Evidence map›Paper›PMID 35790417›Full record

ArticleJournal of neurology, neurosurgery, and psychiatry2022

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

Michael C B David, Martina Del Giovane, Kathy Y Liu, Benjamin Gostick, James Benedict Rowe, Imafidon Oboh, Robert Howard, Paresh A Malhotra

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurology, neurosurgery, and psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
8.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Cortical synchrony is reduced in Alzheimer's disease and relates to arousal state.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  4. Review
  5. Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Catecholaminergic nucleus integrity and Alzheimer's pathology, symptoms, and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  12. αPharmaceuticals (Basel, Switzerland) · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Caregiver perspectives enable accurate diagnosis of neurodegenerative disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  20. Light-exercise-induced dopaminergic and noradrenergic stimulation in the dorsal hippocampus: Using a rat physiological exercise model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 2 countries.

Michael C B DavidImperial College London and the University of Surrey, UK Dementia Research Institute Care Research and Technology Centre, London, UK md2012@ic.ac.uk.ORCID http://orcid.org/0000-0002-8724-2840
Martina Del GiovaneImperial College London and the University of Surrey, UK Dementia Research Institute Care Research and Technology Centre, London, UK.
Kathy Y LiuDivision of Psychiatry, University College London, London, UK.ORCID http://orcid.org/0000-0002-7482-2758
Benjamin GostickDivision of Psychiatry, University College London, London, UK.
James Benedict RoweDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-7216-8679
Imafidon ObohSouth West London and St George's Mental Health NHS Trust, London, UK.
Robert HowardDivision of Psychiatry, University College London, London, UK.
Paresh A MalhotraImperial College London and the University of Surrey, UK Dementia Research Institute Care Research and Technology Centre, London, UK.ORCID http://orcid.org/0000-0002-1897-0780
University College London · GBImperial College Healthcare NHS Trust · GBSouth West London and St George's Mental Health NHS Trust · GBUniversity of Cambridge · GBUniversity of Surrey · GB

Funding

Medical Research Council MC_UU_00005/12Medical Research Council MR/S021418/1Medical Research Council MR/T033371/1Medical Research Council MR/W016095/1Wellcome Trust 220258
6 · The paper itself

Abstract

backgroundDysfunction 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.

objectiveTo assess the efficacy of drugs with principally noradrenergic action in improving cognitive and neuropsychiatric symptoms in Alzheimer's disease.

methodsThe MEDLINE, Embase and ClinicalTrials.gov databases were searched from 1980 to December 2021. We generated pooled estimates using random effects meta-analyses.

resultsWe 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 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 minimise risks and maximise therapeutic effects. PROSPERO REGISTERATION NUMBER: CRD42021277500.

Indexed as

Alzheimer's diseaseapathycognitiondementiapsychiatry

Identifiers

PMID35790417
PMCPMC9484390
OpenAlexW4283837764

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.