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Psychiatry Research Nov 2023Dementia is a major cause of disability and dependency. Pharmacological interventions are commonly provided to patients with dementia to delay the deterioration of... (Meta-Analysis)
Meta-Analysis Review
Effects of music therapy on cognition, quality of life, and neuropsychiatric symptoms of patients with dementia: A systematic review and meta-analysis of randomized controlled trials.
Dementia is a major cause of disability and dependency. Pharmacological interventions are commonly provided to patients with dementia to delay the deterioration of cognitive functions but cannot alter the course of disease. Nonpharmacological interventions are now attracting increasing scholarly interest. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we aim to assess the effectiveness of music-based therapies on the cognition, quality of life (QoL), and neuropsychiatric symptoms of patients with dementia through a systematic review and meta-analysis of randomized controlled trials (RCTs). The PubMed, Embase, and Cochrane databases were searched for reports of RCTs examining the effectiveness of music-based therapies for dementia published as of April 2023. A total of 674 articles were screened, and 22 trials from 21 studies (1780 patients) met the eligibility criteria. In 15 trials, music-based therapies significantly improved the cognition of patients with dementia compared with non-music therapies. In 11 trials, music-based therapies also significantly improved the QoL of patients with dementia compared with non-music therapies. In six trials, music-based therapies significantly improved patients' neuropsychiatric symptoms compared with non-music therapies. In conclusion, music-based therapy is recognized as a safe and effective alternative approach for patients with dementia.
Topics: Humans; Music Therapy; Dementia; Randomized Controlled Trials as Topic; Cognition; Quality of Life
PubMed: 37783097
DOI: 10.1016/j.psychres.2023.115498 -
Neuroscience and Biobehavioral Reviews Sep 2023Oldest-old is the fastest growing segment of society. A substantial number of these individuals are cognitively impaired or demented. Given the lack of a cure, attention... (Review)
Review
Oldest-old is the fastest growing segment of society. A substantial number of these individuals are cognitively impaired or demented. Given the lack of a cure, attention is directed to lifestyle interventions that could help alleviate the stress in patients, their families, and society. The aim of this review was to identify lifestyle factors with important roles in dementia prevention in oldest-old. Searches were conducted in PubMed, EMBASE, Scopus and Web of Science. We identified 27 observational cohort studies that met the inclusion criteria. Results showed that eating a healthy diet with plenty of fruits and vegetables, and participation in leisure and physical activities may protect against cognitive decline and cognitive impairment among oldest-old regardless of the APOE genotype. Combined lifestyles may generate multiplicative effects than individual factors. This is the first review known to systematically examine the association between lifestyle and cognitive health in oldest-old. Lifestyle interventions for diet, leisure, or a combination of lifestyles could be beneficial for cognitive function in oldest-old. Interventional studies are warranted to strengthen the evidence.
Topics: Humans; Aged, 80 and over; Dementia; Cognitive Dysfunction; Cognition; Life Style; Diet
PubMed: 37321363
DOI: 10.1016/j.neubiorev.2023.105286 -
The Lancet. Healthy Longevity Jan 2024Cognitive impairment and dementia are highly prevalent among stroke survivors and represent a major burden for patients, carers, and health-care systems. We studied the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cognitive impairment and dementia are highly prevalent among stroke survivors and represent a major burden for patients, carers, and health-care systems. We studied the risk factors for post-stroke cognitive impairment (PSCI) and dementia (PSD) beyond the well established risk factors of age and stroke severity.
METHODS
In this systematic review and meta-analysis we conducted a systematic literature search from database inception until Sept 15, 2023. We selected prospective and retrospective cohort studies, post-hoc analyses from randomised controlled trials, and nested case-control studies of patients with acute stroke (ischaemic, haemorrhagic, and transient ischaemic attack), exploring associations between risk factors at baseline and PSCI or PSD over a follow-up period of at least 3 months. Study quality was assessed using the Newcastle-Ottawa quality assessment scale. We calculated pooled relative risks (RRs) with random-effects meta-analyses and performed subgroup, meta-regression, and sensitivity analyses. This study was preregistered with PROSPERO, CRD42020164959.
FINDINGS
We identified 162 eligible articles for our systematic review, of which 113 articles (89 studies, 160 783 patients) were eligible for meta-analysis. Baseline cognitive impairment was the strongest risk factor for PSCI (RR 2·00, 95% CI 1·66-2·40) and PSD (3·10, 2·77-3·47). We identified diabetes (1·29, 1·14-1·45), presence or history of atrial fibrillation (1·29, 1·04-1·60), presence of moderate or severe white matter hyperintensities (WMH; 1·51, 1·20-1·91), and WMH severity (1·30, 1·10-1·55, per SD increase) as treatable risk factors for PSCI, independent of age and stroke severity. For PSD, we identified diabetes (1·38, 1·10-1·72), presence of moderate or severe WMH (1·55, 1·01-2·38), and WMH severity (1·61, 1·20-2·14, per SD increase) as treatable risk factors. Additional risk factors included lower educational attainment, previous stroke, left hemisphere stroke, presence of three or more lacunes, brain atrophy, and low baseline functional status. Associations of risk factors with PSD were weaker in studies conducted and published more recently. We found substantial interstudy heterogeneity and evidence of reporting bias.
INTERPRETATION
Our results highlight the importance of cognitive impairment in the acute phase after stroke for long-term prediction of PSCI and PSD. Treatable risk factors include diabetes, atrial fibrillation, and markers of cerebral small vessel disease (ie, white matter hyperintensities and lacunes). Future trials should explore these risk factors as potential targets for prevention of PSCI and PSD.
FUNDING
German Research Foundation.
Topics: Humans; Brain Ischemia; Prospective Studies; Retrospective Studies; Atrial Fibrillation; Stroke; Cognitive Dysfunction; Risk Factors; Dementia; Diabetes Mellitus
PubMed: 38101426
DOI: 10.1016/S2666-7568(23)00217-9 -
Ageing Research Reviews Sep 2023The risk-benefit profile of anti-Aβ monoclonal antibodies (mAbs) in Alzheimer's disease (AD) remains unclear, especially concerning their safety and overall effects on... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of anti-amyloid-β monoclonal antibodies in current Alzheimer's disease phase III clinical trials: A systematic review and interactive web app-based meta-analysis.
The risk-benefit profile of anti-Aβ monoclonal antibodies (mAbs) in Alzheimer's disease (AD) remains unclear, especially concerning their safety and overall effects on AD progression and cognitive function. Here, we investigated cognitive, biomarker and side effects of anti-Aβ mAbs in large phase III randomized placebo-controlled clinical trials (RCTs) in sporadic AD. The search was performed on Google Scholar, PubMed and ClinicalTrials.gov by applying Jadad score to evaluate the methodological quality of the reports. Studies were excluded if they scored < 3 on Jadad scale or if they analyzed less than 200 sporadic AD patients. We followed PRISMA guidelines and DerSimonian-Laird random-effects model in R. Primary outcomes were cognitive: AD Assessment Scale-Cognitive Subscale (ADAS-Cog), Mini Mental State Examination (MMSE) and Clinical Dementia Rating Scale-sum of Boxes (CDR-SB). Secondary and tertiary outcomes included biomarkers of Aβ and tau pathology, adverse events, and performance on Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale. The meta-analysis included 14,980 patients in 14 studies and four mAbs: Bapineuzumab, Aducanumab, Solanezumab and Lecanemab. The results of this study suggest that anti-Aβ mAbs statistically improved cognitive and biomarker outcomes, particularly Aducanumab and Lecanemab. However, while cognitive effects were of small effect sizes, these drugs considerably increased risk of side effects such as Amyloid Related Imaging Abnormalities (ARIA), especially in APOE-ε4 carriers. Meta-regression revealed that higher (better) baseline MMSE score was associated with improved ADAS Cog and CDR-SB. In order to improve reproducibility and update the analysis in the future, we developed AlzMeta.app, web-based application freely available at https://alzmetaapp.shinyapps.io/alzmeta/.
Topics: Humans; Alzheimer Disease; Reproducibility of Results; Activities of Daily Living; Mobile Applications; Amyloid beta-Peptides; Antibodies, Monoclonal; Biomarkers
PubMed: 37423541
DOI: 10.1016/j.arr.2023.102012 -
Ageing Research Reviews Feb 2024The comparative clinical utility of the disease-modifying treatments for mild cognitive impairment and Alzheimer's disease that are approved or under review by the Food... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy, tolerability and acceptability of donanemab, lecanemab, aducanumab and lithium on cognitive function in mild cognitive impairment and Alzheimer's disease: A systematic review and network meta-analysis.
BACKGROUND
The comparative clinical utility of the disease-modifying treatments for mild cognitive impairment and Alzheimer's disease that are approved or under review by the Food and Drug Administration (i.e., donanemab, lecanemab and aducanumab), and lithium, which is a potential disease-modifying agent for this condition, remains elusive.
OBJECTIVE
We aimed to compare the efficacy on cognitive decline, tolerability and acceptability of these drugs in this condition.
METHODS
We systematically searched in MEDLINE, CENTRAL, CINHAL and ClinicalTrials,gov for randomized controlled trials from their inception to 7 November 2023, and then performed a random-effect network meta-analysis.
RESULTS
The analysis included 8 randomized placebo-controlled trials with 6547 participants. On the Mini-Mental State Examination, lithium significantly outperformed donanemab, aducanumab and placebo. On the Alzheimer's Disease Assessment Scale-cognitive subscale, the efficacy of all active drugs was significantly higher than placebo. In addition, in the Clinical Dementia Rating sum of boxes, the efficacy of donanemab and lecanemab was significantly higher than placebo. Compared to placebo, donanemab and lecanemab were significantly less acceptable and tolerable. Aducanumab was also less well tolerated compared to placebo. There were no significant differences in the other comparisons.
CONCLUSION
Although it is yet to be determined which is more effective between lithium or lecanemab or donanemab, lithium may be more effective than aducanumab. Aducanumab, lecanemab and donanemab do not appear to differ in their effectiveness on cognitive function. Low-dose lithium may be safer than aducanumab, lecanemab and donanemab.
Topics: Humans; Alzheimer Disease; Lithium; Network Meta-Analysis; Cognitive Dysfunction; Cognition; Antibodies, Monoclonal, Humanized
PubMed: 38253184
DOI: 10.1016/j.arr.2024.102203 -
JAMA Neurology Nov 2023Published data about the impact of poststroke seizures (PSSs) on the outcomes of patients with stroke are inconsistent and have not been systematically evaluated, to the... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Published data about the impact of poststroke seizures (PSSs) on the outcomes of patients with stroke are inconsistent and have not been systematically evaluated, to the authors' knowledge.
OBJECTIVE
To investigate outcomes in people with PSS compared with people without PSS.
DATA SOURCES
MEDLINE, Embase, PsycInfo, Cochrane, LILACS, LIPECS, and Web of Science, with years searched from 1951 to January 30, 2023.
STUDY SELECTION
Observational studies that reported PSS outcomes.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was used for abstracting data, and the Joanna Briggs Institute tool was used for risk-of-bias assessment. Data were reported as odds ratio (OR) and standardized mean difference (SMD) with a 95% CI using a random-effects meta-analysis. Publication bias was assessed using funnel plots and the Egger test. Outlier and meta-regression analyses were performed to explore the source of heterogeneity. Data were analyzed from November 2022 to January 2023.
MAIN OUTCOMES AND MEASURES
Measured outcomes were mortality, poor functional outcome (modified Rankin scale [mRS] score 3-6), disability (mean mRS score), recurrent stroke, and dementia at patient follow-up.
RESULTS
The search yielded 71 eligible articles, including 20 110 patients with PSS and 1 166 085 patients without PSS. Of the participants with PSS, 1967 (9.8%) had early seizures, and 10 605 (52.7%) had late seizures. The risk of bias was high in 5 studies (7.0%), moderate in 35 (49.3%), and low in 31 (43.7%). PSSs were associated with mortality risk (OR, 2.1; 95% CI, 1.8-2.4), poor functional outcome (OR, 2.2; 95% CI, 1.8-2.8), greater disability (SMD, 0.6; 95% CI, 0.4-0.7), and increased dementia risk (OR, 3.1; 95% CI, 1.3-7.7) compared with patients without PSS. In subgroup analyses, early seizures but not late seizures were associated with mortality (OR, 2.4; 95% CI, 1.9-2.9 vs OR, 1.2; 95% CI, 0.8-2.0) and both ischemic and hemorrhagic stroke subtypes were associated with mortality (OR, 2.2; 95% CI, 1.8-2.7 vs OR, 1.4; 95% CI, 1.0-1.8). In addition, early and late seizures (OR, 2.4; 95% CI, 1.6-3.4 vs OR, 2.7; 95% CI, 1.8-4.1) and stroke subtypes were associated with poor outcomes (OR, 2.6; 95% CI, 1.9-3.7 vs OR, 1.9; 95% CI, 1.0-3.6).
CONCLUSIONS AND RELEVANCE
Results of this systematic review and meta-analysis suggest that PSSs were associated with significantly increased mortality and severe disability in patients with history of stroke. Unraveling these associations is a high clinical and research priority. Trials of interventions to prevent seizures may be warranted.
Topics: Humans; Stroke; Seizures; Outcome Assessment, Health Care; Dementia
PubMed: 37721736
DOI: 10.1001/jamaneurol.2023.3240 -
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 -
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 -
Neurology and Therapy Aug 2023Alzheimer's disease (AD) is a disease continuum from pathophysiologic, biomarker and clinical perspectives. With the advent of advanced technologies, diagnosing and...
INTRODUCTION
Alzheimer's disease (AD) is a disease continuum from pathophysiologic, biomarker and clinical perspectives. With the advent of advanced technologies, diagnosing and managing patients is evolving.
METHODS
A systematic literature review (SLR) of practice guidelines for mild cognitive impairment (MCI) and AD dementia was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic literature review (SLR) aimed to summarize current clinical practice guidelines for screening, testing, diagnosis, treatment and monitoring in the AD continuum. The results of this SLR were used to propose a way forward for practice guidelines given the possible introduction of biomarker-guided technology using blood- or plasma-based assays and disease-modifying treatments (DMTs) targeted for early disease.
RESULTS
53 clinical practice guidelines were identified, 15 of which were published since 2018. Screening for asymptomatic populations was not recommended. Biomarker testing was not included in routine diagnostic practice. There was no consensus on which neurocognitive tests to use to diagnose and monitor MCI or AD dementia. Pharmacologic therapies were not recommended for MCI, while cholinesterase inhibitors and memantine were recommended for AD treatment.
DISCUSSION
The pre-2018 and post-2018 practice guidelines share similar recommendations for screening, diagnosis and treatment. However, once DMTs are approved, clinicians will require guidance on the appropriate use of DMTs in a clinical setting. This guidance should include strategies for identifying eligible patients and evaluating the DMT benefit-to-risk profile to facilitate shared decision-making among physicians, patients and care partners.
CONCLUSION
Regular evidence-based updates of existing guidelines for the AD continuum are required over the coming decades to integrate rapidly evolving technologic and medical scientific advances and bring emerging approaches for management of early disease into clinical practice. This will pave the way toward biomarker-guided identification and targeted treatment and the realization of precision medicine for AD.
PubMed: 37261607
DOI: 10.1007/s40120-023-00504-6 -
JAMA Network Open Sep 2023The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested.
OBJECTIVES
To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group.
DATA SOURCE AND STUDY SELECTION
Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece).
DATA EXTRACTION AND SYNTHESIS
Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines.
MAIN OUTCOMES AND MEASURES
The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group.
RESULTS
The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses.
CONCLUSIONS AND RELEVANCE
This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.
Topics: Humans; Female; Aged; Male; Blood Pressure; Antihypertensive Agents; Longitudinal Studies; Hypertension; Dementia
PubMed: 37698858
DOI: 10.1001/jamanetworkopen.2023.33353