Predictors of Poor Outcome After Traumatic Brain Injury

The outcome following traumatic brain injury (TBI) is often unpredictable and variable.

Two individuals with similar types of TBI can have quite different outcomes ranging from total disability to functional employment.

Torun Finnanger and colleagues from Norway and Australia recently reported on a study that examined a number of predictor variables on self-reported outcome following TBI.

In this study, 67 adolescents and adults with moderate to severe TBI completed baseline assessments and were followed for a period of 2 to 5 years. 

The key outcome variables in this study was self-reported executive, behavioral and emotional impairment at the follow-up time point. TBI subjects were compared on a variety of variables with a control group without injury.

Early assessment variables that were examined for correlation with outcome after TBI included:

• Pre-trauma level of education
• Brain injury severity rating: Glasgow Coma Score
• Duration of post-traumatic amnesia
• Brain imaging: presence of imaging markers for brain traumatic axonal injury on brain MRI with inclusion of diffusion tensor imaging (DTI) data
• Neuropsychological assessment obtained three months after injury including: Motor function, information processing speed, attention, visual memory, verbal memory and executive function
• Presence of the symptoms of depression using Beck Depression Inventory 3 and 12 months after injury

The key findings from this longitudinal predictor study included:

• Self-reported impairment in executive function at 2-5 years follow up was linked to fewer years of education, early depression symptoms and traumatic axonal injury
• Injury at a younger age predicted increased aggression and conduct disorder behavioral problems
• Traumatic axonal injury and early depression symptoms predicted increased depression and anxiety symptoms at follow up.

The authors conclude their study supports inclusion of self-reported executive, emotional and behavioral assessments in the monitoring of TBI subjects.

Additionally, they note early MRI imaging assessment of axonal injury (in the first two weeks following TBI) and early assessment of depressive symptoms add information to standard neuropsychological assessment batteries.

They note accurately defining high-risk groups more poor outcome may allow targeting of more aggressive treatment strategies. 

"Furthermore, psychological and/or pharmaceutical interventions, with a focus on depressive symptomatology may be helpful in reducing the long-term problems experienced by persons sustaining a TBI.."

This study is filled with a ton of data. Readers with more interest in the study can find the free full-text manuscript by clicking on the PMID link in the citation below.

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Image of brain white matter pathways is an iPad screen shot from the 3D Brain app from the authors files.

Finnanger TG, Olsen A, Skandsen T, Lydersen S, Vik A, Evensen KA, Catroppa C, Håberg AK, Andersson S, & Indredavik MS (2015). Life after Adolescent and Adult Moderate and Severe Traumatic Brain Injury: Self-Reported Executive, Emotional, and Behavioural Function 2-5 Years after Injury. Behavioural neurology, 2015 PMID: 26549936

Screening for Cognitive Impairment in Parkinson's Disease

Sunset in Blanchard, OK courtesy of Dr. Tim Yates

There is a significant need for improvement in the tools available for screening for cognitive impairment in a variety of disorders in neuroscience medicine.

The Mini-Mental State Examination Score (MMSE) is a widely used 30-item scale for screening dementia and other neurological conditions.

However, the MMSE has some significant weaknesses for use in the clinical setting.

Jin Qiao and colleagues from China recently published a study testing the MMSE to screen for cognitive problems in a group of patients with Parkinson's disease (PD).

A score of 24 or lower is commonly used as a marker for evidence of cognitive impairment in adults from typical educational backgrounds. This would mean individuals with scores above 24 would typically be screened as not having significant cognitive impairment.

In the Chinese study, a series of PD subjects with scores over 24 were studied in detail with more intense neuropsychological testing including the Montreal Cognitive Assessment (MoCA). The MoCA tests seven cognitive domains including visuospatial/excutive, naming, attention, language, abstraction, delayed recall and orientation.

The key findings from this study included:

• 65% of the subjects screened cognitively normal with the MMSE had evidence of cognitive impairment on the MoCA (score <26)
• Cognitive impairment domains in screened impaired PD subjects included: visuospatial/executive, attention, language, abstraction and delayed recall
• Analysis of the MMSE screening data supported raising the threshold for screening impairment in PD subjects from a score of 24 to a score of 28 in higher educated samples

This is an important study with implications for practice assessment and management of patients with PD. The study supports using the MoCA over the MMSE for screening cognitive impairment in PD.

Additionally, this study highlights the need to study screening tools in specific disease populations. Screening thresholds and best cognitive screening practices may be disease specific.

More information and a paper copy of the MoCA can be found here.

Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link in the citation below.

Photo of sunset in Blanchard, Oklahoma is provided courtesy of Dr. Tim Yates

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Qiao J, Zheng X, Wang X, Lu W, Cao H, & Qin X (2015). Neuropsychological profile in Chinese patients with Parkinson's disease and normal global cognition according to Mini-Mental State Examination Score. International journal of clinical and experimental medicine, 8 (8), 13755-61 PMID: 26550322

What is Neurofeedback Training for ADHD?

There are a variety of behavioral strategies for treating the attention and activity components of attention deficit hyperactivity disorder (ADHD).

One of these strategies is known as neurofeedback. 

A recent study in the journal Pediatrics found evidence for effectiveness of in-school neurofeedback for ADHD in a randomized controlled trial.

In this trial, 104 children between the ages of 7 and 11 years of age were randomized to one of three research arms: in-school neurofeedback, cognitive therapy and control condition.

Subject children in the study received a supervised 45 minute intervention three times per week over a 5 month period.

The in-school neurofeedback system utilized in this study was the Play Attention system by Unique Logic and Technology. This system is a computer-based program that is installed by CD on a Mac or PC computer. Users wear a bicycle helmet with sensors and manipulate screen figures. The goal is to decrease brain EEG theta activity and increase EEG beta activity. The feedback provided by the system allows users to get real time information on EEG activity.

In the clinical trial students randomized to the in-school neurofeedback arm outperformed on key outcome variables including:

• Conners 3-P Inattention scale
• Conners 3-P Executive function scale
• Conners 3-P Hyperactivity/Impulsivity scale
• BRIEF Global Executive Composite scale

Children were allowed to be on stimulant medication in this study. Stimulant dosages were independently monitored over the course of the study. Subjects in the neurofeedback arm received a equal dose of stimulant during the study while the other two groups had a naturalistic increase in dose. This suggests the neurofeedback intervention reduced need for escalating doses of stimulant.

The authors note that the use of a helmet in the neurofeedback group alone prevented complete blinding in the study and could confound their findings.

Readers with more information about this study can access the free full-text manuscript by clicking on the PMID link below. Additionally, the Play Attention neurofeedback website can be accessed here. I am not paid for this post and receive no money from the neurofeedback company.

Figure of frontal lobe known to be involved in attention and executive function is a screen shot from the iPad app Brain Tutor.

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Steiner NJ, Frenette EC, Rene KM, Brennan RT, & Perrin EC (2014). In-school neurofeedback training for ADHD: sustained improvements from a randomized control trial. Pediatrics, 133 (3), 483-92 PMID: 24534402

Exercise in the Elderly: BDNF and Executive Function

Exercise promotes cognitive function in children, adults and elderly individuals.

The mechanism for this effect is unclear. Some of the effect may be due to a general improvement in vascular function and health.

Another potential mechanism is via increased neuroplasticity mediated by neurotrophic factors.

Brain-derived neurotrophic factor (BNDF) is a known contributor to brain neuroplasticity. Levels of BNDF can be determined with serum assays.

RL Leckie and colleagues recently found support for BNDF mediation in an exercise in an interventional study with an elderly population.

The key elements of the design for their study included the following elements.

• Participants: Adults between the ages of 55 and 80
• Exercise intervention: Daily supervised walking sessions beginning with 10 minutes increasing to 40 minutes. Control intervention included stretching and toning sessions lead by an exercise professional
• Cognitive assessment: Task-switching paradigm commonly used to assess executive function
• Blood assay: Serum brain-derived neurotropic factor (BNDF) levels and BDNF genotype
• Statistical analysis: Multivariate linear regression analysis with key dependent variable being cognitive performance after one year of intervention

The main findings from the study included:

• Serum BDNF increased in the exercise group
• This effect was limited to primarily the participants over 70 years of age
• Enhanced executive function following exercise was demonstrated in those over 70
• BDNF level increases in the over 70 age group correlated with cognitive performance

The authors note their does not mean exercise is not important for cognitive function in the younger age group (55-70 years of age). Their study only highlights the age interaction with BDNF in moderating a single executive function task.

BDNF levels decrease with age and the level of decrease in BDNF correlates with reduction in volume of the brain hippocampus. The hippocampus plays a key role in memory function and in decline in memory associated with aging.

It is quite possible that regular exercise after age 70 reduces the age related effect on cognition moderated by BDNF.

Readers with more interest in this study can access the free full text manuscript by clicking on the PMID link in the citation below.

Photo of ring kingfisher is from the author's files.

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Leckie RL, Oberlin LE, Voss MW, Prakash RS, Szabo-Reed A, Chaddock-Heyman L, Phillips SM, Gothe NP, Mailey E, Vieira-Potter VJ, Martin SA, Pence BD, Lin M, Parasuraman R, Greenwood PM, Fryxell KJ, Woods JA, McAuley E, Kramer AF, & Erickson KI (2014). BDNF mediates improvements in executive function following a 1-year exercise intervention. Frontiers in human neuroscience, 8 PMID: 25566019

Sleep and Cognition in Late-Life Depression

Depression commonly occurs with subjective as well as objective impairment in sleep and cognition.   However, few studies have examined the interaction between sleep impairment, cognition and depression in elderly cohorts.   Sleep disturbances predict increased risk for new onset depression and recurrence of depression in those with previous episodes.  Impaired sleep appears to reduce memory function and possibly reduce neurogenesis. 

Naismith and colleagues recently examined the correlations between sleep parameter and cognition in a group of 44 subjects with a lifetime history of depression (minimum age >45 years, mean 63 years) and a group of similarly aged adults without depression.  Neuropsychological testing in this study focused on domains felt to be impaired in mood disorders including: 1.) processing speed, 2.) attention, 3.)visual memory, 4.) verbal memory, 5.) language-as tested by counting number of animal names produced in one minute and 6.) executive function-planning, problem solving and response inhibition.

Sleep function was measured using actigraphy and sleep diaries.  Actigraphy typically involves using a wrist watch type device that measures movement during the night and provides an estimate of key sleep parameters including: 1.) total rest interval 2.) sleep latency—time from going to bed to falling asleep (in minutes), 3.) wake after sleep onset (WASO), 4.) arousals—number of periods during night where activity indicated being awake and 5.) sleep efficiency—the percent time asleep during the night

Elderly subjects with a history of depression (current depression ratings suggest a relatively mild depression cohort at time of study) showed increased WASO and decreased sleep efficiency (two highly correlated sleep variables).   WASO and sleep efficiency variables correlated with reduced cognitive function particularly in the domains of attention, memory (semantic and visual) and executive function.  Of note, late onset of depression tended to be associated with poorer sleep quality than earlier age of onset.  The authors controlled for depression severity in this study so the findings appear outside of this influence.

The authors suggest greater cognitive impairment in late onset depression may relate to white matter changes due to cerebrovascular disease.   White matter changes in frontal cortex-subcortical circuits have been associated with reduction in psychomotor speed and executive function.

The authors also note this study is unable to identify the sequencing and causal pathway for these relationships.  If impaired sleep directly impairs cognition, early identification of sleep abnormalities and treatment may limit associated cognitive impairment.  Sleep apnea also needs to be considered in this population, although the authors found no association between measures of sleep apnea and cognitive impairment.

The take home message from this study is that sleep impairment (poor efficiency) may be a marker for depression and cognitive impairment in those over 50.  Clinicians caring for the older adult, should carefully assess the health of the sleep of their patients and keep the sleep, cognition and depression triad in mind.  Sleep complaints in older adults need thorough assessment and should not be dismissed simply as age-related physiological in nature. 

Photo of Tiger Woods putting during practice for 2010 PGA championship courtesy of Yates Photography.

Naismith SL, Rogers NL, Lewis SJ, Terpening Z, Ip T, Diamond K, Norrie L, & Hickie IB (2011). Sleep disturbance relates to neuropsychological functioning in late-life depression. Journal of affective disorders PMID: 21435728