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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 -
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 -
Dialogues in Clinical Neuroscience 2009More than 25 million people in the world today are affected by dementia, most suffering from Alzheimer's disease. In both developed and developing nations, Alzheimer's... (Review)
Review
More than 25 million people in the world today are affected by dementia, most suffering from Alzheimer's disease. In both developed and developing nations, Alzheimer's disease has had tremendous impact on the affected individuals, caregivers, and society. The etiological factors, other than older age and genetic susceptibility, remain to be determined. Nevertheless, increasing evidence strongly points to the potential risk roles of vascular risk factors and disorders (eg, cigarette smoking, midlife high blood pressure and obesity, diabetes, and cerebrovascular lesions) and the possible beneficial roles of psychosocial factors (eg, high education, active social engagement, physical exercise, and mentally stimulating activity) in the pathogenetic process and clinical manifestation of the dementing disorders. The long-term multidomain interventions toward the optimal control of multiple vascular risk factors and the maintenance of socially integrated lifestyles and mentally stimulating activities are expected to reduce the risk or postpone the clinical onset of dementia, including Alzheimer's disease.
Topics: Aging; Alzheimer Disease; Cardiovascular Diseases; Cognition; Humans; Incidence; Models, Biological; Prevalence; Risk Factors; Risk Reduction Behavior
PubMed: 19585947
DOI: 10.31887/DCNS.2009.11.2/cqiu -
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 -
The Medical Journal of Australia Mar 2023Young-onset dementia comprises a heterogeneous range of dementias, with onset at less than 65 years of age. These include primary dementias such as Alzheimer disease,... (Review)
Review
Young-onset dementia comprises a heterogeneous range of dementias, with onset at less than 65 years of age. These include primary dementias such as Alzheimer disease, frontotemporal and vascular dementias; genetic/familial dementias; metabolic disorders; and secondary dementias such as those that result from alcohol use disorder, traumatic brain injury, and infections. The presentation of young-onset dementia is varied and may include cognitive, psychiatric and neurological symptoms. Diagnostic delay is common, with a frequent diagnostic conundrum being, "Is this young-onset dementia or is this psychiatric?". For assessment and accurate diagnosis, a thorough screen is recommended, such as collateral history and investigations such as neuroimaging, lumbar puncture, neuropsychology, and genetic testing. The management of young-onset dementia needs to be age-appropriate and multidisciplinary, with timely access to services and consideration of the family (including children).
Topics: Child; Humans; Delayed Diagnosis; Dementia; Alzheimer Disease; Alcoholism; Frontotemporal Dementia
PubMed: 36807325
DOI: 10.5694/mja2.51849 -
Folia Neuropathologica 2013More than 100 years after description of Alzheimer's disease (AD), two major pathological processes observed already by Alois Alzheimer, remain as the main explanation... (Review)
Review
More than 100 years after description of Alzheimer's disease (AD), two major pathological processes observed already by Alois Alzheimer, remain as the main explanation of the pathogenesis of Alzheimer's disease. Important molecular interactions leading to AD neuropathology were described in amyloid cascade and in tau protein function. No clinical trials with novel therapies based on amyloid cascade and tau protein hypotheses have been successful. The main aim of recent research is focused on the question what is primary mechanism leading to the molecular development of AD pathology. Promising explanation of triggering mechanism can be seen in vascular pathology that have direct influence on the development of pathological processes typical for Alzheimer disease. Novel insight into a number of cellular signaling mechanisms, as well as mitochondrial function in Alzheimer disease could also bring explanations of initial processes leading to the development of this pathology.
Topics: Alzheimer Disease; Animals; Humans
PubMed: 23553131
DOI: 10.5114/fn.2013.34190 -
Journal of Alzheimer's Disease : JAD 2022Effective therapeutics for Alzheimer's disease are needed. However, previous clinical trials have pre-determined a single treatment modality, such as a drug candidate or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Effective therapeutics for Alzheimer's disease are needed. However, previous clinical trials have pre-determined a single treatment modality, such as a drug candidate or therapeutic procedure, which may be unrelated to the primary drivers of the neurodegenerative process. Therefore, increasing data set size to include the potential contributors to cognitive decline for each patient, and addressing the identified potential contributors, may represent a more effective strategy.
OBJECTIVE
To determine whether a precision medicine approach to Alzheimer's disease and mild cognitive impairment is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial.
METHODS
Twenty-five patients with dementia or mild cognitive impairment, with Montreal Cognitive Assessment (MoCA) scores of 19 or higher, were evaluated for markers of inflammation, chronic infection, dysbiosis, insulin resistance, protein glycation, vascular disease, nocturnal hypoxemia, hormone insufficiency or dysregulation, nutrient deficiency, toxin or toxicant exposure, and other biochemical parameters associated with cognitive decline. Brain magnetic resonance imaging with volumetrics was performed at baseline and study conclusion. Patients were treated for nine months with a personalized, precision medicine protocol, and cognition was assessed at t = 0, 3, 6, and 9 months.
RESULTS
All outcome measures revealed improvement: statistically significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and Alzheimer's Questionnaire Change score were documented. No serious adverse events were recorded. MRI volumetrics also improved.
CONCLUSION
Based on the cognitive improvements observed in this study, a larger, randomized, controlled trial of the precision medicine therapeutic approach described herein is warranted.
Topics: Alzheimer Disease; Cognition; Cognitive Dysfunction; Humans; Pilot Projects; Precision Medicine
PubMed: 35811518
DOI: 10.3233/JAD-215707 -
Journal of Alzheimer's Disease : JAD 2015Although meditation is believed to be over five thousand years old, scientific research on it is in its infancy. Mitigating the extensive negative biochemical effects of... (Review)
Review
Although meditation is believed to be over five thousand years old, scientific research on it is in its infancy. Mitigating the extensive negative biochemical effects of stress is a superficially discussed target of Alzheimer's disease (AD) prevention, yet may be critically important. This paper reviews lifestyle and stress as possible factors contributing to AD and meditation's effects on cognition and well-being for reduction of neurodegeneration and prevention of AD. This review highlights Kirtan Kriya (KK), an easy, cost effective meditation technique requiring only 12 minutes a day, which has been successfully employed to improve memory in studies of people with subjective cognitive decline, mild cognitive impairment, and highly stressed caregivers, all of whom are at increased risk for subsequent development of AD. KK has also been shown to improve sleep, decrease depression, reduce anxiety, down regulate inflammatory genes, upregulate immune system genes, improve insulin and glucose regulatory genes, and increase telomerase by 43%; the largest ever recorded. KK also improves psycho-spiritual well-being or spiritual fitness, important for maintenance of cognitive function and prevention of AD. KK is easy to learn and practice by aging individuals. It is the premise of this review that meditation in general, and KK specifically, along with other modalities such as dietary modification, physical exercise, mental stimulation, and socialization, may be beneficial as part of an AD prevention program.
Topics: Alzheimer Disease; Cognition Disorders; Humans; Life Style; Meditation; Stress, Psychological
PubMed: 26445019
DOI: 10.3233/JAD-142766 -
International Journal of Molecular... Nov 2019While Alzheimer's disease (AD) classical diagnostic criteria rely on clinical data from a stablished symptomatic disease, newer criteria aim to identify the disease in... (Review)
Review
While Alzheimer's disease (AD) classical diagnostic criteria rely on clinical data from a stablished symptomatic disease, newer criteria aim to identify the disease in its earlier stages. For that, they incorporated the use of AD's specific biomarkers to reach a diagnosis, including the identification of Aβ and tau depositions, glucose hypometabolism, and cerebral atrophy. These biomarkers created a new concept of the disease, in which AD's main pathological processes have already taken place decades before we can clinically diagnose the first symptoms. Therefore, AD is now considered a dynamic disease with a gradual progression, and dementia is its final stage. With that in mind, new models were proposed, considering the orderly increment of biomarkers and the disease as a continuum, or the variable time needed for the disease's progression. In 2011, the National Institute on Aging and the Alzheimer's Association (NIA-AA) created separate diagnostic recommendations for each stage of the disease continuum-preclinical, mild cognitive impairment, and dementia. However, new scientific advances have led them to create a unifying research framework in 2018 that, although not intended for clinical use as of yet, is a step toward shifting the focus from the clinical symptoms to the biological alterations and toward changing the future diagnostic and treatment possibilities. This review aims to discuss the role of biomarkers in the onset of AD.
Topics: Alzheimer Disease; Biomarkers; Humans; Risk Factors
PubMed: 31698826
DOI: 10.3390/ijms20225536