Change in Connectivity After mTBI Depending on Cognitive Reserve

Different Courses of Change in Connectivity After mTBI Depending on Cognitive Reserve and How This is Related to Symptoms and Symptom Resolution?

The purpose of this study is to investigate the role of cognitive reserve in change in connectivity in the brain (measured with functional magnetic resonance imaging, fMRI) and how this is related to symptoms and symptom resolution.

Study Overview

• Status: Completed
• Conditions: Mild Traumatic Brain Injury

Detailed Description

The population-based rate of mild traumatic brain injury (mTBI) is estimated to exceed 600/100000 population per year in total, if including only patients seeking emergency care the estimated rate is approximately 100-300/100000. Many patients recover within 3 months after injury but a sustainable proportion suffer from persisting symptoms, for instance fatigue, headaches, irritability. As conventional neuroimaging techniques have failed to detect the subtle alterations that may be important for prognosis and long-term outcome after mTBI, studies using fMRI have shown some interesting results. Other variables, for instance demographic and cognitive variables, also need to be incorporated with imaging biomarkers when investigating the relationship between fMRI biomarkers with outcome after mTBI. A marker related to demographic status and cognition that have shown to be relevant for outcome in brain injury or pathology is cognitive reserve. Cognitive reserve is defined as an aspect of the brain's function or structure that impacts the relationship between injury/pathology and outcome. Higher cognitive reserve is related to better outcome in conditions ranging from Alzheimer, MS and mTBI.

In this study 15 patients with mTBI and 15 patients with minor orthopedic injury underwent assessment, including cognitive testing, self-assessment of symptoms, testing of visual functions and resting-state fMRI at approximately one week after injury and 4 months after injury. Cognitive reserve was assessed with a lexical decision test designed to measure pre-morbid IQ.

Descriptive statistics will be used to depict demographics, injury characteristics, results on neuropsychological tests and psychological screening instruments. Multi-subject and multi-session analysis based on general linear model will be performed and assessed using statistical tools including regression analysis and 2-way ANOVA.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 18288
    • Department of Rehabilitation Medicine, Danderyd Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants were all adults presenting at the emergency departement at Danderyd Hospital, (Stockholm, Sweden) during the given time frame, with minor head injury or minor orthopedic injury. An upper age limit of 40 years were set due to avoiding interference with age-related visual disturbances.

Description

Inclusion Criteria mTBI group:

• presenting at the emergency departement between January 2015 and April 2016 due to an mTBI to such an extent that CT was indicated.
• mTBI was defined by a Glasgow Coma Scale score between 13-15 and one or more of the following symptoms: <30 minutes loss of consciousness, <24 hours post-traumatic amnesia and/or a transient neurological deficit according to the WHO Collaborating center of Neurotrauma Task Force

Inclusion Criteria orthopedic group:

• presenting at the emergency departement between January 2015 and April 2016 due to minor traumatic injuries to the hand, foot, arm or leg that did not require surgical intervention.

Exclusion Criteria:

• uncertain duration of loss of consciousness
• contraindications to MR
• previously acquired brain injury, a progressive neurological disorder or another injury/illness with short expected survival
• were dependent of help in daily living before the current damage
• severe visual impairment
• non-Swedish speaking.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Mild traumatic brain injury; 15 consecutive patients presenting at the emergency departement with mild traumatic brain injury
Minor orthopedic injury; 15 patients, recruited during the same time-frame as the mTBI-patients, presenting at the emergency departement with a minor orthopedic injury

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
State fatigability	Difference between score during the first 60 and the last 60 seconds of the Digit Symbol Substitution Test/Coding (DSST). The lower the score, the stronger the indication of fatigability	Measured at approximately one week after injury
State fatigability	Difference between score during the first 60 and the last 60 seconds of the Digit Symbol Substitution Test/Coding (DSST). The lower the score, the stronger the indication of fatigability	Measured at approximately 4 months after injury
Self rated post-concussion symptoms	For assessment of self-rated symptoms The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) was used. RPQ is based on a Likert scale and includes 16 items with ratings from 0 to 4. Higher score indicates more symptoms	Measured at approximately one week after injury
Self rated post-concussion symptoms	For assessment of self-rated symptoms The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) was used. RPQ is based on a Likert scale and includes 16 items with ratings from 0 to 4. Higher score indicates more symptoms	Measured at approximately 4 months after injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trait fatigability	The Fatigue Severity Scale (FSS) was used to measure trait fatigue. FSS consists of 9 questions and is based on a 7 point Likert scale A high score implies a higher level of fatigue.	Measured at approximately one week after injury
Trait fatigability	The Fatigue Severity Scale (FSS) was used to measure trait fatigue. FSS consists of 9 questions and is based on a 7 point Likert scale A high score implies a higher level of fatigue.	Measured at approximately 4 months after injury
Anxiety and depression	Hospital Anxiety and Depression (HADS) scale was used to screen for depression and anxiety, range (0-42) higher scores indicate more severe problems	Measured at approximately one week after injury
Anxiety and depression	Hospital Anxiety and Depression (HADS) scale was used to screen for depression and anxiety, range (0-42) higher scores indicate more severe problems	Measured at approximately 4 months after injury
Self-rated visual symptoms in near work	Convergence Insufficiency Symptom Survey (CISS) was used to assess near work-related visual symptoms. Total score is 60 and a value above 21 indicates a high level of symptoms.	Measured at approximately one week after injury
Self-rated visual symptoms in near work	Convergence Insufficiency Symptom Survey (CISS) was used to assess near work-related visual symptoms. Total score is 60 and a value above 21 indicates a high level of symptoms.	Measured at approximately 4 months after injury
Convergence	A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria	Measured at approximately one week after injury
Convergence	A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria	Measured at approximately 4 months after injury
Accommodation	A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria	Measured at approximately one week after injury
Accommodation	A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria	Measured at approximately 4 months after injury
Fusional vergence	A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria	Measured at approximately one week after injury
Fusional vergence	A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria	Measured at approximately 4 months after injury

Collaborators and Investigators

• Sponsor: Danderyd Hospital
• Investigators: Principal Investigator: Marika C Moller, PhD, Departement of Rehabilitation Medicine, Danderyd Hospital

Publications and helpful links

General Publications

• Cassidy JD, Carroll LJ, Peloso PM, Borg J, von Holst H, Holm L, Kraus J, Coronado VG; WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med. 2004 Feb;(43 Suppl):28-60. doi: 10.1080/16501960410023732.
• McInnes K, Friesen CL, MacKenzie DE, Westwood DA, Boe SG. Mild Traumatic Brain Injury (mTBI) and chronic cognitive impairment: A scoping review. PLoS One. 2017 Apr 11;12(4):e0174847. doi: 10.1371/journal.pone.0174847. eCollection 2017. Erratum In: PLoS One. 2019 Jun 11;14(6):e0218423.
• Puig J, Ellis MJ, Kornelsen J, Figley TD, Figley CR, Daunis-I-Estadella P, Mutch WAC, Essig M. Magnetic Resonance Imaging Biomarkers of Brain Connectivity in Predicting Outcome after Mild Traumatic Brain Injury: A Systematic Review. J Neurotrauma. 2020 Aug 15;37(16):1761-1776. doi: 10.1089/neu.2019.6623. Epub 2020 Apr 24.
• Madhavan R, Joel SE, Mullick R, Cogsil T, Niogi SN, Tsiouris AJ, Mukherjee P, Masdeu JC, Marinelli L, Shetty T. Longitudinal Resting State Functional Connectivity Predicts Clinical Outcome in Mild Traumatic Brain Injury. J Neurotrauma. 2019 Mar 1;36(5):650-660. doi: 10.1089/neu.2018.5739. Epub 2018 Oct 3.
• Palacios EM, Yuh EL, Chang YS, Yue JK, Schnyer DM, Okonkwo DO, Valadka AB, Gordon WA, Maas AIR, Vassar M, Manley GT, Mukherjee P. Resting-State Functional Connectivity Alterations Associated with Six-Month Outcomes in Mild Traumatic Brain Injury. J Neurotrauma. 2017 Apr 15;34(8):1546-1557. doi: 10.1089/neu.2016.4752. Epub 2017 Jan 13.
• Jones RN, Manly J, Glymour MM, Rentz DM, Jefferson AL, Stern Y. Conceptual and measurement challenges in research on cognitive reserve. J Int Neuropsychol Soc. 2011 Jul;17(4):593-601. doi: 10.1017/S1355617710001748.
• Nelson ME, Jester DJ, Petkus AJ, Andel R. Cognitive Reserve, Alzheimer's Neuropathology, and Risk of Dementia: A Systematic Review and Meta-Analysis. Neuropsychol Rev. 2021 Jun;31(2):233-250. doi: 10.1007/s11065-021-09478-4. Epub 2021 Jan 8.
• Sumowski JF, Rocca MA, Leavitt VM, Dackovic J, Mesaros S, Drulovic J, DeLuca J, Filippi M. Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS. Neurology. 2014 May 20;82(20):1776-83. doi: 10.1212/WNL.0000000000000433. Epub 2014 Apr 18.
• Oldenburg C, Lundin A, Edman G, Nygren-de Boussard C, Bartfai A. Cognitive reserve and persistent post-concussion symptoms--A prospective mild traumatic brain injury (mTBI) cohort study. Brain Inj. 2016;30(2):146-55. doi: 10.3109/02699052.2015.1089598. Epub 2015 Nov 30.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2015
• Primary Completion (Actual): May 3, 2016
• Study Completion (Actual): May 3, 2016

Study Registration Dates

• First Submitted: October 10, 2022
• First Submitted That Met QC Criteria: October 21, 2022
• First Posted (Actual): October 25, 2022

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 21, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Fatigue; Visual disturbances; rs-fMRI; Cognitive reserve
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Brain Injuries, Traumatic; Brain Concussion
• Other Study ID Numbers: fMRICogRev

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No