worldwide. As population ages, this number is projected to triple by 2050 unless effective interventions are developed and implemented. Urgent efforts are required for an early detection of this disease. The ultimate goal is the identification of viable targets for the development of molecular markers and validation of their use for early diagnosis of AD that may improve treatment and the disease outcome in patients. The diagnosis of AD has been difficult to resolve since approaches for early and accurate detection and follow-up of AD patients at the clinical level have been reported only recently. Some proposed AD biomarkers include the detection of pathophysiological processes in the brain in vivo with new imaging techniques and novel PET ligands, and the determination of pathogenic proteins in cerebrospinal fluid showing anomalous levels of hyperphosphorylated tau and low Aβ peptide. These biomarkers have been increasingly accepted by AD diagnostic criteria and are important tools for the design of clinical trials, but difficulties in accessibility to costly and invasive procedures have not been completely addressed in clinical settings. New biomarkers are currently being developed to allow determinations of multiple pathological processes including neuroinflammation, synaptic dysfunction, metabolic impairment, protein aggregation and neurodegeneration. Highly specific and sensitive blood biomarkers, using less-invasive procedures to detect AD, are derived from the discoveries of peripheric tau oligomers and amyloid variants in human plasma and platelets. We have also developed a blood tau biomarker that correlates with a cognitive decline and also with neuroimaging determinations of brain atrophy.
Topics: Alzheimer Disease; Biomarkers; Humans
PubMed: 31099321
DOI: 10.2174/1567205016666190517121140 -
Journal of Alzheimer's Disease : JAD 2019Although Alzheimer's disease (AD) is the world's leading cause of dementia and the population of patients with AD continues to grow, no new therapies have been approved... (Review)
Review
Although Alzheimer's disease (AD) is the world's leading cause of dementia and the population of patients with AD continues to grow, no new therapies have been approved in more than a decade. Many clinical trials of single-agent therapies have failed to affect disease progression or symptoms compared with placebo. The complex pathophysiology of AD may necessitate combination treatments rather than monotherapy. The goal of this narrative literature review is to describe types of combination therapy, review the current clinical evidence for combination therapy regimens (both symptomatic and disease-modifying) in the treatment of AD, describe innovative clinical trial study designs that may be effective in testing combination therapy, and discuss the regulatory and drug development landscape for combination therapy. Successful combination therapies in other complex disorders, such as human immunodeficiency virus, may provide useful examples of a potential path forward for AD treatment.
Topics: Alzheimer Disease; Drug Therapy, Combination; Humans; Nootropic Agents
PubMed: 30689575
DOI: 10.3233/JAD-180766 -
Journal of Alzheimer's Disease : JAD 2017Alzheimer's disease (AD) is a neurodegenerative disorder that nowadays affects more than 40 million people worldwide and it is predicted to exponentially increase in the... (Review)
Review
Alzheimer's disease (AD) is a neurodegenerative disorder that nowadays affects more than 40 million people worldwide and it is predicted to exponentially increase in the coming decades. Because no curative treatment exists, research on the pathophysiology of the disease, as well as the testing of new drugs, are mandatory. For these purposes, animal models constitute a valuable, although perfectible tool. This review takes a tour through several aspects of mouse models of AD, such as the generation of transgenic models, the relevance of the promoter driving the expression of the transgenes, and the concrete transgenes used to simulate AD pathophysiology. Then, transgenic mouse lines harboring mutated human genes at several loci such as APP, PSEN1, APOEɛ4, and ob (leptin) are reviewed. Therefore, not only the accumulation of the Aβ peptide is emulated but also cholesterol and insulin metabolism. Further novel information about the disease will allow for the development of more accurate animal models, which in turn will undoubtedly be helpful for bringing preclinical research closer to clinical trials in humans.
Topics: Alzheimer Disease; Animals; Disease Models, Animal; Humans; Mice, Transgenic
PubMed: 28304309
DOI: 10.3233/JAD-170045 -
Alzheimer's & Dementia : the Journal of... Jun 2016Several attempts have been made to treat Alzheimer's disease (AD) using anti-amyloid strategies with disappointing results. It is clear that the "amyloid cascade... (Review)
Review
Several attempts have been made to treat Alzheimer's disease (AD) using anti-amyloid strategies with disappointing results. It is clear that the "amyloid cascade hypothesis" alone cannot fully explain the neuronal damage in AD, as evidenced both by autopsy and imaging studies. Neuroinflammation plays a significant role in neurodegenerative diseases, whereas the debate is ongoing about its precise role, whether it is protective or harmful. In this review, we focus on the potential mechanism of glial activation and how local and systemic factors influence disease progression. We focus on neuroinflammation in AD, especially in the earliest stages, a vicious cycle of glial priming, release of pro-inflammatory factors, and neuronal damage. We review the evidence from imaging studies, regarding the temporal relationship between amyloid deposition and neuroinflammation, the influence of systemic inflammation on glial activation, both in acute and chronic stimulation and the relevance of inflammation as a diagnostic and therapeutic target.
Topics: Alzheimer Disease; Cytokines; Encephalitis; Humans; Neuroimaging
PubMed: 27179961
DOI: 10.1016/j.jalz.2016.02.010