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The Comparative Efficacy of Multiple Interventions for Mild Cognitive Impairment in Alzheimer's Disease: A Bayesian Network Meta-Analysis.

ABSTRACT: Background: Mild cognitive impairment (MCI) is the early phase of Alzheimer's disease (AD). The aim of early intervention for MCI is to decrease the rate of conversion from MCI to AD. However, the efficacy of multiple interventions in MCI, and the optimal methods of delivery, remain controversial. We aimed to compare and rank the treatment methods for MCI in AD, in order to find an optimal intervention for MCI and a way to prevent or delay the occurrence of AD. Methods: Pair-wise and network meta-analysis were conducted to integrate the treatment effectiveness through direct and indirect evidence. Four English databases and three Chinese databases were searched for international registers of eligible published, single or double blind, randomized controlled trials up to September 31st 2019. We included nine comparative interventions: pharmacological therapies which incorporated cholinesterase inhibitors (ChEI), ginkgo, nimodipine, and Chinese medicine; non-pharmacological therapies comprising of acupuncture, music therapy, exercise therapy, and nutrition therapy; and a placebo group. The primary outcome was the Mini-Mental State Examination (MMSE) score. The secondary outcome was the AD Assessment Scale-cognitive subscale (ADAS-cog). Results: Twenty-eight trials were eligible, including 6,863 participants. In the direct meta-analysis, as for the Mini-Mental State Examination scale, the ChEIs (MD: -0.38; 95% CI: -0.74, -0.01), Chinese medicine (MD: -0.31; 95% CI: -0.75, 0.13), exercise therapy (MD: -0.50; 95% CI: -0.65, -0.35), music therapy (MD: -1.71; 95% CI: -4.49, 1.07), were statistically more efficient than placebo. For AD Assessment Scalecognitive subscale outcome, ChEIs (MD: 1.20; 95% CI: 0.73, 1.68), Acupuncture (MD: 1.36; 95% CI: 1.28, 1.44), Chinese medicine (MD: 0.61; 95% CI: 0.49, 0.73) and exercise (MD: 0.61; 95% CI: 0.49, 0.73) were better than placebo. In the network meta-analysis, the MMSE outcome ranked music therapy (59%) as the best and Acupuncture (26%) as second. Nutrition and Ginkgo treatment had the lowest rank among all interventions. For ADAS-cog outcome, acupuncture (52) ranked the best. Conclusion: Among the nine treatments studied, music therapy appears to be the best treatment for MCI, followed by acupuncture. Our study provides new insights into potential clinical treatments for MCI due to AD, and may aid the development of guidelines for MCI in AD.

SUBMITTER: Lai X

PROVIDER: S-EPMC7289916 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlzheimer disease (AD) is the most common type of dementia with cognitive decline as one of the core symptoms in older adults. Numerous studies have suggested the value of psychosocial interventions to improve cognition in this population, but which one should be preferred are still matters of controversy. Consequently, we aim to compare and rank different psychosocial interventions in the management of mild to moderate AD with cognitive symptoms.MethodsWe did a network meta-analysis to identify both direct and indirect evidence in relevant studies. We searched MEDLINE, EMBASE, PsycINFO through the OVID database, CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating psychosocial interventions of cognitive symptoms in patients with Alzheimer disease, published up to August 31, 2017. We included trials of home-based exercise(HE), group exercise(GE), walking program(WP), reminiscence therapy(RT), art therapy(AT) or the combination of psychosocial interventions and acetylcholinesterase inhibitor (ChEIs). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. The outcomes investigated were Mini-Mental State Examination (MMSE) and compliance. We did a pair-wise meta-analysis using the fixed-effects model and then did a random-effects network meta-analysis within a Bayesian framework.ResultsWe deemed 10 trials eligible, including 682 patients and 11 treatments. The quality of included study was rated as low in most comparison with Cochrane tools. Treatment effects from the network meta-analysis showed WP was better than control (SMD 4.89, 95% CI -0.07 to 10.00) while cognitive training and acetylcholinesterase inhibitor (CT + ChEIs) was significantly better than the other treatments, when compared with simple ChEIs treatment, assessed by MMSE. In terms of compliance, the pair-wise meta-analysis indicated that WP and HE are better than GE and AT, while CT + ChEIs, CST + ChEIs are better than other combined interventions.ConclusionOur study confirmed the effectiveness of psychosocial interventions for improving cognition or slowing down the progression of cognitive impairment in AD patients and recommended several interventions for clinical practice.

Project description:BackgroundDepressive symptoms play an essential role in cognition decline, while the benefit and acceptability of treatments for depressive symptoms in cognitive impairment are still unknown.ObjectiveTo comprehensively evaluate the comparative efficacy and acceptability of treatments for depressive symptoms in cognitive impairment based on the quantitative Bayesian network meta-analysis method (NMA).MethodWe searched MEDLINE, Embase, the Cochrane Library, CINAHL, and PsycINFO from inception until August 2022 to identify randomized clinical trials (RCTs) evaluating treatments for depressive symptoms in cognitive impairment. Efficacy was evaluated by the Cornell Scale for Depression in Dementia (CSDD), the Hamilton Depression Rating Scale (HDRS), and the Geriatric Depression Scale (GDS) for depression; the Neuropsychiatric Inventory (NPI) and the Cohen-Mansfeld Agitation Inventory (CMAI) for behavior; and the Mini-Mental State Examination (MMSE) for cognition. Safety was evaluated by total adverse events (AEs), serious AEs, diarrhea, headache, and nausea.ResultsIn this study, 13,043 participants from 107 RCTs were included, involving 28 treatments and the discontinuation of antidepressants. On CSDD, aerobic exercise (MD -4.51, 95%CrI -8.60 to -0.37), aripiprazole (MD -1.85, 95%CrI -3.66 to -0.02), behavioral training (MD -1.14, 95%CrI -2.04 to -0.34), electrical current stimulation (MD -3.30, 95%CrI -5.94 to -0.73), massage (MD -12.67, 95%CrI -14.71 to -10.59), music therapy (MD -2.63, 95%CrI -4.72 to -0.58), and reminiscence therapy (MD -2.34, 95%CrI -3.51 to -1.25) significantly outperformed the placebo. On MMSE, cognitive stimulation therapy (MD 1.42, 95%CrI 0.49 to 2.39), electrical current stimulation (MD 4.08, 95%CrI 1.07 to 7.11), and reminiscence therapy (MD 1.31, 95%CrI 0.04 to 2.91) significantly outperformed the placebo. Additionally, no treatments showed a significantly higher risk than the placebo.ConclusionOur NMAs indicated that non-pharmacological interventions were more efficacious and safe than pharmacological treatments for reducing depressive symptoms as well as improving cognitive impairment. Electrical current stimulation, aerobic exercise, and reminiscence therapy could be first recommended considering their beneficial performance on both depression and cognition. Hence, non-pharmacological treatments deserve more attention and extensive application and should at least be considered as an alternative or assistance in clinical settings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021239621, identifier: CRD42021239621.

Project description: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.

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The Comparative Efficacy of Multiple Interventions for Mild Cognitive Impairment in Alzheimer's Disease: A Bayesian Network Meta-Analysis.

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