2008 Galveston Brain Injury Conference

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2008 Galveston Brain Injury Conference
Group Presentations

• Moody Gardens Convention Center
• Galveston Texas

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TRAUMATIC BRAIN INJURY, AGING AND COGNITIVE
FUNCTIONING

• Presented by
• Wayne A. Gordon, PhD ABPP-CN,
• Amanda L. Sacks PhD, Angela S. Yi PhD
• (Group 2)

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Purpose of Review

• To examine the literature on the impact of aging
  on Post-TBI cognitive function.
• Research Implications
• Examine current literature.
• Provide methodological recommendations for future
  research.
• Clinical Implications
• Provide prognostic information to patients on how
  aging will affect cognitive functioning after a
  TBI.

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Research Questions

• 1. Are there changes in cognitive function in
  individuals with TBI as they get older?
• 2. If so, what are the specific changes in
  cognitive function in individuals with TBI as
  they get older?

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Review ProcessKey Words used

• word finding fluency
• pragmatics
• expressive language
• receptive language
• visuospatial
• visual perception
• visual construction
• neglect
• visual scanning
• orientation
• alertness

• arousal
• memory
• retrieval
• retention
• encoding
• concentration
• speed of information processing
• concept formation
• verbal abstraction
• nonverbal abstraction
• executive dysfunction
• intelligence

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Review Process
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Study Designs

• Longitudinal Designs - studies that measure
  cognitive functioning of the same individual at
  two or more time points.
• Question What happens to my cognitive
• functioning over time?
• Cohort Design studies that compare the
  cognitive performance between two groups at one
  time point.
• Age 1 vs. Age 2 (TBI)
• TBI vs. Controls (Age-matched)
• Question How does my cognitive functioning
• compare to different age groups?

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2 Cohort Studies

• AAN ratings
• AAN Rating 3 1
• AAN Rating 4 1
• Strobe ratings
• Klein et al (1996) 78
• Ogden et al (1998) 72

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9 Longitudinal Studies

• AAN ratings summary (M 3 Range 2-4)
• AAN Rating 1 0
• AAN Rating 2 3
• AAN Rating 3 4
• AAN Rating 4 2
• Strobe ratings (M 74 Range 57-87)
• 50 lt 1 Article
• 60-70 2 Articles
• 70-80 4 Articles
• 80-90 2 Articles

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Cohort Studies
Demographics Klein (1996)¹ Ogden (1998)²
Age at Injury Middle Age 23 Old 34.1 Young Age 18.33 Middle Age 27
Age at Eval (N) Middle Age TBI 49.4 (25) Middle Controls 48.9 (25) Older Age TBI 69.8 (25) Older Controls 70.4 (25) Young TBI 20.88 (9) Young Controls 21.11 (9) Middle Age TBI 48.66 (9) Middle Controls 48.22 (9)
Severity Mild to Moderate Mild to Moderate but unclear of distribution of severity w/in groups
Education Primary School to University degree (matched control) FSIQ TBI 104-113 FSIQ Control 108-115
Measures VVLT, Stroop Color Word Test, Concept Shifting Test WMS-III Logical Memory, Selective Reminding, Visual Sequencing Test, Central Reaction Times, Digit Symbol, Trails B
RedSimilarities Yellow Differences
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Cohort Studies Cognitive Domains
Domains Age Effect TBI Effect Interaction
Memory Visual Verbal Learning Test total (Middle gt Older)¹ Logical Memory, Selective Reminding, Visual Sequence (Younger gt Older)² Visual Verbal Learning Test (TBI lt Controls), all age groups¹ Logical Memory Immediate² Young TBIltControls Middle Age TBI gt Controls ???
Executive Functioning Stroop Color Word Test (Olderlt Middle Age)¹ Concept Shifting Test (Older lt Middle Age)¹ None Trails B² Young TBIltControl Middle Age TBI Control ???
Speed None Central Reaction Time, Digit Symbol² (TBI lt Controls) None
Summary As expected, both studies As expected, both studies Unexpected, conflicting findings
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Cohort Studies

• TBI Age Interaction
• Klein (1996) Middle age TBI group performance
  was similar to older controls on executive
  functioning task. Interpretation of authors TBI
  accelerates aging.
• Ogden (1998) Younger TBI group does worse than
  age-matched controls. Middle aged TBI group does
  equal to or better than age-matched controls.
  (Memory and executive functioning)

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TBI Accelerates Aging ? Or!
Visual Verbal Learning Test, Raw Scores Klein et
al. (1996)
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Longitudinal Studies Cognition Improved
Demographics Thomsen (1984) Millis (2001)
Age at Injury Males 21.5 Females 27.3 M 34
Age at 1st Assessment Males 25 Females 31 M 35
Time between Assessments T1 to T2 8-10 years T1 to T2 4 years
N N40 N141-182
Severity Severe Mild-Severe
Education Not reported ()27ltHS, 34HS, 7 college graduates
Measures Self-Report WAIS-III (digit span, block design), Symbol Digit Modalities, COWAT, RAVLT
Red Similarities Yellow Differences
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Longitudinal Studies Cognition Declined
Corkin (1989) Luukinnen (1999) Thomsen (1989)
Age at Injury M 23.9 Injuries occurred between T1 T2 Group 1 15-21 Group 2 22-44
Age at 1st Eval M 32.2 lt80 years (76) gt80 years (24) Group 1 17- 23 Group 2 24- 46
Time btwn Eval T1 to T2 30 years T1 to T2 2.5 years T1 to T2 2-5 years
N N57 BI (penetrating) N27 Controls N 617 N40
Severity Severe Mild to Severe Very severe
Education M12 years Not reported Not reported
Measures Army General Classification Test (AGCT) (Vocab, Arithmetic, Block Counting) and Hidden Figures Test. MMSE Self-report questionnaires
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Longitudinal Studies Cognition Stable
Demographics Ashman (2008) Wood (2006)
Age at Injury M 42.4 M 30.58
Age at 1st Eval M65 1 year post injury
Time between Eval T1 to T4 4.5 years T1 to T2 15 years
N TBI N 54 Controls N 40 N 74
Severity Mild-Severe PTA gt 14 min PTA lt 14 min
Education Education () High School 21.5 post secondary 32.3 Bachelors Degree and up 46.2 lt11 44 gt11 30
Measures WMS-Logical Memory, COWAT, CVLT-II, Trails A, Boston Naming Test NART, WAIS-R or III
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Longitudinal Studies Mixed Findings
Himanen (2006) Jonsson (2004)
Age at Injury M 29.4 M 14
Age at 1st Assessment M31 M 15
Time between Assessments T1 to T2 27-32 years T1 to T3 13 years
N TBI 61 Controls 31 N 8
Severity Mild-Very Severe 3-21 LOC days
Education M10 years Not reported
Measures WMS-III, BVRT, WAIS-III (Similarities, Block Design, Digit Span) WISC, WAIS, FAS, Peabody Pictures and Vocabulary
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Longitudinal Studies Cognitive Domains
Improved Declined Stable
Memory RAVLT (1) BVRT immed, (1) RAVLT (1), WMS-LM I, CVLT (1), self-report (1)
Attention Digit Span (2), self-report (1) Arithmetic (2) Digit Span (2)
Language COWAT (1) Vocabulary (1) Boston Naming Test (1), COWAT (2), Vocabulary (1)
Executive Similarities (1) Similarities (1)
Visual-Spatial Block Design (2) Block Design (1), Hidden Figures (1)
Speed Symbol Digit Modalities (1) Digit Symbol (1) Self-report (1) Trails A (1)
Intelligence VIQ (1) IQ (1)
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Longitudinal Cognitive Conclusions
Attention Simple attention may improve, however more complex attention may decline. Digit Span 2 IMPROVED (Millis 01 Wood 06) 2 STABLE (Ashman 08 Himanen 06) Arithmetic 2 DECLINED (Corkin 89 Himanen 06) Self-report 1 IMPROVED (Thomsen 84)
Speed Speed may improve or remain stable over time. Symbol Digit 1 IMPROVE (Millis 01) Digit Symbol 1 IMPROVE (Wood 06) Trails A 1 STABLE (Ashman 08) Self-report 1 STABLE (Thomsen 84)
Memory Memory may decline or remain stable over time . CVLT 1 STABLE (Ashman 08) LM I 1 STABLE (Ashman 08) Self-Report 1 STABLE (Thomsen 84) BVRT I 1 DECLINE (Himanen 06) RAVLT 1 DECLINE (Jonsson 04) 1 STABLE (Millis 01)
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Longitudinal Cognitive Conclusions
Language Verbal fluency may improve or remain stable over time. COWAT 1 IMPROVED (Millis 01) 2 STABLE (Jonsson 04 Ashman 08) Vocabulary 1 DECLINED (Wood 06) 1 STABLE (Corkin89) Boston Naming Test 1 STABLE (Ashman 08)
Executive Abstract reasoning may improve or remain stable over time. Similarities 1 IMPROVED (Himanen 06) 1 STABLE (Wood 06)
Visual-Spatial Visual-spatial construction may improve over time. Block Design 2 IMPROVED (Millis 01 Wood 06) 1 DECLINED (Himanen 06) Hidden Figures Test 1 DECLINED (Corkin 89)
Intelligence No conclusions. VIQ 1 DECLINED (Jonsson 04) FIQ 1 STABLE (Wood 06)
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Overall Conclusions

• What will happen to
• my cognitive functioning
• over time?
• No definitive conclusions can be made regarding
  Post-TBI cognitive functioning over time.

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Differences In Study Design Varied Findings

• There was no pattern to variability among
  studies
• Different tests
• Different samples
• Age
• Severity
• Time since injury
• Age at injury
• Different age at injury, time since injury and
  interval between assessments

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Normal Aging 2 Vectors
TIME BETWEEN ASSESSMENTS
SHORT
LONG
AGE AT INITIAL EVAL
YOUNG
OLD

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Aging TBI 4 Vectors
TIME BETWEEN ASSESSMENTS
SHORT
LONG
TIME SINCE INJURY AT ASSESSMENT
EARLY
LATE
YOUNG
OLD
AGE AT INITIAL EVAL
AGE AT INJURY
YOUNG
OLD

POTENTIAL CONFOUNDS -Re-injury
- Onset of co-morbidity
-Treatment - Change in
psychosocial status
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Additional Variability Across Studies

• Sampling issues
• Differences in demographics (i.e. education,
  ethnicity, gender)
• Differences in severity
• Variability of control group (i.e. matched
  control v. convenience sample)
• Variability of Tests used (i.e. self report vs.
  objective measures)
• Diversity of objective measures used NO GOLD
  STANDARD for examining cognitive change over time

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Recommendations for Future Research

• Take into account interactions between all 4
  vectors
• Age at injury
• Age at initial evaluation
• Time since injury at initial assessment
• Time between assessment.
• Assess a diverse range of cognitive abilities
  across as many domains as possible.
• Give same battery to all pts. at all assessment
  points.
• Use terminology that appropriately describes
  methodology used (i.e. follow-up should have
  two points of assessment).

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• Thank You!

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Ageing with Traumatic Brain Injury Medical Issues

• Steven Flanagan, M.D.
• Theodore Tsaousides, Ph.D.
• Dana W. Moore, Ph.D.
• Kenneth Ottenbacher
• Cindy Harrison-Felix, Ph.D.

(Group 3)
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Overarching Issue

• What happens to individuals with TBI from a
  medical perspective as they age?
• Are there differences from general population re
• Mortality/survival
• Medical problems

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Variation From Other Groups

• Less concerned with age as opposed to ageing
• No age cutoff
• Assessments made years post-injury

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Process

• Initial research questions
• What are the 10 leading causes of mortality gt 10
  years post injury?
• What are the risk factors associated with
  mortality gt 10 years post injury?
• What are the most common long-term health
  problems gt10 years post injury?

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Process

• Key words (multiple variations of)
• Brain injuries
• Risk, mortality, health
• Age

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Results to Those Specific Question

• Little more than

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Process Adaptation

• Is risk of early mortality different from the
  general population and if so, how?
• What risk factors are associated with premature
  mortality?
• What are the causes of death beyond the acute
  (sub-acute) phase following TBI?
• What long-term health problems afflict
  individuals post-TBI?
• Self-reported
• Diagnosed

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Process Adaptation

• Questions changed to include those 5 years post
  to increase hit rate.

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Initial Search Results

• 2709 abstracts screened
• 350 selected for further review
• 72 deemed appropriate for research questions
• 71 located
• 25 addressed research questions

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AAN Grade

• Most studies reviewed achieved a grade III-IV
• 4 Received grade II

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3 Broad Categories

• Mortality/Survival
• 15 studies
• Self-Reported Health Symptoms
• 9 studies
• Endocrine/Pituitary Dysfunction
• 1 Study

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Mortality
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Hospitalized
Harrison-Felix 2004 2006 2178, TBIMS compared to US general population 37 severe Up to 13 (1-13) TBI 2x as likely to die 5 increased death risk/additional year at age of injury, lack of employment and disability risk factors for death. Seizures, septicemia, pneumonia, digestive and injuries were causes of death greater than expected in the general population.
Ratcliff 2005 640 eligible (received inpatient rehab) Moderate-severe 8-24 2x increase risk of mortality assoc w/ premorbid EtOH (6.1) substance abuse (8), personal/social problem (7). Increased mortality combined post-morbid functional dependence and premorbid risk.
McMillan 2007 767 with mild-mod-severe TBI compared to Scottish population 1-7 Risk of death 2x general population. Death rate higher in younger group compared to general population. Cause of death similar to general Scottish population but in higher frequencies. Increased risk with EtOH, gt age at injury, pre-morbid-brain illness, physical impairment.
Whitnall 2006 Initial pool 334 219 participated 80/334 died gt1 year post injury no control 5-7 24 died gt 1 year post injury. Age at injury predictive gt40 54 lt 4015
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Hospitalized
Pentland 2005 1919 TBIs, mostly mild. 21 yrs Increased risk of suicide, accidental deaths, substance abuse related deaths.
Lewin, 1979 469 Amnesia or unconsciousness gt1 week compared to general population 10-24 yrs Five years reduced among ambulatory. TBI more likely to die from meningitis, szs, drowning, pulmonary disease than general population not significantly different for cardiovascular disease, cerebrovascular disease, malignancy.
Baguley 2000 476 adult inpatient rehab. compared to Australian general population Up to 11 yrs 6 mortality as of 8/1997 (vs 2 expected rate in general population). Risk factors function, psychiatric history, alcohol.
Teasdale 2001 145,440 TBIs, mostly mild Up to 15 yrs Increased risk of suicide across all severities. Increased risk associated with females, substance abuse, age of injury 20-60, intracranial lesions. No evidence for a specific risk period.
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Mortality in This Sample

• Literature suggests
• Increased likelihood of pre-mature death
• Older age at injury more likely to die
  prematurely although younger age more likely to
  die compared to age-matched population
• Increased risk associated with physical
  disability, premorbid social/personal problems,
  substance abuse, pre-morbid neurological illness
• Seizures, sepsis, pneumonia, digestive, injuries
  causes of death greater than general population

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Outpatient Services
Sample Years post-injury Assessment method Outcome
Shavelle, 2000 2629 TBIs ages 15 receiving services btw. 1988 - 1997 from CA Dept. of Develop. Services death data from state death registry and certificates Up to 10 years post-injury SMR Overall SMR 2.77. Increased mortality observed particularly among patients with decreased mobility. Stratified by mobility Non-ambulatory SMR 6.60 Partially ambulatory 1.96 Ambulatory 1.80
Shavelle, 2001 2320 TBIs ages 10 receiving services btw. 1988 - 1997 from CA Dept. of Develop. Services death data from state death registry and certificates Mortality of cohort during 10 year period beginning at 1 year post-injury SMR SMR for those 5years post non-ambulatory 6.4, some ambulation 2.4, stair negotiator 1.3 SMR by cause of death (5 year post injury) Choking/suffocating 24.9 epilepsy 22.5 genitourinary 10.0 respiratory 9.3 digestive 3.3 circulatory 3.2 cancer and other 1.1.
Strauss 1998 946 pediatric TBI compared to general population and CP. Up to 10 Mortality 4 mortality btw. 1987-1995. No relationship btw. age at injury mortality except 1st few weeks post-TBI. After 1-2 yrs the two mortality rates converge. After 10 years, 3-5 years life expectancy reduction. Risk factor mobility feeding.
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Mortality

• Literature suggests
• Increased likelihood of premature mortality
  post-TBI, associated with residual disability
• Causes of death choking, epilepsy, GU,
  respiratory, circulatory, digestive

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War Veterans
Corkin, 1984 190 World War II male veterans with penetrating TBI whose survival status was determined on 5/1/1983. Matched controls 40 years Head injury coupled with epilepsy reduced life expectancy compared to the control group, but that head injury alone did not.
Walker, 1989 244 World War II male veterans with brain wounds and seizures followed in 1985 compared to general population 40 years SMR Death rate several times higher than in the general population. Causes after 10 years same as general population.
Rish, 1983 1127 male Vietnam veterans with penetrating injury ages 21-35 surviving at least 1 week Up to 15 years post-injury SMR The all-cause SMR over the 15 year study exceeded 4 during years 1-3, ranged from 2-4 during years 4-11 and 13 post-injury and was probably less than 1 for years 12. Life expectancy and causes of death approached normal after 3 yrs. Most deaths occurred early in 1st yr post-injury and were secondary to direct effects of TBI or sequelae of coma.
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Vegetative State
Strauss, 1999 1021 TBIs in persistent vegetative state 1981-1996 Mortality during 16 year period Life expectancy markedly reduced. Risk factors ventilator, feeding tube.
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Mortality

• 13 studies reported increased likelihood of
  premature death
• Different populations
• WWI, WWII, Vietnam vets, inpatient rehab,
  outpatient services, others
• Cause of injury/Severity
• Penetrating/varying severity
• Time
• Varying times post injury
• Different levels and places of care

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Risk Factors

• 13 studies addressed risk factors
• Age at injury
• Employment status
• Pre-morbid EtOH/social problems
• Post-morbid functional skills
• Epilepsy (in vet studies only).

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Cause of Death

• 7 studies assessed cause of death
• Individuals with TBI more likely to die from
• Meningitis, seizures, drowning,
  choking/suffocation, genitourinary, respiratory,
  circulatory, gastrointestinal related conditions,
  sepsis, injuries.

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Mortality/Survival

• Literature suggests that
• TBI increases likelihood of premature death
  beyond acute/subacute phase
• Some reports suggest mortality rate decreased
  over time
• Pre-morbid problems, post-morbid functional
  limitations, epilepsy and older age increase risk
  of early death
• Premorbid EtOH abuse often reported as a risk
  factor

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Mortality questions not answered

• Does (how does) mortality risk change among
  survivors of TBI as time passes?
• Why do individuals post-TBI have a higher rate of
  premature mortality?
• What are the etiologies of premature death?
• Why are individuals with TBI more likely to die
  of certain causes?

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Self-reported Health Problems
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Sample Years post injury Assessment Method Outcome
Colantonio 2004a 286 with mod to severe TBI Compared to CDC data 14.2 (7-24) Self-reported health symptoms from a health survey Arthritis gt Nervousness gt Vision problems gt Sleeping problems gt Allergies
Hibbard 1998 338 with mild to severe TBI Compared to 273 controls 10.2 Structured Health Survey Significantly gt problems Endocrine, neurological, arthritis. Time post-injury no impact.
Hillier 1997 67 with moderate to severe TBI No control 5 Self-reported health symptoms Headache gt balance gt fatigue gt sensory ?s, slowness, tremors gt inc tone gt incoordinated gt decreased tone
Vanderploeg 2007 254 with mTBI 539 in MVA no TBI 3214 control 8 Structured medical interview, visual/physical/neurological examination More post-concussion symptoms in mTBI (balance, dizziness, light sensitivity, HA, sleep, vision, fatigue).
OConnor 2005 61 with mild to severe TBI Controls from previous study 10.2 Head Injury Symptom Checklist Mild easily tired gt HA gt poor sleep Mod Irritable gt anxiety gt looses temper Severe Anxiety All groups reported all symptoms except sensitivity to light and noise
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Self-reported Symptoms

• Literature suggests increased complaints of
• Miscellaneous
• HA, vision, hearing, arthritis, fatigue,
  allergies
• Neurological
• Weakness, muscle tone, tremors, coordination,
  dizziness
• Endocrine
• No assessment re complaints correlating with
  actual endocrine dysfunction
• Emotional
• Nervousness/anxiety/irritability/insomnia

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Health Status Questions Not Answered

• What are the actual (diagnosable) health problems
  afflicting individuals with TBI as they age?
• How do they impact general health, survival, QOL,
  etc?

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Self-Perceived Health
Sample Years post injury Assessment Method Outcome
Colantonio 2004b 286 with moderate to severe TBI 14.2 Self-rated health item from SF-36 Poor-fair 22 Good 38 V. goodexcellent 40
Jakola 2007 28 with mTBI matched to controls 5-7 Rivermead, VAS Post-concussion symptom questionnaire self-reported general health and health-related QOL Poorer QOL assoc with more gt post-concussion symptoms No difference in general health b/t TBI and control
Steadman-Pare 2007 275 with mild-severe TBI 14.2 QOL assessed on a VAS Positive relationship b/t self-reported health and QOL
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Perceived Health

• Literature suggests
• More TBI related symptoms associated with lower
  perceived health
• Perception of health positively associated with
  QOL
• Self-perceived health comparable b/t TBI and
  non-TBI

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Self-perceived Health

• Not clear how individuals post-TBI perceive their
  long-term health.

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Sexuality
Sample Years Post-injury Assessment Method Outcome
Hibbard 2000 322 with mild-severe TBI 264 Control Males 9.64 (SD 8.17) Females9.3 (SD 9.17 Structure Health Survey- Sexuality Males Diff with energy, initiation, organism, sustaining erection, positioning Females Diff with arousal, pain, masturbation, lubrication, body movements , sensation
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Sexuality

• Limited literature suggests
• TBI associated with greater likelihood of
  self-reported sexual dysfunction than general
  population

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Sexuality Questions Not Answered

• What are the diagnosable sexually related
  problems afflicting individuals with TBI as they
  age?
• How do they differ from the general population?
• What are the risk factors or associated medical
  problems?

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Pituitary Dysfunction

• Several studies
• Only one fit our criteria

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Pituitary Dysfunction
Sample Years Post Injury Assessment Method Outcome
Bondanelli 2004 50 with Mild-severe TBI 12-64 months (22 gt 5 years post) Pituitary screen including growth hormone response to stimulation tests. 54 developed pituitary dysfunction within 5 years post-injury Hypogonadism14 Central Hypothyroidism 8 Prolactin abnormality 16 Partial GHD 20 GHD 8. Older age assoc w/ GHD (plt.05) Negative correlation w/ age GH response to GHD
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Pituitary Dysfunction

• Literature suggests
• Common
• Older individuals at increased risk
• Can occur at various times post-injury
• May contribute to post-TBI morbidity

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Pituitary Dysfunction

• Consensus guideline for assessment published
• Ghigo et al. Brain Injury 2005

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Questions?
67
Aging with TBI Psychosocial/Functional Focus

• Group 4
• Facilitator Gary S. Seale, MS

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Group IV Participants

• Teresa Ashman, Ph.D. Mount Sinai
• Tim Reistetter, Ph.D. East Carolina Univ.
• Margaret Brown, Ph.D. Mount Sinai
• Betty Abreu, Ph.D. TLC/UTMB

69
Initial Question(s)

• As a person ages with TBI, what is the impact on
  psychosocial outcome?
• in terms of demographics and injury
  characteristics, who is reaching old age with
  TBI?
• as people age with TBI, what is the impact on
  activities and participation?
• as people age with TBI, how does this affect
  life satisfaction and quality of life?
• as people age with TBI, are there changes in
  emotional function what coping strategies are
  used?
• as people age with TBI, are there changes in
  spirituality, search for meaning, etc.?
• as people age with TBI, what is the impact of
  injury severity (mild, moderate, severe) on
  psychosocial outcome?

70
Initial Search Strategy

• Initial set of search terms derived from ICF
  activities/participation taxonomy (130 terms).
• Terms placed in 8 domain areas coping and
  adaptation, mobility, self-care, domestic life,
  relationships, productive activities,
  leisure/recreation, and life satisfaction.
• Terms in each domain area were combined with AND
  statements for the age and TBI terms agreed upon
  by all groups.

71
Initial Search Strategy (cont.)

• Example
• quality of life or life satisfaction or
  satisfaction or happiness or subjective
  well-being, or satisfaction with life, or
  subjective quality of life or well-being or
  positive affect or positive emotion or
  health-related quality of life
• AND
• Aging or aged or elderly or mature or senior or
  old or old age or late life or age
• AND
• TBI or traumatic brain injury or closed head
  injury or diffuse axonal injury or rapid
  acceleration/deceleration injury or concussion or
  post-concussional syndrome

72
Search Strategy - Revised

• Question As a person with TBI ages, does
  his/her functioning in terms of basic functioning
  (excluding cognitive functioning) activities1,
  participation, emotional functioning2, and
  satisfaction with life change?
• 1Marquez de la Plata, CD et al. 2008, Arch PMR
• 2Menzel, JC 2008, Brain Injury

73
Search Strategy - Revised

• Criteria for inclusion (AGE)
• Correlational at least 10-year age range is
  found AND the top of the range is at least 45
• Cross-sectional youngest reported group is
  under 30 (on average) AND oldest group is at
  least 40 (on average) OR youngest group is over
  30 AND oldest group is at least 45
• Longitudinal at measurement point 1, the
  average subject is under 30 and at last
  measurement point at least 10 years have elapsed,
  OR at measurement point 1 the average subject is
  over 30 and at last measurement point at least 5
  years have elapsed

74
Final Search Strategy

• Psychosocial domain divided into four sub domain
  areas
• - Gary Seale Quality of Life/Life Satisfaction
• - Teresa Ashman Emotional Functioning
• - Tim Reistetter Community Integration
• - Margaret Brown Productive Activities
• Additional literature searches conducted by each
  participant, including hand searches
• Studies selected were forwarded to Renee for
  inclusion in RefWorks

75
Objectives of Presentations

• Brief discussion of individual search strategies
• Quality of evidence
• Limitations of studies
• Despite limitations, what information can be
  gleaned from studies cited
• Gaps/future directions (discussion points for
  break-out sessions)

76
Life Satisfaction/Quality of Life and Aging with
TBI

• Gary S. Seale, MS
• Transitional Learning Center at Galveston

77
Guiding Question

• As a person ages with TBI does his/her life
  satisfaction/quality of life change?

78
Quality of Evidence Life Satisfaction/Quality
of Life

• All studies received an AAN grade of III
• Study Designs the majority of studies were
  cross-sectional, evaluating QOL/Life satisfaction
  at a single time point.
• Other issues affecting quality poor description
  of demographics (including age) and injury
  characteristics, mixed injury etiologies (1
  study),
• Few studies used a comparison group (1 study used
  a non-disabled comparison, 2 studies used persons
  with spinal cord injury as comparison

79
Limitations

• Aim/Objective of studies
• Aging with a TBI, changes in life
  satisfaction/QOL as one ages with TBI, and
  relationship of age to life satisfaction/QOL was
  not the primary objective.
• One study (Wood Rutterford,2006) examined
  demographic and cognitive predictors of
  psychosocial outcome following TBI

80
Limitations (cont.)

• Terms/Measures
• Life satisfaction/Quality of Life was
  operationally defined in only 1 study (Seibert,
  2002).
• Life satisfaction/QOL measured differently across
  studies
• - Satisfaction with Life Scale (5 studies)
• - Life Satisfaction Index-A (2)
• - LiSat11 Checklist (1)
• - Life Satisfaction Checklist (1)
• - Rand-36 item health survey (2)
• - home grown measures (2)
• for review, see Dijkers, MP 2004 Arch PMR

81
Limitations (cont.)

• Length of follow-up period
• Majority of studies reported only one follow-up
  after discharge from rehabilitation.
• Majority of studies used 1 year (from D/C or
  anniversary of injury) as follow-up time point.
• - Corrigan, 1998 examined changes over a 5 year
  period (sample stratified by time post
  discharge).
• - Corrigan, 2001 conducted follow up at 1 and 2
  years.
• - Tomberg, 2007 conducted follow up at 2 and 5
  years.

82
Findings

• Findings regarding the association of age to life
  satisfaction/QOL are mixed.
• - Age not a predictor of life satisfaction as
  measured by the SWLS (5 studies) or LiSat II (I
  study).
• - Those who were older at time of injury
  reported higher life satisfaction/QOL (Burleigh,
  1997 using Life Satisfaction Index-A Heinemann,
  1995 Seibert, 2002 using measures developed
  specifically for the study)

83
Findings (cont.)

• - Studies examining change in life satisfaction
  over time were mixed. Corrigan, 2001 and
  Tomberg, 2007 reported no significant change over
  time. Corrigan, 1998 reported significant change
  (decline year 1 followed by gradual increase up
  to year 5 using SWLS).
• - Using RAND-36 (health-related QOL), younger
  reported greater level of physical health.

84
Additional Findings

• Optimism increased over time (Tomberg, 2007)
• Psychological growth associated with time from
  injury (Powell, 2007). Late (i.e., those
  assessed at 10-12 years post injury) showed
  positive change in appreciation of life,
  spirituality, relating to others, etc. as
  compared to early (those assessed 1-3 years
  post injury).

85
Gaps Future Directions

• Asking the right question Age, aging with TBI,
  and association with life satisfaction/QOL as the
  primary aim/objective of study.
• Prospective cohort/longitudinal design.
• Duration and frequency of follow-up.
• Operationally define SWL/QOL and select
  appropriate measures.
• Account for changes that occur as one ages
  (without TBI)

86
2008 Galveston Brain Injury Conference
Emotional Functioning Aging with TBI

• Moody Gardens Convention Center
• Galveston Texas

87
Group 4 Subgroup Emotional Functioning

• Teresa Ashman, PhD
• Guido Mascialino, PhD
• Mount Sinai School of Medicine

This presentation is supported in part by NIDRR
grants H133B040033 and H133A070083, as well as
CDC grant 1R 49CE 001171 to the Department of
Rehabilitation Medicine, Mount Sinai School of
Medicine, New York City.
88
Emotional Functioning Aging with TBI

• Questions for the review
• How does emotional functioning change across the
  life span for people who have experienced a TBI?
• Are these changes associated with aging, not
  just recovery from TBI?
• Are there differences in emotional functioning
  for different age cohorts after TBI?

89
Abstract Retrieval Review

• Reviewed abstracts generated for Group IV which
  yielded three articles on emotional functioning.
  None of these met the criteria for the review.
• Independent search identified 412 abstracts
  derived from a PubMed search using variants of
  search terms for TBI and emotional functioning
• Reviewed 30 articles from the 412 abstracts

90
Abstract Retrieval Review (cont.)

• Each of the 30 papers was reviewed for relevance
  using the following criteria
• Age had to be documented in terms of age at
  injury, or current age and time since injury
• Emotional functioning had to be documented for
  each participant at a baseline assessment and at
  each follow-up assessment
• Only 6 met criteria for inclusion for in-depth
• review
• Only 4 were retained for the evidence tables
• after closer review and scoring

91
Evaluation

• STROBE procedures were used to evaluate the
  quality of these observational studies.
• Evidence Tables were created for the 4 studies
  assessed to met criteria, including information
  on

• Methods
• Measures
• Statistics
• Findings
• Limitations
• Class of Study
• AAN Grade
• STROBE Rating
• Subjective Rating

• Study Design
• Objectives
• Inclusion Criteria
• Exclusion Criteria
• Sample Size
• Severity of Injury
• Age (at assessment or injury)
• Gender

92
Emotional Functioning Articles

• Number of Articles 4
• Locations of Study
• Australia - 2
• Finland - 2

• AAN Classifications
• 4 Class III
• Study Designs
• 4 Cross-sectional

93
Aging with TBI Retrospective Follow-up
Demographics Koponen et al. (2002) Koponen et al. (2002)
Sample Size 60 58
Age at Assessment 60.8 10.3, 44-84 60.7 10.2, 44-84
Age at Injury 29.4 10.3, 10-53 29.4 10.3, 10-53
Time since Injury 31.4 4.4, 27-48 31.5 4.5, 27-48
Severity Mild to Severe Mild to Severe
Gender Female 33 Male 67 Female 32 Male 68
Measures Schedules for Clinical Assessment in Neuropsychiatry Interview Schedules for Clinical Assessment in Neuropsychiatry Interview
Findings Current dx 40 Lifetime dx 62 Current dx 40 Lifetime dx 62 n.s. dx presence/ location lesion (MRI)
94
Cross-sectional and Retrospective Follow-up
Baguley et al. (2006) Baguley et al. (2006) Baguley et al. (2006) Baguley et al. (2006)
Sample Size 228 Measures Overt Aggression Scale Beck Depression Inventory Satisfaction With Life Scale Alcohol Use Disorders Inventory
Age at Injury 34.3 14 Measures Overt Aggression Scale Beck Depression Inventory Satisfaction With Life Scale Alcohol Use Disorders Inventory
Time since Injury 6, 24 60 months Findings Prevalence of aggression n.s. between time points (approx 25) Longitudinal analysis suggests an overall tendency for within-subject aggression to improve over time. Depression was predictive of aggression.
Severity Mild to Severe Findings Prevalence of aggression n.s. between time points (approx 25) Longitudinal analysis suggests an overall tendency for within-subject aggression to improve over time. Depression was predictive of aggression.
Gender Female 22 Male 78 Findings Prevalence of aggression n.s. between time points (approx 25) Longitudinal analysis suggests an overall tendency for within-subject aggression to improve over time. Depression was predictive of aggression.
95
Cross-sectional
Anstey et al. (2004) Anstey et al. (2004) Anstey et al. (2004) Anstey et al. (2004)
Sample Size 428 TBI 6733 ND Measures Goldberg Anxiety Scale Goldberg Depression Scale SF-12 Psychiatric Symptoms Frequency Scale Positive Negative Affect Scales World Health Organization Alcohol Use Disorder Identification Test
Age at Injury 20-24 (n144 TBI, 2124 ND) 40-44 (n142 TBI, 2301 ND) 60-64 (n142 TBI, 2308 ND) Measures Goldberg Anxiety Scale Goldberg Depression Scale SF-12 Psychiatric Symptoms Frequency Scale Positive Negative Affect Scales World Health Organization Alcohol Use Disorder Identification Test
Time since Injury Mean entire sample 24 yrs Findings Less symptoms of depression, anxiety other negative affect in 2 older cohorts compared to youngest. All TBI cohorts reported more psychiatric symptoms than their age-matched peers
Severity Mild to Severe Findings Less symptoms of depression, anxiety other negative affect in 2 older cohorts compared to youngest. All TBI cohorts reported more psychiatric symptoms than their age-matched peers
Gender 20-24 TBI (F 28, M 72) 20-24 ND (F 54, M 46) 40-44 TBI (F 32, M 68) 40-44 ND (F 55, M 45) 60-64 TBI (F 26, M 74) 60-64 ND (F 50, M 50) Findings Less symptoms of depression, anxiety other negative affect in 2 older cohorts compared to youngest. All TBI cohorts reported more psychiatric symptoms than their age-matched peers
96
Results

• How does emotional functioning change across the
  life span for people who have experienced a TBI?
• Most studies report that emotional functioning
  improves over time
• Are these changes associated with aging, not just
  recovery from TBI?
• None of the current literature can answer this
  question.
• Are there differences in emotional functioning
  for different age cohorts after TBI?
• In the one study that compared cohorts, there was
  lower rates of negative affect in the middle age
  and older cohorts as compared to the younger
  cohort.
• However, rates for middle and older age groups
  with TBI was significantly greater than for their
  age-matched peers

97
Limitations

• Lack of Longitudinal Studies
• Lack of long-term longitudinal follow-up
• Most follow-up is limited to 6 months up to 2
  years
• Most follow-up studies do not have
  prospectively gathered baseline data
• Often these follow-up studies have no baseline
  data
• Samples
• Small sample size
• Lack of control group
• Sampling bias who enrolls and who stays in over
  time
• Variations in measures
• Few use clinical assessments
• Pre-injury prevalence usually missing

98
Recommendations for Future

• Prospective studies that compare distinct age
  groups
• Longer term prospective studies using within
  individual comparisons to measure change over
  time, not just group means
• Age-matched control samples for each cohort of
  inquiry
• Establishing measures for standard use within TBI
  (e.g., clinical assessment vs. self-report)
• Reporting pre-injury functioning

99
Thank you
100
2008 Galveston Brain Injury Conference

• Moody Gardens Convention Center
• Galveston Texas

101
Community Integration and Aging

• Timothy A. Reistetter, PhD, OTR
• East Carolina University
• University of Texas Medical Branch Galveston

102
Original Guiding Questions

• Is there a significant relationship between age
  and community integration for adults (over the
  age of 50) who have sustained a traumatic brain
  injury?
• Is there a difference between community
  integration at 2, 5 and 10 years after injury for
  those who sustain a TBI prior to age 30 compared
  to those who sustained a TBI at age 50 or later?

103
Abstract Retrieval Review

• 709 abstracts Initial Group IV searches
• Yielded 9 articles
• Independent search Identified additional 72
  abstracts
• 4 more articles, two use same data differently
• (Fleming et al, 1999 Doig et al, 2001)
• Total articles 13

104
Community Integration Articles

• Number of Studies - 13 studies
• AAN Classifications
• 12 AAN III
• 1 AAN IV
• Study Designs
• 10 cross-sectional
• 3 cohort study

• Location of Study
• 2 Australia
• 3 Canada
• 1 Demark
• 1 Israel
• 1 UK
• 5 US

105
Limitations

• Lack of clear groups (young vs. old) explain
  differences
• Lack of a control group
• cannot know if association between age or time
  since injury community integration is due to
  TBI or other changes
• Differences in measurement strategies between
  objective and subjective measures
• Limited information on the longitudinal effects
  of TBI
• Analysis differences between studies made
  comparisons of findings difficult.
• Correlations
• differences
• regression techniques
• cluster analysis

106
Instruments Employed

• Community Integration Questionnaire (CIQ)
• Craig Handicap Assessment and Reporting Technique
  (CHART)
• Community Integration Measure (CIM)
• Extended Activity of Daily Living Questionnaire
  (EADLQ)
• European Brain Injury Questionnaire (EBIQ)
• Health Activity Limitation Survey (HALS)
• Sydney Psychosocial Reintegration Scale (SPRS)

107
Revised Question One Findings Connection Between
Age and CI

• Younger individuals Higher social integration
• Burleigh et al (1998) CIQ
• Dawson et al (1995) HALS
• Fleming et al (1999) Doig et al (2001) CIQ
• Schmidt et al (1995) CIQ
• Whiteneck et al (2004) CHART
• Whiteneck et al (2006)
• Older individuals Higher social integration
• Winkler et al (2006) CIM, CIQ, SPRS
• No significant difference or relationship
• Hoofien et al (2002) EADL
• Teasdale et al (2005) EBIQ

108
Revised Question Two Time Since Injury and
Community Integration

• Five studies examine long term issues and
  community integration after TBI
• Significant improvement in home integration from
  years 3 to 5 post injury - Corrigan et al (1998)
  
• Longer time since injury - NOT a predictor of
  community integration - Devitt et al (2006)
• Significant increase in isolation at 10 years
  with traumatic cerebral lesions - Teasdale
  Engberg (2005)
• Increasing years since injury is connected with
  lower social participation greater perceived
  barriers - Whiteneck et al (2006)
• 10 years post injury relationship status
  predicted community integration In a
  relationship had lower community integration -
  Wood Rutherford (2006)

109
Considering Age and Community Integration

• Younger individuals had higher communality
  integration
• Instruments objective
• Design consistent with ICF or disability based
  measures.
• When older individuals did better
• One instrument was subjective (CIM)
• One instrument measured change (SPRS)
• One measure was objective (CIQ)
• When there was no relation
• Measuring the quality of relationships
• Select items from a population survey

110
Considering Time Since Injury and Community
Integration

• Results mixed
• Some studies Steady improvement in one or more
  area of community integration
• Some studies No relation
• Others Declines in social integration
• Two studies linking changes to additional areas
• Relationships
• Perceived barriers

111
Additional Findings

• Several Studies attempted to predict future
  community integration scores using age or time in
  the equation
• Three studies indicate that age DID NOT
  contribute to prediction of community integration
• Devitt et al (2006)
• Hoofien et al (2002)
• Wood Rutterford (2006)
• Age alone predicted community integration
• Fleming et al (1999)
• Age with PTA predicted community integration
• Winkler et al (2006)

112
Future Considerations Questions

• Need for prospective studies with typical older
  adult controls
• Considerations of measurement approaches with
  older adults
• Objective measures
• Subjective measures
• Longitudinal studies are needed
• Researcher looking at barriers and supports
• Attitudinal
• Environmental
• Community mobility
• Relationships

113
Post-TBI Vocational Status and Aging

• Margaret Brown, Ph.D.
• Mount Sinai School of Medicine

This presentation is supported in part by NIDRR
grants H133B040033 and H133A070083, as well as
CDC grant 1R 49CE 001171 to the Department of
Rehabilitation Medicine, Mount Sinai School of
Medicine, New York City.
114
Question Nos. 1a and 1b
1a.How do the vocational changes associated with
normal aging across the life span differ for
people who have experienced a TBI, particularly
within the prime productive years (18-65)? 1b.How
do we know that these changes are associated with
aging, not just recovery from TBI?
115
Question Nos. 1a and 1b

• Only one study addressed 1a, and none addressed
  1b
• McLeod et al., 2004 focuses on retention in the
  British military, comparing soldiers with TBI or
  orthopedic injuries and healthy soldiers, over
  six years

116
Question Nos. 1a and 1b

• Problems
• Narrow focus military
• Narrow age range approximately 17-39
• Therefore, provides limited evidence on aging
  after TBI and how that affects vocational
  functioning

117
How to Proceed?

• Does the person experience TBI differently across
  the productive years in terms of vocational
  outcome?
• Several reviews focus on how age affects
  vocational status
• Results of reviews (1) being older at TOI is
  problematic, OR (2) age has no effect on return
  to productivity

118
Question Nos. 2 and 3

• Does age predict return to pre-injury vocational
  status? (ie, pre-post analyses)
• Does age predict achieving a productive vs
  non-productive status post injury? (ie, post
  injury only)

119
Procedure Followed

• Reviewed all abstracts generated in the Texas
  search for Groups 1-5. Then reviewed hundreds
  more, based on my search of PubMed, using as
  search terms variants on TBI and variants on
  employment.
• Judged the possible relevance of many hundreds of
  studies using the following preliminary criteria
• Relationship between age and vocational status is
  probably analyzed, whether it is the primary
  focus or not
• Excluded studies that clearly constituted a
  follow-up of people injured in childhood

120
Procedure Followed

• The full paper was obtained for the abstracts
  that passed muster, plus additional relevant
  publications cited in the review articles. Each
  of 106 papers was reviewed for relevance using
  the following criteria
• Confirmation of preliminary relevance review
• No mixed etiologies, unless data from the TBI
  group was separately analyzed
• Age had to be documented in terms of age at TOI,
  current age or time since injury (as a proxy for
  age)
• For Question 2, vocational status had to be
  documented for each participant at TOI and at
  each point of follow-up

121
Procedure Followed

• 46 studies were judged relevant. Each was
  evaluated for quality of evidence bearing on the
  age x vocational analysis only, using the
  following criteria (numbers refer to codes in
  evidence tables
• 1 Vocational status variable is objective
  (neutral rating) vs a subjective judgment (eg,
  rating the persons voc. potential) (-)
• 2 Sample size gt 100 () vs lt100 (-)
• 3 Mean age 30-39 () vs lt30 or gt39 (-)
• 4 Range restricted eg, 15-35 (-) vs broad
  eg, 16-60 ()
• 5 Transition problems I.e., unsuccessfully
  addressing the problem of inappropriately
  classifying a normal change in vocational
  status as a success post TBI or a failure due
  to TBI eg, retiring at age 65 being classified
  as a poor outcome, when it may have had nothing
  to do with the injury -- no problem () vs
  potential or actual problem (-)

122
Procedure Followed

• Evaluation criteria (continued)
• 6 Severity of injury mild, moderate OR severe
  () vs moderate-severe OR all severities (-)
• 7 Data source TBI registries or TBI MS (),
  military or all graduates of an ER visit (-),
  all others (neutral)
• 8 Follow-up No reference is made to FU sample
  being compared to sample from which it was drawn
  (-), analysis of FU sample was done but
  differences not clear (neutral), description of
  FU sample indicated no difference or minor
  differences compared to full sample ()
• 9 Time of FU lt 5yrs (-) vs 5 yrs ()

123
Procedure Followed

• Evaluation criteria (continued)
• 10 Number of points of FU at which vocational
  status is assessed One (-) vs two or more --
  cross-sectional or longitudinal ()
• 11 Appropriateness of analysis analysis by
  logistic regression, by age group or other
  methods to avoid weakness of correlational
  approaches (), analysis by outcome group
  (neutral), correlational (-)
• 12 Purpose of study primary focus on age x
  vocational status (), age is one predictor of
  several (neutral), age is solely a correlate (eg,
  in a regression analysis) (-)

124
Procedure Followed

• Rated each study based on Criteria 1-12, focusing
  solely on the age x vocational analysis only
  6-pt scale, where 5 indicates most useful
  findings in addressing Questions 2 and 3, and 0
  indicates the study was not at all useful, based
  on criteria such as restricted age range,
  specialized sample (eg, military), etc. 36
  studies rated 1-5 10 studies were dropped.
• Selected best studies from the 36 acceptable,
  based on the following criteria
• An overall rating of 3 or higher
• Transition problems were avoided ( on Criterion
  5)
• No sole focus on time since injury (as age
  proxy)

125
Procedure Followed

• 13 studies passed muster
• Asikainen, Kaste Sarna, 1996, 1998
• Bogner, Corrigan, Mysiw, Clinchot Fugate, 2003
• Corrigan, Lineberry, Kormaroff, Langlois,
  Selassie Wood, 2007
• Dawson, Schwartz, Winocur Stuss, 2007
• Greenspan, Wrigley, Kresnow, Branche-Dorsey
  Fine, 1996
• Keyser-Marcus, Bricout, Wehman, et a., 2002
• Kreutzer, Marwitz, Walker, et al. 2003
• Sherer, Yablon, Nakase-Richardson Nick, 2008
• Skeel, Bounds, Johnstone, Lloyd Harns, 2003
• Teasdale Engberg, Brain Injury, 19, 1041-1048,
  2005
• Tennant, MacDermott Neary, 1995
• Wood Rutterford, 2006

126
Procedure Followed

1. Results of looking at all 13 Same conclusions as
   in prior reviews Some showed no effect of age on
   outcome others found that younger did better
   than older in achieving post-TBI productivity.
2. In line with a suggestion by Ruff et al. (1993)
   that it is easier to return to school than to
   work, I formulated the hypothesis that if the
   vocational variable selected in a study included
   school as a good outcome, the results would
   indicate that younger people did better but if
   the vocational outcome selected focused solely on
   achieving or returning to employment, the results
   would suggest that age had no relationship with
   vocational status at FU.

127
Conclusions

• Results from the table included in handout
  indicate that the hypothesis held for 10 of 13
  studies.
• Where the hypothesis missed, more complex
  vocational status measures had been used (rather
  than Yes/No) or more complex analyses had been
  implemented
• Using more complex outcome measures, both the
  Dawson and the Kreutzer studies found similar
  results younger people achieve a productivity
  status with problems, while older people achieve
  a productivity status with no problems or fail to
  achieve a productive status
• The Corrigan study revealed very complex
  findings productive hours decreased by age
  group, but mostly for women for the latter, as
  age groups got older, women were more likely to
  be employed than in younger age groups
• Overall conclusions
  
  ? No age relationship when
  employment is the focus
• ? Younger do better if productivity, including
  school, is the outcome measure selected

128
The Consequences of TBI Occurring to the Elderly
A Systematic Review

• Marcel Dijkers Ph.D.
• Joshua Cantor Ph.D.
• Mary Hibbard Ph.D.
• Stacy Belkonen PhD
• Adam Warshowsky PhD
• David Layman PhD
• (group 5)

129
Source

• Interim projections consistent with Census 2000,
  Table 2a. Projected Population of the United
  States, by Age and Sex 2000 to 2050 (released
  March 2004)
• http//www.census.gov/ipc/www/usinterimproj/natpro
  jtab02a.xls

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134
Source

• Langlois JA, Rutland-Brown W, Thomas KE.
  Traumatic Brain Injury in the United States
  Emergency Department Visits, Hospitalizations,
  and Deaths. Atlanta (GA) Centers for Disease
  Control and Prevention, National Center for
  Injury Prevention and Control 2006.

135
Average annual TBI-related rates for ED visits,
hospitalizations, and deaths, by age group and
external cause, US, 19952001
136
Motor vehicle traffic 9
Unknown 21
Falls 52
Other 17
Assault 1
137
Shameless Plug

• Help Seniors Live Better, Longer Prevent Brain
  Injury CDC initiative to raise awareness among
  children and other caregivers of older adults
  about ways to prevent, recognize, and respond to
  TBI in adults 75 and older
• CDC has developed easy-to-use English- and
  Spanish-language materials for older adults and
  their caregivers
• Questionand-answer format to provide information
  that older adults and their caregivers can use to
  take an active role in preventing, recognizing,
  and responding to TBI

138
Average annual TBI-related rates for ED-visits,
hospitalizations, and deaths, by age group,
United States, 19952001
139
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143
The Aging Brain Anatomy and Functioning

• Dura becomes more adherent to skull
• Bridging veins more exposed
• Decreasing synaptic density and neural plasticity
• Decreased production of nerve growth factor
• Decreased cerebral perfusion
• decreased cognitive capacity
• increased risk for TBI