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Journal of Biomedical Science Feb 2022The increasing amount of particulate matter (PM) in the ambient air is a pressing public health issue globally. Epidemiological studies involving data from millions of... (Review)
Review
The increasing amount of particulate matter (PM) in the ambient air is a pressing public health issue globally. Epidemiological studies involving data from millions of patients or volunteers have associated PM with increased risk of dementia and Alzheimer's disease in the elderly and cognitive dysfunction and neurodegenerative pathology across all age groups, suggesting that PM may be a risk factor for neurodegenerative diseases. Neurodegenerative diseases affect an increasing population in this aging society, putting a heavy burden on economics and family. Therefore, understanding the mechanism by which PM contributes to neurodegeneration is essential to develop effective interventions. Evidence in human and animal studies suggested that PM induced neurodenegerative-like pathology including neurotoxicity, neuroinflammation, oxidative stress, and damage in blood-brain barrier and neurovascular units, which may contribute to the increased risk of neurodegeneration. Interestingly, antagonizing oxidative stress alleviated the neurotoxicity of PM, which may underlie the essential role of oxidative stress in PM's potential effect in neurodegeneration. This review summarized up-to-date epidemiological and experimental studies on the pathogenic role of PM in neurodegenerative diseases and discussed the possible underlying mechanisms.
Topics: Aged; Aging; Alzheimer Disease; Animals; Humans; Oxidative Stress; Particulate Matter
PubMed: 35189880
DOI: 10.1186/s12929-022-00799-x -
Medical Sciences (Basel, Switzerland) Nov 2021Due to a difference in genetics, environmental factors, and nutrition, just like in people, dogs age at different rates. Brain aging in people and dogs share similar... (Review)
Review
Due to a difference in genetics, environmental factors, and nutrition, just like in people, dogs age at different rates. Brain aging in people and dogs share similar morphological changes including irreversible cortical atrophy, cerebral amyloid angiopathy, and ventricular enlargement. Due to severe and irreversible brain atrophy, some aging dogs develop cognitive dysfunction syndrome (CDS), which is equivalent to dementia or Alzheimer's disease (AD) in people. The risk factors and causes of CDS in dogs have not been fully investigated, but age, gender, oxidative stress, and deficiency of sex hormones appears to be associated with increased risk of accelerated brain aging and CDS in dogs. Both AD and CDS are incurable diseases at this moment, therefore more efforts should be focused on preventing or reducing brain atrophy and minimizing the risk of AD in people and CDS in dogs. Since brain atrophy leads to irreversible cognitive decline and dementia, an optimal nutritional solution should be able to not only enhance cognitive function during aging but also reduce irreversible brain atrophy. Up to now, only one nutritional intervention has demonstrated both cognition-enhancing benefits and atrophy-reducing benefits.
Topics: Aging; Alzheimer Disease; Animals; Atrophy; Brain; Cognition; Dogs; Humans; Nutrients
PubMed: 34842769
DOI: 10.3390/medsci9040072 -
Journal of Alzheimer's Disease : JAD 2023Long-increasing dementia incidence and prevalence trends may be shifting. Whether such shifts have reached the very old is unknown.
BACKGROUND
Long-increasing dementia incidence and prevalence trends may be shifting. Whether such shifts have reached the very old is unknown.
OBJECTIVE
To investigate temporal trends in the incidence of dementia and cognitive impairment and prevalence of dementia, cognitive impairment, Alzheimer's disease, vascular dementia, and unclassified dementia among 85-, 90-, and ≥ 95-year-olds in Sweden during 2000-2017.
METHODS
This study was conducted with Umeå 85 + /Gerontological Regional Database data from 2182 85-, 90-, and ≥ 95-year-olds in Sweden collected in 2000-2017. Using logistic regression, trends in the cumulative 5-year incidences of dementia and cognitive impairment; prevalences of dementia, cognitive impairment, Alzheimer's disease, and vascular dementia; and Mini-Mental State Examination thresholds for dementia diagnosis were estimated.
RESULTS
Dementia and cognitive impairment incidences decreased in younger groups, which generally showed more-positive temporal trends. The prevalences of overall dementia, cognitive impairment, and Alzheimer's disease were stable or increasing; longer disease durations and increasing dementia subtype classification success may mask positive changes in incidences. Vascular dementia increased while unclassified dementia generally decreased.
CONCLUSION
The cognitive health of the very old may be changing in the 21st century, possibly indicating a trend break.
Topics: Humans; Alzheimer Disease; Dementia, Vascular; Cognitive Dysfunction; Sweden
PubMed: 36938733
DOI: 10.3233/JAD-220915 -
Genes Nov 2021Alzheimer's disease is a complex and multifactorial condition regulated by both genetics and lifestyle, which ultimately results in the accumulation of β-amyloid (Aβ)...
Alzheimer's disease is a complex and multifactorial condition regulated by both genetics and lifestyle, which ultimately results in the accumulation of β-amyloid (Aβ) and tau proteins in the brain, loss of gray matter, and neuronal death [...].
Topics: Alzheimer Disease; Animals; Humans
PubMed: 34828400
DOI: 10.3390/genes12111794 -
American Journal of Alzheimer's Disease... Aug 2019Alzheimer's disease (AD), a neurological disorder, is as a complex chronic disease of brain cell death that usher to cognitive decline and loss of memory. Its prevalence... (Review)
Review
Alzheimer's disease (AD), a neurological disorder, is as a complex chronic disease of brain cell death that usher to cognitive decline and loss of memory. Its prevalence differs according to risk factors associated with it and necropsy performs vital role in its definite diagnosis. The stages of AD vary from preclinical to severe that proceeds to death of patient with no availability of treatment. Biomarker may be a biochemical change that can be recognized by different emerging technologies such as proteomics and metabolomics. Plasma biomarkers, 5-protein classifiers, are readily being used for the diagnosis of AD and can also predict its progression with a great accuracy, specificity, and sensitivity. In this review, upregulation or downregulation of few plasma proteins in patients with AD has also been discussed, when juxtaposed with control, and thus serves as potent biomarker in the diagnosis of AD.
Topics: Alzheimer Disease; Biomarkers; Humans
PubMed: 31072117
DOI: 10.1177/1533317519848239 -
Alzheimer's & Dementia : the Journal of... Aug 2021At present, there is limited data on the risks, disparity, and outcomes for COVID-19 in patients with dementia in the United States.
INTRODUCTION
At present, there is limited data on the risks, disparity, and outcomes for COVID-19 in patients with dementia in the United States.
METHODS
This is a retrospective case-control analysis of patient electronic health records (EHRs) of 61.9 million adult and senior patients (age ≥ 18 years) in the United States up to August 21, 2020.
RESULTS
Patients with dementia were at increased risk for COVID-19 compared to patients without dementia (adjusted odds ratio [AOR]: 2.00 [95% confidence interval (CI), 1.94-2.06], P < .001), with the strongest effect for vascular dementia (AOR: 3.17 [95% CI, 2.97-3.37], P < .001), followed by presenile dementia (AOR: 2.62 [95% CI, 2.28-3.00], P < .001), Alzheimer's disease (AOR: 1.86 [95% CI, 1.77-1.96], P < .001), senile dementia (AOR: 1.99 [95% CI, 1.86-2.13], P < .001) and post-traumatic dementia (AOR: 1.67 [95% CI, 1.51-1.86] P < .001). Blacks with dementia had higher risk of COVID-19 than Whites (AOR: 2.86 [95% CI, 2.67-3.06], P < .001). The 6-month mortality and hospitalization risks in patients with dementia and COVID-19 were 20.99% and 59.26%, respectively.
DISCUSSION
These findings highlight the need to protect patients with dementia as part of the strategy to control the COVID-19 pandemic.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alzheimer Disease; Black People; Brain Injuries, Traumatic; COVID-19; Case-Control Studies; Dementia; Dementia, Vascular; Demography; Electronic Health Records; Female; Healthcare Disparities; Hospitalization; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; United States; White People; Young Adult
PubMed: 33559975
DOI: 10.1002/alz.12296 -
Pharmaceutical Research Jul 2022Positron emission tomography (PET), a medical imaging technique allowing for studies of the living human brain, has gained an important role in clinical trials of novel... (Review)
Review
Positron emission tomography (PET), a medical imaging technique allowing for studies of the living human brain, has gained an important role in clinical trials of novel drugs against Alzheimer's disease (AD). For example, PET data contributed to the conditional approval in 2021 of aducanumab, an antibody directed towards amyloid-beta (Aβ) aggregates, by showing a dose-dependent reduction in brain amyloid after treatment. In parallel to clinical studies, preclinical studies in animal models of Aβ pathology may also benefit from PET as a tool to detect target engagement and treatment effects of anti-Aβ drug candidates. PET is associated with a high level of translatability between species as similar, non-invasive protocols allow for longitudinal rather than cross-sectional studies and can be used both in a preclinical and clinical setting. This review focuses on the use of preclinical PET imaging in genetically modified animals that express human Aβ, and its present and potential future role in the development of drugs aimed at reducing brain Aβ levels as a therapeutic strategy to halt disease progression in AD.
Topics: Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Animals; Brain; Drug Development; Positron-Emission Tomography
PubMed: 35501533
DOI: 10.1007/s11095-022-03277-z -
Problemy Endokrinologii Jun 2022Alzheimer's disease (AD) is a neurodegenerative disease that causes dementia in half of the cases. Asthma is usually found in people over 65 years of age. The...
Alzheimer's disease (AD) is a neurodegenerative disease that causes dementia in half of the cases. Asthma is usually found in people over 65 years of age. The etiopathogenesis of the disease is multifactorial and includes genetic factors, nutritional disorders, mitochondrial dysfunction, oxidative stress, and aging. Sex hormones have an important influence on the development of AD, as evidenced by a higher incidence in women than in men. Considering the significant influence of T on the maintenance of normal brain function, the present study is aimed at evaluating the impact of androgen deprivation therapy (ADT), as well as testosterone therapy, on the risk of AD development and progression. Although there is some clinical inconsistency between studies, androgens have a significant effect on brain function and are beneficial for AD patients. Low levels of circulating androgens should be considered as a significant risk factor for the development of AD and memory loss. With a reduced level of T in the plasma of men, its administration improves cognitive performance and memory, treatment should be started at an early stage of the disease. In men and women with AD, androgens improve mental state and slow the progression of the disease, providing a protective effect. In the future, it is necessary to conduct studies on a large population, taking into account personality factors and a more specific approach to assessing cognitive functions and the causal relationship of T administration in AD.
Topics: Male; Humans; Alzheimer Disease; Testosterone; Androgens; Neurodegenerative Diseases; Androgen Antagonists; Prostatic Neoplasms
PubMed: 36337024
DOI: 10.14341/probl13136 -
The American Journal of Geriatric... Jan 2020Psychosis in Alzheimer Disease (AD) represents a distinct clinicopathologic variant associated with increased cognitive and functional morbidity and an accelerated... (Review)
Review
Psychosis in Alzheimer Disease (AD) represents a distinct clinicopathologic variant associated with increased cognitive and functional morbidity and an accelerated disease course. To date, extant treatments offer modest benefits with significant risks. The development of new pharmacologic treatments for psychosis in AD would be facilitated by validated preclinical models with which to test candidate interventions. The current review provides a brief summary of the process of validating animal models of human disease together with a critical analysis of the challenges posed in attempting to apply those standards to AD-related behavioral models. An overview of phenotypic analogues of human cognitive and behavioral impairments, with an emphasis on those relevant to psychosis, in AD-related mouse models is provided, followed by an update on recent progress in efforts to translate findings in the pathophysiology of psychotic AD into novel models. Finally, some future directions are suggested to expand the catalogue of psychosis-relevant phenotypes that may provide a sturdier framework for model development and targets for preclinical treatment outcomes.
Topics: Alzheimer Disease; Animals; Behavior, Animal; Disease Models, Animal; Psychotic Disorders
PubMed: 31278012
DOI: 10.1016/j.jagp.2019.05.009 -
Alzheimer's Research & Therapy Aug 2022Patient stratification is the division of a patient population into distinct subgroups based on the presence or absence of particular disease characteristics. As patient... (Review)
Review
BACKGROUND
Patient stratification is the division of a patient population into distinct subgroups based on the presence or absence of particular disease characteristics. As patient stratification can be used to account for the underlying pathology of a disease, it can help physicians to tailor therapeutic interventions to individuals and optimize their care management and treatment regime. Alzheimer's disease, the most common form of dementia, is a heterogeneous disease and its management benefits from patient stratification in clinical trials, and the development of personalized care and treatment strategies for people living with the disease.
MAIN BODY
In this review, we discuss the importance of the stratification of people living with Alzheimer's disease, the challenges associated with early diagnosis and patient stratification, and the evolution of patient stratification once disease-modifying therapies become widely available.
CONCLUSION
Patient stratification plays an important role in drug development in clinical trials and may play an even larger role in clinical practice. A timely diagnosis and stratification of people living with Alzheimer's disease is paramount in determining people who are at risk of progressing from mild cognitive impairment to Alzheimer's dementia. There are key issues associated with stratifying patients which include the heterogeneity and complex neurobiology behind Alzheimer's disease, our inadequately prepared healthcare systems, and the cultural perceptions of Alzheimer's disease. Stratifying people living with Alzheimer's disease may be the key in establishing precision and personalized medicine in the field, optimizing disease prevention and pharmaceutical treatment to slow or stop cognitive decline, while minimizing adverse effects.
Topics: Alzheimer Disease; Cognitive Dysfunction; Humans
PubMed: 35964143
DOI: 10.1186/s13195-022-01055-y