Cognitive issues in brain injury and other CNS disorders

Author(s): Anne F. Ambrose, MD MS, Tanya Verghese, MA(Hons), and Jennifer Russo, MD

Originally published:01/30/2014

Last updated:09/21/2018

1. DISEASE/DISORDER:

Definition

Cognitive impairments are commonly encountered in rehabilitation, both in neurological conditions such as traumatic brain injury (TBI), stroke, and non-neurological conditions such as cardiac dysfunction and delirium. Cognitive impairments can involve several domains, including:

  1. Memory: anterograde and/or retrograde amnesia, inability to form new memories, recall of short or long-term events
  2. Processing speed: the time taken to perceive, manipulate and respond to stimuli
  3. Executive function: integrated cognitive processes required to complete daily activities. These include inhibition (self-control—resisting temptations and resisting acting impulsively) and interference control (selective attention and cognitive inhibition)], working memory, and cognitive flexibility (seeing anything from different perspectives, and quickly and flexibly adapting to changed circumstances)1
  4. Attention: the ability to sustain one’s focus on a particular task or subject2
  5. Perceptual neglect: the inability to recognize visuospatial objects on the contralateral side3

Etiology

Cognitive impairment can result from many causes including direct trauma, hypoxia, edema, metabolic disturbance, and neurodegenerative processes. The impairment depends upon the area of the brain affected and whether the lesion is focal or diffuse.

Epidemiology

Worldwide, the annual incidence of TBI is estimated at 10 million4.  In 2013 there were 2.5 million TBI-related ED visits; 282,000 hospitalizations; and 56,000 deaths in the US. The highest rate of injuries were observed among persons aged >75 years. Falls have surpassed motor vehicle accident (MVA) as the most common etiology of TBI in the US, likely reflecting the increased incidence of TBI in the elderly5.  Worldwide, road traffic accidents remain the most common cause of morbidity and mortality6.

Approximately 33% of stroke survivors experience cognitive impairment directly due to stroke. In a prospective study, 7% of stroke survivors were shown to develop dementia at year 1 and 48% at year 25, a twofold increase over the general population7.  Additionally, Jokinen et al. found mild post-stroke cognitive impairment in 71% of patients exhibiting full clinical recovery8.

Risk factors for cognitive deficits include advanced age, co-morbid cognitive impairment, depression, PTSD, diabetes, emphysema, sleep disorders, thyroid dysfunction and a history of falls.  Infections such as HIV or syphilis, alcohol and recreational substance abuse, B12 deficiency, exposure to organic solvents, and lead, may all increase vulnerability to the development of cognitive dysfunction following TBI or stroke9.

Pathophysiology

Neuronal cell death and demyelination may result from direct cortical trauma, focal ischemia, edema, radiation, or locally invasive processes such as tumors.  Diffuse axonal injury, seen in TBI, results from shearing forces generated by rapid acceleration-deceleration10.  In Alzheimer’s disease, in addition to amyloid plaque deposition and cholinergic pathway disturbances, increased and unregulated inflammatory free radical accumulation can promote neuronal apoptosis within the hippocampus and amygdala11.  Lewy bodies may be found in Parkinson’s disease, Lewy body dementia, and in some cases of Alzheimer’s disease12.

In general, clinical manifestation of cognitive impairment may be correlated with the site of neuroanatomical injury.  Damage to the frontal cortex affects executive function, emotional and behavioral impulse control; temporal lobe lesions affect memory; and parietal lobe damage may impair visuospatial ability. Cognition may be globally affected as a result of hypoxia in anoxic brain injury, metabolic disturbances or traumatic injury.

Disease Progression including Natural History, Disease Phases or Stages, Disease Trajectory

Disease progression varies by injury and underlying vulnerability.  The acute symptoms of mild TBI, including headache, nausea, photophobia and cognitive dysfunction, typically resolve within a 3-month period, but for a poorly characterized and likely underestimated percent of patients, symptoms may persist for months or years13. A recent scoping review showed that contrary to the classic teaching of 15% prolonged impairment, just over 50% of subjects reviewed experienced persistent cognitive impairment14. For moderate to severe injuries, deficits in memory, attention, speed of processing, and planning can persist in varying extents.  As in stroke, earlier onset of dementia has been linked with TBI15.

Cognitive deficits are not generally progressive following stroke, but stroke increases the risk for both additional stroke and dementia onset.  In Alzheimer’s Disease, short-term memory loss is generally followed by impairment in long-term memory, language, and executive functioning. This differs from normal aging, in which short-term memory and speed of recall may be impaired, but performance of activities of daily living and insight into the deficit are not affected16.

Specific Secondary or Associated Conditions and Complications

Several secondary changes and complications are associated with cognitive deficits due to central nervous system disorders.  Monitor patients for the development of seizures, insomnia, personality changes including aggression or disinhibition, depression, anxiety, and emotional lability, especially following stroke or TBI. Polypharmacy may contribute to worsening cognitive impairment, particularly with use of anti-cholinergic, antidepressant, and antiepileptic medications17.  Strained familial relationships and issues of identity, employment, and independence are other important non-medical factors that affect cognitive outcomes.

2. ESSENTIALS OF ASSESSMENT

History

A full medical history should be taken. This includes time course of cognitive deficits; details of any associated injury, co-morbid psychiatric illness; substance abuse; neurological disorders, and medications that may impact cognition.  Education level, community support, family support systems, occupation, and prior functional status are other significant aspects to be evaluated18.

Physical Examination

The physical exam should include assessment of all the cognitive domains – orientation, ability to follow commands, attention, concentration, memory (both short- and long-term), naming, repetition, abstract thinking and judgment.  Behavior assessment should include assessment of depressive symptoms, anxiety, irritability, agitation and disinhibition.  A complete neurological and general medical assessment should also be performed.

Functional Assessment

Brain injury leads to changes in both behavior and cognition, both of which impact recovery.  Injury assessment tools include Glasgow Coma Scale (GCS) and JFK Coma Recovery scale.  The Galveston Orientation and Amnesia Test (GOAT), Orientation Log (O-Log), and Westmead PTA scale are early prognostication measures.  Both the Disability Rating Scale (DRS) and Community Integration Questionnaire (CIQ) assess functional independence and can be used to measure outcomes19,20.  Validated cognitive, behavioral, psychosocial questionnaires can be found at the TBI Model Systems Center for Outcome Measurement in Brain Injury (COMBI) website.

Laboratory Studies

Patients with cognitive dysfunction should be evaluated for reversible causes of delirium, such as infection, hypoxia, and metabolic disturbance.  Persistent symptoms after TBI may warrant endocrine workup for cortisol levels, thyroid function, IGF, and gonadal hormone levels.  Patients with polyuria should be assessed for posterior pituitary dysfunction21.

Imaging

A non-contrast head CT is indicated in TBI patients with loss of consciousness or posttraumatic amnesia if one or more of the following is present: headache, vomiting, drug or alcohol intoxication, deficits in short-term memory, physical evidence of trauma above the clavicle, posttraumatic seizure, Glasgow Coma Scale < 15, focal neurological deficit, coagulopathy, or being older than 6022.  MRI may be helpful in characterizing extent of injury. Specialized MRI techniques include magnetic resonance spectroscopy, functional MRI, fluid attenuated inversion recovery, fast field echo T2-weighted, gradient-echo, susceptibility-weighted, diffusion-weighted/tensor imaging23.

Supplemental Assessment Tools

For full assessment of cognitive function, a comprehensive neuropsychological evaluation may be warranted.  RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) is useful in evaluation of cognitive function among dementia and stroke patients24. Computer Assessment of Mild Cognitive Impairment (CAMCI), a computer-administered neuropsychological screen for mild cognitive impairment and CNS Vital Signs are computerized programs that can be used as screening tools in the older population25,26.

Early Predictions of Outcomes

Among TBI patients, severity of injury, duration of post-traumatic amnesia (PTA) (especially under 2 months), etiology (penetrating vs closed), age of onset, complicating factors such as hypotension, hypoxia, and premorbid educational level are important factors that may be used to predict functional and neuropsychological outcomes27. For a TBI population in an acute rehabilitation setting, duration of PTA was found to be the best predictor of behavioral, memory and executive functioning outcomes28.  In a veteran sample, higher scores on PTSD symptomatology scales and greater severity of depressive symptoms were associated with poorer cognitive outcomes29.

Environmental

It is important to ensure a safe living environment for the patient.  Home therapist assessments provide useful information to provide appropriate therapy, equipment, and modifications.

Social Role and Social Support System

Family education and involvement is vital.  It provides family members coping mechanisms and manages expectations about the disease or injury course.  Their ability and willingness to provide the level of supervision required, as well as ongoing support for medical care, is crucial for patient recovery and is associated with better outcomes overall.

Professional Issues

Collaboration with allied medical professionals such as neuropsychologists, speech therapists, and social workers facilitates return to school or work.  Decision-making capacity; compensation; and issues of advocacy for the patient’s vocational, legal, and medical benefits may all need to be addressed30.

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

Rehabilitation of cognitive function uses comprehensive neuropsychological techniques in the remediation of memory, attention, visuospatial and executive function31.  Memory remediation utilizes techniques such as errorless learning, compensatory strategy training, and external memory orthotics32.  Executive function remediation utilizes metacognitive and self-regulation skills, while attentional remediation focuses on attention training.  Remediation of visuospatial functioning utilizes visual scanning training and gestural strategies to allow for compensation of visual neglect and paraxial deficits.  Cognitive behavior therapy teaches patients to think through emotionally challenging problems.  The role of physical activity in recovery from traumatic brain injury has been controversial, with classical teaching recommending a period of cognitive and physical rest following mild traumatic brain injury, but recent literature suggests that early return to physical activity, defined as within 7 days, is associated with a reduction in persistent post-concussive symptoms33.  Further study will be needed. Computer-assisted training programs may also be utilized34,35.

At Different Disease Stages

In the acute period, numerous strategies for enhancing cognitive outcomes have been investigated with variable, and largely negative, outcomes, including inducing mild hypothermia, strict glucose control, and preventing intracranial hypertension36-38.   Other approaches include regular physical exercise, diets low in fat and rich in fruit and vegetables, Omega-3 fatty acids, vitamins E and D, glutamine, and gingko, although poor evidence exists to support any specific nutritional strategy39.  Treating medical conditions like high blood pressure, depression, hyperglycemia and sleep apnea can improve overall mental function.  For long-term management, studies have shown that intellectual stimulation, social engagement, and memory training may improve patient outcomes and promote cognitive health.

Emerging Interventions

Treatment Outcome Measures help to identify impairment domains and to document continuing improvement.  Many instruments exist to assess independence levels.  O-Log and GCS are used for early cognitive prognostication.  The modified Rankin scale is used to measure degree of disability following stroke.  These tests focus on the components of cognition and highlight areas for remediation.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Cutting Edge Concepts and Practice

This includes the study of proteomic and imaging biomarkers to identify disease process characteristics that may assist with predicting rehabilitation outcomes.  Specialized imaging modalities, including fMRI and DTI, identify structural changes that may underlie persistent cognitive deficit following mild TBI.  In investigational studies, DTI has revealed changes in connectivity that may serve as a biomarker for continued cognitive impairment40,41.

Pharmacologically, a number of agents have been studied to enhance cognitive recovery.  In a placebo-controlled trial, patients with TBI 4-16 weeks post-injury taking amantadine for 1 month had increased functional recovery42.  However citicholine, a naturally occurring nucleotide cell membrane component which showed promise in treating cognitive impairment from vascular causes, Alzheimer’s disease, post-TBI, and stroke43-45, failed in follow-up trials.  In acute CNS injury, preclinical studies suggested that progesterone may possess neuroprotective properties, but this promise has not held up in clinical trials46. Currently, no strong evidence supports the use of any single pharmacological agent to enhance cognitive outcome following TBI47. Agents under investigation include growth hormone, statins, N-acetyl cysteine, Cerebrolysin, Ciclosporin and nitric oxide synthase inhibitor (VAS203)  and Disgenic-Rich Yam48.

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

Gaps in evidence-based knowledge include elucidating the relationship between genetics and outcomes, pharmacologic therapies and their long-term impact, research regarding efficacy and tailoring of specific rehabilitation exercises and therapies for individual cognitive domains.

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Original Version of the Topic

Anne F. Ambrose, MD MS, Robin Gay, PhD, Richard G. Chang, MD, MPH. Cognitive issues in brain injury and other CNS disorders. Original Publication Date: 01/30/2014.

Author Disclosures

Anne F. Ambrose, MD MS
Nothing to Disclose

Tanya Verghese, MA(Hons),
Nothing to Disclose

Jennifer Russo, MD
Nothing to Disclose

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