Supplementary Appendix

Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Schneider ALC, Wang D, Ling G, Gottesman RF, Selvin E. Prevalence of self-reported head injury in the United States. N Engl J Med 2018;379:1176-8. DOI: 10.1056/NEJMc1808550

1 Table of Contents Page Number Supplementary Methods 2 Supplementary Table 1. Prevalence of and Associations of Additional Risk Factors with Prior Head Injury with Loss of Consciousness, U.S. Adults Aged 40 Years or Older, Overall and by Categories, NHANES 2011-2014 6 Supplementary Table 2. Model Diagnostics 8 Supplementary Table 3. Number of Participants with Missing Data that was Imputed, NHANES 2011-2014 Supplementary Figure 1. Percent (95% CI) and Numbers of U.S. Adults Aged 40 Years or Older with Prior Head Injury, According to Sex and Race/Ethnicity, NHANES 2011-2014 10 11 References 12

2 Supplementary Methods Study Population The National Health and Nutrition Examination Survey (NHANES) is a series of crosssectional surveys conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. NHANES participants were selected using a stratified multistage probability sampling design of the noninstitutionalized civilian population of the U.S. For the present study, data from the 2011-2012 and 2013-2014 survey cycles were used 1,2, as head injury was assessed during these surveys. The 2011-2012 and 2013-2014 cycles oversampled Hispanics, non-hispanic blacks, non-hispanic Asians, older adults, and low income persons in order to provide more reliable estimates for these subpopulations. Detailed in-person interviews, physical examinations, and blood samples were obtained from 9,338 individuals in 2011-2012 and from 9,813 individuals in 2013-2014. Information on head injury was obtained from all participants aged ³40 years (3,603 individuals in 2011-2012 and 3,815 individuals in 2013-2014). Of the 7,418 eligible individuals aged ³40 years, 19 were excluded due to missing head injury data, leaving a total of 7,399 included in the present analyses. The NHANES protocol was approved by the research ethics review board and written informed consent was obtained from all participants 3. Head Injury with Loss of Consciousness Definition Head injury with loss of consciousness was self-reported based on the question, Have you ever had loss of consciousness because of a head injury? This question was a part of the taste and smell questionnaire (https://wwwn.cdc.gov/nchs/nhanes/2013-2014/csq_h.htm#csq240), which was administered to all participants aged ³40 years and questions on taste and smell were previously validated. Although the head injury question was

3 not specifically included in this validation study, other prior studies have shown self-reported head injury to be valid when compared to medical chart review and reliable over time 5-7. Other Variables of Interest Information on age, sex, race/ethnicity, military service, education, ratio of family income to poverty, occupation, physical activity, sleep, alcohol consumption, and tobacco use were obtained based on self-report during the interview part of the surveys. In our tables, we categorized age as 40-49 years, 50-59 years, 60-69 years and 70+ years. In the logistic regression models, we included age as a continuous variable. Race/ethnicity was categorized as non- Hispanic white, non-hispanic black, Mexican-American, and other. We categorized education as less than high school, high school or equivalent, and some college or above. The family income to poverty ratio is the ratio of the participant s self-reported annual family income to the federal poverty threshold specific for the year of the interview 8. In these analyses, the family income to poverty ratio was categorized as 350%+, 130-349%, and <130%. We categorized current occupation as employed by private company/business, employed by government, self-employed, retired, and unemployed/work without pay. We dichotomized physical activity as yes or no moderate/vigorous work or recreational activity. We categorized the number of hours of sleep per night as <6 hours, 6-8 hours, and >8 hours. Alcohol consumption was categorized as never, ever non-heavy drinking, ever heavy drinking (with heavy drinking defined by the question, Have you ever had 4 or 5 drinks every day? ). Smoking status was categorized as never, former, and current. During the in-person interview, participants were also asked about medical conditions, including sleep disorders, coronary heart disease, prior myocardial infarction, stroke, diabetes, and hypertension. Participants were also asked to report on their general health, which we

4 categorized as excellent/very good/good or fair/poor. Depression was assessed using the Patient Health Questionnaire (PHQ-9); we used a cut-point of 10 or more points to define depression 9. Detailed information on the data collection for the in-person interviews, physical examinations, and blood samples obtained in NHANES are documented elsewhere (2011-2012 1 and 2013-2014 2 ). Statistical Analyses We performed all statistical analyses incorporating appropriate survey weights to account for the complex NHANES sampling design and to make the estimates reported here nationally representative of the noninstitutionalized civilian population of adults aged 40 years and over in the U.S. in 2011-2014. Standard errors were obtained using the Taylor series (linearization) method in accordance with analysis recommendations from the National Center for Health Statistics 10. We applied prevalence estimates to the 2013 American Community Survey Annual Public Use Microdata Sample to obtain estimates of the number of individuals with prior head injury in the U.S. in the year 2013 11. We used logistic regression models adjusted for a priori hypothesized confounders to quantify the associations between risk factors and past head injury. All associations are presented as odds ratios with corresponding 95% confidence intervals. Model 1 was adjusted for age (continuous), sex, and race/ethnicity. Model 2 was adjusted for all variables in Model 1 plus education, ratio of family income to poverty, physical activity, alcohol consumption, and military status. Model diagnostics including goodness-of-fit P-values, tolerance, variance inflation factors (VIF), leverage, and misspecification Linktest P-values, and are shown in Supplementary Table 2.

5 Multiple imputation by chained equations methods 12 with 25 imputations was used to impute missing risk factor data. The number of participants with missing data that was imputed is shown for each risk factor variable in Supplementary Table 3. Stata SE Version 15 (StataCorp, College Station, Texas) was used to perform analyses.

6 Supplementary Table 1. Prevalence of and Associations of Additional Risk Factors with Prior Head Injury with Loss of Consciousness, U.S. Adults Aged 40 Years or Older, Overall and by Categories, NHANES 2011-2014 Risk Factor Military veteran status Moderate/ vigorous physical activity Smoking status Current occupation diagnosed coronary heart disease diagnosed diabetes diagnosed hypertension Risk Factor Category Prevalence of Head Injury, % (SE) Odds Ratios (95% Confidence Interval) Model 1* Model 2 No 15.2 (0.81) 1 (reference) 1 (reference) Yes 19.5 (1.76) 1.08 (0.82-1.41) 1.00 (0.75-1.32) No 13.6 (0.94) 1 (reference) 1 (reference) Yes 16.9 (1.00) 1.12 (0.93-1.36) 1.14 (0.94-1.38) Never smoker 13.0 (0.92) 1 (reference) 1 (reference) Former smoker 18.2 (1.23) 1.39 (1.11-1.73) 1.30 (1.03-1.64) Current smoker 19.6 (1.48) 1.46 (1.19-1.80) 1.35 (1.08-1.69) Employee of private company/business 15.1 (1.19) 1 (reference) 1 (reference) Employee of government 15.0 (2.24) 1.06 (0.72-1.56) 1.05 (0.70-1.56) Self-employed 17.5 (2.59) 1.08 (0.73-1.59) 1.00 (0.68-1.49) Retired 14.0 (1.02) 1.26 (0.94-1.69) 1.24 (0.91-1.68) Unemployed/work without pay 18.9 (1.80) 1.62 (1.22-2.17) 1.57 (1.17-2.11) No 15.4 (0.78) 1 (reference) 1 (reference) Yes 19.5 (1.92) 1.35 (1.02-1.79) 1.33 (0.97-1.82) No 15.7 (0.82) 1 (reference) 1 (reference) Yes 15.9 (1.48) 1.15 (0.91-1.45) 1.14 (0.89-1.46) No 16.1 (1.02) 1 (reference) 1 (reference) Yes 15.3 (1.00) 1.05 (0.86-1.28) 1.01 (0.82-1.24)

7 Self-reported health status Excellent/very good/good 15.0 (0.86) 1 (reference) 1 (reference) Fair/poor 18.5 (1.28) 1.53 (1.24-1.88) 1.55 (1.24-1.94) *Model 1: Adjusted for age (continuous), sex, and race/ethnicity. Model 2: Adjusted for all variables in Model 1 plus education, family income to poverty ratio, physical activity, alcohol consumption, and military status.

8 Supplementary Table 2. Model diagnostics. Model includes risk factor of interest and age (continuous), sex, race/ethnicity, education, ratio of family income to poverty, physical activity, alcohol consumption, and military status (Model 2). Variable Goodnessof-fit P- value Tolerance VIF Mean (SD) Leverage Median (Range) Misspecification Linktest P-value Age 0.99 0.89 1.12 0.007 (0.007) (0.001-0.049) 0.47 Sex 0.44 0.81 1.23 (0.006) 0.88 Race/ethnicity 0.44 0.91 1.10 (0.006) 0.88 Military veteran status 0.44 0.81 1.23 (0.006) 0.88 Education 0.44 0.76 1.31 (0.006) 0.88 Family income to poverty ratio 0.44 0.77 1.30 (0.006) 0.88 Current occupation 0.94 0.78 1.28 () (0.001-0.048) 0.59 Moderate/vigorous work or recreational activity 0.44 0.93 1.07 (0.006) 0.88 Sleep time, hours 0.96 0.97 1.03 () (0.001-0.036) 0.33 diagnosed sleep disorder 0.42 0.98 1.02 () (0.001-0.038) 0.94 diagnosed coronary heart disease 0.91 0.92 1.08 () (0.001-0.032) 0.75

9 diagnosed stroke 0.63 0.95 1.05 () (0.001-0.041) 0.95 diagnosed diabetes 0.39 0.95 1.05 () 0.71 diagnosed hypertension 0.63 0.89 1.13 () 0.003 (0.001-0.032) 0.79 Alcohol consumption 0.44 0.91 1.10 (0.006) 0.88 Smoking status 0.23 0.83 1.20 (0.003) 0.003 (0.001-0.026) 0.73 Depression 0.42 0.93 1.09 () (0.001-0.045) 0.86 Self-reported health status 0.48 0.86 1.16 () 0.003 (0.001-0.043) 0.96 Abbreviations: VIF, variance inflation factor

10 Supplementary Table 3. Number of Participants with Missing Data that was Imputed, NHANES 2011-2014 Variable Number with nonmissing data Number with imputed data Head injury status 7,399 0 Age 7,399 0 Sex 7,399 0 Race/ethnicity 7,399 0 Military veteran status 7,399 0 Education 7,392 7 Family income to poverty ratio 6,734 665 Current occupation 7,380 19 Moderate/vigorous work or recreational activity 7,397 2 Sleep time 7,382 17 diagnosed sleep disorder 7,384 15 diagnosed coronary heart disease 7,374 25 diagnosed stroke 7,391 8 diagnosed diabetes 7,394 5 diagnosed hypertension 7,391 8 Alcohol consumption 6,432 967 Smoking status 7,392 7 Depression 6,412 987 Self-reported health status 6,485 914

Supplementary Figure 1. Percent (95% CI) and Numbers of U.S. Adults Aged 40 Years or Older with Prior Head Injury, According to Sex and Race/Ethnicity, NHANES 2011-2014. Vertical bars are 95% confidence intervals for the prevalence estimate. Estimate of the number of persons in each category (in millions) is indicated above each bar. 11

12 References 1. National Health and Nutrition Examination Survey, 2011-2012. (Accessed April 17, 2018, at https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?beginyear=2011.) 2. National Health and Nutrition Examination Survey, 2013-2014. (Accessed April 17, 2018, at https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?beginyear=2013.) 3. National Health and Nutrition Examination Survey Research Ethics Review Board Approval. (Accessed April 17, 2018, at https://www.cdc.gov/nchs/nhanes/irba98.htm.) 4. Rawal S, Hoffman HJ, Honda M, Huedo-Medin TB, Duffy VB. The Taste and Smell Protocol in the 2011-2014 US National Health and Nutrition Examination Survey (NHANES): Test-Retest Reliability and Validity Testing. Chemosens Percept 2015;8:138-48. 5. Wilmoth K, LoBue C, Clem MA, et al. Consistency of traumatic brain injury reporting in older adults with and without cognitive impairment. Clin Neuropsychol 2017:1-6. 6. Corrigan JD, Bogner J. Initial reliability and validity of the Ohio State University TBI Identification Method. J Head Trauma Rehabil 2007;22:318-29. 7. Schofield P, Butler T, Hollis S, D'Este C. Are prisoners reliable survey respondents? A validation of self-reported traumatic brain injury (TBI) against hospital medical records. Brain Inj 2011;25:74-82. 8. Gutierrez OM, Isakova T, Enfield G, Wolf M. Impact of poverty on serum phosphate concentrations in the Third National Health and Nutrition Examination Survey. J Ren Nutr 2011;21:140-8. 9. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001;16:606-13.

13 10. National Health and Nutrition Examination Survey Methods and Analytic Guidelines. (Accessed April 17, 2018, at https://wwwn.cdc.gov/nchs/nhanes/analyticguidelines.aspx.) 11. National Health and Nutrition Examination Survey Response Rates and Population Totals. (Accessed April 17, 2018, at https://wwwn.cdc.gov/nchs/nhanes/responserates.aspx.) 12. White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues and guidance for practice. Stat Med 2011;30:377-99.