Endocannabinoid system alterations in Alzheimer's disease: A systematic review of human studies.

Berry et al. ·Brain research Impact 2.9

Unclear GRADE Moderate 53 citations

Samplek = 22 Studien

Durationunclear

EndpointECS component…

Blindingunklar

DesignSystematic Review

Key finding

Systematic review identified mixed findings on ECS alterations in Alzheimer's disease without a clear characteristic profile.

Summary

Systematic review on endocannabinoid system alterations in Alzheimer's dementia and MCI in human studies (k=22: neuroimaging, serum/CSF biomarkers, post-mortem); examined CB1R, CB2R, AEA, 2-AG, MAGL, FAAH, TRPV1. Mixed findings for most ECS components; no uniform profile of ECS alterations characteristic for AD identifiable. Included studies small, methodologically heterogeneous, often without control for AD pathology progression.

PopulationPersons with Alzheimer's disease (AD) or mild cognitive impairment (MCI), included in human studies (neuroimaging, biomarker studies, post-mortem studies)

InterventionMeasurement of endocannabinoid system components (CB1/CB2 receptors, AEA, 2-AG, MAGL, FAAH, TRPV1)

OutcomePredominantly mixed findings on ECS alterations in AD; no consistent ECS profile identifiable; 8 studies correlated ECS alterations with neuropsychometric measures

Confidence in the evidence

Moderate

The third of four GRADE levels, the effect estimate is probably reliable.

Downgraded for

Indirectness

Quality profile

Sample size ★★★★★

Blinding —

Effect size —

Citations / year ★★★★★

Authors

Berry AJ, Zubko O, Reeves SJ, Howard RJ

DOI 10.1016/j.brainres.2020.147135↗

Design: Systematic Review

Abstract

Studies investigating alterations of the endocannabinoid system (ECS) in Alzheimer's disease (AD) in humans have reported inconsistent findings so far. We performed a systematic review of studies examining alterations of the ECS specifically within humans with AD or mild cognitive impairment (MCI), including neuroimaging studies, studies of serum and cerebrospinal fluid biomarkers, and post-mortem studies. We attempted to identify reported changes in the expression and activity of: cannabinoid receptors 1 and 2; anandamide (AEA); 2-arachidonoylglycerol (2-AG); monoacylglycerol lipase (MAGL); fatty acid amide hydrolase (FAAH); and transient receptor potential cation channel V1 (TRPV1). Twenty-two studies were identified for inclusion. Mixed findings were reported for most aspects of the ECS in AD, making it difficult to identify a particular profile of ECS alterations characterising AD. The included studies tended to be small, methodologically heterogeneous, and frequently did not control for important potential confounders, such as pathological progression of AD. Eight studies correlated ECS alterations with neuropsychometric performance measures, though studies infrequently examined behavioural and neuropsychiatric correlates. PROSPERO database identifier: CRD42018096249.

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