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The Journal of Prevention of... 2022A systematic review of randomized controlled trials was conducted to determine the effect of physical exercise on physical-functional capacity, cognitive performance,...
OBJECTIVE
A systematic review of randomized controlled trials was conducted to determine the effect of physical exercise on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life in a population of older people with Alzheimer´s disease.
DATA SOURCES
Pubmed, Scopus, PEDro, Web of Science, CINAHL, Cochrane Library, grey literature and a reverse search from inception to April 2021 were searched to identify documents.
STUDY SELECTION
Publications investigating the effect of any type of physical exercise-based intervention in any of its multiple modalities on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life were searched.
DATA EXTRACTION
The data were extracted into predesigned data extraction tables. Risk of bias was evaluated through the PEDro scale and its internal validity scale.
DATA SYNTHESIS
A total of 8 different randomized controlled trials with a total sample of 562 non-overlap Alzheimer disease patients between 50-90 years and a mean age of 75.2 ± 3.9 years were eligible for analyses. Physical-functional capacity was evaluated in 6 of 8 studies and cognitive performance was evaluated in 5 of 8 studies, all of them showed improvements in these variables when compared with the controls, except for two studies in physical-functional capacity and one study for cognitive performance. In the physical-functional capacity and cognitive performance variables, aerobic physical exercise was used in isolation, or in a multimodal way, combining aerobic, strength and balance exercise, from 2 to 7 weekly sessions with doses between 30 and 90 minutes, and a duration of the program comprised of 9 weeks to 6 months. Neuropsychiatric symptoms and quality of life were evaluated in 2 of 8 studies, which the intervention groups experienced significant improvements when compared with the control groups, except for one study that found similar differences in quality of life between both groups. In the neuropsychiatric symptoms and quality of life variables, only aerobic physical exercise was used, in a more homogeneous way, from 2 to 3 weekly sessions with doses of 30 to 60 minutes, and a total program duration of 9 to 16 weeks.
CONCLUSIONS
Despite the scarcity of studies, especially those based on multimodal proposals, and the heterogeneity in the protocols, this systematic review found moderate to limited evidence that aerobic physical exercise on its own or combined in a multimodal program that also includes strength and balance exercise can be a useful tool in the management of patients with Alzheimer's disease with the aim of maintaining and/or improving physical-functional capacity and cognitive performance. In addition, this review found moderate evidence of the positive impact that aerobic physical exercise could have in reducing neuropsychiatric symptoms and improving quality of life in patients with Alzheimer´s disease. PROSPERO registration number: CRD42021229891.
Topics: Aged; Aged, 80 and over; Humans; Middle Aged; Alzheimer Disease; Exercise; Exercise Therapy; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36281664
DOI: 10.14283/jpad.2022.57 -
Gut microbiota in patients with Alzheimer's disease spectrum: a systematic review and meta-analysis.Aging Jan 2022Gut dysbiosis has been proposed as one of pathologies in patients with Alzheimer's disease (AD) spectrum. Despite such enthusiasm, the relevant results remain... (Meta-Analysis)
Meta-Analysis
CONTEXT
Gut dysbiosis has been proposed as one of pathologies in patients with Alzheimer's disease (AD) spectrum. Despite such enthusiasm, the relevant results remain substantially controversial.
OBJECTIVE
A systematic review and meta-analysis were performed to investigate the differences of gut microbiota (GM) between patients with AD spectrum (including mild cognitive impairment [MCI] and AD) and healthy controls (HC).
DATA SOURCES
PubMed, MEDLINE, Scopus, and Cochrane Library from January 2000 to August 2021. Eligibility criteria for study selection: Observational trials and pre-intervention data of intervention trials that investigated the abundance of GM in patients with AD spectrum and HC.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently identified articles, extracted data, and evaluated the risk of bias. The effect sizes were performed by a random-effect, inverse-variance weighted model. The effects of different countries and of clinical stages on GM abundance were also examined.
RESULTS
11 studies consisting of 378 HC and 427 patients with AD spectrum were included in the meta-analysis. Patients with AD, but not MCI, showed significantly reduced GM diversity as compared to HC. We also found more abundance of , and , but less abundance of , , and in patients with AD spectrum as compared with HC. The profiles of abundance of and in HC and AD spectrum were differentially affected by countries. Finally, when considering clinical stage as a moderator, the comparisons of abundance in and showed large effect sizes, with gradient changes from MCI to AD stage.
LIMITATIONS
The inclusion of studies originating only from China and the U.S. was a possible limitation.
CONCLUSIONS
Patients with AD spectrum demonstrated altered GM abundance, which was differentially mediated by countries and clinical stages.
Topics: Aged; Alzheimer Disease; Bacteria; Female; Gastrointestinal Microbiome; Humans; Male; Middle Aged
PubMed: 35027502
DOI: 10.18632/aging.203826 -
Ageing Research Reviews May 2022Multiple structural brain changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI) have been revealed on magnetic resonance imaging (MRI). There is a... (Review)
Review
INTRODUCTION
Multiple structural brain changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI) have been revealed on magnetic resonance imaging (MRI). There is a fast-growing effort in applying artificial intelligence (AI) to analyze these data. Here, we review and evaluate the AI studies in brain MRI analysis with synthesis.
METHODS
A systematic review of the literature, spanning the years from 2009 to 2020, was completed using the PubMed database. AI studies using MRI imaging to investigate normal aging, mild cognitive impairment, and AD-dementia were retrieved for review. Bias assessment was completed using the PROBAST criteria.
RESULTS
97 relevant studies were included in the review. The studies were typically focused on the classification of AD, MCI, and normal aging (71% of the reported studies) and the prediction of MCI conversion to AD (25%). The best performance was achieved by using the deep learning-based convolution neural network algorithms (weighted average accuracy 89%), in contrast to 76-86% using Logistic Regression, Support Vector Machines, and other AI methods.
DISCUSSION
The synthesized evidence is paramount to developing sophisticated AI approaches to reliably capture and quantify multiple subtle MRI changes in the whole brain that exemplify the complexity and heterogeneity of AD and brain aging.
Topics: Alzheimer Disease; Artificial Intelligence; Brain; Cognitive Dysfunction; Humans; Magnetic Resonance Imaging
PubMed: 35358720
DOI: 10.1016/j.arr.2022.101614 -
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 -
European Journal of Medical Research Nov 2023Alzheimer's disease (AD) is a worldwide public health problem and is difficult to cure. Drugs aimed at slowing the progression of the disease have been developed, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alzheimer's disease (AD) is a worldwide public health problem and is difficult to cure. Drugs aimed at slowing the progression of the disease have been developed, with the Food and Drug Administration (FDA) granting accelerated approval for aducanumab on June 21, 2021 and a new accelerated approval for lecanemab on January 22, 2023. We performed this systematic review and meta-analysis to assess the efficacy and safety of FDA-approved anti-amyloid-β (anti-Aβ) monoclonal antibodies (mabs) for the treatment of AD.
METHOD
PubMed, Embase, and Cochrane Library were systematically searched to identify relevant studies published before May 2023. Efficacy outcomes included Aβ, neuroimaging, and biomarker outcomes. Safety outcomes included amyloid-related imaging abnormalities with edema or effusions (ARIA-E) and ARIA with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (ARIA-H). Review Manager 5.4 software was used to assess the data. The standard mean differences (SMDs) or odds ratio (OR) with 95% confidence interval (95% CI) were analyzed and calculated with a random effect model or a fixed effect model.
RESULT
Overall, 4471 patients from 6 randomized controlled trials (RCTs), with 2190 patients in the treatment group and 2281 patients in the placebo group meeting the inclusion criteria. FDA-approved anti-Aβ mabs showed statistically significant improvements in clinical outcomes, including CDR-SB (P = 0.01), ADCS-ADL-MCI (P = 0.00003), ADCOMS (P < 0.00001), ADAS-Cog (P < 0.00001). Moreover, FDA-approved anti-Aβ mabs increased cerebrospinal fluid (CSF) Aβ1-42 (P = 0.002) and plasma Aβ42/40 ratios (P = 0.0008). They also decreased CSF P-Tau (P < 0.00001), CSF T-Tau (P < 0.00001), and plasma p-tau181 (P < 0.00001). FDA-approved anti-Aβ mabs perform neuroimaging changes in amyloid Positron Emission Tomography Standardized Uptake Value ratio (PET SUVr) (P < 0.00001). However, compared with placebo, FDA-approved anti-Aβ mabs had higher risk of ARIA-E (P < 0.00001) and ARIA-H (P < 0001).
CONCLUSION
FDA-approved anti-Aβ mabs have a role in slowing disease progression in patients with AD, at the cost of an increased probability of side effects.
Topics: United States; Humans; Alzheimer Disease; United States Food and Drug Administration; Randomized Controlled Trials as Topic; Amyloid beta-Peptides; Biomarkers
PubMed: 38017568
DOI: 10.1186/s40001-023-01512-w -
Neurologia Mar 2020Alzheimer disease (AD) is a neurodegenerative disease characterised by progressive dementia associated with global cognitive dysfunction. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Alzheimer disease (AD) is a neurodegenerative disease characterised by progressive dementia associated with global cognitive dysfunction.
METHODS
We conducted a systematic review and meta-analysis of clinical trials evaluating omega-3 supplementation in patients with AD.
OBJECTIVE
To determine if there is scientific evidence of the effectiveness of omega-3 supplementation in improving cognitive function in patients with AD.
SEARCH STRATEGY
We included only randomised controlled trials (RCTs) from the following databases: Medline, Cochrane Central, Cinahl, and LILACS. An electronic search was also conducted using Google Scholar.
STUDY SELECTION
Six articles met the eligibility criteria. The risk of bias was assessed following the Cochrane method.
CONCLUSION
There is no consistent evidence to support the effectiveness of omega-3 supplementation in improving cognitive function in AD patients in the short and medium term.
Topics: Alzheimer Disease; Cognitive Dysfunction; Dietary Supplements; Fatty Acids, Omega-3; Humans; Randomized Controlled Trials as Topic
PubMed: 28986068
DOI: 10.1016/j.nrl.2017.07.009 -
Molecular Neurobiology Sep 2019Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the...
Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the accumulation of amyloid-beta plaques and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significantly deregulated in the peripheral blood. These deregulated miRNAs were cross-referenced against the miRNAs deregulated in the brain at Braak Stage III. This resulted in a panel of 10 miRNAs (hsa-mir-107, hsa-mir-26b, hsa-mir-30e, hsa-mir-34a, hsa-mir-485, hsa-mir200c, hsa-mir-210, hsa-mir-146a, hsa-mir-34c, and hsa-mir-125b) hypothesised to be deregulated early in Alzheimer's disease, nearly 20 years before the onset of clinical symptoms. After network analysis of the 10 miRNAs, they were found to be associated with the immune system, cell cycle, gene expression, cellular response to stress, neuron growth factor signalling, wnt signalling, cellular senescence, and Rho GTPases.
Topics: Alzheimer Disease; Animals; Biomarkers; Brain; Gene Regulatory Networks; Humans; MicroRNAs
PubMed: 30734227
DOI: 10.1007/s12035-019-1500-y -
Journal of Medical Internet Research Aug 2019Among areas that have challenged the progress of dementia care has been the assessment of change in symptoms over time. Digital biomarkers are defined as objective,...
Current State of Digital Biomarker Technologies for Real-Life, Home-Based Monitoring of Cognitive Function for Mild Cognitive Impairment to Mild Alzheimer Disease and Implications for Clinical Care: Systematic Review.
BACKGROUND
Among areas that have challenged the progress of dementia care has been the assessment of change in symptoms over time. Digital biomarkers are defined as objective, quantifiable, physiological, and behavioral data that are collected and measured by means of digital devices, such as embedded environmental sensors or wearables. Digital biomarkers provide an alternative assessment approach, as they allow objective, ecologically valid, and long-term follow-up with continuous assessment. Despite the promise of a multitude of sensors and devices that can be applied, there are no agreed-upon standards for digital biomarkers, nor are there comprehensive evidence-based results for which digital biomarkers may be demonstrated to be most effective.
OBJECTIVE
In this review, we seek to answer the following questions: (1) What is the evidence for real-life, home-based use of technologies for early detection and follow-up of mild cognitive impairment (MCI) or dementia? And (2) What transformation might clinicians expect in their everyday practices?
METHODS
A systematic search was conducted in PubMed, Cochrane, and Scopus databases for papers published from inception to July 2018. We searched for studies examining the implementation of digital biomarker technologies for mild cognitive impairment or mild Alzheimer disease follow-up and detection in nonclinic, home-based settings. All studies that included the following were examined: community-dwelling older adults (aged 65 years or older); cognitively healthy participants or those presenting with cognitive decline, from subjective cognitive complaints to early Alzheimer disease; a focus on home-based evaluation for noninterventional follow-up; and remote diagnosis of cognitive deterioration.
RESULTS
An initial sample of 4811 English-language papers were retrieved. After screening and review, 26 studies were eligible for inclusion in the review. These studies ranged from 12 to 279 participants and lasted between 3 days to 3.6 years. Most common reasons for exclusion were as follows: inappropriate setting (eg, hospital setting), intervention (eg, drugs and rehabilitation), or population (eg, psychiatry and Parkinson disease). We summarized these studies into four groups, accounting for overlap and based on the proposed technological solutions, to extract relevant data: (1) data from dedicated embedded or passive sensors, (2) data from dedicated wearable sensors, (3) data from dedicated or purposive technological solutions (eg, games or surveys), and (4) data derived from use of nondedicated technological solutions (eg, computer mouse movements).
CONCLUSIONS
Few publications dealt with home-based, real-life evaluations. Most technologies were far removed from everyday life experiences and were not mature enough for use under nonoptimal or uncontrolled conditions. Evidence available from embedded passive sensors represents the most relatively mature research area, suggesting that some of these solutions could be proposed to larger populations in the coming decade. The clinical and research communities would benefit from increasing attention to these technologies going forward.
Topics: Accelerometry; Aged; Alzheimer Disease; Automobile Driving; Biomarkers; Cognition; Cognitive Dysfunction; Disease Progression; Early Diagnosis; Geographic Information Systems; Humans; Independent Living; Surveys and Questionnaires; Technology; Telemedicine; Wearable Electronic Devices
PubMed: 31471958
DOI: 10.2196/12785 -
Acta Diabetologica Jun 2021Mild Cognitive impairment (MCI) is common in type 2 diabetes mellitus (T2DM) patients. The impaired cognitive function had harmful effect on patients' diabetic... (Meta-Analysis)
Meta-Analysis
AIMS
Mild Cognitive impairment (MCI) is common in type 2 diabetes mellitus (T2DM) patients. The impaired cognitive function had harmful effect on patients' diabetic conditions. This study aimed to estimate the prevalence of MCI in T2DM (T2DM-MCI) patients by conducting a systematic review and meta-analysis of observational studies.
METHODS
We carried out a literature search until June 1, 2020, for all observational studies in the following databases: Medline (PubMed), Web of Science, and Embase. Two independent reviewers initially screened the eligible articles. Then, a meta-analysis (random effects model) was conducted to estimate the prevalence of MCI in people with T2DM with STATA 16.
RESULTS
A total of 1808 articles were first considered after reading title and abstract, 12 of which remained after reviewing the full text. The combined prevalence of MCI in T2DM patients was estimated to be 45.0% (95% CI=36.0, 54.0). There was no significant heterogeneity through meta-regression and sensitivity analysis. Overall, Europe (n=2, r=36.6%, 95% CI=26.3, 46.9, I=82.3%) had a lower prevalence than Asia (n=10, r=46.4%, 95% CI=36.2, 56.6, I=98%). The overall prevalence in female patients (n=14, r=46.9%, 95% CI=34, 59.8, I=98.3%) was higher than that in male patients (n=14, r=38.8%, 95% CI=27, 50.7, I=98%). Subgroup analysis based on age demonstrated a lower prevalence in patients older than 60 years (n=9, r=44.3%, 95% CI=33.1, 55.6, I=98.3%) than patients younger than 60 years (n=3, r=46.4%, 95% CI=33.3, 59.5, I=91.2%).
CONCLUSION
Our results demonstrate that the pooled estimated prevalence of mild cognitive impairment in type 2 diabetes mellitus patients is high worldwide, especially in China Asia. Primary care clinicians should pay more attention to the cognitive function of T2DM patients, as mild cognitive impairment is one of the risk factors for Alzheimer's disease.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Asia; China; Cognitive Dysfunction; Diabetes Mellitus, Type 2; Europe; Female; Humans; Male; Middle Aged; Prevalence; Risk Factors
PubMed: 33417039
DOI: 10.1007/s00592-020-01648-9 -
Clinica Chimica Acta; International... Jun 2022The potential of disease-modifying therapies for Alzheimer's disease has greatly stimulated interest in the development of minimally invasive testing for early... (Review)
Review
BACKGROUND AND AIMS
The potential of disease-modifying therapies for Alzheimer's disease has greatly stimulated interest in the development of minimally invasive testing for early identification of at-risk individuals. Accordingly, identification of blood-based biomarkers is paramount. The recent discovery of plasma phosphorylated at threonine217 (p-tau217) may provide a turning point in Alzheimer's disease detection. This systematic review aims to evaluate the available evidence on the use of plasma p-tau217 as a marker to predict Alzheimer's disease and to monitor disease progression.
MATERIAL AND METHODS
This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Study quality was assessed using the QUADAS-2 tool. In total, 676 publications were identified, of which 16 were in accordance with the pre-defined eligibility criteria.
RESULTS
Current evidence shows that plasma p-tau217 is a sensitive maker of the clinical manifestation and progression of Alzheimer's disease and of pathological changes associated with this condition, including amyloid accumulation, tau burden, brain atrophy and physical degradation. Moreover, given that plasma p-tau217 does not predict such changes in patients with other neurodegenerative disorders, plasma p-tau217 is also specific to Alzheimer's disease.
CONCLUSION
More large, diverse community studies are needed to harmonize plasma p-tau217 measurements and to determine widely applicable diagnostic cut-off values.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Disease Progression; Humans; tau Proteins
PubMed: 35341762
DOI: 10.1016/j.cca.2022.03.018