Cognitive issues in brain injury and other CNS disorders

Author(s): Anne F. Ambrose, MD MS, Robin Gay, PhD, Richard G. Chang, MD, MPH

Originally published:01/30/2014

Last updated:01/30/2014

1. DISEASE/DISORDER:

Definition

Cognition is a group of mental processes that includes the ability to perceive external stimuli, process the information, respond appropriately, encode and recall the information, problem-solve, and communicate. Cognitive impairments are commonly encountered in rehabilitation, both in neurological conditions such as traumatic brain injury (TBI), stroke, multiple sclerosis (MS) and non-neurological conditions such as cardiac dysfunction and delirium.

Cognitive impairments can involve several different domains.

  1. Memory alterations, which may manifest as anterograde or retrograde amnesia, where there is an inability to form new memories or to recall long-term events, respectively.
  2. Processing speed involves the time taken to perceive and manipulate information as well as respond to stimuli.
  3. Executive function is a set of integrated cognitive processes required to complete daily activities. This includes organization, planning, self-monitoring and regulation, and goal development.1
  4. Attention is ability to sustain one’s focus to a particular task or subject at hand.2
  5. Perceptual neglect is the inability to recognize visuospatial objects on the contralateral side, usually due to right-sided non-dominant posterior hemispheric damage.3

Etiology

Cognitive deficits can arise from multiple causes, including direct trauma, diffuse axonal injury (DAI), brain edema, hypoxia, infection, metabolic disturbances, amyloid plaque deposition and neurodegenerative processes. Specific deficits generally depend upon the region of the brain affected. Lesions that cause cognitive deficits can be focal, such as those caused by local trauma affecting only a limited domain of cogntive fucntion, or be more diffuse, such as DAI that can affect numerous cognitive domains.

Epidemiology including risk factors and primary prevention

Worldwide, the annual incidence of TBI is estimated at 10 million, with 1.7 million in the USA, of whom 30% will have persistent cognitive deficits.4The incidence of stroke in the US is about 795,000. About 25% of stroke survivors will present with cognitive complaints. In a prospective study by Kokmen et al, 7% will go on to develop dementia at year 1 and 48% at year 25, which is a 2-fold increase.5,6 The incidence of Alzheimer’s dementia dramatically increases after the age of 65 (53 new cases per 1000 people aged 65-74; 170 per 1000 people aged 75 to 84; 231 per 1000 people older than 85).7 Cognitive complaints occur in many neurological conditions, including multiple sclerosis (40-70%), Parkinson’s disease (21–62%), ALS (50%), and Huntington’s disease (40%).8-12 Risk factors for increased cognitive deficits with most conditions include prior head injuries, stroke, advanced age, pre-existing dementia or cognitive impairment, depression, diabetes, emphysema, sleep disorders, thyroid dysfunction, white matter lesions, and history of falls. Other potential causes include infections such as AIDS or syphilis, toxins such as alcohol, vitamin B12 deficiency, recreational drugs, organic solvents, and lead.13

Patho-anatomy/physiology

Multiple mechanisms may lead to cognitive deficits. Neuronal cell death and demyelination may result from direct cortical trauma, focal ischemia, local invasive processes such as tumors, cerebral edema, or radiation therapy.14 DAI, seen in traumatic brain jury, is strongly correlated to shearing forces seen in acceleration-deceleration injuries.14 In Alzheimer’s, besides amyloid plaque deposition and cholinergic pathway disturbances, increased and unregulated inflammatory free radical accumulation appears to promote neuronal apoptosis at vulnerable regions such as the hippocampus and amygdala.15 Lewy bodies are associated with Parkinson’s disease, dementia with Lewy bodies and in some cases of Alzheimer’s disease.16 Shrinkage of hippocampus, enlargement of ventricles and abnormal glucose metabolism also impact cognition. In general, clinical manifestations of cognitive impairment may be correlated with the site of neuroanatomical injury. For example, damage to the frontal cortex will affect executive function, as well as emotional and behavioral impulses/control; temporal lobe (hippocampus and amygdala) with memory; and parietal lobe with visuospatial abilities. However, many domains may be globally affected, as seen in cases of anoxic brain injury from hypoxia, metabolic causes such as hyperglycemia, and in traumatic brain injuries.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Disease progression for cognitive disorders differs depending upon the initial neurologic insult. For mild TBI, cognitive dysfunction is expected to resolve within a 3-month time period, but in 7 to 33%, symptoms may persist.17 Newer studies have linked earlier onset of dementia with TBI.18 For moderate to severe injuries, deficits in memory, attention, speed of processing and planning persist to varying degrees in most cases.4Cognitive deficits are not progressive in stroke, unlike diseases such as multiple sclerosis, Alzheimer’s dementia, or Huntington’s disease.5 In Alzheimer’s disease, what is commonly lost first is short-term memory, followed by problems with long-term memory, language (e.g., paraphasias due to inability to recall appropriate vocabulary), and executive functioning. This is in contrast to normal aging, where short-term memory and speed of recall may be impaired, but these issues do not affect activities of daily living and awareness of such problems.19

Specific secondary or associated conditions and complications

Several seocndary conditions and complications may occur in patients with congitive deficits due to CNS disorders. The possibility of seizures, insomnia, personality changes, depression, anxiety, and emotional lability should be monitored, especially after TBI and stroke. Normal pressure hydrocephalus may occur and worsen cognition. Polypharmacy is another important factor, as older patients may have cognitive impairment from drugs such as anti-cholinergics, antidepressants, and antiepileptic medications.20 Strained familial relationships and issues of identity, employment, and independence are other important non-medical factors that affect cognitive outcome.21

2. ESSENTIALS OF ASSESSMENT

History

The history should include a full medical history, time course of cognitive decline, details of any associated injury, especially etiology and mechanics, psychiatric illness, substance abuse, neurological disorders and medications that may impact cognition. Education level, community support, family support systems and prior functional status are other significant aspects to be evaluated.

Physical examination

The physical exam should encompass assessment of all the cognitive domains–orientation, ability to follow commands, attention, concentration, memory (both short- and long-term), naming, repetition, and abstract thinking and judgment. Behavior assessment includes assessment of depression, anxiety, irritability, agitation and disinhibition. A complete neurological and general medical assessment should 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 can assess specific cognitive domains and are early prognostication measures. Both Disability Rating Scale (DRS) and Community Integration Questionnaire (CIQ) can assess functional independence and can be used to measure outcomes and community integration.22,23 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 potential causes of delirium such as infection, hypoxia, and metabolic disturbances. Persistent symptoms after TBI may warrant endocrine workup, which could include cortisol, thyroid function, IGF, and gonadal hormone levels.24 Patients with polyuria should be assessed for posterior pituitary dysfunction.24

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, age greater than 60 years, drug or alcohol intoxication, deficits in short-term memory, physical evidence of trauma above the clavicle, posttraumatic seizure, GCS less than 15, focal neurologic deficit, or coagulopathy.25 MRI is up to 30% more sensitive than CT scan and may also detect functional abnormalities associated with mild TBI. MRI techniques include magnetic resonance spectroscopy, functional MRI, fluid attenuated inversion recovery, fast field echo T2-weighted, gradient-echo, susceptibility-weighted, diffusion-weighted/tensor imaging.26

Supplemental assessment tools

For further delienation of cogntive function, a comprehensive neuropsychological evaluation may be warrented. RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) is a neuropsychology test shown to be useful in evaluation of cognitive function among dementia and stroke patients. A recent study by Lippa et al. seems to show promise of this relatively brief 30-minute test in assessing presence of acute TBI, but not severity.27 Computer Assessment of Mild Cognitive Impairment (CAMCI), a computer-administered neuropsychological screen for mild cognitive impairment and CNS vital signs are three computerized programs that can be used as screening tools in the older population.28-29 In addition, functional imaging modalities may be considered to further delienate correlations with functional deficits not visualized on static imaging.

Early predictions of outcomes

Among TBI patients, severity of injury, duration of PTA especially if less than 2 months, etiology (penetrating vs. closed), age of onset, complicating factors such as hypotension and hypoxia, as well as premorbid educational level are several important factors that may be used to predict functional and neuropsychological outcomes. Presence of prior cognitive impairments or dementia is associated with poor outcomes.30

Environmental

An evaluation of the patient’s home is important for patients to prevent any adverse events such as falls and to ensure a safe living environment. Home therapist assessments provide useful information to provide appropriate therapy, and equipment and home modifications.

Social role and social support system

Family education and involvement is vital and provides family members ways of coping and understanding of what to expect from the injury or disease course.29 Their ability and willingness to provide the level of supervision required and ongoing support for medical care is crucial toward patient recovery and is associated with better outcomes overall.21

Professional Issues

Collaboration with allied medical professionals such as neuropsychologists, speech therapists and social workers are helpful for patients to facilitate return to school or work. Other issues that may need to be addressed are decision-making capacity, compensation, and advocating for the patient’s vocational, legal and medical benefits.30

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

Management of cognitive function focuses on remediation of memory, attention, visual spatial functioning, and executive functioning using comprehensive holistic neuropsychological techniques.31 Specifically, remediation of memory utilizes techniques such as errorless learning, compensatory strategy training, and external memory orthotics.32Remediation of executive functioning utilizes metacognitive and self-regulation skills, while remediation of attention focuses on using attention training and metacognitive training, as well as computer-assisted training programs.33 Remediation of visual spatial functioning should utilize visual scanning training and gestural strategies that allow for compensation of visual neglect and paraxial deficits, respectively.34-35

At different disease stages

Rehabilitation management and treatment focuses on restoring function in patients presenting with a variety of diagnoses. Currently, there are no FDA-approved drugs for management of cognitive impairment associated with TBI. However, cholinesterase inhibitors have been approved in Alzheimer dementia, which can help delay or prevent symptoms from becoming worse for a limited time. These include: Razadyne (galantamine), Exelon (rivastigmine), and Aricept (donepezil). Namenda (memantine) is an N-methyl D-aspartate (NMDA) antagonist in moderate to severe Alzheimer’s disease. Because NMDA antagonists work very differently from cholinesterase inhibitors, the two types of drugs can be prescribed in combination. Treating conditions like high blood pressure, depression, and sleep apnea can help improve overall mental functioning. Other approaches including regular physical exercise, diets low in fat and rich in fruits and vegetables, Omega-3 fatty acids, vitamin E, and ginkgo. Studies have shown that intellectual stimulation, social engagement, and memory training have been shown to adjuvant treatment. Cognitive remediation therapy is a behavioral treatment that uses drill and practice, compensatory and adaptive strategies to facilitate improvement in targeted cognitive areas like attention, memory, planning, organization, abstract thinking and problem solving. Cognitive behavior therapy teaches patients to think through emotionally challenging problems.

Emerging/unique Interventions

Treatment outcome measures help to identify areas of impairment requiring improvement and are useful to document improvement over time. Many instruments exist in order to assess level of independence. In regards to cognitive measures, tests that are often included for TBI consist of the O-Log and GCS, which measure early prognostication. For stroke patients, the modified Rankin scale is commonly used. These tests focus on the various components of cognition and highlight areas available for remediation.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Cutting edge concepts and practice

Some cutting edge and unique concepts include the study of proteomic biomarkers in order to help identify disease process characteristics, which may potentially assist in predicting rehabilitation outcomes. Pharmacologically, a number of agents have been studied that may benefit cognition in some disorders. For example, it was demosntrated that, compared to placebo, patients with TBI 4-16 weeks post-injury taking amantadine had increased functional recovery with a month’s treatment.36 Similarly, citicholine, a naturally occurring nucleotride component of cell membranes, appears to show some promise in treating cognitive impairments secondary to vascular causes, Alzheimer’s disease, or post-TBI or stroke.37-39 In acute CNS injuries, progesterone is believed to possess neuroprotective properties, in addition to its role as a hormone.40

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, various pharmacologic therapies and their long-term impact, and research regarding efficacy and tailoring of specific rehabilitation exercises and therapies for individual cognitive domains.

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Author Disclosures

Anne F. Ambrose, MD MS
Nothing to Disclose

Robin Gay, PhD
Nothing to Disclose

Richard G. Chang, MD, MPH
Nothing to Disclose

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