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Brain and Behavior Jan 2023In recent years, longitudinal studies of Alzheimer's disease (AD) have been successively concluded. Our aim is to determine the efficacy of amyloid-β (Aβ) PET in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In recent years, longitudinal studies of Alzheimer's disease (AD) have been successively concluded. Our aim is to determine the efficacy of amyloid-β (Aβ) PET in diagnosing AD and early prediction of mild cognitive impairment (MCI) converting to AD. By pooling studies from different centers to explore in-depth whether diagnostic performance varies by population type, radiotracer type, and diagnostic approach, thus providing a more comprehensive theoretical basis for the subsequent widespread application of Aβ PET in the clinical setting.
METHODS
Relevant studies were searched through PubMed. The pooled sensitivities, specificities, DOR, and the summary ROC curve were obtained based on a Bayesian random-effects model.
RESULTS
Forty-eight studies, including 5967 patients, were included. Overall, the pooled sensitivity, specificity, DOR, and AUC of Aβ PET for diagnosing AD were 0.90, 0.80, 35.68, and 0.91, respectively. Subgroup analysis showed that Aβ PET had high sensitivity (0.91) and specificity (0.81) for differentiating AD from normal controls but very poor specificity (0.49) for determining AD from MCI. The pooled sensitivity and specificity were 0.84 and 0.62, respectively, for predicting the conversion of MCI to AD. The differences in diagnostic efficacy between visual assessment and quantitative analysis and between C-PIB PET and F-florbetapir PET were insignificant.
CONCLUSIONS
The overall performance of Aβ PET in diagnosing AD is favorable, but the differentiation between MCI and AD patients should consider that some MCI may be at risk of conversion to AD and may be misdiagnosed. A multimodal diagnostic approach and machine learning analysis may be effective in improving diagnostic accuracy.
Topics: Humans; Alzheimer Disease; Bayes Theorem; Amyloid beta-Peptides; Cognitive Dysfunction; Sensitivity and Specificity; Positron-Emission Tomography
PubMed: 36573329
DOI: 10.1002/brb3.2850 -
Journal of Alzheimer's Disease : JAD 2017Depression is common in people with Alzheimer's disease (AD) affecting overall outcomes and decreasing quality of life. Although depression in AD is primarily treated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Depression is common in people with Alzheimer's disease (AD) affecting overall outcomes and decreasing quality of life. Although depression in AD is primarily treated with antidepressants, there are few randomized controlled trials (RCTs) assessing efficacy and results have been conflicting.
OBJECTIVES
To systematically review evidence on efficacy of antidepressant treatments for depression in AD.
METHODS
Systematic review and meta-analysis of double blind RCTs comparing antidepressants versus placebo for depression in AD. We searched MEDLINE, CINAHL, EMBASE, PsycINFO, the Cochrane Controlled Trials Register and on line national and international registers. Primary outcomes were treatment response and depressive symptoms. Secondary outcomes were cognition, acceptability, and tolerability. Risk of bias was also assessed.
RESULTS
Seven studies met inclusion criteria. Three compared sertraline with placebo; one compared both sertraline and mirtazapine to placebo; imipramine, fluoxetine, and clomipramine were evaluated in one study each. In terms of response to treatment (6 studies, 297 patients treated with antidepressants and 223 with placebo), no statistically significant difference between antidepressants and placebo was found (odds ratio (OR) 1.95, 95% CI 0.97-3.92). We found no significant drug-placebo difference for depressive symptoms (5 studies, 311 patients, SMD -0.13; 95% CI -0.49 to 0.24). Overall quality of the evidence was moderate because of methodological limitations in studies and the small number of trials.
CONCLUSION
Despite the importance of depression in people with AD, few RCTs are available on efficacy of antidepressants, limiting clear conclusions of their potential role. There is a need for further high quality RCTs.
Topics: Alzheimer Disease; Antidepressive Agents; Depressive Disorder; Humans; Randomized Controlled Trials as Topic
PubMed: 28505970
DOI: 10.3233/JAD-161247 -
The Journal of Clinical Psychiatry Oct 2022To summarize the breadth of data exploring the relationship between major depressive disorder (MDD) and both the incidence and the disease course of a range of...
To summarize the breadth of data exploring the relationship between major depressive disorder (MDD) and both the incidence and the disease course of a range of comorbidities. The authors searched MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews, and several prespecified congresses. Searches included terms related to MDD and several comorbidity categories, restricted to those published in the English language from 2005 onward. Eligibility criteria included observational studies within North America and Europe that examined the covariate-adjusted impact of MDD on the risk and/or severity of comorbidities. A total of 6,811 articles were initially identified for screening. : Two investigators extracted data and assessed study quality. In total, 199 articles were included. Depression was significantly ( < .05) associated with an increased incidence of dementia and Alzheimer's disease as well as cognitive decline in individuals with existing disease; increased incidence and worsening of cardiovascular disease/events (although mixed results were found for stroke); worsening of metabolic syndrome; increased incidence of diabetes, particularly among men, and worsening of existing diabetes; increased incidence of obesity, particularly among women; increased incidence and worsening of certain autoimmune diseases; increased incidence and severity of HIV/AIDS; and increased incidence of drug abuse and severity of both alcohol and drug abuse. The presence of MDD was identified as a risk factor for both the development and the worsening of a range of comorbidities. These results highlight the importance of addressing depression early in its course and the need for integrating mental and general health care.
Topics: Female; Humans; Male; Alzheimer Disease; Cognitive Dysfunction; Comorbidity; Depressive Disorder, Major
PubMed: 36264099
DOI: 10.4088/JCP.21r14328 -
Annals of Family Medicine 2024We conducted a meta-analysis to evaluate clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer dementia. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We conducted a meta-analysis to evaluate clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer dementia.
METHODS
We searched PubMed, Cochrane CENTRAL, and 5 trial registries, as well as the reference lists of identified studies. We included randomized controlled trials comparing a monoclonal antibody with placebo at a dose consistent with that used in phase 3 trials or for Food and Drug Administration approval. Studies had to report at least 1 clinically relevant benefit or harm. Data were extracted independently by at least 2 researchers for random effects meta-analysis. Changes in cognitive and functional scales were compared between groups, and each difference was assessed to determine if it met the minimal clinically important difference (MCID).
RESULTS
We identified 19 publications with 23,202 total participants that evaluated 8 anti-amyloid antibodies. There were small improvements over placebo in the Alzheimer's Disease Assessment Scale (ADAS)-Cog-11 to -14 score (standardized mean difference = -0.07; 95% CI, -0.10 to -0.04), Mini Mental State Examination score (0.32 points; 95% CI, 0.13 to 0.50), and Clinical Dementia Rating-Sum of Boxes scale score (mean difference =-0.18 points; 95% CI, -0.34 to -0.03), and the combined functional scores (standardized mean difference = 0.09; 95% CI, 0.05 to 0.13). None of the changes, including those for lecanemab, aducanumab, and donanemab, exceeded the MCID. Harms included significantly increased risks of amyloid-related imaging abnormalities (ARIA)-edema (relative risk [RR] = 10.29; number needed to harm [NNH] = 9), ARIA-hemorrhage (RR = 1.74; NNH = 13), and symptomatic ARIA-edema (RR = 24.3; NNH = 86).
CONCLUSIONS
Although monoclonal antibodies targeting amyloid provide small benefits on cognitive and functional scales in patients with Alzheimer dementia, these improvements are far below the MCID for each outcome and are accompanied by clinically meaningful harms.
Topics: United States; Humans; Alzheimer Disease; Antibodies, Monoclonal; Mental Status and Dementia Tests; Edema; Antibodies, Monoclonal, Humanized
PubMed: 38253509
DOI: 10.1370/afm.3050 -
BMC Psychiatry Sep 2019Dementia represents a mental and economic burden for both patients and their caregivers. Therefore, the aim of this study is to explore the effectiveness of animal...
BACKGROUND
Dementia represents a mental and economic burden for both patients and their caregivers. Therefore, the aim of this study is to explore the effectiveness of animal assisted therapy (AAT) with special focus on canis therapy among people with dementia, specifically Alzheimer's disease.
METHODS
The key method of this review study is a systematic review of the research studies detected in the Web of Science, Scopus and PubMed. The search was conducted for the studies dating from 2016 till 31 August 2018 because several review studies were published before. Eventually, only six studies were involved into the final analysis.
RESULTS
The findings of this review, based on significant effect sizes, reveal that AAT may work as a beneficial and effective complementary treatment, especially in the area of behavioral and psychological symptoms, for patients with different degree of dementia severity if AAT is targeted at their specific needs and interests.
CONCLUSIONS
More research in the area of methodology for the implementation of AAT is necessary, and more research should be conducted with respect to the use of AAT for the improvement of cognitive functions in people with dementia.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Animal Assisted Therapy; Animals; Caregivers; Dementia; Dogs; Female; Humans; Male; Middle Aged; Treatment Outcome
PubMed: 31492131
DOI: 10.1186/s12888-019-2245-x -
International Journal of Environmental... Jan 2022The purpose of this meta-analysis was to examine the effects of physical activity (PA) on cognition and activities of daily living in adults with Alzheimer's Disease... (Meta-Analysis)
Meta-Analysis Review
Physical Activity Improves Cognition and Activities of Daily Living in Adults with Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
OBJECTIVE
The purpose of this meta-analysis was to examine the effects of physical activity (PA) on cognition and activities of daily living in adults with Alzheimer's Disease (AD).
METHODS
Six electronic databases (MEDLINE, CINAHL, PsycArticles, SPORTDiscus, EMBASE and CNKI) were used to search for potential studies from inception until October 2021. Randomized controlled trials (RCTs) investigating the effect of physical activity (PA) on cognition and activities of daily living in AD patients compared to a control condition were included. The effect sizes were synthesized using a random effects model with a 95% confidence interval (CI).
RESULTS
Sixteen articles including 945 participants (aged 70 to 88 years, 34.6% male) met the inclusion criteria. The pooled effect sizes demonstrated that PA intervention was associated with significant improvements in global cognition (Standard Mean Difference (SMD) = 0.41, 95% CI [0.24, 0.58], < 0.01) and activities of daily living (SMD = 0.56, 95% CI [0.32, 0.79], < 0.01) in AD patients. Subgroup analyses suggested that PA for 3-4 times per week for 30-45 min for more than 12 weeks had a relatively strong effect on improving global cognition in AD patients. The sensitivity analysis showed robust results.
CONCLUSIONS
The findings from the current meta-analysis suggested that AD patients can improve their global cognition and Activities of Daily Living (ADL) through engaging in aerobic and mixed exercise (aerobic and anaerobic exercise).
Topics: Activities of Daily Living; Adult; Aged; Aged, 80 and over; Alzheimer Disease; Cognition; Exercise; Female; Humans; Male; Randomized Controlled Trials as Topic
PubMed: 35162238
DOI: 10.3390/ijerph19031216 -
Clinical Interventions in Aging 2008Pharmacologic treatments for Alzheimer's disease include the cholinesterase inhibitors donepezil, galantamine, and rivastigmine. We reviewed their evidence by searching... (Comparative Study)
Comparative Study Meta-Analysis Review
Pharmacologic treatments for Alzheimer's disease include the cholinesterase inhibitors donepezil, galantamine, and rivastigmine. We reviewed their evidence by searching MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 through 2007 (July) for placebo-controlled and comparative trials assessing cognition, function, behavior, global change, and safety. Thirty-three articles on 26 studies were included in the review. Meta-analyses of placebo-controlled data support the drugs' modest overall benefits for stabilizing or slowing decline in cognition, function, behavior, and clinical global change. Three open-label trials and one double-blind randomized trial directly compared donepezil with galantamine and rivastigmine. Results are conflicting; two studies suggest no differences in efficacy between compared drugs, while one study found donepezil to be more efficacious than galantamine, and one study found rivastigmine to be more efficacious than donepezil. Adjusted indirect comparison of placebo-controlled data did not find statistically significant differences among drugs with regard to cognition, but found the relative risk of global response to be better with donepezil and rivastigmine compared with galantamine (relative risk = 1.63 and 1.42, respectively). Indirect comparisons also favored donepezil over galantamine with regard to behavior. Across trials, the incidence of adverse events was generally lowest for donepezil and highest for rivastigmine.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Galantamine; Humans; Indans; Phenylcarbamates; Piperidines; Rivastigmine; Treatment Outcome
PubMed: 18686744
DOI: No ID Found -
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 -
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 -
Alzheimer's Research & Therapy Feb 2019The objective of this systematic review was (1) to give an overview of the available short screening instruments for the early detection of Alzheimer's disease (AD) and...
OBJECTIVES
The objective of this systematic review was (1) to give an overview of the available short screening instruments for the early detection of Alzheimer's disease (AD) and (2) to review the psychometric properties of these instruments.
METHODS
First, a systematic search of titles and abstracts of PubMed and Web of Science was conducted between February and July 2015 and updated in April 2016 and May 2018. Only papers written in English or Dutch were considered. All full-text papers about cognitive screening instruments for the early detection of AD were included, resulting in the identification of 38 pencil and paper tests and 12 computer tests. In a second step, the psychometric quality of these instruments was evaluated. Therefore, the same databases were searched again to identify papers that described the psychometric properties of the instruments meanwhile applying diagnostic criteria for the diagnostic groups included.
RESULTS
Out of 1454 papers, 96 clearly discussed the psychometric properties of the instruments. Eighty-nine papers discussed pencil and paper tests of which 80 were validated in a memory clinic setting. Based on the number of studies (31 articles) and the sensitivity (84%) and specificity (74%) values, the Montreal Cognitive Assessment (MoCA) seems to be a promising (pencil and paper) screening test for memory clinic testing as well as for population screening. Regarding computer tests, validation studies were only available for 7 out of 12 tests.
CONCLUSIONS
A large number of screening tests for AD are available. However, most tests are only validated in a memory clinic setting and description of the psychometric properties of the instruments is limited. Especially, computer tests require further research. The MoCA is a promising instrument, but the specificity to detect early AD is rather low.
Topics: Alzheimer Disease; Brief Psychiatric Rating Scale; Cognition; Cognitive Dysfunction; Early Diagnosis; Humans; Mental Status and Dementia Tests
PubMed: 30819244
DOI: 10.1186/s13195-019-0474-3