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Disease/ Disorder


Cognitive impairments are commonly encountered during rehabilitation, in both neurological conditions such as traumatic brain injury (TBI), stroke, dementias, and in other non-neurological conditions such as delirium, metabolic encephalopathies and CNS infections.  Cognitive impairments can be classified into six major domains as described in the DSM-5.1

  • Perceptual-motor function: synchronized perceptual and motor skills that develop progressively, compromising of visual perception, visuo-constructional reasoning and perceptual-motor coordination.
  • Language: system of communicating information between individuals, including sign language, compromising of object naming, word finding, fluency, grammar, syntax and receptive language.
  • Executive function: integrated cognitive processes required to complete daily activities, consisting of planning, decision making, working memory, responding to feedback, inhibition and flexibility.
  • Learning and memory: acquisition and expression of skills or knowledge, consists of free or cued recall, recognition, semantic and autobiographical long-term memory and implicit learning.
  • Complex attention: Compromising of sustained, divided, and selective attention, and processing speed.
  • Social cognition: cognitive skills that enable individuals to function within a social group by interpreting their own and other’s behaviors, comprising recognition of emotions, theory of mind and insight.


Cognitive impairment can result from direct and indirect trauma to the brain, hypoxia, edema, metabolic disturbances, neurodegenerative processes, metabolic encephalopathies, electrolyte abnormalities, organ failure, pesticides, toxins, medications, and infective processes.2 “Brain Fog” is one such manifestation seen among Post SarsCoV-19 patients.3 One study found patients who had recovered from COVID-19 scored lower on cognitive measures, especially attention and executive memory, seven months post-infection, compared to those without the disease,4 Other risk factors for cognitive deficits include advanced age, depression, PTSD, poorly controlled diabetes, emphysema, sleep disorders, and thyroid dysfunction, infections such as HIV or syphilis, alcohol and recreational substance abuse, B12 deficiency, exposure to organic solvents, and lead. These may all increase vulnerability to the development of cognitive dysfunction independently or following TBI or stroke.5 Polypharmacy may contribute to worsening cognitive impairment, particularly with use of anti-cholinergic, antidepressant, and antiepileptic medications.6 


Cognitive deficits are a common consequence of acute TBI, even at the lowest level of injury severity—concussion and mild TBI (mTBI). Approximately 65% of moderate-to-severe TBI patients report long-term problems with cognitive functioning, and as many as 15% of mTBI patients have persistent cognitive problems.7 The prevalence of cognitive impairment following stroke varies widely – 20%-70% depending on screening tools, cut-offs for normality, exclusion criteria used8. In the Framingham study, the prevalence of dementia was found to be 19.3%, 10 years following a stroke.9

The prevalence of mild cognitive impairment (MCI), a pre-dementia syndrome causing subtle cognitive changes. among persons over 60 is 12% to 18%. 10% to 15% will convert to dementia each year.10 Dementia increases with age. About 3% of adults ages 70 to 74 have dementia, compared with 22% of adults ages 85 to 89 and 33% of adults ages 90 and older.11 Among Parkinson’s patients, the cumulative prevalence is very high. At least 75% of PD patients who survive for more than 10 years will develop dementia.12 


In general, clinical manifestation of cognitive impairment may be correlated with site of neuroanatomical injury. Damage to the frontal cortex affects executive function, emotional and behavioral impulse control, temporal lobe lesions: memory; parietal lobe damage: visuospatial ability. Neuroanatomical lesions caused by the stroke on strategic areas such as the hippocampus, white matter lesions (WMLs), cerebral microbleeds (CMBs) due to the small cerebrovascular diseases and mixed AD with stroke, contribute to the pathogenesis of post-stroke cognitive impairment13. Cognition may be globally affected as a result of hypoxia in anoxic brain injury, metabolic disturbances or traumatic injury. The mechanism for cognitive impairment by COVID-19 has not been elucidated.

Disease progression including natural history, disease phases or stages, disease trajectory

Having a TBI is associated with an increased risk of developing dementia.14 The ARIC study studied the relationship between history of TBI and development of dementia over the next 25-year period in 14,000 participants with arthritis.15 The study found having a history of a single prior head injury was associated with a 1.25 fold increased risk of dementia, and a history of two or more prior head injuries was associated with over 2 times increased risk of dementia.15 Overall, 9.5% of all dementia cases in the study population could be attributed to at least one prior head injury.15 Females and White participants were more likely to experience dementia because of head injury than males or Blacks.15

Among athletes exposed to repetitive head trauma, chronic traumatic encephalopathy (CTE), a dementing disorder, has been found in increased numbers.16 True numbers are difficult to establish as the diagnosis is made post-mortem and most studies are done in highly selected samples. However, one study of all brains in a Mayo clinic autopsy tissue registry revealed 5.6% of the brains showed CTE, with the highest rates being among former football players (15%).17

Among stroke patients, the risk of dementia in population-based studies is about 10% after a first stroke and 30% after recurrent stroke.18 While cognitive deficits do not generally progress following stroke, it is a risk factor for subsequent strokes and dementia onset.

In Alzheimer’s Disease, short-term memory loss generally precedes long-term memory, language, and executive functioning.2 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 affected.19 In a study of Parkinson’s disease, 20-50% were found to have mild cognitive impairment, progressing to dementia in as many as 80% of the patients.20

Specific secondary or associated conditions and complications

Several secondary changes and complications are associated with cognitive deficits due to CNS disorders, including seizures, insomnia, personality changes including aggression, disinhibition, depression, anxiety, and emotional lability, especially following stroke or TBI. Strained familial relationships, issues of identity, employment and independence are other important non-medical factors affecting cognitive outcomes.7,21

Essentials of Assessment


The full medical history includes time course of cognitive deficits, details of any associated injury, sleep disturbances, co-morbid psychiatric illness, substance abuse, neurological disorders, and medications that may impact cognition.22 Education level, community support, family support systems, occupation, and prior functional status are other significant aspects to be evaluated.21

Physical examination

The physical exam should include assessment of all 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

All six cognitive domains should be examined. Validated cognitive, behavioral, psychosocial questionnaires can be found at the TBI Model Systems Center for Outcome Measurement in Brain Injury (COMBI) website.23

Injury assessment tools include Glasgow Coma Scale (GCS)24 and JFK Coma Recovery scale.25 However, these are assessments of consciousness, not cognition. Test such as the Galveston Orientation and Amnesia Test (GOAT),26 Orientation Log (O-Log),27 and Westmead PTA scale28 are prognostication measures. The most commonly used screening tool for the detection of cognitive impairment has been the MMSE, with a cut-off score of >= 26.29 It tests orientation, concentration, attention, verbal memory, naming and visuospatial skills. However, the MMSE has limited sensitivity and specificity compared to other tests of global impairment and is more appropriate in cases of moderate-to-severe impairment. In mild brain injury, MoCA is preferred as a screening and outcome tool as it includes executive function.30

For patients with sport related concussions, assessment tools include Post-Concussion Symptom Scale (PCSS),31 Standard Assessment of Concussion (SAC),32 Standard Concussion Assessment Tool (SCAT5),33 Immediate Post-Concussion Assessment, Cognitive Testing (ImPACT),34 Concussion Resolution Index (CRI),35 CogSport,36 and King-Devick (KD) tests.37 The strengths and limitations of these tests are well described by Dessy at al.38

The Social Skills Rating System is the most commonly used assessment tool for social cognition by clinicians.39 Autobiographical memory may be assessed by asking patients about events from their childhood, mid-life, and recent past, as well as “flashbulb” events that are likely triggers of strong emotional responses (such as 9/11).40 In addition, both the Disability Rating Scale (DRS)41 and Community Integration Questionnaire (CIQ)42 assess functional independence in the community.

Rivermead Behavioral Memory Test (RBMT)43 and Behavioral Assessment of the Dysexecutive Syndrome (BADS)44   identifying limitations in functional abilities rather than discriminating brain injured from healthy people. However, these tests, particularly in the domain of executive functioning, lack specificity, even when they are sensitive to dysfunction.

The assessment of cognitive impairments in TBI must factor in mental fatigue, which can strongly impact performance, especially attention. The clinician should consider staggering the cognitive test to the end of the session, in order to obtain a more ecologically valid measure of cognition. Conversely, allowing the patient a break between measures can prevent fatigue-related variability that is not a true reflection of specific cognitive impairment.

Laboratory studies

Patients with cognitive dysfunction should be evaluated for reversible causes of delirium, such as infection, hypoxia, and metabolic disturbance. This would include complete blood count, vitamin B12, thiamine, folate, homocysteine, 1,25-dihydroxy vitamin D, magnesium, liver function tests, comprehensive metabolic panel thyroid function tests (thyroid stimulating hormone, free T3, free T4). Persistent symptoms after TBI may warrant endocrine workup for cortisol levels, IGF, and gonadal hormone levels.  Patients with polyuria should be assessed for posterior pituitary dysfunction. In high-risk patients, consider syphilis rapid plasma regain and HIV testing.


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 64.45  MRI, especially specialized protocols like fluid attenuated inversion recover(FLAIR)y, fast field echo T2-weighted, gradient-echo, susceptibility-weighted, diffusion-weighted/tensor imaging provide valuable information.46 DTI permits an in-vivo investigation of fiber tract integrity that correlates with histopathological evidence of diffuse axonal injury delineating the extent, quantity and location of axonal injuries.47 FLAIR shows areas of tissue T2 prolongation as bright while suppressing (darkening) cerebrospinal fluid (CSF) signal, thus clearly revealing lesions in proximity to CSF, such as cerebral cortical lesions.48 FLAIR has been superior to T2-weighted images in detecting traumatic axonal injuries in mild TBI.49

Supplemental assessment tools

For a 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 patients50 Computer Assessment of Mild Cognitive Impairment (CAMCI), a computer-administered neuropsychological screen for mild cognitive impairment and CNS Vital Signs51 are computerized programs that can be used as screening tools in the older population.52

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 outcomes53. 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 outcomes54.  In a veteran sample, higher scores on PTSD symptomatology scales and greater severity of depressive symptoms were associated with poorer cognitive outcomes 55.


Moving a patient from the relative safety of a hospital environment to the community could be problematic. The Safety Assessment Measure comprising of 6 primary scales – Cognitive Capacity, Visuomotor Capacity, Wheelchair Use, Risk Perception, Self-Regulation, and Compliance Failures with Safety Recommendations – in which family caregivers or clinicians rate the risk for unintentional injury or harm encompass a broad spectrum of everyday activities that pose risk in the home and community may be a useful tool.56

Social role and social support system

Family education and involvement is vital for patient recovery and overall outcomes. Families should be educated on safe transfers, assisting in ADLS, managing cognitive and behavioral issues, and their own self-care. The Family Caregiver Alliance has put together some useful videos on these topics.57 Tools such as Independent Living Skills58 Community Integration Questionnaire42 help the clinician identify ongoing issues.

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 need to be addressed. The Family Caregiver Alliance has put together information describing resources and services for patients and caregivers, listing agencies that may provide information and benefits.59

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 function.60 These interventions fall into three broad categories: 1) process-specific remediation, focusing on very targeted areas of cognitive functioning 2) functional skills training, which focuses on improving cognitive functions by improving performance in functional activities of daily life; and 3) metacognitive remediation, focusing on self-monitoring and self-regulation through the use of “top-down” strategies for addressing a range of problems and life situations of varying complexity.55 Memory remediation utilizes techniques such as errorless learning, compensatory strategy training, and external memory orthotics.61  Executive function remediation utilizes metacognitive and self-regulation skills, while attentional remediation focuses on attention training.61  Remediation of visuospatial functioning utilizes visual scanning training and gestural strategies to allow for compensation of visual neglect and paraxial deficits.61 

The three main classes of pharmacological agents utilized to treat the cognitive sequelae of TBI are psychostimulants, cholinergics, and NMDA receptor antagonists. Psychostimulant medications are commonly used to improve arousal/attention and related neurobehavioral symptoms after TBI. Methylphenidate is the first-line agent and may improve arousal, attention, and processing speed and general cognitive function in the subacute and chronic phase of injury in addition to reducing daytime sleepiness and depression following TBI.62 Among cholinesterase inhibitors, Donepezil and Rivastigmine are more commonly used. Donepezil, a centrally selective acetylcholinesterase inhibitor, improves attention and memory during the subacute and chronic phase of injury and enhances sensory gating during the chronic TBI period. Rivastigmine, which inhibits both acetylcholinesterase and butyrylcholinesterase improved scores on the Hopkins Verbal Learning Test and the Cambridge Neuropsychological Test Automated Battery Rapid Visual Information Processing mean latency, but only in patients with severe memory impairment at baseline.63 Amantadine and memantine are non-competitive antagonists at the NMDA receptor which enhance dopamine release, decrease presynaptic dopamine reuptake, stimulate dopamine receptors, and enhance postsynaptic dopamine receptor sensitivity.64 Amantadine improves arousal in the acute TBI period and with attention, visuospatial function, and executive functions, especially impulsivity, disinhibition, and poor motivation in chronic TBI in persons with moderate to severe TBI.64 

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 suggesting an early return to physical activity, defined as within 7 days, is associated with a reduction in persistent post-concussive symptoms.65 Visual spatial rehabilitation and interventions that address aphasia and apraxia are particularly beneficial for patients who have suffered from strokes.66

New research finds that neuropsychological rehabilitation can also be beneficial to patients with cognitive deficits from COVID-19 even if they don’t make full recovery, while more research is still needed in this area as we continue to learn more about the disease.67

At Different Disease Stages

In acute injury, strategies like inducing hypothermia, strict glucose control, and preventing intracranial hypertension, among others, have been investigated, with varying results.68 Other approaches include regular physical exercise, diets low in fat and rich in fruit and vegetables,69 Omega-3 fatty acids, vitamins E and D, glutamine, and gingko. Recent studies suggest that Mediterranean, DASH, MIND, Nordic, and ketogenic diets directly correlate to reversing cognitive decline and neurodegenerative disease.70 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.

Cutting Edge/ Emerging and Unique Concepts and Practice

Several new imaging modalities are currently showing promising preliminary results. These include an experimental PET (positron emission tomography) scan on living people to detect abnormal tau protein in patterns similar to CTE after death.71 MRS data can provide information on TBI-induced physiological changes, cerebral regions susceptible to injury, individual susceptibility to injury, and the predictive role of metabolic alterations on outcomes post-TBI not feasible with conventional imaging.72 Functional MRI (fMRI) may be used to assesses the combination of regional blood flow and local metabolic activity that occurs during cerebral activity, while Functional near infrared spectroscopy(fNIRS) can assess cerebral activity during motor or cognitive tasks.73 Transcranial magnetic stimulation(TMS) can evaluate excitability of central motor pathways, map cortical representations, predict motor impairments74 and may also improve working memory in dementia, Parkinson’s disease, stroke and TBI.75 Transcranial Direct Current Stimulation (tDCS)  showed an additional benefit for attention/vigilance in these diagnoses.76 Transcranial electrical stimulation (tES)  has been reported to improve arousal in minimally conscious state demonstrating following prefrontal stimulation.77 Similarly, noninvasive auricular vagus nerve stimulation demonstrated behavioral improvement and increased default mode network connectivity.78 Magnetoencephalography (MEG) has been used to identify regions activated during specific cognitive tasks and the relative time course of activations.79

Identifying biomarker signatures associated with distinct aspects of TBI pathophysiology may increase accuracy, characterization and risk stratification of TBI patients. The US FDA has approved The Brain Trauma Indicator™ (BTI™), which measures UCH-L1 and GFAP biomarkers levels in the blood within 12 hours post-injury. This test provides results withing 4 hours and can predict presence of intracranial lesions on CT scans.80 The i-STAT-device can determine plasma levels of GFAP within 24 hours post-injury and discriminate between magnetic resonance imaging (MRI)-positive patients and MRI-negative patients.81 Further research is still needed on biomarker biology, standardizing mTBI inclusion criteria, and increasing detection sensitivity and assay speed.

Pharmacologically, a number of agents thought to enhance cognitive recovery have been studied. A recent metanalysis of twenty-six studies showed that Amantadine significantly enhanced the cognitive function relative to control group especially if started in the first week after TBI  and administered for less than 1 month, in patients below 18 years of age or with less severe traumatic brain injury.82 Citicholine, a naturally occurring nucleotide cell membrane component has been able to prevent degradation of choline and ethanolamine phospholipids during brain ischemia, and to restore the integrity of the blood−brain barrier in animal studies. In human studies, the results have been more promising in TBI patients than stroke.83 Currently, no strong evidence supports the use of any single pharmacological agent to enhance cognitive outcomes following TBI84. Additional agents under investigation include regenerative stem cell therapies, growth hormone, statins, N-acetyl cysteine, Cerebrolysin, Ciclosporin and nitric oxide synthase inhibitor (VAS203) and Disgenic-Rich Yam.85      

Other approaches like  Wearables such as Apple Watch, iPhone, and the RIFitTest app have been used for fall detection in older adults who are at high risk of recurrent falls.86 Stem cell therapies, have shown some promise.87  The presence of the ɛ4 allele has been associated with increased risk of several neurological diseases, including late onset familial and sporadic Alzheimer’s disease,88 stroke,89 amyloid angiopathy, and HIV-related dementia.90 Meta-analysis demonstrated higher odds of a favorable outcome following TBI in those not possessing an ApoE ɛ4 allele compared with ɛ4 carriers and homozygotes. The influence of APOE4 on neuropsychological functioning following TBI remains uncertain, with multiple conflicting studies.91

Alternative and complementary treatments encompass a variety of approaches including herbal supplements, homeopathy, hyperbaric oxygen, EEG-based therapy, craniosacral therapy, arts and recreational therapies (such as dance, music, art, horticulture), and interventions of Asian origin such as mindfulness and meditation practice, Tai Chi Chuan, Ayurvedic medicine, and acupuncture. There are numerous anecdotal reports and small studies that show promising results, but further research is needed before recommendations may be given.92-96

Gaps in the Evidence-Based Knowledge

Major gaps and challenges exist in all these aspects of TBI care, as well as in the research enterprise that supports it. We lack a granular understanding of the natural history of recovery after TBI and the factors that predict outcomes. There is a lack of sufficiently precise criteria and terminology for classifying TBI, tools for precision diagnosis, prognosis, and monitoring

More information is needed on use and timing of intracranial monitors, surgical interventions, including decompressive craniectomy, vasoactive agents to augment cerebral perfusion pressure, and management of hypotension, especially in pediatric and geriatric populations.

Further understanding is also needed on the roles and indications for emerging therapies, such as superoxide radicals, deep brain stimulators, vagal nerve stimulators, or use of stimulating devices to treat post-TBI depression, newer imaging technologies, acute prehospital management, preexisting risk factors, such as hypertension, diabetes, hypercholesterolemia, and prior cardiovascular disease. 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. Long-term disadvantages from anti-convulsant use on neuropsychological recovery in relation with timing and dosage are not yet fully understood and merit further prospective evaluation


  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 2013. doi:10.1176/appi.books.9780890425596
  2. Hugo J, Ganguli M. Dementia and cognitive impairment: epidemiology, diagnosis, and treatment. Clin Geriatr Med. 2014 Aug;30(3):421-42. doi: 10.1016/j.cger.2014.04.001. Epub 2014 Jun 12. PMID: 25037289; PMCID: PMC4104432.
  3. Fine JS, Ambrose AF, Didehbani N, et al. Multi‐Disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post‐acute sequelae of SARS‐COV‐2 infection (PASC). PM&R. 2022;14(1):96-111. doi:10.1002/pmrj.12745
  4. Crivelli L, Palmer K, Calandri I, et al. Changes in cognitive functioning after COVID‐19: A systematic review and meta‐analysis. Alzheimer’s & Dementia. 2022;18(5):1047-1066. doi:10.1002/alz.12644
  5. Rapoport MJ, McCullagh S, Shammi P, Feinstein A. Cognitive impairment associated with major depression following mild and moderate traumatic brain injury. The Journal of Neuropsychiatry and Clinical Neurosciences. 2005;17(1):61-65. doi:10.1176/jnp.17.1.61
  6. Gellad WF, Grenard JL, Marcum ZA. A systematic review of barriers to medication adherence in the elderly: Looking beyond cost and regimen complexity. The American Journal of Geriatric Pharmacotherapy. 2011;9(1):11-23. doi:10.1016/j.amjopharm.2011.02.004
  7. Whiteneck GG, Gerhart KA, Cusick CP. Identifying environmental factors that influence the outcomes of people with traumatic brain injury. Journal of Head Trauma Rehabilitation. 2004;19(3):191-204. doi:10.1097/00001199-200405000-00001
  8. Rist PM, Chalmers J, Arima H, et al. Baseline cognitive function, recurrent stroke, and risk of dementia in patients with stroke. Stroke. 2013;44(7):1790-1795. doi:10.1161/strokeaha.111.680728
  9. Satizabal CL, Beiser AS, Chouraki V, Chêne G, Dufouil C, Seshadri S. Incidence of Dementia over Three Decades in the Framingham Heart Study. N Engl J Med. 2016 Feb 11;374(6):523-32. doi: 10.1056/NEJMoa1504327. PMID: 26863354; PMCID: PMC4943081.
  10. Alzheimer’s Association. Mild cognitive impairment (MCI). Available at: https://www.alz.org/alzheimers-dementia/ what-is-dementia/related_conditions/mild-cognitive impairment.
  11. Freedman, Cornman, and Kasper, National Health and Aging Trends Study Chart Book: Key Trends, Measures and Detailed Tables
  12. Aarsland D, Kurz MW. The epidemiology of dementia associated with Parkinson disease. J Neurol Sci. 2010 Feb 15;289(1-2):18-22. doi: 10.1016/j.jns.2009.08.034. Epub 2009 Sep 4. PMID: 19733364.
  13. Szabo K, Förster Alex, Jäger Theodor, et al. Hippocampal lesion patterns in acute posterior cerebral artery stroke. Stroke. 2009;40(6):2042-2045. doi:10.1161/strokeaha.108.536144
  14. Moretti L, Cristofori I, Weaver SM, Chau A, Portelli JN, Grafman J. Cognitive decline in older adults with a history of traumatic brain injury. The Lancet Neurology. 2012;11(12):1103-1112. doi:10.1016/s1474-4422(12)70226-0
  15. Schneider AL, Selvin E, Latour L, et al. Head injury and 25‐year risk of dementia. Alzheimer’s & Dementia. 2021;17(9):1432-1441. doi:10.1002/alz.12315
  16. Bieniek KF, Blessing MM, Heckman MG, et al. Association between contact sports participation and chronic traumatic encephalopathy: A retrospective cohort study. Brain Pathology. 2019;30(1):63-74. doi:10.1111/bpa.12757
  17. Bieniek KF, Ross OA, Cormier KA, et al. Chronic traumatic encephalopathy pathology in a neurodegenerative disorders Brain Bank. Acta Neuropathologica. 2015;130(6):877-889. doi:10.1007/s00401-015-1502-4
  18. D’Souza CE, Greenway MR, Graff-Radford J, Meschia JF. Cognitive impairment in patients with stroke. Seminars in Neurology. 2021;41(01):075-084. doi:10.1055/s-0040-1722217
  19. Normal cognitive changes in aging. Australian family physician. https://pubmed.ncbi.nlm.nih.gov/15532151/. Published 2004. Accessed September 11, 2022.
  20. Goldman JG, Vernaleo BA, Camicioli R, et al. Cognitive impairment in parkinson’s disease: A report from a multidisciplinary symposium on unmet needs and future directions to maintain cognitive health. npj Parkinson’s Disease. 2018;4(1). doi:10.1038/s41531-018-0055-3
  21. Hibbard MR, Cantor J, Charatz H, et al. Peer support in the community. Journal of Head Trauma Rehabilitation. 2002;17(2):112-131. doi:10.1097/00001199-200204000-00004
  22. Gellad WF, Grenard JL, Marcum ZA. A systematic review of barriers to medication adherence in the elderly: Looking beyond cost and regimen complexity. The American Journal of Geriatric Pharmacotherapy. 2011;9(1):11-23. doi:10.1016/j.amjopharm.2011.02.004
  23. Combi: Featured scales. COMBI-Featured Scales. https://www.tbims.org/combi/list.html. Accessed September 11, 2022.
  24. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. The Lancet. 1974;304(7872):81-84. doi:10.1016/s0140-6736(74)91639-0
  25. Kalmar K, Giacino J. The JFK coma recovery scale—revised. Neuropsychological Rehabilitation. 2005;15(3-4):454-460. doi:10.1080/09602010443000425
  26. Fürbringer e Silva SC, Sousa RM. Galveston orientation amnesia test (GOAT). Revista da Escola de Enfermagem da USP. 2009;43(spe):1027-1033. doi:10.1590/s0080-62342009000500006
  27. Alderson AL, Novack TA. Measuring recovery of orientation during acute rehabilitation for traumatic brain injury. Journal of Head Trauma Rehabilitation. 2002;17(3):210-219. doi:10.1097/00001199-200206000-00003
  28. Meares S, Shores EA, Taylor AJ, Lammél A, Batchelor J. Validation of the abbreviated Westmead Post-traumatic amnesia scale: A brief measure to identify acute cognitive impairment in mild traumatic brain injury. Brain Injury. 2011;25(12):1198-1205. doi:10.3109/02699052.2011.608213
  29. Folstein M, Folsten S, McHugh P. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatry Res. 1975;12:189–198. doi: 10.1016/0022-3956(75)90026-6.
  30. de Guise E, Alturki AY, LeBlanc J, et al. The Montreal Cognitive Assessment in Persons with Traumatic Brain Injury. Applied Neuropsychology: Adult. 2013;21(2):128-135. doi:10.1080/09084282.2013.778260
  31. Eckner JT, Kutcher JS. Concussion symptom scales and sideline assessment tools. Current Sports Medicine Reports. 2010;9(1):8-15. doi:10.1249/jsr.0b013e3181caa778
  32. McCrea M. Standardized mental status assessment of sports concussion. Clinical Journal of Sport Medicine. 2001;11(3):176-181. doi:10.1097/00042752-200107000-00008
  33. Petit KM, Savage JL, Bretzin AC, Anderson M, Covassin T. The Sport Concussion Assessment Tool-5 (SCAT5): Baseline assessments in NCAA Division I collegiate student-athletes. International journal of exercise science. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449330/. Published August 1, 2020. Accessed September 11, 2022.
  34. Broglio SP. Concussion history is not a predictor of computerised neurocognitive performance * commentary. British Journal of Sports Medicine. 2006;40(9):802-805. doi:10.1136/bjsm.2006.028019
  35. Broglio SP, Ferrara MS, Macciocchi SN, Baumgartner TA, Elliott R. Test-retest reliability of computerized concussion assessment programs. Journal of athletic training. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2140077/. Published 2007. Accessed September 11, 2022.
  36. Neuroscience *Cfor. Cogsport: Reliability and correlation with conventional… : Clinical Journal of Sport Medicine. LWW. https://journals.lww.com/cjsportsmed/Abstract/2003/01000/CogSport__Reliability_and_Correlation_with.6.aspx. Published 2003. Accessed September 11, 2022.
  37. Tjarks BJ, Dorman JC, Valentine VD, et al. Comparison and utility of King-Devick and impact® composite scores in adolescent concussion patients. Journal of the Neurological Sciences. 2013;334(1-2):148-153. doi:10.1016/j.jns.2013.08.015
  38. Dessy AM, Yuk FJ, Maniya AY, et al. Review of assessment scales for diagnosing and monitoring sports-related concussion. Cureus. 2017. doi:10.7759/cureus.1922
  39.  Kelly M, McDonald S, Frith MHJ. Assessment and rehabilitation of social cognition impairment after brain injury: Surveying practices of clinicians. Brain Impairment. 2017;18(1):11-35. doi:10.1017/brimp.2016.34
  40. Robinson, J. A. (1976). Sampling autobiographical memory. Cognitive Psychology, 8(4), 578–595. https://doi.org/10.1016/0010-0285(76)90020-7
  41. Ashley MJ, Persel CS. Long term follow up of Post Acute Traumatic Brain Injury Rehabilitation: A statistical analysis to test for stability and predictability of outcome. Brain Injury. 1997;11(9):677-690. doi:10.1080/026990597123223
  42. Corrigan JD, Deming R. Psychometric Characteristics of the Community Integration Questionnaire: Replication and extension. Journal of Head Trauma Rehabilitation. 1995;10(4):41-53. doi:10.1097/00001199-199508000-00005
  43. Wilson BA, Cockburn J, Baddeley AD. The Rivermead Behavioural Memory Test. Bury St. Edmunds, UK: Thames Valley Test Company; 1991.
  44. Wilson BA. Bads Behavioural Assessment of the Dysexecutive Syndrome: Manual. Bury St Edmunds: Thames Valley Test Company; 1996.
  45. Jagoda AS, Bazarian JJ, Bruns JJ, et al. Clinical policy: Neuroimaging and decision making in adult mild traumatic brain injury in the acute setting. Journal of Emergency Nursing. 2009;35(2). doi:10.1016/j.jen.2008.12.010
  46. Hunter JV, Wilde EA, Tong KA, Holshouser BA. Emerging imaging tools for use with Traumatic Brain Injury Research. Journal of Neurotrauma. 2012;29(4):654-671. doi:10.1089/neu.2011.1906
  47. Benson RR, Meda SA, Vasudevan S, et al. Global white matter analysis of diffusion tensor images is predictive of injury severity in traumatic brain injury. Journal of Neurotrauma. 2007;24(3):446-459. doi:10.1089/neu.2006.0153
  48. Moen KG, Brezova V, Skandsen T, Håberg AK, Folvik M, Vik A. Traumatic axonal injury: the prognostic value of lesion load in corpus callosum, brain stem, and thalamus in different magnetic resonance imaging sequences. J Neurotrauma. 2014 Sep 1;31(17) :1486-96. doi: 10.1089/neu.2013.3258. Epub 2014 Jul 1. PMID: 24773587.
  49. Ashikaga R, Araki Y, Ishida O. MRI of head injury using FLAIR. Neuroradiology. 1997 Apr;39(4):239-42. doi: 10.1007/s002340050401. PMID: 9144669.
  50. Lippa SM, Hawes S, Jokic E, Caroselli JS. Sensitivity of the RBANS to acute traumatic brain injury and length of post-traumatic amnesia. Brain Injury. 2013;27(6):689-695. doi:10.3109/02699052.2013.771793
  51. Plourde V, Brooks BL. Is computerized cognitive testing useful in children and adolescents with moderate-to-severe traumatic brain injury? Journal of the International Neuropsychological Society. 2017;23(4):304-313. doi:10.1017/s1355617717000066
  52. Ashman TA, Cantor JB, Gordon WA, et al. A comparison of cognitive functioning in older adults with and without traumatic brain injury. Journal of Head Trauma Rehabilitation. 2008;23(3):139-148. doi:10.1097/01.htr.0000319930.69343.64
  53. van der Naalt J, Timmerman ME, de Koning ME, et al. Early predictors of outcome after mild traumatic brain injury (upfront): An observational cohort study. The Lancet Neurology. 2017;16(7):532-540. doi:10.1016/s1474-4422(17)30117-5
  54. de Guise E, LeBlanc J, Feyz M, Lamoureux J, Greffou S. Prediction of behavioural and cognitive deficits in patients with traumatic brain injury at an acute rehabilitation setting. Brain Injury. 2017;31(8):1061-1068. doi:10.1080/02699052.2017.1297485
  55. Merz ZC, et al. Impact of psychiatric symptomatology on neuropsychological assessment performance in persons with TBI: a comparison of OEF/OIF veteran and civilian samples. Brain Injury. 2017. Doi:10.1080/02699052.2017.1339124.
  56. Seel RT, Macciocchi S, Velozo CA, Shari K, Thompson N, Heinemann AW, Sander AM, Sleet D. The Safety Assessment Measure for persons with traumatic brain injury: Item pool development and content validity. NeuroRehabilitation. 2016 Jun 30;39(3):371-87. doi: 10.3233/NRE-161369. PMID: 27497470; PMCID: PMC6784539.
  57. https://www.caregiver.org/caregiver-resources/all-resources/
  58. Ashley MJ, Persel CS, Clark MC. Validation of an independent living scale for post-acute rehabilitation applications. Brain Injury. 2001;15(5):435-442. doi:10.1080/02699050010005896
  59. https://www.caregiver.org/resource/traumatic-brain-injury/
  60. Belanger HG, Curtiss G, Demery J, Lebowitz B, Vanderploeg R. Factors moderating neuropsychological outcomes following mild traumatic brain injury: A meta-analysis. Journal of the International Neuropsychological Society. 2005;11(3):215-227. doi:10.1017/s1355617705050277
  61. Cicerone KD, Goldin Y, Ganci K, et al. Evidence-based cognitive rehabilitation: Systematic review of the literature from 2009 through 2014. Archives of Physical Medicine and Rehabilitation. 2019;100(8):1515-1533. doi:10.1016/j.apmr.2019.02.011
  62. Lee H, Kim S-W, Kim J-M, Shin I-S, Yang S-J, Yoon J-S. Comparing effects of methylphenidate, sertraline and placebo on neuropsychiatric sequelae in patients with traumatic brain injury. Human Psychopharmacology: Clinical and Experimental. 2005;20(2):97-104. doi:10.1002/hup.668
  63. Silver JM, Koumaras B, Chen M, et al. Effects of rivastigmine on cognitive function in patients with traumatic brain injury. Neurology. 2006;67(5):748-755. doi:10.1212/01.wnl.0000234062.98062.e9
  64. Wheaton P, Mathias JL, Vink R. Impact of early pharmacological treatment on cognitive and behavioral outcome after traumatic brain injury in adults. Journal of Clinical Psychopharmacology. 2009;29(5):468-477. doi:10.1097/jcp.0b013e3181b66f04
  65. Grool AM, Aglipay M, Momoli F, et al. Association between early participation in physical activity following acute concussion and persistent postconcussive symptoms in children and adolescents. JAMA. 2016;316(23):2504. doi:10.1001/jama.2016.17396
  66. Cicerone KD, Langenbahn DM, Braden C, et al. Evidence-based cognitive rehabilitation: Updated review of the literature from 2003 through 2008. Archives of Physical Medicine and Rehabilitation. 2011;92(4):519-530. doi:10.1016/j.apmr.2010.11.015
  67. García-Molina A, García-Carmona S, Espiña-Bou M, Rodríguez-Rajo P, Sánchez-Carrión R, Enseñat-Cantallops A. Rehabilitación neuropsicológica en el síndrome post-covid-19: Resultados de un Programa Clínico y Seguimiento a los 6 meses. Neurología. 2022. [Neuropsychological rehabilitation for post-COVID-19 syndrome: Results of a clinical program and six-month follow up.]. doi:10.1016/j.nrl.2022.06.008
  68. Kim YS, Kim C, Jung K-H, et al. Range of glucose as a glycemic variability and 3–month outcome in diabetic patients with acute ischemic stroke. PLOS ONE. https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0183894. Published 2017. Accessed September 11, 2022.
  69. Scrimgeour AG, Condlin ML. Nutritional treatment for traumatic brain injury. Journal of Neurotrauma. 2014;31(11):989-999. doi:10.1089/neu.2013.3234
  70. Angeloni C, Businaro R, Vauzour D. The role of diet in preventing and reducing cognitive decline. Current Opinion in Psychiatry. 2020;33(4):432-438. doi:10.1097/yco.0000000000000605
  71. Stern RA, Adler CH, Chen K, et al. Tau Positron-emission tomography in former National Football League players. New England Journal of Medicine. 2019;380(18):1716-1725. doi:10.1056/nejmoa1900757
  72. Yeo RA, Phillips JP, Jung RE, Brown AJ, Campbell RC, Brooks WM. Magnetic resonance spectroscopy detects brain injury and predicts cognitive functioning in children with brain injuries. Journal of Neurotrauma. 2006;23(10):1427-1435. doi:10.1089/neu.2006.23.1427
  73. Villringer A. Non-invasive optical spectroscopy and imaging of human brain function. Trends in Neurosciences. 1997;20(10):435-442. doi:10.1016/s0166-2236(97)01132-6
  74. Caramia MD, lani C, Bernardi G. Cerebral plasticity after stroke as revealed by ipsilateral responses to magnetic stimulation. NeuroReport. 1996;7(11):1756-1760. doi:10.1097/00001756-199607290-00012
  75. Lee SA, Kim M-K. Effect of low frequency repetitive transcranial magnetic stimulation on depression and cognition of patients with traumatic brain injury: A randomized controlled trial. Medical Science Monitor. 2018;24:8789-8794. doi:10.12659/msm.911385
  76. Begemann MJ, Brand BA, Ćurčić-Blake B, Aleman A, Sommer IE. Efficacy of non-invasive brain stimulation on cognitive functioning in brain disorders: A meta-analysis. Psychological Medicine. 2020;50(15):2465-2486. doi:10.1017/s0033291720003670
  77. Peng Y, Zhao J, Lu X, et al. Efficacy of transcranial direct current stimulation over dorsolateral prefrontal cortex in patients with minimally conscious state. Frontiers in Neurology. 2022;13. doi:10.3389/fneur.2022.821286
  78. Konjusha A, Colzato L, Mückschel M, Beste C. Auricular transcutaneous vagus nerve stimulation diminishes alpha-band–related inhibitory gating processes during conflict monitoring in frontal cortices. International Journal of Neuropsychopharmacology. 2022;25(6):457-467. doi:10.1093/ijnp/pyac013
  79. Lewine JD, Davis JT, Bigler ED, et al. Objective documentation of traumatic brain injury subsequent to mild head trauma. Journal of Head Trauma Rehabilitation. 2007;22(3):141-155. doi:10.1097/01.htr.0000271115.29954.27
  80. Wang KKW, Kobeissy FH, Shakkour Z, Tyndall JA. Thorough overview of Ubiquitin C‐terminal hydrolase‐L1 and glial fibrillary acidic protein as tandem biomarkers recently cleared by US Food and Drug Administration for the evaluation of intracranial injuries among patients with traumatic brain injury. Acute Medicine & Surgery. 2021;8(1). doi:10.1002/ams2.622
  81. Martin CL. i-STAT – Combining Chemistry and Haematology in PoCT. Clin Biochem Rev. 2010 Aug;31(3):81-4. PMID: 24150509; PMCID: PMC2924126.
  82. Mohamed MS, El Sayed I, Zaki A, Abdelmonem S. Assessment of the effect of amantadine in patients with traumatic brain injury: A meta-analysis. Journal of Trauma and Acute Care Surgery. 2021;92(3):605-614. doi:10.1097/ta.0000000000003363
  83. Premi E, Cantoni V, Benussi A, et al. Citicoline treatment in acute ischemic stroke: A randomized, single-blind TMS Study. Frontiers in Neurology. 2022;13. doi:10.3389/fneur.2022.915362
  84. Gruenbaum SE, Zlotnik A, Gruenbaum BF, Hersey D, Bilotta F. Pharmacologic neuroprotection for functional outcomes after traumatic brain injury: A systematic review of the clinical literature. CNS Drugs. 2016;30(9):791-806. doi:10.1007/s40263-016-0355-2
  85. Tohda C, Yang X, Matsui M, et al. Diosgenin-rich yam extract enhances cognitive function: A placebo-controlled, randomized, double-blind, crossover study of Healthy Adults. Nutrients. 2017;9(10):1160. doi:10.3390/nu9101160
  86. Strauss DH, Davoodi NM, Healy M, et al. The geriatric acute and post-acute fall prevention intervention (gapcare) II to assess the use of the Apple Watch in older emergency department patients with falls: Protocol for a mixed methods study. JMIR Research Protocols. 2021;10(4). doi:10.2196/24455
  87. Wood H. Stem cell implants show promise in Chronic Traumatic Brain Injury. Nature Reviews Neurology. 2021;17(2):64-64. doi:10.1038/s41582-021-00459-y
  88. Bejanin A, Iulita MF, Vilaplana E, et al. Association of apolipoprotein E Ɛ4 allele with clinical and multimodal biomarker changes of alzheimer disease in adults with down syndrome. JAMA Neurology. 2021;78(8):937. doi:10.1001/jamaneurol.2021.1893
  89. Konialis C, Spengos K, Iliopoulos P, et al. The APOE E4 allele confers increased risk of ischemic stroke among Greek carriers. Advances in Clinical and Experimental Medicine. 2016;25(3):471-478. doi:10.17219/acem/38841
  90. Wendelken LA, Jahanshad N, Rosen HJ, et al. Apoe ε4 is associated with cognition, brain integrity, and atrophy in HIV over age 60. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2016;73(4):426-432. doi:10.1097/qai.0000000000001091
  91. McFadyen CA, Zeiler FA, Newcombe V, et al. Apolipoprotein E4 polymorphism and outcomes from traumatic brain injury: A Living Systematic Review and meta-analysis. Journal of Neurotrauma. 2021;38(8):1124-1136. doi:10.1089/neu.2018.6052
  92. Elovic EP, Zafonte RD. Ginkgo biloba: applications in traumatic brain injury. J Head Trauma Rehabil. 2001;16:603–7.
  93. Rockswold GL, Ford SE, Anderson DC, et al. Results of a prospective randomized trial for treatment of severely brain-injured patients with hyperbaric oxygen. J Neurosurg. 1992;76:929–34.
  94. Munivenkatappa A, Rajeswaran J, Indira Devi B, Bennet N, Upadhyay N. EEG Neurofeedback therapy: Can it attenuate brain changes in TBI? NeuroRehabilitation. 2014;35(3):481-4. doi: 10.3233/NRE-141140. PMID: 25238859.
  95. Wetzler G, Roland M, Fryer-Dietz S, Dettmann-Ahern D. CranioSacral Therapy and Visceral Manipulation: A New Treatment Intervention for Concussion Recovery. Med Acupunct. 2017 Aug 1;29(4):239-248. doi: 10.1089/acu.2017.1222. PMID: 28874926; PMCID: PMC5580370.
  96. Sipe WE, Eisendrath SJ. Mindfulness-based cognitive therapy: theory and practice. Can J Psychiatry. 2012 Feb;57(2):63-9. doi: 10.1177/070674371205700202. PMID: 22340145.

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. 1/30/2014.

Previous Revision(s) of the Topic

Anne F. Ambrose, MD MS, Tanya Verghese, MA (Hons), Jennifer Russo, MD. Cognitive issues in brain injury and other CNS disorders. 1/30/2014.

Author Disclosures

Anne F. Ambrose, MD MS
Montefiore Medical Center, Salary support, Physician; NIH, Grant support, Co-investigator

Tanya Verghese, MA(Hons),
Nothing to Disclose

Eric Martinez, DO
Nothing to Disclose

Daniella Lipnick, MD
Nothing to Disclose

Alicia Roldan, DO
Nothing to Disclose