Identification of Pure Subcortical Vascular Dementia Using 11C-Pittsburgh Compound B

Supplementary Online ContentTable e-1. Demographic, clinical, and MRI characteristics of patients with higher and lower cerebral small vessel disease (SVD) burden Table e-2. Baseline neuropsychological scores of patients with higher and lower cerebral small vessel disease (SVD) burdenTable e-3. Univariate analyses: Association of baseline PiB-positivity or the burden of small vessel disease (SVD) MRI markers with neuropsychological change Table e-4. Interaction effect of the burden of each small vessel disease MRI marker and PiB-positivity on longitudinal cognitive decline Table e-5. Effects of PiB-positivity on longitudinal cognitive decline in subgroups with higher and lower small vessel disease burdenTable e-6. Independent and interaction effects of baseline global PiB retention ratio and the burden of small vessel disease MRI markers on neuropsychological changeTable e-7. Multivariate analyses after exclusion of the third follow-up data: Independent effects of baseline PiB-positivity and the burden of small vessel disease MRI markers on neuropsychological changeMethods e-1. Study participants and AMPETIS study proceduresMethods e-2. Detailed description of the Seoul Neuropsycholgical Screening BatteryMethods e-3. Imaging parameters for MR image acquisitionMethods e-4. Measurement of WMH volume and rating of lacunes and microbleeds on MRIMethods e-5. [11C]PiB-PET scanning protocol and methods for the calculation of global PiB retention ratioMethods e-6. The rate of MMSE decrease and CDR SOB increase eReferences Table e-1. Demographic, clinical and MRI characteristics of patients with higher and lower cerebral small vessel disease (SVD) burden WMH burden / Lacunar burden / Microbleed burden Higher / Lower / p-valueb / Higher / Lower / p-valueb / Higher / Lower / p-valueb Number / 21 / 40 / 23 / 38 / 20 / 41 Female, N (%) / 9 (42.8) / 27 (67.5) / 0.063 / 12 (52.2) / 24 (63.2) / 0.398 / 9 (45.0) / 27 (65.9) / 0.120 Baseline age (years) / 74.1 ± 5.7 / 73.3 ± 7.3 / 0.655 / 70.6 ± 6.5 / 75.7 ± 5.3 / 0.002 / 70.3 ± 7.4 / 75.5 ± 4.8 / 0.008 Disease duration (years) / 5.4 ± 4.2 / 3.9 ± 2.4 / 0.135 / 4.7 ± 3.2 / 4.9 ± 4.0 / 0.875 / 6.1 ± 4.3 / 4.2 ± 3.2 / 0.073 Education (years) / 9.0 ± 4.6 / 10.0 ± 6.0 / 0.430 / 9.6 ± 5.1 / 9.1 ± 5.2 / 0.722 / 10.8 ± 4.7 / 8.6 ± 5.2 / 0.117 Risk factors, N (%) DM / 4 (19.0) / 14 (35.0) / 0.194 / 6 (26.1) / 12 (31.6) / 0.649 / 7 (35.0) / 11 (26.8) / 0.511 HTN / 16 (76.2) / 33 (82.5) / 0.736 / 19 (82.6) / 30 (78.9) / > 0.999 / 17 (85.0) / 32 (78.0) / 0.734 Hyperlipidemia / 9 (42.9) / 16 (40.0) / 0.829 / 9 (39.1) / 16 (42.1) / 0.819 / 9 (45.0) / 16 (39.0) / 0.656 Cardiac disease / 2 (9.5) / 6 (15.0) / 0.703 / 0 / 8 (21.1) / 0.020 / 0 / 8 (19.5) / 0.044 Previous stroke / 8 (38.1) / 11 (27.5) / 0.396 / 9 (39.1) / 10 (26.3) / 0.295 / 10 (50.0) / 9 (22.0) / 0.026 Geriatric Depression Scale / 15.7 ± 7.0 / 17.7 ± 10.1 / 0.444 / 20.2 ± 8.6 / 14.2 ± 7.2 / 0.005 / 17.4 ± 9.3 / 15.9 ± 7.6 / 0.496 WMH volume / 32.2 ± 8.6 / 59.9 ± 16.5 / < 0.001 / 41.4 ± 15.9 / 41.9 ± 19.0 / 0.917 / 46.6 ± 24.5 / 39.4 ± 13.0 / 0.136 Number of lacunes / 13.8 ± 13.2 / 21.2 ± 21.7 / 0.160 / 32.2 ± 17.9 / 6.7 ± 4.3 / < 0.001 / 25.4 ± 21.0 / 11.9 ± 12.5 / 0.014 Number of microbleeds / 8.4 ± 16.4 / 13.1 ± 21.5 / 0.350 / 19.8 ± 26.2 / 4.1 ± 6.3 / 0.009 / 26.6 ± 24.9 / 1.9 ± 2.3 / < 0.001 APOE ε4 allele, N (%)a / 20 / 38 / 0.120 / 21 / 37 / 0.020 / 20 / 38 / 0.752 Carrier / 3 (15.0) / 13 (34.2) / 2 (9.5) / 14 (37.8) / 4 (22.2) / 12 (30.0) Non-carrier / 17 (85.0) / 25 (65.8) / 19 (90.5) / 23 (62.2) / 14 (77.8) / 28 (70.0) Hippocampal volume (cc) / 2.9 ± 0.5 / 2.7 ± 0.8 / 0.254 / 3.2 ± 0.5 / 2.6 ± 0.5 / < 0.001 / 3.0 ± 0.5 / 2.7 ± 0.6 / 0.028 Intracranial volume (*103cc) / 1.4 ± 0.1 / 1.4 ± 0.2 / 0.127 / 1.4 ± 0.1 / 1.4 ± 0.2 / 0.771 / 1.4 ± 0.1 / 1.4 ± 0.2 / 0.070 Follow-up information, N (%) Incident stroke / 1 (4.8) / 5 (12.5) / 0.654 / 2 (8.7) / 4 (10.5) / > 0.999 / 1 (5.0) / 5 (12.2) / 0.653 MMSE < 10 during follow-up / 2 (9.5) / 5 (12.5) / > 0.999 / 1 (4.3) / 6 (15.8) / 0.238 / 1 (5.0) / 6 (14.6) / 0.409 Dropout / 2 (9.5) / 5 (12.5) / > 0.999 / 4 (17.4) / 3 (7.9) / 0.409 / 5 (25.0) / 2 (4.9) / 0.033 Cancer occurrence / 0 / 1 (2.5) / > 0.999 / 0 / 1 (2.6) / > 0.999 / 1 (5.0) / 0 / 0.328 Death / 2 (9.5) / 1 (2.5) / 0.270 / 1 (4.3) / 2 (5.3) / > 0.999 / 1 (5.0) / 2 (4.9) / > 0.999 Abbreviations: APOE, apolipoprotein E; DM, Diabetes mellitus; HTN, hypertension; MMSE, Mini-Mental State Examination; PiB, Pittsburgh Compound B.aAPOE genotyping was analyzed in 58 patients because three patients refused the test.bp-values are results of independent t-tests or chi-square tests.Table e-2. Baseline neuropsychological scores of patients with higher and lower cerebral small vessel disease (SVD) burden WMH burden / Lacunar burden / Microbleed burden Higher (N = 21) / Lower (N = 40) / p-valuea / Higher (N = 21) / Lower (N = 40) / p-valuea / Higher (N = 20) / Lower (N = 41) / p-valuea Attention Digit span forward / 4.7 (1.1) / 5.1 (1.1) / 0.432 / 5.0 (1.2) / 4.9 (1.1) / 0.943 / 5.1 (1.3) / 4.9 (1.0) / 0.880 Digit span backward / 2.6 (1.4) / 2.8 (0.9) / 0.448 / 2.3 (1.1) / 3.0 (1.1) / 0.290 / 2.7 (1.0) / 2.7 (1.2) / 0.767 Language and related functions K-BNT / 29.9 (11.2) / 31.8 (10.7) / 0.138 / 34.7 (10.5) / 29.4 (10.6) / 0.638 / 33.7 (9.8) / 30.0 (11.2) / 0.492 Visuospatial function RCFT copy / 18.4 (10.6) / 22.2 (10.1) / 0.325 / 19.8 (11.2) / 21.5 (10.0) / 0.465 / 20.5 (10.3) / 21.1 (10.5) / 0.432 Memory SVLT Immediate recall / 11.6 (5.7) / 11.6 (5.1) / 0.857 / 11.8 (5.3) / 11.4 (5.3) / 0.536 / 12.7 (4.1) / 11.0 (5.7) / 0.851 SVLT Delayed recall / 2.3 (2.4) / 1.2 (1.8) / 0.078 / 1.7 (2.1) / 1.4 (2.1) / 0.587 / 1.7 (2.1) / 1.5 (2.1) / 0.735 SVLT Recognition / 16.8 (3.6) / 17.0 (3.0) / 0.993 / 17.0 (2.8) / 16.9 (3.4) / 0.776 / 17.8 (2.5) / 16.5 (3.4) / 0.369 RCFT Immediate recall / 4.3 (5.7) / 3.7 (3.8) / 0.802 / 4.4 (5.2) / 3.6 (4.1) / 0.427 / 4.9 (5.2) / 3.4 (4.2) / 0.504 RCFT Delayed recall / 2.8 (5.0) / 3.4 (3.7) / 0.139 / 3.7 (4.7) / 2.9 (3.8) / 0.670 / 3.7 (4.8) / 2.9 (3.8) / 0.692 RCFT Recognition / 16.6 (2.3) / 16.5 (3.1) / 0.786 / 17.2 (3.2) / 16.2 (2.6) / 0.698 / 16.9 (3.2) / 16.4 (2.7) / 0.695 Frontal/executive function COWAT Animals / 7.4 (3.8) / 7.5 (3.1) / 0.711 / 7.4 (2.7) / 7.5 (3.6) / 0.346 / 8.6 (3.1) / 7.0 (3.3) / 0.227 COWAT Supermarket / 6.7 (4.2) / 6.3 (4.5) / 0.441 / 5.2 (3.1) / 7.1 (4.8) / 0.174 / 6.3 (3.2) / 6.5 (4.9) / 0.688 COWAT Phonemic fluency / 8.5 (5.5) / 10.0 (6.0) / 0.350 / 8.1 (5.4) / 10.2 (6.0) / 0.580 / 9.7 (5.2) / 9.3 (6.1) / 0.462 Stroop Test color reading / 31.9 (23.2) / 36.7 (26.5) / 0.531 / 32.2 (24.4) / 36.4 (26.0) / 0.646 / 30.8 (20.3) / 37.1 (27.5) / 0.526 MMSE / 19.8 (5.0) / 21.3 (4.8) / 0.216 / 20.8 (4.8) / 20.7 (4.9) / 0.540 / 21.6 (4.4) / 20.3 (5.0) / 0.346 CDR SOB / 6.4 (3.7) / 6.1 (3.7) / 0.675 / 6.2 (3.0) / 6.2 (4.1) / 0.460 / 6.7 (4.0) / 6.0 (3.5) / 0.108 Abbreviations: APOE4, apolipoprotein E ε4; CDR SOB, Clinical Dementia Rating sum of boxes; COWAT, Controlled Oral Word Association Test; K-BNT, Korean version of the Boston Naming Test; MMSE, Mini-Mental State Examination; PiB, Pittsburgh Compound B; RCFT, Rey-Osterrieth Complex Figure Test; SVLT, Seoul Verbal Learning Test.ap-values are results of the generalized linear models with a negative binomial distribution comparing neuropsychological scores between patients with higher cerebrovascular disease burden and those with lower burden after controlling for age, gender, education, and APOE4 allele. Table e-3. Univariate analyses: Association of baseline PiB-positivity or the burden of small vessel disease (SVD) MRI markers with neuropsychological changePiB-positivity / Higher WMH burden / Higher lacunar burden / Higher microbleed burden Neuropsychological tests / β (SE) / p-value / β (SE) / p-value / β (SE) / p-value / β (SE) / p-value Attention Digit span forward / -0.05 (0.07) / 0.528 / -0.04 (0.03) / 0.239 / 0.02 (0.04) / 0.687 / -0.02 (0.03) / 0.553 Digit span backward / -0.10 (0.04) / 0.026 / 0.005 (0.04) / 0.890 / 0.08 (0.04) / 0.042 / 0.05 (0.04) / 0.167 Language K-BNT / -0.09 (0.05) / 0.081 / -0.07 (0.04) / 0.125 / 0.07 (0.03) / 0.046 / 0.002 (0.04) / 0.967 Visuospatial function RCFT copy / -0.19 (0.10) / 0.066 / -0.16 (0.08) / 0.048 / 0.09 (0.06) / 0.168 / 0.12 (0.10) / 0.226 Verbal Memory SVLT Immediate recall / -0.10 (0.05) / 0.058 / -0.04 (0.05) / 0.402 / -0.03 (0.06) / 0.637 / -0.07 (0.05) / 0.226 SVLT Delayed recall / 0.30 (0.29) / 0.302 / -0.19 (0.12) / 0.108 / -0.06 (0.13) / 0.665 / -0.16 (0.17) / 0.360 SVLT Recognition / -0.04 (0.04) / 0.325 / -0.02 (0.02) / 0.425 / 0.02 (0.02) / 0.367 / 0.02 (0.02) / 0.381 Visual Memory RCFT Immediate recall / -0.39 (0.43) / 0.361 / -0.18 (0.16) / 0.263 / 0.09 (0.12) / 0.478 / -0.06 (0.12) / 0.626 RCFT Delayed recall / -0.42 (0.21) / 0.046 / -0.11 (0.13) / 0.376 / 0.15 (0.13) / 0.241 / -0.09 (0.14) / 0.524 RCFT Recognition: / -0.003 (0.03) / 0.915 / -0.05 (0.02) / 0.006 / 0.002 (0.02) / 0.935 / -0.01 (0.02) / 0.588 Frontal/executive function COWAT Animals / 0.02 (0.08) / 0.848 / -0.10 (0.06) / 0.106 / 0.07 (0.05) / 0.197 / -0.04 (0.06) / 0.456 COWAT Supermarket / -0.13 (0.13) / 0.327 / -0.25 (0.11) / 0.018 / 0.16 (0.08) / 0.046 / -0.01 (0.10) / 0.925 COWAT Phonemic fluency / 0.07 (0.09) / 0.446 / -0.37 (0.10) / < 0.001 / 0.17 (0.09) / 0.047 / -0.11 (0.18) / 0.550 Stroop Test color reading / -0.04 (0.20) / 0.831 / -0.08 (0.09) / 0.370 / 0.01 (0.17) / 0.954 / 0.16 (0.20) / 0.415 MMSE / -0.09 (0.03) / 0.002 / -0.07 (0.04) / 0.069 / 0.06 (0.04) / 0.107 / 0.05 (0.04) / 0.268 CDR SOB / 0.17 (0.04) / < 0.001 / -0.001 (0.05) / 0.984 / -0.03 (0.05) / 0.541 / -0.05 (0.04) / 0.265 Abbreviations: APOE4, apolipoprotein E4; CDR, Clinical Dementia Rating; COWAT, Controlled Oral Word Association Test; K-BNT, Korean version of the Boston Naming Test; MMSE, Mini-Mental State Examination; PiB, Pittsburgh Compound B; RCFT, Rey-Osterrieth Complex Figure Test; SVLT, Seoul Verbal Learning Test; WMHs, white matter hyperintensities.Summary of generalized estimation equations used to measure cognitive change. Covariates included baseline age, gender, education, APOE4 allele, and follow-up interval from baseline. Predictors were baseline PiB-positivity and the burden of SVD markers including WMH, lacune, and microbleed. The burden of SVD markers was dichotomized using the second tertile of WMH volume and the number of lacunes and microbleeds as cut-off values. To study the longitudinal effect of each predictor, the interaction effect between each predictor and follow-up interval from baseline was investigated. Regression coefficients (β), standard errors (SE), and p-values for the interaction between predictors and follow-up interval are presented.Table e-4. Interaction effect of the burden of each small vessel disease MRI marker and PiB-positivity on longitudinal cognitive declinePiB × WMH burden / PiB × Lacunar burden / PiB × microbleed burden Neuropsychological tests / β (SE) / p-value / β (SE) / p-value / β (SE) / p-value Attention Digit span forward / 0.12 (0.06) / 0.046 / -0.04 (0.06) / 0.461 / 0.11 (0.06) / 0.062 Digit span backward / 0.07 (0.09) / 0.461 / 0.04 (0.09) / 0.642 / -0.0005 (0.08) / 0.996 Language K-BNT / -0.23 (0.13) / 0.081 / 0.04 (0.07) / 0.574 / -0.26 (0.18) / 0.142 Visuospatial function RCFT copy / -0.28 (0.25) / 0.271 / -0.19 (0.22) / 0.400 / 0.07 (0.13) / 0.565 Verbal Memory SVLT Immediate recall / 0.03 (0.12) / 0.763 / -0.24 (0.10) / 0.018 / 0.04 (0.09) / 0.686 SVLT Delayed recall / * / -1.70 (0.48) / < 0.001 / * SVLT Recognition / -0.03 (0.04) / 0.348 / -0.13 (0.05) / 0.005 / -0.12 (0.03) / < 0.001 Visual Memory RCFT Immediate recall / -0.22 (0.31) / 0.475 / 0.30 (0.74) / 0.689 / -0.003 (0.29) / 0.991 RCFT Delayed recall / 0.16 (0.45) / 0.718 / 0.04 (0.40) / 0.912 / 0.47 (0.37) / 0.204 RCFT Recognition: / -0.03 (0.05) / 0.510 / -0.04 (0.04) / 0.346 / -0.02 (0.05) / 0.657 Frontal/executive function COWAT Animals / -0.26 (0.12) / 0.032 / 0.34 (0.45) / 0.452 / -0.25 (0.15) / 0.093 COWAT Supermarket / -0.34 (0.17) / 0.047 / 0.29 (0.18) / 0.098 / -0.30 (0.30) / 0.318 COWAT Phonemic fluency / -0.68 (0.40) / 0.092 / 0.07 (0.17) / 0.678 / 0.07 (0.17) / 0.708 Stroop Test color reading / -0.22 (0.24) / 0.361 / -0.28 (0.16) / 0.083 / -0.47 (0.32) / 0.132 MMSE / -0.04 (0.08) / 0.627 / -0.09 (0.08) / 0.233 / -0.15 (0.08) / 0.046 CDR SOB / -0.13 (0.07) / 0.074 / 0.01 (0.10) / 0.933 / 0.17 (0.06) / 0.005 Abbreviations: APOE4, apolipoprotein E4; CDR, Clinical Dementia Rating; COWAT, Controlled Oral Word Association Test; K-BNT, Korean version of the Boston Naming Test; MMSE, Mini-Mental State Examination; PiB, Pittsburgh Compound B; RCFT, Rey-Osterrieth Complex Figure Test; SVLT, Seoul Verbal Learning Test; WMHs, white matter hyperintensities.Summary of generalized estimation equations used to measure cognitive change. Covariates included baseline age, gender, education, APOE4 allele, and follow-up interval from baseline. Predictor was a 3-way interaction effect between PiB-positivity, each SVD marker, and follow-up interval from baseline. Regression coefficients (β), standard errors (SE), and p-values for the interaction effects between predictors and follow-up interval are presented.*Results could not be obtained due to the lack of model fitness.Table e-5. Effects of PiB-positivity on longitudinal cognitive decline in subgroups with higher and lower small vessel disease burden Neuropsychological tests / Subgroup / β (SE) / p-valuea Digit span forward / Higher WMH burden / 0.03 (0.04) / 0.362 Lower WMH burden / -0.07 (0.07) / 0.316 SVLT immediate recall / Higher lacunar burden / -0.16 (0.09) / 0.080 Lower lacunar burden / -0.05 (0.06) / 0.440 SVLT delayed recall / Higher lacunar burden / -0.14 (0.32) / 0.657 Lower lacunar burden / 1.19 (0.53) / 0.025 SVLT recognition / Higher lacunar burden / -0.03 (0.03) / 0.324 Lower lacunar burden / 0.02 (0.02) / 0.464 COWAT animal / Higher WMH burden / -0.23 (0.10) / 0.017 Lower WMH burden / 0.08 (0.16) / 0.593 COWAT supermarket / Higher WMH burden / -0.39 (0.13) / 0.002 Lower WMH burden / -0.09 (0.12) / 0.429 CDR SOB / Higher microbleed burden / 0.26 (0.04) / < 0.001 Lower microbleed burden / 0.14 (0.05) / 0.006 Abbreviations: APOE4, apolipoprotein E ε4; CDR SOB, Clinical Dementia Rating Sum of Boxes; COWAT, Controlled Oral Word Association Test; K-BNT, Korean version of the Boston naming test; MMSE, Mini-Mental State Examination; RCFT, Rey-Osterrieth Complex Figure Test.

Identification of Pure Subcortical Vascular Dementia Using 11C-Pittsburgh Compound B

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