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EBioMedicine Jul 2016
Topics: Alzheimer Disease; Animals; Biomarkers; Disease Management; Drug Discovery; Early Diagnosis; Humans
PubMed: 27412262
DOI: 10.1016/j.ebiom.2016.07.001 -
Journal of Alzheimer's Disease : JAD 2016With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has... (Review)
Review
With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD.
Topics: Alzheimer Disease; Auditory Perception; Autonomic Nervous System; Dopamine; Humans; Memory Disorders; Music Therapy
PubMed: 26967216
DOI: 10.3233/JAD-150998 -
Journal of Alzheimer's Disease : JAD 2023Alzheimer's disease (AD) primarily affects older adults. In this report, we present the case of a 19-year-old male with gradual memory decline for 2 years and World...
Alzheimer's disease (AD) primarily affects older adults. In this report, we present the case of a 19-year-old male with gradual memory decline for 2 years and World Health Organization-University of California Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT) results also showing memory impairment. Positron emission tomography-magnetic resonance imaging with 18F fluorodeoxyglucose revealed atrophy of the bilateral hippocampus and hypometabolism in the bilateral temporal lobe. Examination of the patient's cerebrospinal fluid showed an increased concentration of p-tau181 and a decreased amyloid-β 42/40 ratio. However, through whole-genome sequencing, no known gene mutations were identified. Considering the above, the patient was diagnosed with probable AD.
Topics: Male; Humans; Aged; Adolescent; Alzheimer Disease; Amyloid beta-Peptides; Fluorodeoxyglucose F18; Positron-Emission Tomography; Magnetic Resonance Imaging
PubMed: 36565128
DOI: 10.3233/JAD-221065 -
Alzheimer's & Dementia : the Journal of... Dec 2018Like virtually all age-related chronic diseases, late-onset Alzheimer's disease (AD) develops over an extended preclinical period and is associated with modifiable... (Clinical Trial)
Clinical Trial Observational Study
Like virtually all age-related chronic diseases, late-onset Alzheimer's disease (AD) develops over an extended preclinical period and is associated with modifiable lifestyle and environmental factors. We hypothesize that multimodal interventions that address many risk factors simultaneously and are individually tailored to patients may help reduce AD risk. We describe a novel clinical methodology used to evaluate and treat patients at two Alzheimer's Prevention Clinics. The framework applies evidence-based principles of clinical precision medicine to tailor individualized recommendations, follow patients longitudinally to continually refine the interventions, and evaluate N-of-1 effectiveness (trial registered at ClinicalTrials.gov NCT03687710). Prior preliminary results suggest that the clinical practice of AD risk reduction is feasible, with measurable improvements in cognition and biomarkers of AD risk. We propose using these early findings as a foundation to evaluate the comparative effectiveness of personalized risk management within an international network of clinician researchers in a cohort study possibly leading to a randomized controlled trial.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Cognition; Female; Humans; Male; Middle Aged; Precision Medicine; Risk Reduction Behavior
PubMed: 30446421
DOI: 10.1016/j.jalz.2018.08.004 -
Journal of Neurochemistry Feb 2016Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. Deposition of amyloid-β (Aβ) remains a hallmark feature of... (Review)
Review
Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. Deposition of amyloid-β (Aβ) remains a hallmark feature of the disease, yet the precise mechanism(s) by which this peptide induces neurotoxicity remain unknown. Neuroinflammation has long been implicated in AD pathology, yet its contribution to disease progression is still not understood. Recent evidence suggests that various Aβ complexes interact with microglial and astrocytic expressed pattern recognition receptors that initiate innate immunity. This process involves secretion of pro-inflammatory cytokines, chemokines and generation of reactive oxygen species that, in excess, drive a dysregulated immune response that contributes to neurodegeneration. The mechanisms by which a neuroinflammatory response can influence Aβ production, aggregation and eventual clearance are now becoming key areas where future therapeutic intervention may slow progression of AD. This review will focus on evidence supporting the combined neuroinflammatory-amyloid hypothesis for pathogenesis of AD, describing the key cell types, pathways and mediators involved. Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. Deposition of intracellular plaques containing amyloid-beta (Aβ) is a hallmark proteinopathy of the disease yet the precise mechanisms by which this peptide induces neurotoxicity remains unknown. A neuroinflammatory response involving polarized microglial activity, enhanced astrocyte reactivity and elevated pro-inflammatory cytokine and chemokine load has long been implicated in AD and proposed to facilitate neurodegeneration. In this issue we discuss key receptor systems of innate immunity that detect Aβ, drive pro-inflammatory cytokine and chemokine production and influence Aβ aggregation and clearance. Evidence summarized in this review supports the combined neuroinflammatory-amyloid hypothesis for pathogenesis of AD and highlights the potential of immunomodulatory agents as potential future therapies for AD patients.
Topics: Alzheimer Disease; Amyloidogenic Proteins; Animals; Cytokines; Encephalitis; Humans; Immunity, Innate; Neuroglia
PubMed: 26509334
DOI: 10.1111/jnc.13411 -
Current Alzheimer Research 2016Alzheimer's disease (AD) is a complex neurodegenerative disorder with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Besides the extensive... (Review)
Review
Alzheimer's disease (AD) is a complex neurodegenerative disorder with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Besides the extensive neuron-oriented research, an increasing body of evidence suggests that glial cells, namely astrocytes, microglia, NG2 glia and oligodendrocytes, may play an important role in the pathogenesis of this disease. In the first part of this review, AD pathophysiology in humans is briefly described and compared with disease progression in routinely used animal models. The relevance of findings obtained in animal models of AD is also discussed with respect to AD pathology in humans. Further, this review summarizes recent findings regarding the role/participation of glial cells in pathogenesis of AD, focusing on changes in their morphology, functions, proteins and gene expression profiles. As for astrocytes and microglia, they are fundamental for the progression and outcome of AD either because they function as effector cells releasing cytokines that play a role in neuroprotection, or because they fail to fulfill their homeostatic functions, ultimately leaving neurons to face excitotoxicity and oxidative stress. Next, we turn our attention towards NG2 glia, a novel and distinct class of glial cells in the central nervous system (CNS), whose role in a variety of human CNS diseases has begun to emerge, and we also consider the participation of oligodendrocytes in the pathogenesis and progression of AD. Since AD is currently an incurable disease, in the last part of our review we hypothesize about possible glia-oriented treatments and provide a perspective of possible future advancements in this field.
Topics: Alzheimer Disease; Animals; Humans; Neuroglia
PubMed: 26825092
DOI: 10.2174/1567205013666160129095924 -
Alzheimer's Research & Therapy Aug 2017Basic research advances in recent years have furthered our understanding of the natural history of Alzheimer's disease (AD). It is now recognized that pathophysiological... (Review)
Review
Basic research advances in recent years have furthered our understanding of the natural history of Alzheimer's disease (AD). It is now recognized that pathophysiological changes begin many years prior to clinical manifestations of disease and the spectrum of AD spans from clinically asymptomatic to severely impaired. Defining AD purely by its clinical presentation is thus artificial and efforts have been made to recognize the disease based on both clinical and biomarker findings. Advances with biomarkers have also prompted a shift in how the disease is considered as a clinico-pathophysiological entity, with an increasing appreciation that AD should not only be viewed with discrete and defined clinical stages, but as a multifaceted process moving along a seamless continuum. Acknowledging this concept is critical to understanding the development process for disease-modifying therapies, and for initiating effective diagnostic and disease management options. In this article, we discuss the concept of a disease continuum from pathophysiological, biomarker, and clinical perspectives, and highlight the importance of considering AD as a continuum rather than discrete stages. While the pathophysiology of AD has still not been elucidated completely, there is ample evidence to support researchers and clinicians embracing the view of a disease continuum in their study, diagnosis, and management of the disease.
Topics: Alzheimer Disease; Biomarkers; Disease Progression; Humans
PubMed: 28793924
DOI: 10.1186/s13195-017-0283-5 -
Journal of Alzheimer's Disease : JAD 2017This is the second part of a three-part review series reviewing the most important advances in Alzheimer's disease (AD) research since 2010. This review covers the... (Review)
Review
This is the second part of a three-part review series reviewing the most important advances in Alzheimer's disease (AD) research since 2010. This review covers the latest research on genetics and epidemiology. Epidemiological and genetic studies are revealing important insights into the etiology of, and factors that contribute to AD, as well as areas of priority for research into mechanisms and interventions. The widespread adoption of genome wide association studies has provided compelling evidence of the genetic complexity of AD with genes associated with such diverse physiological function as immunity and lipid metabolism being implicated in AD pathogenesis.
Topics: Alzheimer Disease; Animals; Humans
PubMed: 28211812
DOI: 10.3233/JAD-161149 -
The Journal of Prevention of... 2022A systematic review of randomized controlled trials was conducted to determine the effect of physical exercise on physical-functional capacity, cognitive performance,...
OBJECTIVE
A systematic review of randomized controlled trials was conducted to determine the effect of physical exercise on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life in a population of older people with Alzheimer´s disease.
DATA SOURCES
Pubmed, Scopus, PEDro, Web of Science, CINAHL, Cochrane Library, grey literature and a reverse search from inception to April 2021 were searched to identify documents.
STUDY SELECTION
Publications investigating the effect of any type of physical exercise-based intervention in any of its multiple modalities on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life were searched.
DATA EXTRACTION
The data were extracted into predesigned data extraction tables. Risk of bias was evaluated through the PEDro scale and its internal validity scale.
DATA SYNTHESIS
A total of 8 different randomized controlled trials with a total sample of 562 non-overlap Alzheimer disease patients between 50-90 years and a mean age of 75.2 ± 3.9 years were eligible for analyses. Physical-functional capacity was evaluated in 6 of 8 studies and cognitive performance was evaluated in 5 of 8 studies, all of them showed improvements in these variables when compared with the controls, except for two studies in physical-functional capacity and one study for cognitive performance. In the physical-functional capacity and cognitive performance variables, aerobic physical exercise was used in isolation, or in a multimodal way, combining aerobic, strength and balance exercise, from 2 to 7 weekly sessions with doses between 30 and 90 minutes, and a duration of the program comprised of 9 weeks to 6 months. Neuropsychiatric symptoms and quality of life were evaluated in 2 of 8 studies, which the intervention groups experienced significant improvements when compared with the control groups, except for one study that found similar differences in quality of life between both groups. In the neuropsychiatric symptoms and quality of life variables, only aerobic physical exercise was used, in a more homogeneous way, from 2 to 3 weekly sessions with doses of 30 to 60 minutes, and a total program duration of 9 to 16 weeks.
CONCLUSIONS
Despite the scarcity of studies, especially those based on multimodal proposals, and the heterogeneity in the protocols, this systematic review found moderate to limited evidence that aerobic physical exercise on its own or combined in a multimodal program that also includes strength and balance exercise can be a useful tool in the management of patients with Alzheimer's disease with the aim of maintaining and/or improving physical-functional capacity and cognitive performance. In addition, this review found moderate evidence of the positive impact that aerobic physical exercise could have in reducing neuropsychiatric symptoms and improving quality of life in patients with Alzheimer´s disease. PROSPERO registration number: CRD42021229891.
Topics: Aged; Aged, 80 and over; Humans; Middle Aged; Alzheimer Disease; Exercise; Exercise Therapy; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36281664
DOI: 10.14283/jpad.2022.57 -
Journal of Alzheimer's Disease : JAD 2023Diet is an important nonpharmacological risk-modifying factor for Alzheimer's disease (AD). The approaches used here to assess diet's role in the risk of AD include... (Review)
Review
Diet is an important nonpharmacological risk-modifying factor for Alzheimer's disease (AD). The approaches used here to assess diet's role in the risk of AD include multi-country ecological studies, prospective and cross-sectional observational studies, and laboratory studies. Ecological studies have identified fat, meat, and obesity from high-energy diets as important risk factors for AD and reported that AD rates peak about 15-20 years after national dietary changes. Observational studies have compared the Western dietary pattern with those of the Dietary Approaches to Stop Hypertension (DASH), Mediterranean (MedDi), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. Those studies identified AD risk factors including higher consumption of saturated and total fats, meat, and ultraprocessed foods and a lower risk of AD with higher consumption of fruits, legumes, nuts, omega-3 fatty acids, vegetables, and whole grains. Diet-induced factors associated with a significant risk of AD include inflammation, insulin resistance, oxidative stress, elevated homocysteine, dietary advanced glycation end products, and trimethylamine N-oxide. The molecular mechanisms by which dietary bioactive components and specific foods affect risk of AD are discussed. Given most countries' entrenched food supply systems, the upward trends of AD rates would be hard to reverse. However, for people willing and able, a low-animal product diet with plenty of anti-inflammatory, low-glycemic load foods may be helpful.
Topics: Humans; Alzheimer Disease; Cross-Sectional Studies; Prospective Studies; Diet; Risk Factors
PubMed: 37955087
DOI: 10.3233/JAD-230418