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The Lancet. Neurology Jun 2016Alzheimer's disease biomarkers are important for early diagnosis in routine clinical practice and research. Three core CSF biomarkers for the diagnosis of Alzheimer's... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alzheimer's disease biomarkers are important for early diagnosis in routine clinical practice and research. Three core CSF biomarkers for the diagnosis of Alzheimer's disease (Aβ42, T-tau, and P-tau) have been assessed in numerous studies, and several other Alzheimer's disease markers are emerging in the literature. However, there have been no comprehensive meta-analyses of their diagnostic performance. We systematically reviewed the literature for 15 biomarkers in both CSF and blood to assess which of these were most altered in Alzheimer's disease.
METHODS
In this systematic review and meta-analysis, we screened PubMed and Web of Science for articles published between July 1, 1984, and June 30, 2014, about CSF and blood biomarkers reflecting neurodegeneration (T-tau, NFL, NSE, VLP-1, and HFABP), APP metabolism (Aβ42, Aβ40, Aβ38, sAPPα, and sAPPβ), tangle pathology (P-tau), blood-brain-barrier function (albumin ratio), and glial activation (YKL-40, MCP-1, and GFAP). Data were taken from cross-sectional cohort studies as well as from baseline measurements in longitudinal studies with clinical follow-up. Articles were excluded if they did not contain a cohort with Alzheimer's disease and a control cohort, or a cohort with mild cognitive impairment due to Alzheimer's disease and a stable mild cognitive impairment cohort. Data were extracted by ten authors and checked by two for accuracy. For quality assessment, modified QUADAS criteria were used. Biomarker performance was rated by random-effects meta-analysis based on the ratio between biomarker concentration in patients with Alzheimer's disease and controls (fold change) or the ratio between biomarker concentration in those with mild cognitive impariment due to Alzheimer's disease and those with stable mild cognitive impairment who had a follow-up time of at least 2 years and no further cognitive decline.
FINDINGS
Of 4521 records identified from PubMed and 624 from Web of Science, 231 articles comprising 15 699 patients with Alzheimer's disease and 13 018 controls were included in this analysis. The core biomarkers differentiated Alzheimer's disease from controls with good performance: CSF T-tau (average ratio 2·54, 95% CI 2·44-2·64, p<0·0001), P-tau (1·88, 1·79-1·97, p<0·0001), and Aβ42 (0·56, 0·55-0·58, p<0·0001). Differentiation between cohorts with mild cognitive impairment due to Alzheimer's disease and those with stable mild cognitive impairment was also strong (average ratio 0·67 for CSF Aβ42, 1·72 for P-tau, and 1·76 for T-tau). Furthermore, CSF NFL (2·35, 1·90-2·91, p<0·0001) and plasma T-tau (1·95, 1·12-3·38, p=0·02) had large effect sizes when differentiating between controls and patients with Alzheimer's disease, whereas those of CSF NSE, VLP-1, HFABP, and YKL-40 were moderate (average ratios 1·28-1·47). Other assessed biomarkers had only marginal effect sizes or did not differentiate between control and patient samples.
INTERPRETATION
The core CSF biomarkers of neurodegeneration (T-tau, P-tau, and Aβ42), CSF NFL, and plasma T-tau were strongly associated with Alzheimer's disease and the core biomarkers were strongly associated with mild cognitive impairment due to Alzheimer's disease. Emerging CSF biomarkers NSE, VLP-1, HFABP, and YKL-40 were moderately associated with Alzheimer's disease, whereas plasma Aβ42 and Aβ40 were not. Due to their consistency, T-tau, P-tau, Aβ42, and NFL in CSF should be used in clinical practice and clinical research.
FUNDING
Swedish Research Council, Swedish State Support for Clinical Research, Alzheimer's Association, Knut and Alice Wallenberg Foundation, Torsten Söderberg Foundation, Alzheimer Foundation (Sweden), European Research Council, and Biomedical Research Forum.
Topics: Alzheimer Disease; Biomarkers; Humans
PubMed: 27068280
DOI: 10.1016/S1474-4422(16)00070-3 -
Journal of Sleep Research Aug 2021Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD... (Review)
Review
Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD dementia cases. However early intervention is needed in the course of AD at Mild Cognitive Impairment (MCI) or mild dementia stages to help prevent decline and maintain good quality of life. This systematic review aims to summarize evidence on sleep interventions in MCI and mild AD dementia. Seven databases were systematically searched for interventional studies where ≥ 75% of participants met diagnostic criteria for MCI/mild AD dementia, with a control group and validated sleep outcome measures. Studies with a majority of participants diagnosed with Moderate to Severe AD were excluded. After removal of duplicates, 22,133 references were returned in two separate searches (August 2019 and September 2020). 325 full papers were reviewed with 18 retained. Included papers reported 16 separate studies, total sample (n = 1,056), mean age 73.5 years. 13 interventions were represented: Cognitive Behavioural Therapy - Insomnia (CBT-I), A Multi-Component Group Based Therapy, A Structured Limbs Exercise Programme, Aromatherapy, Phase Locked Loop Acoustic Stimulation, Transcranial Stimulation, Suvorexant, Melatonin, Donepezil, Galantamine, Rivastigmine, Tetrahydroaminoacridine and Continuous Positive Airway Pressure (CPAP). Psychotherapeutic approaches utilising adapted CBT-I and a Structured Limbs Exercise Programme each achieved statistically significant improvements in the Pittsburgh Sleep Quality Index with one study reporting co-existent improved actigraphy variables. Suvorexant significantly increased Total Sleep Time and Sleep Efficiency whilst reducing Wake After Sleep Onset time. Transcranial Stimulation enhanced cortical slow oscillations and spindle power during daytime naps. Melatonin significantly reduced sleep latency in two small studies and sleep to wakefulness transitions in a small sample. CPAP demonstrated efficacy in participants with Obstructive Sleep Apnoea. Evidence to support other interventions was limited. Whilst new evidence is emerging, there remains a paucity of evidence for sleep interventions in MCI and mild AD highlighting a pressing need for high quality experimental studies exploring alternative sleep interventions.
Topics: Alzheimer Disease; Cognitive Dysfunction; Humans; Quality of Life; Sleep
PubMed: 33289311
DOI: 10.1111/jsr.13229 -
Journal of Neurology Jun 2019Research utilizing magnetic resonance imaging (MRI) has been crucial to the understanding of the neuropathological mechanisms behind and clinical identification of...
Research utilizing magnetic resonance imaging (MRI) has been crucial to the understanding of the neuropathological mechanisms behind and clinical identification of Alzheimer's disease (AD) and mild cognitive impairment (MCI). MRI modalities show patterns of brain damage that discriminate AD from other brain illnesses and brain abnormalities that are associated with risk of conversion to AD from MCI and other behavioural outcomes. This review discusses the application of various MRI techniques to and their clinical usefulness in AD and MCI. MRI modalities covered include structural MRI, diffusion tensor imaging (DTI), arterial spin labelling (ASL), magnetic resonance spectroscopy (MRS), and functional MRI (fMRI). There is much evidence supporting the validity of MRI as a biomarker for these disorders; however, only traditional structural imaging is currently recommended for routine use in clinical settings. Future research is needed to warrant the inclusion for more advanced MRI methodology in forthcoming revisions to diagnostic criteria for AD and MCI.
Topics: Alzheimer Disease; Cognitive Dysfunction; Humans; Magnetic Resonance Imaging; Neuroimaging
PubMed: 30120563
DOI: 10.1007/s00415-018-9016-3 -
Ageing Research Reviews Aug 2022Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique. When stimulation is applied over the primary motor cortex and coupled with... (Meta-Analysis)
Meta-Analysis Review
Cortical excitability and plasticity in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis of transcranial magnetic stimulation studies.
BACKGROUND
Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique. When stimulation is applied over the primary motor cortex and coupled with electromyography measures, TMS can probe functions of cortical excitability and plasticity in vivo. The purpose of this meta-analysis is to evaluate the utility of TMS-derived measures for differentiating patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) from cognitively normal older adults (CN).
METHODS
Databases searched included PubMed, Embase, APA PsycInfo, Medline, and CINAHL Plus from inception to July 2021.
RESULTS
Sixty-one studies with a total of 2728 participants (1454 patients with AD, 163 patients with MCI, and 1111 CN) were included. Patients with AD showed significantly higher cortical excitability, lower cortical inhibition, and impaired cortical plasticity compared to the CN cohorts. Patients with MCI exhibited increased cortical excitability and reduced plasticity compared to the CN cohort. Additionally, lower cognitive performance was significantly associated with higher cortical excitability and lower inhibition. No seizure events due to TMS were reported, and the mild adverse response rate is approximately 3/1000 (i.e., 9/2728).
CONCLUSIONS
Findings of our meta-analysis demonstrate the potential of using TMS-derived cortical excitability and plasticity measures as diagnostic biomarkers and therapeutic targets for AD and MCI.
Topics: Aged; Alzheimer Disease; Cognitive Dysfunction; Cortical Excitability; Humans; Neuronal Plasticity; Transcranial Magnetic Stimulation
PubMed: 35680080
DOI: 10.1016/j.arr.2022.101660 -
Neurobiology of Aging Feb 2020Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI)... (Meta-Analysis)
Meta-Analysis
Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, however, the effectiveness of this therapy is unclear because of the low statistical power and heterogeneity of previous trials. The purpose of the meta-analysis was to systematically characterize the effectiveness of various combinations of rTMS parameters on different cognitive domains in patients with MCI and AD. Thirteen studies comprising 293 patients with MCI or AD were included in this analysis. Random-effects analysis revealed an overall medium-to-large effect size (0.77) favoring active rTMS over sham rTMS in the improvement of cognitive functions. Subgroup analyses revealed that (1) high-frequency rTMS over the left dorsolateral prefrontal cortex and low-frequency rTMS at the right dorsolateral prefrontal cortex significantly improved memory functions; (2) high-frequency rTMS targeting the right inferior frontal gyrus significantly enhanced executive performance; and (3) the effects of 5-30 consecutive rTMS sessions could last for 4-12 weeks. Potential mechanisms of rTMS effects on cognitive functions are discussed.
Topics: Alzheimer Disease; Cognition; Cognitive Dysfunction; Humans; Memory; Prefrontal Cortex; Transcranial Magnetic Stimulation
PubMed: 31783330
DOI: 10.1016/j.neurobiolaging.2019.08.020 -
International Journal of Environmental... Jul 2022Aging is characterized by changes in the structure and quality of sleep. When the alterations in sleep become substantial, they can generate or accelerate cognitive... (Review)
Review
Aging is characterized by changes in the structure and quality of sleep. When the alterations in sleep become substantial, they can generate or accelerate cognitive decline, even in the absence of overt pathology. In fact, impaired sleep represents one of the earliest symptoms of Alzheimer's disease (AD). This systematic review aimed to analyze the studies on sleep quality in aging, also considering mild cognitive impairment (MCI) and AD. The review process was conducted according to the PRISMA statement. A total of 71 studies were included, and the whole sample had a mean age that ranged from 58.3 to 93.7 years (62.8-93.7 healthy participants and 61.8-86.7 pathological populations). Of these selected studies, 33 adopt subjective measurements, 31 adopt objective measures, and 10 studies used both. Pathological aging showed a worse impoverishment of sleep than older adults, in both subjective and objective measurements. The most common aspect compromised in AD and MCI were REM sleep, sleep efficiency, sleep latency, and sleep duration. These results underline that sleep alterations are associated with cognitive impairment. In conclusion, the frequency and severity of sleep disturbance appear to follow the evolution of cognitive impairment. The overall results of objective measures seem more consistent than those highlighted by subjective measurements.
Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Cognitive Dysfunction; Humans; Middle Aged; Sleep Quality; Sleep Wake Disorders
PubMed: 35886309
DOI: 10.3390/ijerph19148457 -
Neurologia 2018Carpal tunnel syndrome (CTS) is the most common peripheral neuropathy. It is characterised by the compression of the median nerve in the carpal tunnel. CTS presents a...
BACKGROUND
Carpal tunnel syndrome (CTS) is the most common peripheral neuropathy. It is characterised by the compression of the median nerve in the carpal tunnel. CTS presents a high prevalence and it is a disabling condition from the earliest stages. Severe cases are usually treated surgically, while conservative treatment is recommended in mild to moderate cases. The aim of this systematic review is to present the conservative treatments and determine their effectiveness in mild-to-moderate cases of CTS over the last 15 years.
METHODS
A systematic review was performed according to PRISMA criteria. We used the Medline, PEDro, and Cochrane databases to find and select randomised controlled clinical trials evaluating the effects of conservative treatment on the symptoms and functional ability of patients with mild to moderate CTS; 32 clinical trials were included. There is evidence supporting the effectiveness of oral drugs, although injections appear to be more effective. Splinting has been shown to be effective, and it is also associated with use of other non-pharmacological techniques. Assessments of the use of electrotherapy techniques alone have shown no conclusive results about their effectiveness. Other soft tissue techniques have also shown good results but evidence on this topic is limited. Various treatment combinations (drug and non-pharmacological treatments) have been proposed without conclusive results.
CONCLUSIONS
Several conservative treatments are able to relieve symptoms and improve functional ability of patients with mild-to-moderate CTS. These include splinting, oral drugs, injections, electrotherapy, specific manual techniques, and neural gliding exercises as well as different combinations of the above. We have been unable to describe the best technique or combination of techniques due to the limitations of the studies; therefore, further studies of better methodological quality are needed.
Topics: Carpal Tunnel Syndrome; Conservative Treatment; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27461181
DOI: 10.1016/j.nrl.2016.05.018 -
Neural Regeneration Research Nov 2022Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring... (Review)
Review
Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease states. An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer's disease. Therefore, we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease. We performed a literature search in PubMed, Web of Science, Embase, and Cochrane Library from their inception to August 15, 2020. The research subjects mainly included Alzheimer's disease, mild cognitive impairment, and preclinical Alzheimer's disease. We identified 34 observational studies, of which 15 were included in the quantitative analysis (Newcastle-Ottawa Scale score 5.87 points) and 19 were used in the qualitative analysis. The meta-analysis results showed that core biomarkers including Aβ, P-T181-tau, P-S396-tau, and T-tau were increased in blood neuron-derived exosomes of preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease patients. Molecules related to additional risk factors that are involved in neuroinflammation (C1q), metabolism disorder (P-S312-IRS-1), neurotrophic deficiency (HGF), vascular injury (VEGF-D), and autophagy-lysosomal system dysfunction (cathepsin D) were also increased. At the gene level, the differential expression of transcription-related factors (REST) and microRNAs (miR-132) also affects RNA splicing, transport, and translation. These pathological changes contribute to neural loss and synaptic dysfunction. The data confirm that the above-mentioned core molecules and additional risk-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer's disease. These findings support further development of exosome biomarkers for a clinical blood test for Alzheimer's disease. This meta-analysis was registered at the International Prospective Register of Systematic Reviews (Registration No. CRD4200173498, 28/04/2020).
PubMed: 35535875
DOI: 10.4103/1673-5374.335832 -
Archives of Disease in Childhood. Fetal... Mar 2020To examine if therapeutic hypothermia reduces the composite outcome of death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To examine if therapeutic hypothermia reduces the composite outcome of death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE).
DATA SOURCE
MEDLINE, Cochrane database, Scopus and ISI Web of Knowledge databases, using 'hypoxic ischaemic encephalopathy', 'newborn' and 'hypothermia', and 'clinical trials' as medical subject headings and terms. Manual search of the reference lists of all eligible articles and major review articles and additional data from the corresponding authors of selected articles.
STUDY SELECTION
Randomised and quasirandomised controlled trials comparing therapeutic hypothermia with usual care.
DATA EXTRACTION
Safety and efficacy data extracted independently by two reviewers and analysed.
RESULTS
We included the data on 117 babies with mild NE inadvertently recruited to five cooling trials (two whole-body cooling and three selective head cooling) of moderate and severe NE, in the meta-analysis. Adverse outcomes occurred in 11/56 (19.6%) of the cooled babies and 12/61 (19.7%) of the usual care babies (risk ratio 1.11 (95% CIs 0.55 to 2.25)).
CONCLUSIONS
Current evidence is insufficient to recommend routine therapeutic hypothermia for babies with mild encephalopathy and significant benefits or harm cannot be excluded.
Topics: Brain Diseases; Developmental Disabilities; Humans; Hypothermia, Induced; Infant, Newborn; Infant, Newborn, Diseases; Randomized Controlled Trials as Topic
PubMed: 30567775
DOI: 10.1136/archdischild-2018-315711 -
Journal of Dentistry Jul 2015A systematic review was conducted to determine whether the etch-and-rinse or self-etching mode is the best protocol for dentin and enamel adhesion by universal adhesives. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
A systematic review was conducted to determine whether the etch-and-rinse or self-etching mode is the best protocol for dentin and enamel adhesion by universal adhesives.
DATA
This report followed the PRISMA Statement. A total of 10 articles were included in the meta-analysis.
SOURCES
Two reviewers performed a literature search up to October 2014 in eight databases: PubMed, Web of Science, Scopus, BBO, SciELO, LILACS, IBECS and The Cochrane Library.
STUDY SELECTION
In vitro studies evaluating the bond strength of universal adhesives to dentin and/or enamel by the etch-and-rinse and self-etch strategies were eligible to be selected. Statistical analyses were conducted using RevMan 5.1 (The Cochrane Collaboration, Copenhagen, Denmark). A global comparison was performed with random-effects models at a significance level of p<0.05.
RESULTS
The analysis of dentin micro-tensile bond strength showed no statistically significant difference between the etch-and-rinse and self-etch strategies for mild universal adhesives (p≥0.05). However, for the ultra-mild All-Bond Universal adhesive, the etch-and-rinse strategy was significantly different than the self-etch mode in terms of dentin micro-tensile bond strength, as well as in the global analysis of enamel micro-tensile and micro-shear bond strength (p≤0.05).
CONCLUSIONS
The enamel bond strength of universal adhesives is improved with prior phosphoric acid etching. However, this effect was not evident for dentin with the use of mild universal adhesives with the etch-and-rinse strategy.
CLINICAL SIGNIFICANCE
Selective enamel etching prior to the application of a mild universal adhesive is an advisable strategy for optimizing bonding.
Topics: Composite Resins; Dentin; Dentin-Bonding Agents; Materials Testing; Methacrylates; Resin Cements; Surface Properties
PubMed: 25882585
DOI: 10.1016/j.jdent.2015.04.003