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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 -
Journal of Alzheimer's Disease : JAD 2018The Religious Orders Study and Rush Memory and Aging Project are both ongoing longitudinal clinical-pathologic cohort studies of aging and Alzheimer's disease (AD). (Review)
Review
BACKGROUND
The Religious Orders Study and Rush Memory and Aging Project are both ongoing longitudinal clinical-pathologic cohort studies of aging and Alzheimer's disease (AD).
OBJECTIVES
To summarize progress over the past five years and its implications for understanding neurodegenerative diseases.
METHODS
Participants in both studies are older adults who enroll without dementia and agree to detailed longitudinal clinical evaluations and organ donation. The last review summarized findings through the end of 2011. Here we summarize progress and study findings over the past five years and discuss new directions for how these studies can inform on aging and AD in the future.
RESULTS
We summarize 1) findings on the relation of neurobiology to clinical AD; 2) neurobiologic pathways linking risk factors to clinical AD; 3) non-cognitive AD phenotypes including motor function and decision making; 4) the development of a novel drug discovery platform.
CONCLUSION
Complexity at multiple levels needs to be understood and overcome to develop effective treatments and preventions for cognitive decline and AD dementia.
Topics: Aging; Alzheimer Disease; Humans; Memory; Religious Personnel; United States
PubMed: 29865057
DOI: 10.3233/JAD-179939 -
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 -
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 -
Ageing Research Reviews Aug 2022Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique. When stimulation is applied over the primary motor cortex and coupled with... (Meta-Analysis)
Meta-Analysis Review
Cortical excitability and plasticity in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis of transcranial magnetic stimulation studies.
BACKGROUND
Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique. When stimulation is applied over the primary motor cortex and coupled with electromyography measures, TMS can probe functions of cortical excitability and plasticity in vivo. The purpose of this meta-analysis is to evaluate the utility of TMS-derived measures for differentiating patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) from cognitively normal older adults (CN).
METHODS
Databases searched included PubMed, Embase, APA PsycInfo, Medline, and CINAHL Plus from inception to July 2021.
RESULTS
Sixty-one studies with a total of 2728 participants (1454 patients with AD, 163 patients with MCI, and 1111 CN) were included. Patients with AD showed significantly higher cortical excitability, lower cortical inhibition, and impaired cortical plasticity compared to the CN cohorts. Patients with MCI exhibited increased cortical excitability and reduced plasticity compared to the CN cohort. Additionally, lower cognitive performance was significantly associated with higher cortical excitability and lower inhibition. No seizure events due to TMS were reported, and the mild adverse response rate is approximately 3/1000 (i.e., 9/2728).
CONCLUSIONS
Findings of our meta-analysis demonstrate the potential of using TMS-derived cortical excitability and plasticity measures as diagnostic biomarkers and therapeutic targets for AD and MCI.
Topics: Aged; Alzheimer Disease; Cognitive Dysfunction; Cortical Excitability; Humans; Neuronal Plasticity; Transcranial Magnetic Stimulation
PubMed: 35680080
DOI: 10.1016/j.arr.2022.101660 -
Journal of Alzheimer's Disease : JAD 2017The field of Alzheimer's disease (AD) research has grown exponentially over the past few decades, especially since the isolation and identification of amyloid-β from... (Review)
Review
The field of Alzheimer's disease (AD) research has grown exponentially over the past few decades, especially since the isolation and identification of amyloid-β from postmortem examination of the brains of AD patients. Recently, the Journal of Alzheimer's Disease (JAD) put forth approximately 300 research reports which were deemed to be the most influential research reports in the field of AD since 2010. JAD readers were asked to vote on these most influential reports. In this 3-part review, we review the results of the 300 most influential AD research reports to provide JAD readers with a readily accessible, yet comprehensive review of the state of contemporary research. Notably, this multi-part review identifies the "hottest" fields of AD research providing guidance for both senior investigators as well as investigators new to the field on what is the most pressing fields within AD research. Part 1 of this review covers pathogenesis, both on a molecular and macro scale. Part 2 review genetics and epidemiology, and part 3 covers diagnosis and treatment. This part of the review, diagnosis and treatment, reviews the latest diagnostic criteria, biomarkers, imaging, and treatments in AD.
Topics: Alzheimer Disease; Biomarkers; Biomedical Research; Humans; Neuroimaging
PubMed: 28269772
DOI: 10.3233/JAD-160907 -
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 -
Frontiers in Immunology 2022Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide, characterized by progressive neuron degeneration or loss due to excessive... (Review)
Review
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide, characterized by progressive neuron degeneration or loss due to excessive accumulation of β-amyloid (Aβ) peptides, formation of neurofibrillary tangles (NFTs), and hyperphosphorylated tau. The treatment of AD has been only partially successful as the majority of the pharmacotherapies on the market may alleviate some of the symptoms. In the occurrence of AD, increasing attention has been paid to neurodegeneration, while the resident glial cells, like microglia are also observed. Microglia, a kind of crucial glial cells associated with the innate immune response, functions as double-edge sword role in CNS. They exert a beneficial or detrimental influence on the adjacent neurons through secretion of both pro-inflammatory cytokines as well as neurotrophic factors. In addition, their endocytosis of debris and toxic protein like Aβ and tau ensures homeostasis of the neuronal microenvironment. In this review, we will systematically summarize recent research regarding the roles of microglia in AD pathology and latest microglia-associated therapeutic targets mainly including pro-inflammatory genes, anti-inflammatory genes and phagocytosis at length, some of which are contradictory and controversial and warrant to further be investigated.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Humans; Microglia; Neurodegenerative Diseases; Neurons
PubMed: 35558075
DOI: 10.3389/fimmu.2022.856376