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Turk Psikiyatri Dergisi = Turkish... 2019Alzheimer's Disease (AD) is a neurodegenerative condition characterized by functional and structural changes in the brain that are increasingly better visualized with... (Review)
Review
OBJECTIVE
Alzheimer's Disease (AD) is a neurodegenerative condition characterized by functional and structural changes in the brain that are increasingly better visualized with the advances in new brain imaging techniques. Connectivity changes under the resting state condition especially in the internal connectivity network, named as the default mode network (DMN), are observed in AD. This paper aimed to investigate and discuss the findings on DMN connectivity.
METHOD
The studies carried out by functional magnetic resonance imaging (fMRI), using the two most widely applied techniques, the seed-based method and independent component analysis (ICA), have been investigated.
RESULTS
Studies generally indicate a progressive impairment in DMN connectivity during the course of AD. It has been also stated that DMN subsystems show differential connectivity patterns in the preclinical and prodromal stages of AD. There is also evidence suggesting that impairment in DMN connectivity could be associated with different connectivity patterns in other networks. Furthermore, findings point towards a relationship between DMN and AD-related neuropathology and genetic risk factors.
CONCLUSION
It may be proposed that AD is a generalized disconnection syndrome that causes functional impairments in resting state networks, particularly in DMN. In addition to this, AD-related functional connectivity changes observed in preclinical cases and risk carriers might be a potential bio-marker for AD.
Topics: Alzheimer Disease; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging
PubMed: 32594490
DOI: No ID Found -
American Journal of Alzheimer's Disease... 2020Understanding Alzheimer's disease (AD) dynamics is essential in diagnosis and measuring progression for clinical decision-making; however, clinical instruments are...
Understanding Alzheimer's disease (AD) dynamics is essential in diagnosis and measuring progression for clinical decision-making; however, clinical instruments are imperfect at classifying true disease stages. This research evaluates sensitivity and determinants of AD stage changes longitudinally using current classifications of "mild," "moderate," and "severe" AD, using Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), and the Clinical Dementia Rating-Sum of Boxes (CDR-SB) thresholds. Age and pre-progression rate were significant determinants of AD progression using MMSE alone to stage AD, and pre-progression was found to impact disease progression with CDR-SB. Sensitivity of these instruments for identifying clinical stages of AD to correctly staging a "moderate" level of disease severity for outcomes MMSE, CDR-SB, and ADAS-Cog was 92%, 78%, and 92%, respectively. This research derives longitudinal sensitivity of clinical instruments used to stage AD useful for clinical decision-making. The MMSE and ADAS-Cog provided adequate sensitivity to classify AD stages.
Topics: Aged; Alzheimer Disease; Disease Progression; Female; Humans; Male; Mental Status and Dementia Tests; Neuropsychological Tests; Severity of Illness Index
PubMed: 32573256
DOI: 10.1177/1533317520918719 -
Journal of Alzheimer's Disease : JAD 2018The production of soluble amyloid-β oligomers (AβOs) and the activation of inflammation are two important early steps in the pathogenesis of Alzheimer's disease (AD).... (Review)
Review
The production of soluble amyloid-β oligomers (AβOs) and the activation of inflammation are two important early steps in the pathogenesis of Alzheimer's disease (AD). The central role of oligomers as responsible for the neuronal dysfunction associated with the clinical features has been extended to the other protein misfolding disorders definable, on this basis, as oligomeropathies. In AD, recent evidence indicates that the mechanism of inflammation as a consequence of neurodegeneration must be assessed in favor of a more direct role of glial activation in the alteration of synaptic function. Our own experimental models demonstrate the efficacy of anti-inflammatory treatments in preventing the cognitive deficits induced acutely by AβOs applied directly in the brain. Moreover, some promising clinical tools are based on immunological activation reducing the presence of cerebral Aβ deposits. However, the strategies based on the control of inflammatory factors as well as the amyloid aggregation show poor or non-therapeutic efficacy. Numerous studies have examined inflammatory factors in biological fluids as possible markers of the neuroinflammation in AD. In some cases, altered levels of cytokines or other inflammatory markers in cerebrospinal fluid correlate with the severity of the disease. Here we propose, according to the precision medicine principles, innovative therapeutic approaches to AD based on the patient's inflammatory profile/state. The earlier intervention and a multifactor approach are two other elements considered essential to improve the chances of effective therapy in AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Humans; Inflammation
PubMed: 29562537
DOI: 10.3233/JAD-170819 -
Journal of Alzheimer's Disease : JAD 2023DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, has shown promise for Alzheimer's disease (AD) prediction. (Review)
Review
BACKGROUND
DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, has shown promise for Alzheimer's disease (AD) prediction.
OBJECTIVE
Testing long-term predictive ability (>15 years) of existing DNAm-based epigenetic age acceleration (EAA) measures and identifying novel early blood-based DNAm AD-prediction biomarkers.
METHODS
EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models (LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16 years before clinical onset, and post-onset follow-up. Novel DNAm biomarkers were generated with epigenome-wide LMMs, and Sparse Partial Least Squares Discriminant Analysis applied at pre- (10-16 years), and post-AD-onset time-points.
RESULTS
EAA did not differentiate cases from controls during the follow-up time (p > 0.05). Three new DNA biomarkers showed in-sample predictive ability on average 8 years pre-onset, after adjustment for age, sex, and white blood cell proportions (p-values: 0.022-<0.00001). Our longitudinally-derived panel replicated nominally (p = 0.012) in an external cohort (n = 146 cases, 324 controls). However, its effect size and discriminatory accuracy were limited compared to APOEɛ4-carriership (OR = 1.38 per 1 SD DNAm score increase versus OR = 13.58 for ɛ4-allele carriage; AUCs = 77.2% versus 87.0%). Literature review showed low overlap (n = 4) across 3275 AD-associated CpGs from 8 published studies, and no overlap with our identified CpGs.
Topics: Female; Humans; Male; Alzheimer Disease; Biomarkers; DNA Methylation; Epigenesis, Genetic; Prospective Studies
PubMed: 37393498
DOI: 10.3233/JAD-230039 -
International Journal of Molecular... May 2024The majority of clinical trials, whose primary aims were to moderate Alzheimer's dementia (AD), have been based upon the prevailing paradigm, i [...].
The majority of clinical trials, whose primary aims were to moderate Alzheimer's dementia (AD), have been based upon the prevailing paradigm, i [...].
Topics: Alzheimer Disease; Humans
PubMed: 38892203
DOI: 10.3390/ijms25116015 -
BioMed Research International 2016Alzheimer's disease (AD) is the most common cause of dementia associated with a progressive neurodegenerative disorder, with a prevalence of 44 million people throughout... (Review)
Review
Alzheimer's disease (AD) is the most common cause of dementia associated with a progressive neurodegenerative disorder, with a prevalence of 44 million people throughout the world in 2015, and this figure is estimated to double by 2050. This disease is characterized by blood-brain barrier disruption, oxidative stress, mitochondrial impairment, neuroinflammation, and hypometabolism; it is related to amyloid-β peptide accumulation and tau hyperphosphorylation as well as a decrease in acetylcholine levels and a reduction of cerebral blood flow. Obesity is a major risk factor for AD, because it induces adipokine dysregulation, which consists of the release of the proinflammatory adipokines and decreased anti-inflammatory adipokines, among other processes. The pharmacological treatments for AD can be divided into two categories: symptomatic treatments such as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists and etiology-based treatments such as secretase inhibitors, amyloid binders, and tau therapies. Strategies for prevention of AD through nonpharmacological treatments are associated with lifestyle interventions such as exercise, mental challenges, and socialization as well as caloric restriction and a healthy diet. AD is an important health issue on which all people should be informed so that prevention strategies that minimize the risk of its development may be implemented.
Topics: Alzheimer Disease; Humans; Obesity; Risk Factors
PubMed: 27547756
DOI: 10.1155/2016/2589276 -
Ugeskrift For Laeger Jan 2016Passive anti-beta-amyloid (Aß) immunotherapy has been shown to clear brain Aß deposits. Results from phase III clinical trials in mild-to-moderate Alzheimer's disease... (Review)
Review
Passive anti-beta-amyloid (Aß) immunotherapy has been shown to clear brain Aß deposits. Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD. Solanezumab and new monoclonal antibodies are being tested in patients with prodromal and preclinical AD in search for a disease-modifying treatment.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Humans; Immunization, Passive; Immunoglobulins, Intravenous
PubMed: 26815584
DOI: No ID Found -
Journal of Alzheimer's Disease : JAD 2021Religious and spiritual interventions may have an effect on Alzheimer's disease prevention. Kirtan Kriya meditation has been shown to mitigate the deleterious effects of... (Review)
Review
BACKGROUND
Religious and spiritual interventions may have an effect on Alzheimer's disease prevention. Kirtan Kriya meditation has been shown to mitigate the deleterious effects of chronic stress on cognition, reverse memory loss, and create psychological and spiritual wellbeing, which may reduce multiple drivers of Alzheimer's disease risk.
OBJECTIVE
To detail a new concept in medicine called Spiritual Fitness, a merging of stress reduction, basic wellbeing, and psycho/spiritual wellbeing to prevent Alzheimer's disease.
METHODS
The literature on the topics mentioned above is described, including an in-depth discussion on why and how each are critical to advancing the future of Alzheimer's disease prevention. The many negative effects of chronic stress, and the benefits of Kirtan Kriya, are reviewed. The four pillars of basic wellbeing, six practical aspects of psychological wellbeing, and the four new non-sectarian features of spiritual fitness are then disclosed. Moreover, instructions on practicing Kirtan Kriya are offered in the Supplementary Material.
CONCLUSION
Religious and spiritual practices, including Kirtan Kriya, are crucial components in the development of enhanced cognition and well-being, which may help prevent and, in some cases, reverse cognitive decline. The key point of this review is that making a commitment to live a brain longevity lifestyle including spiritual fitness is a critically important way for aging Alzheimer's disease free. We hope that this article will inspire scientists, clinicians, and patients to embrace this new concept of spiritual fitness and make it a part of every multidomain program for the prevention of cognitive disability.
Topics: Alzheimer Disease; Humans; Life Style; Love; Meditation; Spirituality
PubMed: 33554917
DOI: 10.3233/JAD-201433 -
Current Neuropharmacology 2020The gene based therapeutics and drug targets have shown incredible and appreciable advances in alleviating human sufferings and complexities. Epigenetics simply means... (Review)
Review
The gene based therapeutics and drug targets have shown incredible and appreciable advances in alleviating human sufferings and complexities. Epigenetics simply means above genetics or which controls the organism beyond genetics. At present it is very clear that all characteristics of an individual are not determined by DNA alone, rather the environment, stress, life style and nutrition play a vital part in determining the response of an organism. Thus, nature (genetic makeup) and nurture (exposure) play equally important roles in the responses observed, both at the cellular and organism levels. Epigenetics influence plethora of complications at cellular and molecular levels that includes cancer, metabolic and cardiovascular complications including neurological (psychosis) and neurodegenerative disorders (Alzheimer's disease, Parkinson disease etc.). The epigenetic mechanisms include DNA methylation, histone modification and non coding RNA which have substantial impact on progression and pathways linked to Alzheimer's disease. The epigenetic mechanism gets deregulated in Alzheimer's disease and is characterized by DNA hyper methylation, deacetylation of histones and general repressed chromatin state which alter gene expression at the transcription level by upregulation, downregulation or silencing of genes. Thus, the processes or modulators of these epigenetic processes have shown vast potential as a therapeutic target in Alzheimer's disease.
Topics: Alzheimer Disease; Animals; Brain; DNA Methylation; Epigenesis, Genetic; Gene Expression; Histone Code; Humans; RNA, Untranslated; Risk Factors
PubMed: 31989902
DOI: 10.2174/1570159X18666200128125641 -
Current Alzheimer Research 2017Alzheimer's disease (AD) is the most common neurodegenerative disorder, neuropathologically characterized by aggregates of β-amyloid peptides, which deposit as senile... (Review)
Review
BACKGROUND
Alzheimer's disease (AD) is the most common neurodegenerative disorder, neuropathologically characterized by aggregates of β-amyloid peptides, which deposit as senile plaques, and of TAU protein, which forms neurofibrillary tangles. It is now widely accepted that neuroinflammation is implicated in AD pathogenesis.
METHOD
Indeed, inflammatory mediators, such as cytokines and chemokines (chemotactic cytokines) can impact on the Alzheimer´s amyloid precursor protein by affecting its expression levels and amyloidogenic processing and/or β -amyloid aggregation. Additionally, cytokines and chemokines can influence kinases' activities, leading to abnormal TAU phosphorylation. To date there is no cure for AD, but several therapeutic strategies have been directed to prevent neuroinflammation. Anti-inflammatory, but also anti-amyloidogenic compounds, such as flavonoids were shown to favourably modulate some pathological events associated with neurodegeneration.
CONCLUSION
This review focuses on the role of cytokines and chemokines in AD-associated pathologies, and summarizes the potential anti-inflammatory therapeutic approaches aimed at preventing or slowing down disease progression.
Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Cytokines; Humans; Nerve Degeneration
PubMed: 28317487
DOI: 10.2174/1567205014666170317113606