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International Journal of Molecular... Feb 2021Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting many individuals worldwide with no effective treatment to date. AD is characterized by the... (Review)
Review
BACKGROUND
Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting many individuals worldwide with no effective treatment to date. AD is characterized by the formation of senile plaques and neurofibrillary tangles, followed by neurodegeneration, which leads to cognitive decline and eventually death.
INTRODUCTION
In AD, pathological changes occur many years before disease onset. Since disease-modifying therapies may be the most beneficial in the early stages of AD, biomarkers for the early diagnosis and longitudinal monitoring of disease progression are essential. Multiple imaging techniques with associated biomarkers are used to identify and monitor AD.
AIM
In this review, we discuss the contemporary early diagnosis and longitudinal monitoring of AD with imaging techniques regarding their diagnostic utility, benefits and limitations. Additionally, novel techniques, applications and biomarkers for AD research are assessed.
FINDINGS
Reduced hippocampal volume is a biomarker for neurodegeneration, but atrophy is not an AD-specific measure. Hypometabolism in temporoparietal regions is seen as a biomarker for AD. However, glucose uptake reflects astrocyte function rather than neuronal function. Amyloid-β (Aβ) is the earliest hallmark of AD and can be measured with positron emission tomography (PET), but Aβ accumulation stagnates as disease progresses. Therefore, Aβ may not be a suitable biomarker for monitoring disease progression. The measurement of tau accumulation with PET radiotracers exhibited promising results in both early diagnosis and longitudinal monitoring, but large-scale validation of these radiotracers is required. The implementation of new processing techniques, applications of other imaging techniques and novel biomarkers can contribute to understanding AD and finding a cure.
CONCLUSIONS
Several biomarkers are proposed for the early diagnosis and longitudinal monitoring of AD with imaging techniques, but all these biomarkers have their limitations regarding specificity, reliability and sensitivity. Future perspectives. Future research should focus on expanding the employment of imaging techniques and identifying novel biomarkers that reflect AD pathology in the earliest stages.
Topics: Alzheimer Disease; Amyloid; Biomarkers; Early Diagnosis; Humans; Longitudinal Studies; Neuroimaging
PubMed: 33672696
DOI: 10.3390/ijms22042110 -
Obesity (Silver Spring, Md.) Jun 2023Chronic diseases of aging are increasingly common. Dementia, often due to multiple etiologies including Alzheimer disease (AD), is at the forefront. Previous studies... (Review)
Review
Chronic diseases of aging are increasingly common. Dementia, often due to multiple etiologies including Alzheimer disease (AD), is at the forefront. Previous studies have reported higher rates of dementia among persons with diabetes, yet less is known about how insulin resistance relates to cognition. This article reviews recently published data on the relationship of insulin resistance to cognition and AD, and remaining knowledge gaps in the field are discussed. A structured review of studies was conducted over a 5-year period, investigating insulin and cognitive function in adults with a baseline mean age of ≥65 years. This search yielded 146 articles, of which 26 met the predetermined inclusion and exclusion criteria. Among the nine studies that specifically examined insulin resistance and cognitive dysfunction and/or decline, eight studies suggest an association, but some only in subanalyses. Results are mixed in studies relating insulin to structural and functional changes on brain imaging, and data on intranasal insulin for cognition remain unclear. Future avenues are proposed to elucidate the impact of insulin resistance on brain structure and function, including cognition, in persons with and without AD.
Topics: Humans; Aged; Alzheimer Disease; Insulin Resistance; Cognition; Cognitive Dysfunction; Insulin
PubMed: 37203336
DOI: 10.1002/oby.23761 -
Alzheimer's & Dementia : the Journal of... Nov 2019Several microRNAs (miRNAs) have been implicated in Alzheimer's disease pathogenesis, but the evidence from individual case-control studies remains inconclusive. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several microRNAs (miRNAs) have been implicated in Alzheimer's disease pathogenesis, but the evidence from individual case-control studies remains inconclusive.
METHODS
A systematic literature review was performed, followed by standardized multistage data extraction, quality control, and meta-analyses on eligible data for brain, blood, and cerebrospinal fluid specimens. Results were compared with miRNAs reported in the abstracts of eligible studies or recent qualitative reviews to assess novelty.
RESULTS
Data from 147 independent data sets across 107 publications were quantitatively assessed in 461 meta-analyses. Twenty-five, five, and 32 miRNAs showed studywide significant differential expression (α < 1·08 × 10) in brain, cerebrospinal fluid, and blood-derived specimens, respectively, with 5 miRNAs showing differential expression in both brain and blood. Of these 57 miRNAs, 13 had not been reported in the abstracts of previous original or review articles.
DISCUSSION
Our systematic assessment of differential miRNA expression is the first of its kind in Alzheimer's disease and highlights several miRNAs of potential relevance.
Topics: Alzheimer Disease; Biomarkers; Brain; Case-Control Studies; Epigenomics; Humans; MicroRNAs
PubMed: 31495604
DOI: 10.1016/j.jalz.2019.06.4952 -
Annals of Nutrition & Metabolism 2021Alzheimer's disease (AD) is the most common form of dementia, particularly in older adults, with clinical manifestations of progressive cognitive decline and functional... (Review)
Review
BACKGROUND
Alzheimer's disease (AD) is the most common form of dementia, particularly in older adults, with clinical manifestations of progressive cognitive decline and functional impairment. The prevalence of AD and related dementia is mounting worldwide, but its etiology remains unresolved, with no available preventative or ameliorative therapy. Emerging evidence suggests that the gut microbiota of patients with AD is different from cognitively normal counterparts.
SUMMARY
Communication between gut and brain (gut-brain axis) plays a crucial role in AD pathology. Bacteria inhabiting the gut strongly influence this gut-brain axis and thus may participate in AD pathology. Diet, one of the strongest modulators of gut microbiota, also strongly influences brain health and AD pathology. Gut microbiota metabolites including short-chain fatty acids, pro-inflammatory factors, and neurotransmitters may also affect AD pathogenesis and associated cognitive decline. Therefore, investigation of diet-microbiota-brain axis is important to better understand its contribution in AD pathology and its potential use as a target to prevent and treat AD. Herein, we discuss the link between AD and gut microbiota and ponder how microbiota modulation through nutritional approaches may offer avenues for discovering novel preventive and therapeutic strategies against AD. Key Message: A strong association exists between lifestyle factors and AD prevalence wherein unhealthy dietary factors have been linked to neurodegeneration. Specific prudent dietary patterns might help in preventing or delaying AD progression by affecting β-amyloid production and tau processing and regulating AD-associated inflammation, metabolism and oxidative stress, plausibly via modulating gut microbiota.
Topics: Aged; Alzheimer Disease; Brain; Cognitive Dysfunction; Diet; Gastrointestinal Microbiome; Humans
PubMed: 33906194
DOI: 10.1159/000515700 -
Dementia and Geriatric Cognitive... 2020Alzheimer disease (AD), the most common form of dementia, is a heterogenous disorder with various pathobiological subtypes. In addition to the 4 major subtypes based on... (Review)
Review
Alzheimer disease (AD), the most common form of dementia, is a heterogenous disorder with various pathobiological subtypes. In addition to the 4 major subtypes based on the distribution of tau pathology and brain atrophy (typical, limbic predominant, hippocampal sparing, and minimal atrophy [MA]), several other clinical variants showing distinct regional patterns of tau burden have been identified: nonamnestic, corticobasal syndromal, primary progressive aphasia, posterior cortical atrophy, behavioral/dysexecutive, and mild dementia variants. Among the subtypes, differences were found in age at onset, sex distribution, cognitive status, disease duration, APOE genotype, and biomarker levels. The patterns of key network destructions parallel the tau and atrophy patterns of the AD subgroups essentially. Interruption of key networks, in particular the default-mode network that is responsible for cognitive decline, is consistent in hetero-genous AD groups. AD pathology is often associated with co-pathologies: cerebrovascular lesions, Lewy pathology, and TDP-43 proteinopathies. These mixed pathologies essentially influence the clinical picture of AD and may accel-erate disease progression. Unraveling the heterogeneity among the AD spectrum entities is important for opening a window to pathogenic mechanisms affecting the brain and enabling precision medicine approaches as a basis for developing preventive and ultimately successful disease-modifying therapies for AD.
Topics: Age of Onset; Alzheimer Disease; Atrophy; Brain; Classification; Cognition; Humans; Phylogeny; Precision Medicine; tau Proteins
PubMed: 33429401
DOI: 10.1159/000508625 -
Biomolecules Feb 2022Alzheimer's disease (AD) incidence is increasing worldwide at an alarming rate. Considering this increase, prevention efforts, stemming from scientific research, health... (Review)
Review
Alzheimer's disease (AD) incidence is increasing worldwide at an alarming rate. Considering this increase, prevention efforts, stemming from scientific research, health education, and public policies, are critical. Clinical studies evidenced that healthy lifestyles along with natural multitarget and disease-modifying agents have a preventative impact on AD or mitigate symptoms in diagnosed patients. The pathological alterations of AD start 30 years before symptoms, and it is essential to develop the capacity to detect those changes. In this regard, molecular biomarkers that detect early pathological manifestations are helpful. Based on markers data, early preventive interventions could reduce more than 40% of AD cases. Protective actions include exercise, shown to induce neurogenesis, cognitive stimulation, intellectual-social activity, and nutrition among others. Mediterranean diet, preprobiotics, and nutraceuticals containing bioactive molecules with antioxidant and anti-inflammatory properties are relevant. Antiprotein aggregation molecules whose mechanisms were described are important. Anti-inflammatory agents with anti-aggregation properties that help to control cognitive impairment, include quercetin, biocurcumin, rosemarinic acid, and Andean . Anthocyanidins, e.g., delphinidin, malvidin, and natural flavonoids, are also included. Quercetin and hydroxy-tyrosol are antiaging molecules and could have anti-AD properties. We emphasize the relevance of nutraceuticals as a main actor in the prevention and/or control of dementia and particularly AD.
Topics: Alzheimer Disease; Antioxidants; Cognitive Dysfunction; Diet, Mediterranean; Dietary Supplements; Humans
PubMed: 35204750
DOI: 10.3390/biom12020249 -
Continuum (Minneapolis, Minn.) Jun 2022Causes of health disparities in Alzheimer disease and related dementias (ADRD) in the United States are multifactorial. This article contextualizes health disparities as... (Review)
Review
PURPOSE OF REVIEW
Causes of health disparities in Alzheimer disease and related dementias (ADRD) in the United States are multifactorial. This article contextualizes health disparities as they relate to the neurodegenerative processes of ADRD.
RECENT FINDINGS
Older adults' life expectancy has increased such that a 65-year-old is expected to live 19 or more years and an 85-year-old can expect to live, on average, 6 to 7 years longer. Individuals of certain ethnoracial groups (Black, Hispanic/Latino, American Indian/Alaska Native, and Native Hawaiian/Pacific Islander) may be at a higher risk of incident ADRD compared to non-Hispanic/Latino White people. These differences in a higher risk of ADRD across ethnoracial groups persist despite no statistically significant differences in the rate of cognitive decline over time. The intersectionality of social determinants of health, experiences with discrimination and oppression, and access to care are related to the issue of justice and the risk for and expression of ADRD. The theoretical frameworks of various health disparities provide organized approaches to tracking the progression of health disparities for diverse patients.
SUMMARY
ADRD health disparities are complex. Neurologists and their care teams must consider the main reasons for clinical ADRD evaluations of members of ethnoracial groups and the factors that may impact patient adherence and compliance with diagnostic and management recommendations.
Topics: Aged; Alzheimer Disease; Humans; United States
PubMed: 35678407
DOI: 10.1212/CON.0000000000001088 -
Brain Pathology (Zurich, Switzerland) Sep 2020Alzheimer's disease (AD) is the most common neurodegenerative disease and, owing to its increasing prevalence, represents one of the leading public health problems in... (Review)
Review
Alzheimer's disease (AD) is the most common neurodegenerative disease and, owing to its increasing prevalence, represents one of the leading public health problems in aging populations. The molecular causes underlying the onset and progression of AD are manifold and hitherto still incompletely understood. Research over nearly four decades has clearly delineated genetics to play a crucial role in AD susceptibility, likely in concert with non-genetic factors. The field has gained considerable momentum and novel insights over the past 10 years owing to the advent and application of high-throughput genomics technologies in datasets of increasing size. In this contribution to the Mini-Symposium on the Molecular Etiology of Alzheimer's Disease, we review the current status of genomics research in AD. To this end, we scrutinize and discuss the main findings from the two largest and most current genome-wide association studies (GWAS) in the field, that is, the papers published by Jansen et al (Nat Genet 51:404-413) and Kunkle et al (Nat Genet 51:414-430). Particular focus is laid on genomics findings overlapping across both studies and on the novel insights they provide in terms of improving our understanding of the "genomic mechanisms" underlying this devastating disease.
Topics: Alzheimer Disease; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomics; Humans; Neurodegenerative Diseases
PubMed: 32657454
DOI: 10.1111/bpa.12882 -
European Journal of Medicinal Chemistry Jul 2023Alzheimer's Disease (AD) remains one of the most challenging health-related issues for our society. It is becoming increasingly prevalent, especially in developed... (Review)
Review
Alzheimer's Disease (AD) remains one of the most challenging health-related issues for our society. It is becoming increasingly prevalent, especially in developed countries, due to the rising life expectancy and, moreover, represents a considerable economic burden worldwide. All efforts at the discovery of new diagnostic and therapeutic tools in the last decades have invariably met with failure, making AD an incurable illness and underscoring the need for new approaches. In recent years, theranostic agents have emerged as an interesting strategy. They are molecules able to simultaneously provide diagnostic information and deliver therapeutic activity, allowing for the assessment of the molecule activity, the organism response and the pharmacokinetics. This makes these compounds promising for streamlining research on AD drugs and for their application in personalized medicine. We review here the field of small-molecule theranostic agents as promising tools for the development of novel diagnostic and therapeutic resources against AD, highlighting the positive and significant impact that theranostics can be expected to have in the near future in clinical practice.
Topics: Humans; Alzheimer Disease; Precision Medicine; Amyloid beta-Peptides
PubMed: 37141706
DOI: 10.1016/j.ejmech.2023.115382 -
Journal of General Internal Medicine Aug 2022The emotional stress of caring for someone with Alzheimer's disease and related dementias is high and results in adverse effects on caregivers and the persons living...
BACKGROUND
The emotional stress of caring for someone with Alzheimer's disease and related dementias is high and results in adverse effects on caregivers and the persons living with disease. In preliminary work, caregiver reports of regularly feeling "completely overwhelmed" were associated with lack of measurable clinical benefit from a comprehensive dementia care program.
OBJECTIVE
To examine the sociodemographic and clinical characteristics of all caregivers who felt overwhelmed at entry into a comprehensive dementia care program, the trajectory of this symptom over 1 year, and its predictive value for 1-year caregiver outcomes.
DESIGN
Longitudinal cohort study SETTING: Academic health center PARTICIPANTS: Caregivers of patients enrolled in a comprehensive dementia care program EXPOSURES: Caregiver report of feeling "completely overwhelmed" at baseline MAIN MEASURES: Caregiver report of feeling "completely overwhelmed" at baseline and 1 year, and validated scales of caregiver strain, distress, depressive symptoms, burden, mortality, and long-term nursing home placement KEY RESULTS: Compared to caregivers who were not overwhelmed, overwhelmed caregivers had more distress from behavioral symptoms of the person living with dementia, worse depression scores, and higher composite dementia burden scores at baseline. They also had worse depressive symptoms, strain, and composite burden scores at 1 year, after adjustment for baseline scores. Having an overwhelmed caregiver did not predict long-term nursing home placement or mortality among persons with dementia.
CONCLUSIONS
A single question about whether a caregiver is overwhelmed might indicate caregivers who have considerable current and future symptom burden and who may benefit from increased support and resources.
Topics: Alzheimer Disease; Caregivers; Dementia; Humans; Nursing Homes; Vital Signs
PubMed: 34389938
DOI: 10.1007/s11606-021-07054-3