Effect of glucagon like peptide-1 receptor agonist exenatide, used as an intracranial pressure lowering agent, on cognition in Idiopathic Intracranial Hypertension

Olivia Grech; James Mitchell; Hannah Lyons; Andreas Yiangou; Mark Thaller; Georgios Tsermoulas; Kristian Brock; Susan Mollan; Alex Sinclair

doi:10.1038/s41433-023-02908-y

Effect of glucagon like peptide-1 receptor agonist exenatide, used as an intracranial pressure lowering agent, on cognition in Idiopathic Intracranial Hypertension

Olivia Grech, James Mitchell, Hannah Lyons, Andreas Yiangou, Mark Thaller, Georgios Tsermoulas, Kristian Brock, Susan Mollan, Alex Sinclair^*

^*Corresponding author for this work

Metabolism and Systems Science

Research output: Contribution to journal › Article › peer-review

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Abstract

Background
Cognitive function can be affected in conditions with raised intracranial pressure (ICP) such as idiopathic intracranial hypertension (IIH). Drugs used off label to treat raised ICP also have cognitive side effects, underscoring the unmet need for effective therapeutics which reduce ICP without worsening cognition. The Glucagon Like Peptide-1 (GLP-1) receptor agonist, exenatide, has been shown to significantly reduce ICP in IIH, therefore this study aimed to determine the effects of exenatide on cognition in IIH.

Methods
This was an exploratory study of the IIH:Pressure trial (ISTCRN 12678718). Women with IIH and telemetric ICP monitors (n = 15) were treated with exenatide (n = 7) or placebo (n = 8) for 12 weeks. Cognitive function was tested using the National Institute of Health Toolbox Cognitive Battery at baseline and 12 weeks.

Results
Cognitive performance was impaired in fluid intelligence ((T-score of 50 = population mean), mean (SD) 37.20 (9.87)), attention (33.93 (7.15)) and executive function (38.07 (14.61)). After 12-weeks there was no evidence that exenatide compromised cognition (no differences between exenatide and placebo). Cognition improved in exenatide treated patients in fluid intelligence (baseline 38.4 (8.2), 12 weeks 52.9 (6.6), p = 0.0005), processing speed (baseline 43.7 (9.4), 12 weeks 58.4 (10.4), p = 0.0058) and episodic memory (baseline 49.4 (5.3), 12 weeks 62.1 (13.2), p = 0.0315).

Conclusions
In patients with raised ICP due to IIH, exenatide, a drug emerging as an ICP lowering agent, does not adversely impact cognition. This is encouraging and has potential to be relevant when considering prescribing choices to lower ICP.

Original language	English
Number of pages	6
Journal	Eye
Early online date	11 Jan 2024
DOIs	https://doi.org/10.1038/s41433-023-02908-y
Publication status	E-pub ahead of print - 11 Jan 2024

Bibliographical note

Funding
This study was funded by Enterprising Birmingham, University of Birmingham, UK, from 1st August 2016. Further funding was sought and from 1st August 2019 an investigator led grant was obtained from Invex therapeutics. OG was funded by Brain research UK. JLM was funded by the Ministry of Defence for the duration of the study. AY was funded by an Association of British Neurologists and Guarantors of the Brain fellowship. AJS was funded by a National Institute for Health Research (NIHR) clinician scientist fellowship (NIHR-CS-011-028), the Medical Research Council, UK (MR/K015184/1) for the duration of the study and a Sir Jules Thorn Award for Biomedical Science.

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10.1038/s41433-023-02908-yLicence: Creative Commons: Attribution (CC BY)

GrechO2024EffectFinal published version, 2.28 MBLicence: Creative Commons: Attribution (CC BY)

Assessing the Therapeutic Efficacy of an 11Beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) in Idiopathic Intracranial Hypertension (IIH)
Sinclair, A. (Principal Investigator), Tomlinson, J. (Co-Investigator) & Stewart, P. (Co-Investigator)
Medical Research Council
12/08/13 → 11/08/17
Project: Research Councils
Sustained treatment of Idiopathic Intracranial Hypertension (IIH) through weight loss induced by bariatric surgery
Sinclair, A. (Principal Investigator)
NIHR TRAINEES COORDINATING CENTRE
1/06/13 → 31/10/18
Project: Research

Cite this

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title = "Effect of glucagon like peptide-1 receptor agonist exenatide, used as an intracranial pressure lowering agent, on cognition in Idiopathic Intracranial Hypertension",

abstract = "BackgroundCognitive function can be affected in conditions with raised intracranial pressure (ICP) such as idiopathic intracranial hypertension (IIH). Drugs used off label to treat raised ICP also have cognitive side effects, underscoring the unmet need for effective therapeutics which reduce ICP without worsening cognition. The Glucagon Like Peptide-1 (GLP-1) receptor agonist, exenatide, has been shown to significantly reduce ICP in IIH, therefore this study aimed to determine the effects of exenatide on cognition in IIH.MethodsThis was an exploratory study of the IIH:Pressure trial (ISTCRN 12678718). Women with IIH and telemetric ICP monitors (n = 15) were treated with exenatide (n = 7) or placebo (n = 8) for 12 weeks. Cognitive function was tested using the National Institute of Health Toolbox Cognitive Battery at baseline and 12 weeks.ResultsCognitive performance was impaired in fluid intelligence ((T-score of 50 = population mean), mean (SD) 37.20 (9.87)), attention (33.93 (7.15)) and executive function (38.07 (14.61)). After 12-weeks there was no evidence that exenatide compromised cognition (no differences between exenatide and placebo). Cognition improved in exenatide treated patients in fluid intelligence (baseline 38.4 (8.2), 12 weeks 52.9 (6.6), p = 0.0005), processing speed (baseline 43.7 (9.4), 12 weeks 58.4 (10.4), p = 0.0058) and episodic memory (baseline 49.4 (5.3), 12 weeks 62.1 (13.2), p = 0.0315).ConclusionsIn patients with raised ICP due to IIH, exenatide, a drug emerging as an ICP lowering agent, does not adversely impact cognition. This is encouraging and has potential to be relevant when considering prescribing choices to lower ICP.",

author = "Olivia Grech and James Mitchell and Hannah Lyons and Andreas Yiangou and Mark Thaller and Georgios Tsermoulas and Kristian Brock and Susan Mollan and Alex Sinclair",

note = "Funding This study was funded by Enterprising Birmingham, University of Birmingham, UK, from 1st August 2016. Further funding was sought and from 1st August 2019 an investigator led grant was obtained from Invex therapeutics. OG was funded by Brain research UK. JLM was funded by the Ministry of Defence for the duration of the study. AY was funded by an Association of British Neurologists and Guarantors of the Brain fellowship. AJS was funded by a National Institute for Health Research (NIHR) clinician scientist fellowship (NIHR-CS-011-028), the Medical Research Council, UK (MR/K015184/1) for the duration of the study and a Sir Jules Thorn Award for Biomedical Science.",

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month = jan,

day = "11",

doi = "10.1038/s41433-023-02908-y",

language = "English",

journal = "Eye",

issn = "0950-222X",

publisher = "Nature Publishing Group",

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TY - JOUR

T1 - Effect of glucagon like peptide-1 receptor agonist exenatide, used as an intracranial pressure lowering agent, on cognition in Idiopathic Intracranial Hypertension

AU - Grech, Olivia

AU - Mitchell, James

AU - Lyons, Hannah

AU - Yiangou, Andreas

AU - Thaller, Mark

AU - Tsermoulas, Georgios

AU - Brock, Kristian

AU - Mollan, Susan

AU - Sinclair, Alex

N1 - Funding This study was funded by Enterprising Birmingham, University of Birmingham, UK, from 1st August 2016. Further funding was sought and from 1st August 2019 an investigator led grant was obtained from Invex therapeutics. OG was funded by Brain research UK. JLM was funded by the Ministry of Defence for the duration of the study. AY was funded by an Association of British Neurologists and Guarantors of the Brain fellowship. AJS was funded by a National Institute for Health Research (NIHR) clinician scientist fellowship (NIHR-CS-011-028), the Medical Research Council, UK (MR/K015184/1) for the duration of the study and a Sir Jules Thorn Award for Biomedical Science.

PY - 2024/1/11

Y1 - 2024/1/11

N2 - BackgroundCognitive function can be affected in conditions with raised intracranial pressure (ICP) such as idiopathic intracranial hypertension (IIH). Drugs used off label to treat raised ICP also have cognitive side effects, underscoring the unmet need for effective therapeutics which reduce ICP without worsening cognition. The Glucagon Like Peptide-1 (GLP-1) receptor agonist, exenatide, has been shown to significantly reduce ICP in IIH, therefore this study aimed to determine the effects of exenatide on cognition in IIH.MethodsThis was an exploratory study of the IIH:Pressure trial (ISTCRN 12678718). Women with IIH and telemetric ICP monitors (n = 15) were treated with exenatide (n = 7) or placebo (n = 8) for 12 weeks. Cognitive function was tested using the National Institute of Health Toolbox Cognitive Battery at baseline and 12 weeks.ResultsCognitive performance was impaired in fluid intelligence ((T-score of 50 = population mean), mean (SD) 37.20 (9.87)), attention (33.93 (7.15)) and executive function (38.07 (14.61)). After 12-weeks there was no evidence that exenatide compromised cognition (no differences between exenatide and placebo). Cognition improved in exenatide treated patients in fluid intelligence (baseline 38.4 (8.2), 12 weeks 52.9 (6.6), p = 0.0005), processing speed (baseline 43.7 (9.4), 12 weeks 58.4 (10.4), p = 0.0058) and episodic memory (baseline 49.4 (5.3), 12 weeks 62.1 (13.2), p = 0.0315).ConclusionsIn patients with raised ICP due to IIH, exenatide, a drug emerging as an ICP lowering agent, does not adversely impact cognition. This is encouraging and has potential to be relevant when considering prescribing choices to lower ICP.

AB - BackgroundCognitive function can be affected in conditions with raised intracranial pressure (ICP) such as idiopathic intracranial hypertension (IIH). Drugs used off label to treat raised ICP also have cognitive side effects, underscoring the unmet need for effective therapeutics which reduce ICP without worsening cognition. The Glucagon Like Peptide-1 (GLP-1) receptor agonist, exenatide, has been shown to significantly reduce ICP in IIH, therefore this study aimed to determine the effects of exenatide on cognition in IIH.MethodsThis was an exploratory study of the IIH:Pressure trial (ISTCRN 12678718). Women with IIH and telemetric ICP monitors (n = 15) were treated with exenatide (n = 7) or placebo (n = 8) for 12 weeks. Cognitive function was tested using the National Institute of Health Toolbox Cognitive Battery at baseline and 12 weeks.ResultsCognitive performance was impaired in fluid intelligence ((T-score of 50 = population mean), mean (SD) 37.20 (9.87)), attention (33.93 (7.15)) and executive function (38.07 (14.61)). After 12-weeks there was no evidence that exenatide compromised cognition (no differences between exenatide and placebo). Cognition improved in exenatide treated patients in fluid intelligence (baseline 38.4 (8.2), 12 weeks 52.9 (6.6), p = 0.0005), processing speed (baseline 43.7 (9.4), 12 weeks 58.4 (10.4), p = 0.0058) and episodic memory (baseline 49.4 (5.3), 12 weeks 62.1 (13.2), p = 0.0315).ConclusionsIn patients with raised ICP due to IIH, exenatide, a drug emerging as an ICP lowering agent, does not adversely impact cognition. This is encouraging and has potential to be relevant when considering prescribing choices to lower ICP.

U2 - 10.1038/s41433-023-02908-y

DO - 10.1038/s41433-023-02908-y

M3 - Article

C2 - 38212401

SN - 0950-222X

JO - Eye

JF - Eye

ER -

Effect of glucagon like peptide-1 receptor agonist exenatide, used as an intracranial pressure lowering agent, on cognition in Idiopathic Intracranial Hypertension

Abstract

Bibliographical note

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Projects

Assessing the Therapeutic Efficacy of an 11Beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) in Idiopathic Intracranial Hypertension (IIH)

Sustained treatment of Idiopathic Intracranial Hypertension (IIH) through weight loss induced by bariatric surgery

Cite this