Cognitive and neuropsychiatric effects of noradrenergic treatment in Alzheimer’s disease: systematic review and meta-analysis

作者：Michael David, Martina Del Giovane, Kathy Liu, Benjamin Gostick, James B. Rowe, Imafidon Oboh, Robert Howard, Paresh Malhotra · 发表于：Journal of Neurology Neurosurgery & Psychiatry · 年份：2022 · DOI：10.1136/jnnp-2022-329136 · 被引用次数：61 · 研究领域：Alzheimer's disease research and treatments、Dementia and Cognitive Impairment Research、GDF15 and Related Biomarkers

Background Dysfunction of the locus coeruleus-noradrenergic system occurs early in Alzheimer’s disease, contributing to cognitive and neuropsychiatric symptoms in some patients. This system offers a potential therapeutic target, although noradrenergic treatments are not currently used in clinical practice. Objective To assess the efficacy of drugs with principally noradrenergic action in improving cognitive and neuropsychiatric symptoms in Alzheimer’s disease. Methods The MEDLINE, Embase and ClinicalTrials.gov databases were searched from 1980 to December 2021. We generated pooled estimates using random effects meta-analyses. Results We included 19 randomised controlled trials (1811 patients), of which six were judged as ‘good’ quality, seven as ‘fair’ and six ‘poor’. Meta-analysis of 10 of these studies (1300 patients) showed a significant small positive effect of noradrenergic drugs on global cognition, measured using the Mini-Mental State Examination or Alzheimer’s Disease Assessment Scale—Cognitive Subscale (standardised mean difference (SMD): 0.14, 95% CI: 0.03 to 0.25, p=0.01; I 2 =0%). No significant effect was seen on measures of attention (SMD: 0.01, 95% CI: −0.17 to 0.19, p=0.91; I 2 =0). The apathy meta-analysis included eight trials (425 patients) and detected a large positive effect of noradrenergic drugs (SMD: 0.45, 95% CI: 0.16 to 0.73, p=0.002; I 2 =58%). This positive effect was still present following removal of outliers to account for heterogeneity across s...