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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 -
Continuum (Minneapolis, Minn.) Jun 2022This article discusses the clinical, neuroimaging, and biomarker profiles of sporadic atypical Alzheimer disease (AD) variants, including early-onset AD, posterior... (Review)
Review
PURPOSE OF REVIEW
This article discusses the clinical, neuroimaging, and biomarker profiles of sporadic atypical Alzheimer disease (AD) variants, including early-onset AD, posterior cortical atrophy, logopenic variant primary progressive aphasia, dysexecutive variant and behavioral variant AD, and corticobasal syndrome.
RECENT FINDINGS
Significant advances are being made in the recognition and characterization of the syndromically diverse AD variants. These variants are identified by the predominant cognitive and clinical features: early-onset amnestic syndrome, aphasia, visuospatial impairments, dysexecutive and behavioral disturbance, or motor symptoms. Although understanding of regional susceptibility to disease remains in its infancy, visualizing amyloid and tau pathology in vivo and CSF examination of amyloid-β and tau proteins are particularly useful in atypical AD, which can be otherwise prone to misdiagnosis. Large-scale research efforts, such as LEADS (the Longitudinal Early-Onset Alzheimer Disease Study), are currently ongoing and will continue to shed light on our understanding of these diverse presentations.
SUMMARY
Understanding the clinical, neuroimaging, and biomarker profiles of the heterogeneous group of atypical AD syndromes improves diagnostic accuracy in patients who are at increased risk of misdiagnosis. Earlier accurate identification facilitates access to important interventions, social services and disability assistance, and crucial patient and family education.
Topics: Alzheimer Disease; Aphasia; Atrophy; Biomarkers; Humans; Neuroimaging; tau Proteins
PubMed: 35678398
DOI: 10.1212/CON.0000000000001082 -
Neurobiology of Aging Nov 2021Reactive oxygen species (ROS) are metabolic byproducts that are necessary for physiological function but can be toxic at high levels. Levels of these oxidative stressors... (Review)
Review
Reactive oxygen species (ROS) are metabolic byproducts that are necessary for physiological function but can be toxic at high levels. Levels of these oxidative stressors increase gradually throughout the lifespan, impairing mitochondrial function and damaging all parts of the body, particularly the central nervous system. Emerging evidence suggests that accumulated oxidative stress may be one of the key mechanisms causing cognitive aging and neurodegenerative diseases such as Alzheimer's disease (AD). Here, we synthesize the current literature on the effect of neuronal oxidative stress on mitochondrial dysfunction, DNA damage and epigenetic changes related to cognitive aging and AD. We further describe how oxidative stress therapeutics such as antioxidants, caloric restriction and physical activity can reduce oxidation and prevent cognitive decline in brain aging and AD. Of the currently available therapeutics, we propose that long term physical activity is the most promising avenue for improving cognitive health by reducing ROS while promoting the low levels required for optimal function.
Topics: Aging; Alzheimer Disease; Antioxidants; Brain; Caloric Restriction; Cognitive Aging; Cognitive Dysfunction; DNA Damage; Exercise; Female; Humans; Male; Mitochondria; Oxidative Stress; Reactive Oxygen Species
PubMed: 34416493
DOI: 10.1016/j.neurobiolaging.2021.07.014 -
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 -
Translational Neurodegeneration Apr 2022Alzheimer's disease (AD) is a complex, heterogeneous, progressive disease and is the most common type of neurodegenerative dementia. The prevalence of AD is expected to... (Review)
Review
Alzheimer's disease (AD) is a complex, heterogeneous, progressive disease and is the most common type of neurodegenerative dementia. The prevalence of AD is expected to increase as the population ages, placing an additional burden on national healthcare systems. There is a large need for new diagnostic tests that can detect AD at an early stage with high specificity at relatively low cost. The development of modern analytical diagnostic tools has made it possible to determine several biomarkers of AD with high specificity, including pathogenic proteins, markers of synaptic dysfunction, and markers of inflammation in the blood. There is a considerable potential in using microRNA (miRNA) as markers of AD, and diagnostic studies based on miRNA panels suggest that AD could potentially be determined with high accuracy for individual patients. Studies of the retina with improved methods of visualization of the fundus are also showing promising results for the potential diagnosis of the disease. This review focuses on the recent developments of blood, plasma, and ocular biomarkers for the diagnosis of AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Humans; MicroRNAs; Retina
PubMed: 35449079
DOI: 10.1186/s40035-022-00296-z -
Behavioural Neurology 2020Patients with Alzheimer's Disease (AD) not only are suffering from amnesia but also are prone to memory distortions, such as experiencing detailed and vivid... (Review)
Review
Patients with Alzheimer's Disease (AD) not only are suffering from amnesia but also are prone to memory distortions, such as experiencing detailed and vivid recollections of episodic events that have never been encountered (i.e., false memories). To describe and explain these distortions, we offer a review to synthesize current knowledge on false memory in AD into a framework allowing for better understanding of the taxonomy and phenomenology of false memories and of the cognitive mechanisms that may underlie false memory formation in AD. According to this review, certain phenomenological characteristics of memories (e.g., high emotional load, high vividness, or high familiarity) result in misattributions in AD. More specifically, this review proposes that generalized decline in cognitive control and inhibition in AD may result in difficulties in suppressing irrelevant information during memory monitoring, especially when irrelevant (i.e., false) information is characterized by high emotion, vividness, or familiarity. This review also proposes that binding deficits in AD decrease the ability to retrieve relevant contextual details, leading to source monitoring errors and false memories. In short, this review depicts how phenomenological characteristics of memories and failures of monitoring during retrieval contribute to the occurrence of false memory in AD.
Topics: Alzheimer Disease; Amnesia; Humans; Inhibition, Psychological; Memory; Memory Disorders; Memory, Episodic; Mental Recall; Neuropsychological Tests
PubMed: 32148564
DOI: 10.1155/2020/5284504 -
Cell Oct 2023Alzheimer's disease (AD) research has entered a new era with the recent positive phase 3 clinical trials of the anti-Aβ antibodies lecanemab and donanemab. Why did it... (Review)
Review
Alzheimer's disease (AD) research has entered a new era with the recent positive phase 3 clinical trials of the anti-Aβ antibodies lecanemab and donanemab. Why did it take 30 years to achieve these successes? Developing potent therapies for reducing fibrillar amyloid was key, as was selection of patients at relatively early stages of disease. Biomarkers of the target pathologies, including amyloid and tau PET, and insights from past trials were also critical to the recent successes. Moving forward, the challenge will be to develop more efficacious therapies with greater efficiency. Novel trial designs, including combination therapies and umbrella and basket protocols, will accelerate clinical development. Better diversity and inclusivity of trial participants are needed, and blood-based biomarkers may help to improve access for medically underserved groups. Incentivizing innovation in both academia and industry through public-private partnerships, collaborative mechanisms, and the creation of new career paths will be critical to build momentum in these exciting times.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Amyloidogenic Proteins; Antibodies, Monoclonal; Biomarkers; Clinical Trials as Topic; Drug Development
PubMed: 37848035
DOI: 10.1016/j.cell.2023.09.023 -
Nature Reviews. Neurology Mar 2022Psychosis is a common and distressing symptom in people with Alzheimer disease, and few safe and effective treatments are available. However, new approaches to symptom... (Review)
Review
Psychosis is a common and distressing symptom in people with Alzheimer disease, and few safe and effective treatments are available. However, new approaches to symptom assessment and treatment are beginning to drive the field forward. New nosological perspectives have been provided by incorporating the emergence of psychotic symptoms in older adults - even in advance of dementia - into epidemiological and neurobiological frameworks as well as into diagnostic and research criteria such as the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders, the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) research criteria for psychosis in neurodegenerative disease, and the ISTAART criteria for mild behavioural impairment. Here, we highlight the latest findings in genomics, neuroimaging and neurobiology that are informing approaches to drug discovery and repurposing. Current pharmacological and non-pharmacological treatment options are discussed, with a focus on safety and precision medicine. We also explore trial data for pimavanserin, a novel agent that shows promise for the treatment of psychosis in people with dementia, and discuss existing agents that might be useful but need further exploration such as escitalopram, lithium, cholinesterase inhibitors and vitamin D. Although the assessment and management of psychosis in people with dementia remain challenging, new opportunities are providing direction and hope to the field.
Topics: Aged; Alzheimer Disease; Humans; Neurocognitive Disorders; Neurodegenerative Diseases; Neuroimaging; Psychotic Disorders
PubMed: 34983978
DOI: 10.1038/s41582-021-00597-3