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GeroScience Jun 2022Vascular contribution to cognitive impairment and dementia (VCID) is a clinical label encompassing a wide range of cognitive disorders progressing from mild to major... (Meta-Analysis)
Meta-Analysis Review
Vascular contribution to cognitive impairment and dementia (VCID) is a clinical label encompassing a wide range of cognitive disorders progressing from mild to major vascular cognitive impairment (VCI), which is also defined as vascular dementia (VaD). VaD diagnosis is mainly based on clinical and imaging findings. Earlier biomarkers are needed to identify subjects at risk to develop mild VCI and VaD. In the present meta-analysis, we comprehensively evaluated the role of inflammatory biomarkers in differential diagnosis between VaD and Alzheimer's disease (AD), and assessed their prognostic value on predicting VaD incidence. We collected literature until January 31, 2021, assessing three inflammatory markers [interleukin(IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α] from blood or cerebrospinal fluid (CSF) samples. Thirteen cross-sectional and seven prospective studies were included. Blood IL-6 levels were cross-sectionally significantly higher in people with VaD compared to AD patients (SMD: 0.40, 95% CI: 0.18 to 0.62) with low heterogeneity (I: 41%, p = 0.13). Higher IL-6 levels were also associated to higher risk of incident VaD (relative risk: 1.28, 95% CI: 1.03 to 1.59, I: 0%). IL-6 in CSF was significantly higher in people with VaD compared to healthy subjects (SMD: 0.77, 95% CI: 0.17 to 1.37, I: 70%), and not compared to AD patients, but due to limited evidence and high inconsistency across studies, we could not draw definite conclusion. Higher blood IL-6 levels might represent a useful biomarker able to differentiate people with VaD from those with AD and might be correlated with higher risk of future VaD.
Topics: Alzheimer Disease; Biomarkers; Cognitive Dysfunction; Cross-Sectional Studies; Dementia, Vascular; Humans; Interleukin-6; Prospective Studies
PubMed: 35486344
DOI: 10.1007/s11357-022-00556-w -
The Cochrane Database of Systematic... Jun 2013Cognitive impairments, particularly memory problems, are a defining feature of the early stages of Alzheimer's disease (AD) and vascular dementia. Cognitive training and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cognitive impairments, particularly memory problems, are a defining feature of the early stages of Alzheimer's disease (AD) and vascular dementia. Cognitive training and cognitive rehabilitation are specific interventional approaches designed to address difficulties with memory and other aspects of cognitive functioning. The present review is an update of previous versions of this review.
OBJECTIVES
The main aim of the current review was to evaluate the effectiveness and impact of cognitive training and cognitive rehabilitation for people with mild Alzheimer's disease or vascular dementia in relation to important cognitive and non-cognitive outcomes for the person with dementia and the primary caregiver in the short, medium and long term.
SEARCH METHODS
The CDCIG Specialized Register, ALOIS, which contains records from MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS and many other clinical trial databases and grey literature sources, was most recently searched on 2 November 2012.
SELECTION CRITERIA
Randomised controlled trials (RCTs), published in English, comparing cognitive rehabilitation or cognitive training interventions with control conditions, and reporting relevant outcomes for the person with dementia and/or the family caregiver, were considered for inclusion.
DATA COLLECTION AND ANALYSIS
Eleven RCTs reporting cognitive training interventions were included in the review. A large number of measures were used in the different studies, and meta-analysis could be conducted for 11 of the primary and secondary outcomes of interest. Several outcomes were not measured in any of the studies. The unit of analysis in the meta-analysis was the change from baseline score. Overall estimates of treatment effect were calculated using a fixed-effect model, and statistical heterogeneity was measured using a standard Chi(2) statistic. One RCT of cognitive rehabilitation was identified, allowing examination of effect sizes, but no meta-analysis could be conducted.
MAIN RESULTS
Cognitive training was not associated with positive or negative effects in relation to any reported outcomes. The overall quality of the trials was low to moderate. The single RCT of cognitive rehabilitation found promising results in relation to a number of participant and caregiver outcomes, and was generally of high quality.
AUTHORS' CONCLUSIONS
Available evidence regarding cognitive training remains limited, and the quality of the evidence needs to improve. However, there is still no indication of any significant benefit derived from cognitive training. Trial reports indicate that some gains resulting from intervention may not be captured adequately by available standardised outcome measures. The results of the single RCT of cognitive rehabilitation show promise but are preliminary in nature. Further, well-designed studies of cognitive training and cognitive rehabilitation are required to obtain more definitive evidence. Researchers should describe and classify their interventions appropriately using available terminology.
Topics: Alzheimer Disease; Cognitive Behavioral Therapy; Dementia, Vascular; Humans; Randomized Controlled Trials as Topic
PubMed: 23740535
DOI: 10.1002/14651858.CD003260.pub2 -
Annals of Internal Medicine Jan 2018The prevalence of cognitive impairment and dementia is expected to increase dramatically as the population ages, creating burdens on families and health care systems.
BACKGROUND
The prevalence of cognitive impairment and dementia is expected to increase dramatically as the population ages, creating burdens on families and health care systems.
PURPOSE
To assess the effectiveness of physical activity interventions in slowing cognitive decline and delaying the onset of cognitive impairment and dementia in adults without diagnosed cognitive impairments.
DATA SOURCES
Several electronic databases from January 2009 to July 2017 and bibliographies of systematic reviews.
STUDY SELECTION
Trials published in English that lasted 6 months or longer, enrolled adults without clinically diagnosed cognitive impairments, and compared cognitive and dementia outcomes between physical activity interventions and inactive controls.
DATA EXTRACTION
Extraction by 1 reviewer and confirmed by a second; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence.
DATA SYNTHESIS
Of 32 eligible trials, 16 with low to moderate risk of bias compared a physical activity intervention with an inactive control. Most trials had 6-month follow-up; a few had 1- or 2-year follow-up. Evidence was insufficient to draw conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. Low-strength evidence showed that multicomponent physical activity interventions had no effect on cognitive function. Low-strength evidence showed that a multidomain intervention comprising physical activity, diet, and cognitive training improved several cognitive outcomes. Evidence regarding effects on dementia prevention was insufficient for all physical activity interventions.
LIMITATION
Heterogeneous interventions and cognitive test measures, small and underpowered studies, and inability to assess the clinical significance of cognitive test outcomes.
CONCLUSION
Evidence that short-term, single-component physical activity interventions promote cognitive function and prevent cognitive decline or dementia in older adults is largely insufficient. A multidomain intervention showed a delay in cognitive decline (low-strength evidence).
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality.
Topics: Aged; Alzheimer Disease; Cognitive Dysfunction; Exercise; Humans; Middle Aged
PubMed: 29255839
DOI: 10.7326/M17-1528 -
Molecular Neurodegeneration Mar 2022Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration. Extensive clinical and genomic... (Review)
Review
Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration. Extensive clinical and genomic studies have revealed biomarkers, risk factors, pathways, and targets of AD in the past decade. However, the exact molecular basis of AD development and progression remains elusive. The emerging single-cell sequencing technology can potentially provide cell-level insights into the disease. Here we systematically review the state-of-the-art bioinformatics approaches to analyze single-cell sequencing data and their applications to AD in 14 major directions, including 1) quality control and normalization, 2) dimension reduction and feature extraction, 3) cell clustering analysis, 4) cell type inference and annotation, 5) differential expression, 6) trajectory inference, 7) copy number variation analysis, 8) integration of single-cell multi-omics, 9) epigenomic analysis, 10) gene network inference, 11) prioritization of cell subpopulations, 12) integrative analysis of human and mouse sc-RNA-seq data, 13) spatial transcriptomics, and 14) comparison of single cell AD mouse model studies and single cell human AD studies. We also address challenges in using human postmortem and mouse tissues and outline future developments in single cell sequencing data analysis. Importantly, we have implemented our recommended workflow for each major analytic direction and applied them to a large single nucleus RNA-sequencing (snRNA-seq) dataset in AD. Key analytic results are reported while the scripts and the data are shared with the research community through GitHub. In summary, this comprehensive review provides insights into various approaches to analyze single cell sequencing data and offers specific guidelines for study design and a variety of analytic directions. The review and the accompanied software tools will serve as a valuable resource for studying cellular and molecular mechanisms of AD, other diseases, or biological systems at the single cell level.
Topics: Alzheimer Disease; Animals; Computational Biology; DNA Copy Number Variations; Data Analysis; Mice; Single-Cell Analysis
PubMed: 35236372
DOI: 10.1186/s13024-022-00517-z -
Advances in Nutrition (Bethesda, Md.) Nov 2019As there is currently no cure for dementia, there is an urgent need for preventive strategies. The current review provides an overview of the existing evidence examining...
The Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Diets Are Associated with Less Cognitive Decline and a Lower Risk of Alzheimer's Disease-A Review.
As there is currently no cure for dementia, there is an urgent need for preventive strategies. The current review provides an overview of the existing evidence examining the associations of the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets and their dietary components with cognitive decline, dementia, and Alzheimer's disease (AD). A systematic search was conducted within Ovid Medline for studies published up to 27 March 2019 and reference lists from existing reviews and select articles were examined to supplement the electronic search results. In total, 56 articles were included. Higher adherence to the Mediterranean diet was associated with better cognitive scores in 9 of 12 cross-sectional studies, 17 of 25 longitudinal studies, and 1 of 3 trials. Higher adherence to the DASH diet was associated with better cognitive function in 1 cross-sectional study, 2 of 5 longitudinal studies, and 1 trial. Higher adherence to the MIND diet was associated with better cognitive scores in 1 cross-sectional study and 2 of 3 longitudinal studies. Evidence on the association of these dietary patterns with dementia in general was limited. However, higher adherence to the Mediterranean diet was associated with a lower risk of AD in 1 case-control study and 6 of 8 longitudinal studies. Moreover, higher adherence to the DASH or MIND diets was associated with a lower AD risk in 1 longitudinal study. With respect to the components of these dietary patterns, olive oil may be associated with less cognitive decline. In conclusion, current scientific evidence suggests that higher adherence to the Mediterranean, DASH, or MIND diets is associated with less cognitive decline and a lower risk of AD, where the strongest associations are observed for the MIND diet.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Case-Control Studies; Cognitive Dysfunction; Cross-Sectional Studies; Diet, Mediterranean; Dietary Approaches To Stop Hypertension; Female; Humans; Longitudinal Studies; MEDLINE; Male; Middle Aged; Neurodegenerative Diseases
PubMed: 31209456
DOI: 10.1093/advances/nmz054 -
International Journal of Molecular... Mar 2021Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on...
BACKGROUND
Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on cognitive tests, imaging techniques and cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ42), total tau protein and hyperphosphorylated tau (p-tau). However, the available methods are expensive and relatively invasive. Artificial intelligence techniques like machine learning tools have being increasingly used in precision diagnosis.
METHODS
We conducted a meta-analysis to investigate the machine learning and novel biomarkers for the diagnosis of AD.
METHODS
We searched PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews for reviews and trials that investigated the machine learning and novel biomarkers in diagnosis of AD.
RESULTS
In additional to Aβ and tau-related biomarkers, biomarkers according to other mechanisms of AD pathology have been investigated. Neuronal injury biomarker includes neurofiliament light (NFL). Biomarkers about synaptic dysfunction and/or loss includes neurogranin, BACE1, synaptotagmin, SNAP-25, GAP-43, synaptophysin. Biomarkers about neuroinflammation includes sTREM2, and YKL-40. Besides, d-glutamate is one of coagonists at the NMDARs. Several machine learning algorithms including support vector machine, logistic regression, random forest, and naïve Bayes) to build an optimal predictive model to distinguish patients with AD from healthy controls.
CONCLUSIONS
Our results revealed machine learning with novel biomarkers and multiple variables may increase the sensitivity and specificity in diagnosis of AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing AD in outpatient clinics.
Topics: Aged; Alzheimer Disease; Biomarkers; Chromatography, High Pressure Liquid; Diagnosis, Computer-Assisted; Female; Humans; Machine Learning; Middle Aged
PubMed: 33803217
DOI: 10.3390/ijms22052761 -
Ageing Research Reviews Dec 2021Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in ageing, affecting around 46 million people worldwide but few treatments are currently... (Review)
Review
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in ageing, affecting around 46 million people worldwide but few treatments are currently available. The etiology of AD is still puzzling, and new drugs development and clinical trials have high failure rates. Urgent outline of an integral (multi-target) and effective treatment of AD is needed. Accumulation of amyloid-β (Aβ) peptides is considered one of the fundamental neuropathological pillars of the disease, and its dyshomeostasis has shown a crucial role in AD onset. Therefore, many amyloid-targeted therapies have been investigated. Here, we will systematically review recent (from 2014) investigational, follow-up and review studies focused on anti-amyloid strategies to summarize and analyze their current clinical potential. Combination of anti-Aβ therapies with new developing early detection biomarkers and other therapeutic agents acting on early functional AD changes will be highlighted in this review. Near-term approval seems likely for several drugs acting against Aβ, with recent FDA approval of a monoclonal anti-Aβ oligomers antibody -aducanumab- raising hopes and controversies. We conclude that, development of oligomer-epitope specific Aβ treatment and implementation of multiple improved biomarkers and risk prediction methods allowing early detection, together with therapies acting on other factors such as hyperexcitability in early AD, could be the key to slowing this global pandemic.
Topics: Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Biomarkers; Humans; Neurodegenerative Diseases
PubMed: 34687956
DOI: 10.1016/j.arr.2021.101496 -
International Journal of Molecular... Jan 2023Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disease typically characterized by memory loss, personality changes, and a decline in... (Review)
Review
Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disease typically characterized by memory loss, personality changes, and a decline in overall cognitive function. Usually manifesting in individuals over the age of 60, this is the most prevalent type of dementia and remains the fifth leading cause of death among Americans aged 65 and older. While the development of effective treatment and prevention for AD is a major healthcare goal, unfortunately, therapeutic approaches to date have yet to find a treatment plan that produces long-term cognitive improvement. Drugs that may be able to slow down the progression rate of AD are being introduced to the market; however, there has been no previous solution for preventing or reversing the disease-associated cognitive decline. Recent studies have identified several factors that contribute to the progression and severity of the disease: diet, lifestyle, stress, sleep, nutrient deficiencies, mental health, socialization, and toxins. Thus, increasing evidence supports dietary and other lifestyle changes as potentially effective ways to prevent, slow, or reverse AD progression. Studies also have demonstrated that a personalized, multi-therapeutic approach is needed to improve metabolic abnormalities and AD-associated cognitive decline. These studies suggest the effects of abnormalities, such as insulin resistance, chronic inflammation, hypovitaminosis D, hormonal deficiencies, and hyperhomocysteinemia, in the AD process. Therefore a personalized, multi-therapeutic program based on an individual's genetics and biochemistry may be preferable over a single-drug/mono-therapeutic approach. This article reviews these multi-therapeutic strategies that identify and attenuate all the risk factors specific to each affected individual. This article systematically reviews studies that have incorporated multiple strategies that target numerous factors simultaneously to reverse or treat cognitive decline. We included high-quality clinical trials and observational studies that focused on the cognitive effects of programs comprising lifestyle, physical, and mental activity, as well as nutritional aspects. Articles from PubMed Central, Scopus, and Google Scholar databases were collected, and abstracts were reviewed for relevance to the subject matter. Epidemiological, pathological, toxicological, genetic, and biochemical studies have all concluded that AD represents a complex network insufficiency. The research studies explored in this manuscript confirm the need for a multifactorial approach to target the various risk factors of AD. A single-drug approach may delay the progression of memory loss but, to date, has not prevented or reversed it. Diet, physical activity, sleep, stress, and environment all contribute to the progression of the disease, and, therefore, a multi-factorial optimization of network support and function offers a rational therapeutic strategy. Thus, a multi-therapeutic program that simultaneously targets multiple factors underlying the AD network may be more effective than a mono-therapeutic approach.
Topics: Humans; Alzheimer Disease; Neurodegenerative Diseases; Cognitive Dysfunction; Cognition; Memory Disorders
PubMed: 36675177
DOI: 10.3390/ijms24021659 -
Alzheimer's & Dementia : the Journal of... Jun 2014Cigarette smoking has been linked with both increased and decreased risk for Alzheimer's disease (AD). This is relevant for the US military because the prevalence of... (Review)
Review
BACKGROUND
Cigarette smoking has been linked with both increased and decreased risk for Alzheimer's disease (AD). This is relevant for the US military because the prevalence of smoking in the military is approximately 11% higher than in civilians.
METHODS
A systematic review of published studies on the association between smoking and increased risk for AD and preclinical and human literature on the relationships between smoking, nicotine exposure, and AD-related neuropathology was conducted. Original data from comparisons of smoking and never-smoking cognitively normal elders on in vivo amyloid imaging are also presented.
RESULTS
Overall, literature indicates that former/active smoking is related to a significantly increased risk for AD. Cigarette smoke/smoking is associated with AD neuropathology in preclinical models and humans. Smoking-related cerebral oxidative stress is a potential mechanism promoting AD pathology and increased risk for AD.
CONCLUSIONS
A reduction in the incidence of smoking will likely reduce the future prevalence of AD.
Topics: Alzheimer Disease; Animals; Brain; Humans; Nicotine; Nicotinic Agonists; Oxidative Stress; Risk Factors; Smoking
PubMed: 24924665
DOI: 10.1016/j.jalz.2014.04.009 -
Cells May 2023Blood biomarkers have been considered tools for the diagnosis, prognosis, and monitoring of Alzheimer's disease (AD). Although amyloid-β peptide (Aβ) and tau are... (Meta-Analysis)
Meta-Analysis Review
Blood biomarkers have been considered tools for the diagnosis, prognosis, and monitoring of Alzheimer's disease (AD). Although amyloid-β peptide (Aβ) and tau are primarily blood biomarkers, recent studies have identified other reliable candidates that can serve as measurable indicators of pathological conditions. One such candidate is the glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein that can be detected in blood samples. Increasing evidence suggests that blood GFAP levels can be used to detect early-stage AD. In this systematic review and meta-analysis, we aimed to evaluate GFAP in peripheral blood as a biomarker for AD and provide an overview of the evidence regarding its utility. Our analysis revealed that the GFAP level in the blood was higher in the Aβ-positive group than in the negative groups, and in individuals with AD or mild cognitive impairment (MCI) compared to the healthy controls. Therefore, we believe that the clinical use of blood GFAP measurements has the potential to accelerate the diagnosis and improve the prognosis of AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cognitive Dysfunction; Glial Fibrillary Acidic Protein
PubMed: 37174709
DOI: 10.3390/cells12091309