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).

Personalized treatment interventions: nonpharmacological and natural treatment strategies in Alzheimer’s disease

“…Music therapy might be active, such as songwriting, singing, and playing musical instruments, or receptive, such as listening, or both, delivered to individuals or groups, with or without a music therapist. Music therapy was also effective in MCI patients [64]. Though targeting multiple symptom domains seems promising, there has been disagreement between published meta-analyses whether active or receptive treatments have similar effects on specific outcomes [13].…”

“…Meta-analytic evidence reported that acupuncture improved cognitive functions in rodent models [72]. Beneficial effects of acupuncture on cognition in clinical trials have also been detected, such as in patients with MCI [64] or in mild, moderate, and severe AD [73]. In the latter population, while acupuncture did not have superior effects compared with drug therapy, acupuncture in combination with pharmacotherapy was beneficial on general cognitive function and activities in daily living [18].…”

“…The aim of intervention for MCI is to decrease the rate of conversion from MCI to AD [85]. Strikingly, in MCI, music therapy had the highest probability of being the best treatment for global cognition, followed by acupuncture and then exercise, among potential pharmacological (including AChE inhibitors) and nonpharmacological treatments, but cognitive interventions were not included [64]. On the other hand, computerized cognitive training had moderate effects on most memory and learning domains in people with MCI, while its effects were much weaker in patients with dementia [46].…”

“…AD is also characterized by excessive production and accumulation of reactive oxygen (ROS) and nitrogen (RNS) species, that cause protein, DNA and tissue damage, activate microglia and astrocytes and immunological response, which lead to mitochondrial dysfunction, intracellular Ca 2+ influx, overexpression of glycogen synthase kinase-3b (GSK-3b) and β-and γ-secretases resulting in generation of protein aggregates such as Aβ and NFT. β-secretase, also known as β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) is over-expressed [64], depression, anxiety and quality of life [45], reduction of apathy [90], facilitation of autobiographical memories [61], reduction of agitation and aggression [12] Music with fast tempos may increase arousal and decrease enjoyment [91], adverse affective responses in vulnerable, depressed individuals…”

Acupuncture Therapy for Cognitive Impairment: A Delphi Expert Consensus Survey

“…No additional SR was identified by the expert panel members during the voting process. Therefore, 11 eligible SRs were included and analyzed in our study eventually (Lee et al, 2009;Cao et al, 2013;Liu et al, 2014;Zhou et al, 2015Zhou et al, , 2017Deng and Wang, 2016;Kwon et al, 2018;Huang et al, 2019;Kim et al, 2019;Wang et al, 2020;Lai et al, 2020). The contained research evidence of interest was extracted out and further assessed with the help of the GRADE tool.…”