Health and Aging after TBI: Current research and future directions

Size: px

Start display at page:

Download "Health and Aging after TBI: Current research and future directions"

Brent Gray
5 years ago
Views:

1 Health and Aging after TBI: Current research and future directions Kristen Dams-O Connor, PhD Associate Professor Co-Director, Brain Injury Research Center Research Director, Mount Sinai Injury Control Research Center Icahn School of Medicine at Mount Sinai Department of Rehabilitation Medicine New York, NY

2 Dams-O Connor: Disclosures Grant #1K01HD A1 National Institutes of Health (NIH)/National Institute of Child Health and Development (NICHD) Grant # 1 U01 NS National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) Grant #H133B National Institute on Disability and Rehabilitation Research (NIDRR) Grant #1R49CE Centers for Disease Control and Prevention (CDC)

(and others) with a history of repetitive brain trauma, including

4 Chronic Traumatic Encephalopathy: Chronic Traumatic Encephalopathy (CTE) is a progressive degenerative disease of the brain found in athletes (and others) with a history of repetitive brain trauma, including symptomatic concussions as well as asymptomatic subconcussive hits to the head. 4

5 Mount Sinai / Presentation Slide / December 5,

6 CHRONIC TRAUMATIC ENCEPHALOPATHY: REMAINING QUESTIONS Has CTE ever been found in the brain of someone with NO history of head trauma? Bieniek 2015: CTE only detected in individuals with contact sport participation Can someone get CTE after 1 concussion or 1 mod-sev TBI? McKee vs. Stewart Given similar head trauma exposure, are there factors that make certain people more vulnerable to developing CTE? Are there factors that make certain people more resilient to developing CTE? What is the prevalence of CTE in the population? How does CTE differ from the pathology associated with TBI? Can CTE be diagnosed during life? How does the clinical presentation of CTE differ from single TBI?

8 Post-TBI Neurodegeneration

9 TBI and Dementia: Inconsistent findings Type of Study Primary Author Year TBI Dementia APOE 4 Interaction Prospective Mehta 1999 No No Prospective Katzman 1989 No N/A Retrospective Williams 1991 No N/A Epidemiological Schofield 1997 Yes N/A Case Control O Meara 1997 Yes No Prospective Plassman 2000 Yes Inconclusive Retrospective Mayeux 1995 Yes Yes IOM IOM 2008 YES N/A Retrospective Barnes 2014 Yes No Retrospective Gardner 2014 Yes No Retrospective Lee 2013 Yes No Case Control Wang 2012 Yes No Prospective Abner 2014 Conditional No Prospective Nordstrom 2014 Conditional No Prospective Sundstrom 2007 Conditional No Case Control Sayed 2013 Conditional No Prospective Helmes 2011 No No Prospective Dams-O Connor 2013 No No

12 Clinical presentation of dementia after TBI National Alzheimer s Coordinating Center (NACC) - Uniform Data set (UDS) - 29 NIA-funded ADRCs Study 1 (Sayed et al., 2013) Cases Any dementia + history of TBI that resulted in chronic deficits (n=62) Controls Matched sample of individuals with Probable AD (NINDS-ADRDA) with no TBI (n=122) Study 2 (Dams-O Connor et al., 2013) Cases Any dementia + history of TBI that resulted in LOC or chronic deficits (n=332) Controls Matched sample of individuals with allcause dementia with no TBI (n=664) 12

13 Clinical Phenotype of Dementia after TBI (NACC) Sayed, Culver, Dams-O Connor, Hammond, Diaz-Arrastia (2013). Journal of Neurotrauma. 13

14 Clinical Phenotype of Dementia after TBI (NACC) Dams-O Connor, Spielman, Hammond, Sayed, Culver, Diaz-Arrastia (2013). Neurorehabilitation. 14

15 15

16 Pooled results Table 4. Adjusted associations between traumatic brain injury with loss of consciousness at any age and neuropathological findings from analysis of pooled data from all three studies* Outcome TBI with LOC < 1 hr (n=176) P RR (95% CI) value TBI with LOC 1 hr (n=37) P RR (95% CI) value Braak Stage 5 or (0.79, 1.33) (0.58, 1.65) 0.93 CERAD intermediate or frequent 1.01 (0.89, 1.15) (0.79, 1.27) 0.98 Amyloid angiopathy 1.08 (0.99, 1.19) ( ) 0.28 Cystic infarcts 0.90 (0.73, 1.12) (0.84, 1.62) 0.34 Hippocampal sclerosis 0.91 (0.51, 1.61) (0.62, 2.89) 0.45 Cerebral Microinfarcts Any 0.94 (0.76, 1.15) (0.85, 1.66) 0.32 Any cortical 0.90 (0.68, 1.19) (1.06, 2.35) Any deep 1.02 (0.78, 1.33) (0.83, 2.05) 0.25 Lewy bodies Any 1.00 (0.73, 1.37) (0.87, 2.39) 0.16 Substantia Nigra / Locus Ceruleus 1.04 (0.74, 1.45) (0.86, 2.55) 0.16 Frontal or temporal cortex 1.59 (1.06, 2.39) (0.82, 3.77) 0.15 Amygdala / limbic 1.22 (0.88, 1.69) (0.59, 2.27) 0.67

17 Exposure younger than Age 25 results Table 5. Adjusted associations between traumatic brain injury with loss of consciousness younger than age 25 and neuropathological findings from joint analysis of data from all three studies* TBI with LOC < 1 hr (n=67) TBI with LOC 1 hr (n=19) Outcome RR (95% CI) P value RR (95% CI) P value Braak Stage 5 or (0.66, 1.52) (0.50, 2.14) 0.94 CERAD intermediate or frequent 1.09 (0.89, 1.32) (0.62, 1.35) 0.65 Amyloid angiopathy 1.07 (0.89, 1.29) (0.62, 1.20) 0.38 Cystic infarcts 0.83 (0.58, 1.21) (0.45, 1.60) 0.60 Hippocampal sclerosis 1.42 (0.68, 2.97) (0.37, 4.76) 0.66 Cerebral Microinfarcts Any 1.04 (0.78, 1.40) (1.19, 2.32) Any cortical 1.10 (0.77, 1.57) (0.71, 2.35) 0.41 Any deep 1.06 (0.72, 1.58) (0.64, 2.40) 0.53 Lewy bodies Any 0.95 (0.56, 1.62) (1.03, 3.35) Substantia Nigra or Locus Ceruleus 1.03 (0.59, 1.80) (0.94, 3.60) 0.08 Frontal or temporal cortex 1.53 (0.77, 3.03) (1.02, 6.24) Amygdala / limbic 1.09 (0.60, 1.98) (0.86, 3.64) 0.12

18 ACT, ROS, MAP 45,000 py follow-up >1,500 ACD cases >1,300 AD cases 1,586 autopsies high Braak stage High CERAD levels 18

Heterogeneity of Change in GOS-E score 2-15 years post TBI Corrigan & Hammond, 2013.

19 Heterogeneity of Change in GOS-E score 2-15 years post TBI Corrigan & Hammond, Traumatic Brain Injury as a chronic health condition. Archives of PM&R; 94:

20 Risk Factors for Dementia Age: Risk of AD doubles every 5 years over age 65. Genetics: ApoE ɛ4 Health: Vascular disease, high cholesterol, high blood pressure, Type 2 diabetes, heart disease, obesity Lifestyle: exercise, diet, cognitive activity Head trauma 20 Mayeux 1995 NEUROLOGY

21 TBI as a Chronic Health Condition

22 TBI as a Chronic Disease World Health Organization: A chronic disease is: Permanent Caused by non-reversible pathological alterations Requires special training of the patient for rehabilitation May require a long period of observation, supervision, or care TBI is associated with: Long-term mortality and reduced life expectancy Increased incidence of: Seizures Sleep disorders Neurodegenerative diseases Neuroendocrine dysregulation Psychiatric diseases Sexual dysfunction Bladder and bowel incontinence Systematic metabolic dysregulation TBI [is] the beginning of an ongoing, perhaps lifelong process, that impacts multiple organ systems and may be disease causative and accelerative (Masel & DeWitt, 2000) 22

Guidelines for the Rehabilitation and Chronic Disease Management of

rehabilitation should adult patients with moderate to severe traumatic

Behavioral, Cognitive, Medical, Functional, Participation/ Vocational

23 Guidelines for the Rehabilitation and Chronic Disease Management of Adults with Moderate to Severe Traumatic Brain Injury How much rehabilitation should adult patients with moderate to severe traumatic brain injury (TBI) receive, in what setting, and at what time? Behavioral, Cognitive, Medical, Functional, Participation/ Vocational Panels What are the most common health conditions experienced by longterm survivors of moderate-severe TBI?

24 BIAA Medical Guidelines Panel: Preliminary Results Condition Prevalence (per 100) Incidence (per 100) Pain/Arthritis Dysosmia/Anosmia Incontinence/Urinary disturbance Neuroendocrine Dysfunction* Fatigue and/or sleep disturbance** Ocular/visual disorder Headaches Diabetes Posttraumatic Seizures/Epilepsy BPPV/vestibular loss Digestive Problems 15 Hypertension 9-11 Heart Problems 11 Breathing Problems 8 *HPA Axis = highest prev **Sleep has changed: 50/63, Prev = 79 (Hoy=9, Global=2). 24

25 Prevalence/Incidence of Health Conditions: Mod-Sev TBI vs. Healthy Controls (Initial Results) Condition N of Sample N of Cases Prev Incid Seizure/Epilepsy TBI (22)** 2s-5p Control (8)** <1 Urinary Incontinence TBI (12)* 6 Control (0)* 2 New Onset Stroke TBI Control Sleep changes TBI Control Fatigue TBI Control *Parcell, 2006 (n=63 TBI, 63 Controls **Hwang 2008, n=475 TBI, 429 Homeless persons 25

26 Chronology of Comorbid Conditions (Holcomb et al. 2012) 26

27 Health in Adults with TBI: Sneak peak 85% of the sample (n=86) report 3 or more chronic medical conditions (avg: 6 conditions, range 3-14) Health Condition Frequency Chronic Pain 29 Anxiety/Depression/Emotional disorder 28 Heart trouble 27 Hypertension 26 Urinary or bladder problems 21 Arthritis, bone or joint disease 20 Sciatica or recurring backache 19 Cancer 19 Diabetes or high blood sugar 14 Chronic sleep problems 10 Mount Sinai / Presentation Slide / December 5,

28 Do health problems precede TBI? Adult Changes in Thought study Mount Sinai BIRU

29 Predictors of incident TBI in older adults Older people tend to have poor functional outcomes after TBI, and many experience deterioration in overall health after TBI. Falls are the most common cause of TBI in older adults. Older adults with mtbi have higher medical care costs in the year before injury relative to matched controls (Unpublished data, September 2011). Individuals presenting to hospital with mtbi are more likely to have health problems relative to individuals with other injuries (McMillan et al., 2014).

31 Premature Mortality Following TBI

32 TBI and Mortality Moderate-severe TBI is associated with reduced life expectancy of 7 years (Harrison-Felix et al., 2004) Individuals with mod/sev TBI who survive 1 year are more likely to die of: (Harrison-Felix et al., 2006) Seizures (37x) - Septicemia (12x) - Pneumonia (4x) Respiratory/Digestive/External Injury (3x) Individuals with TBI who survive 1 year after rehab are more likely to die of: (Harrison-Felix et al., 2009) Aspiration Pneumonia (49x) - Seizures (22x) Pneumonia (4x) - Suicide (3x) Digestive Conditions (2.5x) 32

33 Mount Sinai / Presentation Slide / December 5,

34 Harrison-Felix, Kolakowsky-Hayner, Hammond, Wang, Englander, Dams-O Connor, Krieder, Novack, Diaz-Arrastia,

35 Functional Trajectories of Survivors vs. Nonsurvivors: A TBI Model Systems Study Age at 1 st GOS-E: 20 Dams-OʼConnor K, Pretz C, Billah T, Hammond FM, Harrison-Felix C. Global Outcome Trajectories After TBI Among Survivors and Nonsurvivors. J Head Trauma Rehabil Jul-Aug;30(4):E1-10.

36 Functional Trajectories of Survivors vs. Nonsurvivors: A TBI Model Systems Study Age at 1 st GOS-E: 60 Dams-OʼConnor K, Pretz C, Billah T, Hammond FM, Harrison-Felix C. Global Outcome Trajectories After TBI Among Survivors and Nonsurvivors. J Head Trauma Rehabil Jul-Aug;30(4):E1-10.

37 TBI and Mortality: Current projects Health and Functioning in Older Adults with TBI Dams-O Connor et al: CDC Injury Control Research Center (BIRC-MS) Pre-Injury Health Post-Injury Health Verbal autopsy Trajectory of health before death Postmortem Verbal Autopsy in the TBI Model Systems Mount Sinai / Presentation Slide / December 5,

39 Prevention in TBI Primary prevention aims to prevent disease or injury before it ever occurs. This is done by preventing exposures to hazards that cause disease or injury, altering unhealthy or unsafe behaviors that can lead to disease or injury, and increasing resistance to disease or injury should exposure occur. Secondary prevention aims to reduce the impact of a disease or injury that has already occurred. This is done by detecting and treating disease or injury as soon as possible to halt or slow its progress, encouraging personal strategies to prevent re-injury or recurrence, and implementing programs to return people to their original health and function to prevent long-term problems. Tertiary prevention aims to soften the impact of an ongoing illness or injury that has lasting effects. This is done by helping people manage long-term, oftencomplex health problems and injuries (e.g. chronic diseases, permanent impairments) in order to improve as much as possible their ability to function, their quality of life and their life expectancy.

Health and Neurodegeneration after TBI: A Continuum of Aging

Health and Neurodegeneration after TBI: A Continuum of Aging Brain Injury Alliance of New Jersey Professional Symposium May 18, 2017 Kristen Dams-O Connor, PhD Associate Professor Director, Brain Injury