IRUS Total

Stratifying drug treatment of cognitive impairments after traumatic brain injury using neuroimaging

File Description SizeFormat 
Manuscript Jenkins et al_accepted version for publication.docxAccepted version1.38 MBMicrosoft WordView/Open
Title: Stratifying drug treatment of cognitive impairments after traumatic brain injury using neuroimaging
Authors: Jenkins, PO
De Simoni, S
Bourke, NJ
Fleminger, J
Scott, G
Towey, DJ
Svensson, W
Khan, S
Patel, MC
Greenwood, R
Friedland, D
Hampshire, A
Cole, JH
Sharp, DJ
Item Type: Journal Article
Abstract: Cognitive impairment is common following traumatic brain injury. Dopaminergic drugs can enhance cognition after traumatic brain injury, but individual responses are highly variable. This may be due to variability in dopaminergic damage between patients. We investigate whether measuring dopamine transporter levels using 123I-ioflupane single-photon emission computed tomography (SPECT) predicts response to methylphenidate, a stimulant with dopaminergic effects. Forty patients with moderate-severe traumatic brain injury and cognitive impairments completed a randomized, double-blind, placebo-controlled, crossover study. 123I-ioflupane SPECT, MRI and neuropsychological testing were performed. Patients received 0.3 mg/kg of methylphenidate or placebo twice a day in 2-week blocks. Subjects received neuropsychological assessment after each block and completed daily home cognitive testing during the trial. The primary outcome measure was change in choice reaction time produced by methylphenidate and its relationship to stratification of patients into groups with normal and low dopamine transporter binding in the caudate. Overall, traumatic brain injury patients showed slow information processing speed. Patients with low caudate dopamine transporter binding showed improvement in response times with methylphenidate compared to placebo [median change = -16 ms; 95% confidence interval (CI): -28 to -3 ms; P = 0.02]. This represents a 27% improvement in the slowing produced by traumatic brain injury. Patients with normal dopamine transporter binding did not improve. Daily home-based choice reaction time results supported this: the low dopamine transporter group improved (median change -19 ms; 95% CI: -23 to -7 ms; P = 0.002) with no change in the normal dopamine transporter group (P = 0.50). The low dopamine transporter group also improved on self-reported and caregiver apathy assessments (P = 0.03 and P = 0.02, respectively). Both groups reported improvements in fatigue (P = 0.03 and P = 0.007). The cognitive effects of methylphenidate after traumatic brain injury were only seen in patients with low caudate dopamine transporter levels. This shows that identifying patients with a hypodopaminergic state after traumatic brain injury can help stratify the choice of cognitive enhancing therapy.
Issue Date: 14-Jun-2019
Date of Acceptance: 9-Apr-2019
URI: http://hdl.handle.net/10044/1/70583
DOI: 10.1093/brain/awz149
ISSN: 1460-2156
Publisher: Oxford University Press (OUP)
Start Page: 2367
End Page: 2379
Journal / Book Title: Brain
Volume: 142
Issue: 8
Copyright Statement: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.For Permissions, please email: journals.permissions@oup.com. This is a pre-copy-editing, author-produced version of an article accepted for publication in Brain following peer review. The definitive publisher-authenticated version is available online at: https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awz149/5519011
Sponsor/Funder: National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: NIHR-RP-011-048
RDC04 79560
Keywords: Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences & Neurology
traumatic brain injury
cognitive enhancement
cognitive enhancement
traumatic brain injury
cognitive enhancement
traumatic brain injury
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Neurology & Neurosurgery
Publication Status: Published
Conference Place: England
Online Publication Date: 2019-06-14
Appears in Collections:Department of Brain Sciences