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Pharmacotherapy of Alzheimer’s disease: an overview of systematic reviews

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Abstract

Background

Alzheimer’s disease (AD) is a neurodegenerative disease and the most common cause of dementia. In this umbrella systematic review (SR), we summarized the efficacy of different pharmacological interventions in improving cognitive function in patients with AD.

Methods

A systematic search was performed through the PubMed, Scopus, Embase, and Cochrane databases for SRs of studies assessing the efficacy of pharmacological interventions versus placebo in improving cognitive function in AD or mild cognitive impairment due to AD. The risk of bias (RoB) was assessed using the Risk of Bias in SRs (ROBIS) tool.

Results

Out of 1748 articles found through the database survey, 33 SR articles were included. These studies assessed effects of immunotherapy, cholinesterase inhibitors (ChEIs), memantine, statins, lithium, nonsteroidal anti-inflammatory drugs (NSAIDs), antidiabetic agents, Cerebrolysin, RAS-targeting antihypertensive drugs (ARBs and ACEIs), psychostimulants, glycogen synthase kinase 3 (GSK-3) inhibitors, melatonin, and herbal medications on cognitive function in AD patients. There was no notable overall RoB in 18 studies (54.5%), the RoB in 14 studies (42.4%) was high, and in one study (3.0%) it was unclear.

Conclusions

The use of ChEIs, including rivastigmine, galantamine, and donepezil, as well as memantine has demonstrated a positive impact on improving cognitive outcomes of AD patients, but no considerable effects were found for immunotherapies. Melatonin, statins, antihypertensive drugs, antidiabetic agents, Cerebrolysin, psychostimulants, and some herbal drugs such as Danggui-Shaoyao-San and Ginkgo biloba seem to be effective in improving cognitive function of AD patients, but the evidence in this regard is limited.

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Availability of data

All the supporting data and information are available within the manuscript.

Abbreviations

AD:

Alzheimer’s Disease

WHO:

World Health Organization

FDA:

US Food and Drug Administration

Aβ:

Amyloid-beta

ChEIs:

Cholinesterase inhibitors

RCT:

Randomized controlled trial

SR:

Systematic review

MA:

Meta-analysis

MCI:

Mild cognitive impairment

RoB:

Risk of bias

ROBIS:

Risk of Bias in Systematic Reviews

ADAS-Cog:

Alzheimer's Disease Assessment Scale–Cognitive Subscale

MMSE:

Mini-Mental State Exam

SIB:

Severe Impairment Battery

WMD:

Weighted mean difference

SMD:

Standard mean difference

MD:

Mean difference

IVIg:

Intravenous immunoglobulin

NSAID:

Nonsteroidal anti-inflammatory drug

GSK-3:

Glycogen synthase kinase 3,

GPCOG:

General Practitioner Assessment of Cognition,

AD8:

Eight-item Informant Interview to Differentiate Aging and Dementia

IQCODE:

Informant Questionnaire on Cognitive Decline in the Elderly

CSF:

Cerebrospinal fluid

GLP-1:

Glucagon-like peptide-1

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Acknowledgements

The research protocol was approved and supported by Student Research Committee, Tabriz University of Medical Sciences (grant number: 66147).

Funding

This study was supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 66147).

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Author notes

  1. Reza Majidazar and Erfan Rezazadeh-Gavgani contributed equally to this work and both of them should be considered as shared co-first authors.

Authors and Affiliations

  1. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Reza Majidazar, Erfan Rezazadeh-Gavgani & Amirreza Naseri

  2. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran

    Saeed Sadigh-Eteghad

  3. Research Center for Evidence-Based Medicine, Center of Excellence, Iranian EBM Centre: A Joanna Briggs Institute (JBI), Tabriz University of Medical Sciences, Golgasht street, Tabriz, Iran

    Amirreza Naseri

Authors
  1. Reza Majidazar
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  2. Erfan Rezazadeh-Gavgani
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  3. Saeed Sadigh-Eteghad
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  4. Amirreza Naseri
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Contributions

RM, ER-G: Investigation; Data curation; Project administration; Methodology; Writing—Original draft; Funding acquisition; SS-S, AN*: Conceptualization; Methodology; Visualization; Investigation; Supervision; Writing—Review & editing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Amirreza Naseri.

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Ethical Approval

The Ethics committee of Tabriz University of Medical Science reviewed and approved the study protocol, according to the Declaration of Helsinki (Ethics code: IR.TBZMED.VCR.REC.1400.313).

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Not applicable.

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Majidazar, R., Rezazadeh-Gavgani, E., Sadigh-Eteghad, S. et al. Pharmacotherapy of Alzheimer’s disease: an overview of systematic reviews. Eur J Clin Pharmacol 78, 1567–1587 (2022). https://doi.org/10.1007/s00228-022-03363-6

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  • DOI: https://doi.org/10.1007/s00228-022-03363-6

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