Quantifying and Examining Reserve in Symptomatic Former National Football League Players (Tables)

Table 1 Demographic, athletic, medical, and APOE carrier status characteristics in former NFL players Characteristic Total Sample (n = 89) Age, mean (SD) y 55.63 (7.77) Education, mean (SD) y 16.44 (0.99) Occupational attainment, n (%) High 59 (66.3) Low 30 (33.7) Racial Identity, n (%) White 52 (58.4) Black or African American 37 (41.6) AFE, mean (SD) y 11.96 (2.52) Duration of football play, mean (SD) y 18.19 (3.54) Duration of play in the NFL, mean (SD) y CHII, mean (SD) 8.04 (2.79) 20,089.58 (6,943.69) Primary position group, n (%) Offensive Line 27 (30.3) Running Back 8 (9.0) Tight End 5 (5.6) Offensive Skill 1 (1.1) Defensive Line 12 (13.5) Linebacker 19 (21.3) Defensive Back 17 (19.1) APOE s4 status, n (%) 23 9 (10.3) 24 2 (2.3) 33 52 (59.8) 34 21 (24.1) 44 3 (3.4) SD, standard deviation; y, years; AFE, age of first exposure; CHII, cumulative head impact index; APOE, Apolipoprotein E. Table 2 Neuropsychiatric and neuropsychological raw scores and standardized scores in the former NFL player sample (N = 89) 1 Neuropsychiatric & Neuropsychological Tests 2 Raw Scores T-Scores Mean SD 95% CI Lower Bound Upper Bound BDI-II: Total score 16.61 12.23 14.07 BRIEF-A BRI 3 Median Mean SD 95% CI Median Lower Bound Upper Bound 19.15 15.00 – – – – – 54.39 11.81 51.94 56.85 55.00 63.47 12.85 60.78 66.15 64.00 4 32.69 10.94 30.41 34.96 31.00 49.27 11.46 46.88 51.67 51.00 4 83.53 46.45 73.88 93.18 70.00 44.14 16.01 40.79 47.48 49.00 6.11 2.88 5.51 6.71 6.00 41.92 13.86 39.03 44.82 40.00 COWAT 43.09 13.10 40.37 45.81 41.00 49.57 11.20 47.23 51.91 49.00 Animal Fluency 20.16 5.66 18.98 21.33 20.00 49.14 11.69 46.69 51.58 49.00 TMT Part A Time TMT Part B Time NAB List Learning Long Delay Recall TMT, Trail Making Test; NAB, Neuropsychological Assessment Battery; COWAT, Controlled Oral Word Association Test; BRIEF-A BRI, Behavior Rating Inventory of Executive Functioning – Adult Version Behavioral Regulation Index; BDI-II, Beck Depression Inventory-II. 1 To limit the number of analyses, a subset of tests were selected a priori based on their ability to assess cognitive domains impaired following RHI exposure [8, 9, 53] 2 All statistical analyses used neuropsychological test raw scores 3 In order to describe the clinical sample, neuropsychological test raw scores were converted into standardized scores accounting for age, sex, and/or educational attainment. Raw BRIEF-A BRI scores were converted into standardized age-adjusted T-scores 4 Before analysis, Trails A and B were reverse coded to correct directionality (i.e., lower scores represented worse performance). Table 3 1 Summary statistics of MRI indices measured in former NFL players (N = 81) 2 MRI Indices (mm3) Mean SD Lower Bound Upper Bound 2116.72 2009.24 1679.16 7.43 0.60 Left Hippocampal Volume 3381.67 Right Hippocampal Volume 3381.56 Total Gray Matter Volume Total White Matter Volume Estimated Intracranial Volume White Matter Hypointensities Log-White Matter Hypointensities 3 95% CI Median Interquartile Range 2554.28 1521.70 989.90 7.30 7.56 7.33 0.63 386.33 3465.80 3297.53 3374.00 474.00 379.79 3464.26 3298.85 3387.00 363.00 617993.74 47254.12 628284.45 607703.03 617091.48 71148.78 480610.40 47633.12 490983.64 470237.16 473970.02 72295.49 1498424.53 237880.08 1550228.57 1446620.48 1546022.42 266048.64 1 Neuroimaging data was available for 81 participants, following the exclusion of those who did not complete MRI and those with inadequate data quality due to motion artifact 2 Before analysis, all variables were coded to ensure that higher scores indicated greater pathology (i.e., left hippocampal volume, right hippocampal volume, total gray matter volume, total white matter volume, and estimated intracranial volume were reverse coded) 3 To normalize their distribution, white matter hypointensity volumes were log-transformed. Table 4 Standardized regression coefficients of residual episodic memory and executive functioning variance and neuropsychological and neuropsychiatric tests Neuropsychiatric & Neuropsychological Tests Residual Executive Functioning Variance Residual Episodic Memory Variance β T Lower Bound Upper Bound 1 0.45 4.43 <0.01 0.25 1 0.36 3.40 <0.01 – – COWAT 0.22 Animal Fluency 0.38 BRIEF-A BRI −0.16 −1.40 BDI-II −0.12 −1.05 TMT Part A TMT Part B NAB List Learning Long Delay Recall β T Lower Bound Upper Bound 0.65 0.44 4.34 <0.01 0.24 0.64 0.15 0.57 – – – – – – – – 0.37 3.55 <0.01 0.16 0.58 1.97 0.08 0.00 0.43 0.18 1.64 0.21 −0.04 0.40 3.67 <0.01 0.17 0.59 0.08 0.69 0.49 −0.15 0.30 0.20 −0.38 0.07 −0.09 −0.82 0.49 −0.31 0.13 0.30 −0.34 0.11 −0.14 −1.29 0.30 −0.37 0.08 2 95% CI p p 2 95% CI TMT, Trail Making Test; NAB, Neuropsychological Assessment Battery; COWAT, Controlled Oral Word Association Test; BRIEF-A BRI, Behavior Rating Inventory of Executive Functioning – Adult Version Behavioral Regulation Index; BDI-II, Beck Depression Inventory-II. 1 TMT Parts A and B were reverse coded to correct directionality (i.e., lower scores represented worse performance) 2 Statistical significance was defined by a false discovery rate adjusted p-value<0.05. Age, racial identity, CHII, and APOE genotype were included as covariates. Table 5 Standardized regression coefficients with leave-one-out residuals as metric of reserve Neuropsychiatric & Neuropsychological Tests β T Lower Bound Upper Bound 1 0.45 4.51 <0.01 0.25 1 0.37 3.59 <0.01 – – COWAT 0.22 Animal Fluency 0.39 BRIEF-A BRI −0.15 −1.33 BDI-II −0.12 −1.04 TMT Part A TMT Part B NAB List Learning Long Delay Recall Leave-one-out residuals for executive functioning Leave-one-out residuals for episodic memory β T Lower Bound Upper Bound 0.65 0.44 4.37 <0.01 0.24 0.64 0.17 0.58 – – – – – – – – 0.37 3.54 <0.01 0.16 0.58 2.01 0.07 0.00 0.44 0.18 1.62 0.22 −0.04 0.40 3.75 <0.01 0.18 0.60 0.09 0.81 0.50 −0.13 0.31 0.23 −0.37 0.07 −0.07 −0.64 0.53 −0.29 0.15 0.30 −0.34 0.11 −0.14 −1.30 0.30 −0.37 0.08 2 95% CI p p 2 95% CI TMT, Trail Making Test; NAB, Neuropsychological Assessment Battery; COWAT, Controlled Oral Word Association Test; BRIEF-A BRI, Behavior Rating Inventory of Executive Functioning – Adult Version Behavioral Regulation Index; BDI-II, Beck Depression Inventory-II. 1 TMT Parts A and B were reverse coded to correct directionality (i.e., lower scores represented worse performance) 2 Statistical significance was defined by a false discovery rate adjusted p-value <0.05. Age, racial identity, CHII, and APOE genotype were included as covariates. Table 6 Bivariate Pearson correlations between residual variance variables and four traditional reserve proxies Neuropsychiatric & Neuropsychological Tests Residual Episodic Memory Variance r p WRAT-4 0.24 Years of Education −0.05 Occupational Attainment Estimated Intracranial Volume WRAT-4, The Wide Range Achievement Test-4. Residual Executive Functioning Variance r p 0.03 0.07 0.55 0.74 −0.01 0.97 −0.10 0.30 −0.06 0.52 −0.02 0.94 0.02 0.82