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Neuroscience and Biobehavioral Reviews Aug 2021Endogenous melatonin levels are inversely associated with age and cognitive deficits. Although melatonin can improve psychopathological behavior disturbances in clinical... (Meta-Analysis)
Meta-Analysis Review
Neurocognitive effects of melatonin treatment in healthy adults and individuals with Alzheimer's disease and insomnia: A systematic review and meta-analysis of randomized controlled trials.
Endogenous melatonin levels are inversely associated with age and cognitive deficits. Although melatonin can improve psychopathological behavior disturbances in clinical trials, whether melatonin may also enhance cognitive function remains elusive. This study examined cognitive outcomes from randomized trials of melatonin treatment for Alzheimer's disease (AD), insomnia, and healthy-subjects. Twenty-two studies met the inclusion criteria (AD = 9, insomnia = 2, healthy-subjects = 11). AD patients receiving >12 weeks of melatonin treatment improved mini-mental state examination (MMSE) score [MD: 1.82 (1.01; 2.63) p < 0.0001]. Importantly, melatonin significantly improved MMSE score in mild stage of AD [MD: 1.89 (0.96; 2.82) p < 0.0001]. In healthy-subjects, although daytime melatonin treatment notably decreased in accuracy by correct responses [SMD: -0.74 (-1.03; -0.45) p < 0.00001], the reaction-time score on different stimuli (p = 0.37) did not increased. Additionally, by pooling of short-term, spatial, and visual memory scores, melatonin did not reduce memory function (p = 0.08). Meta-analysis of MMSE score suggested that melatonin is effective in treatment for mild stage of AD. Additionally, we propose that melatonin may be preferable to traditional hypnotics in management of insomnia.
Topics: Adult; Alzheimer Disease; Cognition Disorders; Humans; Melatonin; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders
PubMed: 33957167
DOI: 10.1016/j.neubiorev.2021.04.034 -
Neurology Mar 2020To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and meta-analysis on AD subtype studies based on postmortem and neuroimaging data.
METHODS
EMBASE, PubMed, and Web of Science databases were consulted until July 2019.
RESULTS
Neuropathology and neuroimaging studies have consistently identified 3 subtypes of AD based on the distribution of tau-related pathology and regional brain atrophy: typical, limbic-predominant, and hippocampal-sparing AD. A fourth subtype, minimal atrophy AD, has been identified in several neuroimaging studies. Typical AD displays tau-related pathology and atrophy both in hippocampus and association cortex and has a pooled frequency of 55%. Limbic-predominant, hippocampal-sparing, and minimal atrophy AD had a pooled frequency of 21%, 17%, and 15%, respectively. Between-subtype differences were found in age at onset, age at assessment, sex distribution, years of education, global cognitive status, disease duration, APOE ε4 genotype, and CSF biomarker levels.
CONCLUSION
We identified 2 core dimensions of heterogeneity: typicality and severity. We propose that these 2 dimensions determine individuals' belonging to one of the AD subtypes based on the combination of protective factors, risk factors, and concomitant non-AD brain pathologies. This model is envisioned to aid with framing hypotheses, study design, interpretation of results, and understanding mechanisms in future subtype studies. Our model can be used along the A/T/N classification scheme for AD biomarkers. Unraveling the heterogeneity within AD is critical for implementing precision medicine approaches and for ultimately developing successful disease-modifying drugs for AD.
Topics: Alzheimer Disease; Humans
PubMed: 32047067
DOI: 10.1212/WNL.0000000000009058 -
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 -
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 -
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 -
Dementia and Geriatric Cognitive... 2021In the absence of a cure, dementia is often managed by minimizing risk factors contributing to quality of life (QOL). Attitudes to dementia in older adults may differ...
INTRODUCTION
In the absence of a cure, dementia is often managed by minimizing risk factors contributing to quality of life (QOL). Attitudes to dementia in older adults may differ from those in relatively younger adults. The aim was to conduct a systematic review of the literature to determine how QOL was assessed in adults, 65 years and older with dementia, and identify factors that influence the reported scores.
METHODS
A systematic review of full-text articles addressing QOL in older adults with dementia, published in English from January 1995 to September 2020, was conducted using PubMed and PsycINFO. We included studies that assessed QOL and involved participants 65 years and older. Studies were evaluated for inclusion by 2 independent pairs of reviewers. We assessed the quality of the studies using the Joanna Briggs Institute's Critical Appraisal Checklist. Study characteristics and findings were summarized. Analysis was by narrative synthesis. We identified social and clinical factors influencing QOL scores.
RESULTS
Of the 1,010 articles identified, 19 met the inclusion criteria. These 19 studies involved 6,279 persons with dementia, with sample sizes from 32 to 1,366. Mean age of participants ranged from 77.1 to 86.6 years. Five measurement tools were identified; Quality of Life in Alzheimer Disease (QOL-AD), Alzheimer Disease-Related Quality of Life (ADRQL), Quality of Life in Late-Stage Dementia (QUALID), QUALIDEM (a dementia-specific QOL tool), and DEMQOL (health-related QOL for people with dementia). Self-ratings of QOL were higher than proxy ratings. Factors commonly influencing self-ratings of QOL included depression, functional impairment, and polypharmacy. Common factors that influenced proxy ratings included functional impairment, presence of neuropsychiatric symptoms, cognitive impairment, and caregiver burden.
CONCLUSION
In evaluating QOL in dementia, self- and proxy reports may complement each other to ensure that all perspectives are addressed.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Caregivers; Dementia; Humans; Proxy; Quality of Life
PubMed: 34167127
DOI: 10.1159/000515317 -
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 -
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 -
Alzheimer's & Dementia : the Journal of... Jul 2023Operationalized research criteria for mild cognitive impairment with Lewy bodies (MCI-LB) were published in 2020. The aim of this systematic review and meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Operationalized research criteria for mild cognitive impairment with Lewy bodies (MCI-LB) were published in 2020. The aim of this systematic review and meta-analysis was to review the evidence for the diagnostic clinical features and biomarkers in MCI-LB set out in the criteria.
METHODS
MEDLINE, PubMed, and Embase were searched on 9/28/22 for relevant articles. Articles were included if they presented original data reporting the rates of diagnostic features in MCI-LB.
RESULTS
Fifty-seven articles were included. The meta-analysis supported the inclusion of the current clinical features in the diagnostic criteria. Evidence for striatal dopaminergic imaging and meta-iodobenzylguanidine cardiac scintigraphy, though limited, supports their inclusion. Quantitative electroencephalogram (EEG) and fluorodeoxyglucose positron emission tomography (PET) show promise as diagnostic biomarkers.
DISCUSSION
The available evidence largely supports the current diagnostic criteria for MCI-LB. Further evidence will help refine the diagnostic criteria and understand how best to apply them in clinical practice and research.
HIGHLIGHTS
A meta-analysis of the diagnostic features of MCI-LB was carried out. The four core clinical features were more common in MCI-LB than MCI-AD/stable MCI. Neuropsychiatric and autonomic features were also more common in MCI-LB. More evidence is needed for the proposed biomarkers. FDG-PET and quantitative EEG show promise as diagnostic biomarkers in MCI-LB.
Topics: Humans; Alzheimer Disease; Lewy Bodies; Sensitivity and Specificity; Cognitive Dysfunction; Biomarkers; Lewy Body Disease
PubMed: 37096339
DOI: 10.1002/alz.13105