Imperial College London
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ProfessorPareshMalhotra

Faculty of Medicine, Department of Brain Sciences

Professor of Clinical Neurology
 
 
 
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Contact

 

+44 (0)20 3313 5525p.malhotra

 
 
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Location

 

Lab BlockCharing Cross Campus

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Summary

 

Publications

Citation

BibTex format

@article{David:2022:10.1136/jnnp-2022-329136,
author = {David, MCB and Del, Giovane M and Liu, KY and Gostick, B and Rowe, JB and Oboh, I and Howard, R and Malhotra, PA},
doi = {10.1136/jnnp-2022-329136},
journal = {Journal of Neurology, Neurosurgery and Psychiatry},
pages = {1080--1090},
title = {Cognitive and neuropsychiatric effects of noradrenergic treatment in Alzheimer's disease: systematic review and meta-analysis},
url = {http://dx.doi.org/10.1136/jnnp-2022-329136},
volume = {93},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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; I2=0%). No significant effect was seen on measures of attention (SMD: 0.01, 95% CI: −0.17 to 0.19, p=0.91; I2=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; I2=58%). This positive effect was still present following removal of outliers to account for heterogeneity across studies.Discussion Repurposing of established noradrenergic drugs is most likely to offer effective treatment in Alzheimer’s disease for general cognition and apathy. However, several factors should be considered before designing future clinical trials. These include targeting of appropriate patient subgroups and understanding the dose effects of individual drugs and their interactions with other treatments to min
AU  - David,MCB
AU  - Del,Giovane M
AU  - Liu,KY
AU  - Gostick,B
AU  - Rowe,JB
AU  - Oboh,I
AU  - Howard,R
AU  - Malhotra,PA
DO  - 10.1136/jnnp-2022-329136
EP  - 1090
PY  - 2022///
SN  - 0022-3050
SP  - 1080
TI  - Cognitive and neuropsychiatric effects of noradrenergic treatment in Alzheimer's disease: systematic review and meta-analysis
T2  - Journal of Neurology, Neurosurgery and Psychiatry
UR  - http://dx.doi.org/10.1136/jnnp-2022-329136
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000818048100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://jnnp.bmj.com/content/93/10/1080
UR  - http://hdl.handle.net/10044/1/103309
VL  - 93
ER  -
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