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Brain Cholinergic Function and Response to Rivastigmine in Patients With Chronic Sequels of Traumatic Brain Injury

A PET Study

Östberg, Anna MD; Virta, Jere MD; Rinne, Juha O. MD, PhD; Oikonen, Vesa MSc; Luoto, Pauliina MSc; Någren, Kjell PhD; Arponen, Eveliina MSc; Tenovuo, Olli MD, PhD

Section Editor(s): Caplan, Bruce PhD, ABPP; Bogner, Jennifer PhD, ABPP; Brenner, Lisa PhD, ABPP; Malec, James PhD, ABPP

The Journal of Head Trauma Rehabilitation: January/February 2018 - Volume 33 - Issue 1 - p 25–32
doi: 10.1097/HTR.0000000000000279
Original Articles

Objective: To investigate quantitative positron emission tomography (PET) findings and to study whether the cholinergic function differs between respondents to cholinergic medication versus nonrespondents.

Setting: Outpatient clinic and university PET imaging center.

Participants: We studied 17 subjects for more than 1 year after at least moderate traumatic brain injury. Ten of the subjects were respondents and 7 nonrespondents to cholinergic medication.

Design: Cholinergic function was assessed with [methyl-11C] N-methylpiperidyl-4-acetate-PET (11C-MP4A-PET), which reflects the activity of the acetylcholinesterase (AChE) enzyme. The subjects were PET scanned twice: without medication and after a 4-week treatment with rivastigmine 1.5 mg twice a day.

Measures: Regional cerebral AChE activity was measured with PET.

Results: At baseline Statistical Parametric Mapping analyses showed significantly lower AChE activity in respondents bilaterally in the frontal cortex as compared with nonrespondents. Region of interest (ROI) analysis revealed that the difference was most pronounced in the lateral frontal cortex (−9.4%, P = .034) and anterior cingulate (−6.0%, P = .049). After rivastigmine treatment, AChE activity was notably lower throughout the cortex in both respondents and nonrespondents, without significant differences between them.

Conclusion: Our study suggests that frontal cholinergic dysfunction is associated with the clinical response to cholinergic stimulation in patients with traumatic brain injury.

The Division of Clinical Neurosciences (Drs Östberg, Rinne, and Tenovuo), and Turku Positron Emission Tomography Centre (Drs Virta and Rinne, Messrs Oikonen and Luoto, and Ms Arponen), Turku University Hospital, Finland; and Department of Nuclear Medicine, PET and Cyclotron Unit, Odense University Hospital, Denmark (Dr Någren).

Corresponding Author: Anna Östberg, MD, The Division of Clinical Neurosciences, Turku University Hospital, Turku 20521, Finland (

We thank the personnel of Turku PET Centre for skillful assistance in performing the PET studies.

This study was financially supported by grants from the Sigrid Juselius Foundation and from Turku University Hospital clinical grants. Author Östberg has received a grant from the Finnish doctoral association Duodecim. Author Virta is involved in contact research with Orion-Pharma Ltd, Bayer Schering Pharma Ltd, and Turku Imanet Oy. Author Tenovuo has received speaker fees from OrionCorp. Author Rinne serves as a consultant for Clinical Research Services Turku (CRST) Ltd.

The authors declare no conflicts of interest.

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