Background
Methods
Participants
Clinical and cognitive data
APOE genotyping
Amyloid classification
MRI acquisition
MRI visual rating
MRI quantitative analysis
Statistical methods
Univariate analysis
Multi-variable analysis
Results
Demographic and cognitive comparisons
Characteristic | Cognitively normal | Mild cognitive impairment | Alzheimer-type dementia | |||
---|---|---|---|---|---|---|
Amyloid negative | Amyloid positive | Amyloid negative | Amyloid positive | Amyloid negative | Amyloid positive | |
N, % within diagnosis | 245 (73) | 92 (27) | 140 (37) | 235 (63) | 3 (3) | 95 (97) |
Age (years) | 66.1 ± 7.2 | 67.5 ± 7.2 | 67.3 ± 8.0 | 70.2 ± 7.0*** | 63.1 ± 8.0 | 67.1 ± 7.7 |
Male gender | 120 (49) | 47 (51) | 73 (52) | 105 (45) | 3 (100) | 48 (51) |
Education (years) | 13.2 ± 3.5 | 12.8 ± 3.8 | 10.8 ± 4.0 | 11.1 ± 3.7 | 10.3 ± 5.1 | 11.1 ± 3.3 |
MMSE | 28.9 ± 1.2 | 28.8 ± 1.2 | 27.1 ± 2.2 | 26.0 ± 2.6*** | 27.7 ± 1.2 | 22.4 ± 4.0** |
Memory immediate | 0.10 ± 1.00 | 0.08 ± 1.10 | − 0.64 ± 1.32 | −1.22 ± 1.44*** | −0.45 ± 0.91 | −2.25 ± 1.06 |
Memory delayed | 0.25 ± 1.01 | 0.30 ± 1.09 | −0.90 ± 1.29 | − 1.37 ± 1.41** | −0.96 ± 1.33 | − 2.28 ± 1.04 |
Language | −0.21 ± 1.01 | 0.01 ± 1.04 | −0.65 ± 1.30 | −0.88 ± 1.27 | −0.76 ± 0.38 | −1.95 ± 1.02* |
Attention | 0.32 ± 1.03 | 0.26 ± 0.89 | −0.74 ± 1.79 | −0.81 ± 1.63 | 0.54 ± 0.52 | − 2.03 ± 1.94* |
Executive functioning | 0.35 ± 1.09 | 0.12 ± 1.15 | − 0.76 ± 1.89 | −1.11 ± 1.98* | 0.46 ± 0.32 | −2.49 ± 2.46* |
Visuo-construction | − 0.23 ± 1.36 | − 0.19 ± 1.20 | 0.18 ± 1.46 | −0.30 ± 1.66* | −0.59 ± 2.09 | −1.30 ± 2.00 |
APOE ε4 genotype | 89 (36) | 53 (58)*** | 27 (19) | 160 (66)*** | 2 (67) | 66 (69) |
Available markers | ||||||
Visual | 245 (100) | 92 (100) | 140 (100) | 235 (100) | 3 (100) | 95 (100) |
Subcortical volumes | 240 (98) | 90 (98) | 130 (93) | 230 (98)* | 2 (67) | 89 (94) |
Cortical thickness | 232 (95) | 88 (96) | 119 (85) | 200 (85) | 2 (67) | 88 (93) |
Univariate association between MRI measures and amyloid pathology
Score | Cognitively normal | Mild cognitive impairment | Alzheimer-type dementia | |||
---|---|---|---|---|---|---|
Amyloid negative | Amyloid positive | Amyloid negative | Amyloid positive | Amyloid negative | Amyloid positive | |
MTA | 0 (0–1) | 0 (0–1) | 0.5 (0–1) | 1 (0.5–1.5)†† | 1 (0.5–2) | 1 (1–2) |
GCA | 0 (0–1) | 0 (0–1) | 0 (0–1) | 1 (0–1)†† | 1 (0–2) | 1 (1–1) |
Parietal | 1 (0–1) | 0.5 (0–1) | 1 (0–1) | 1 (0–1.63)† | 2 (0–2) | 1 (1–2) |
Fazekas | 1 (0–1) | 1 (0–1) | 1 (0–1) | 1 (1–2) | 1 (1–1) | 1 (0–2) |
Microbleeds present | 6 (21%) | 4 (20%) | 29 (25%) | 56 (29%) | 1 (50%) | 17 (22%) |
MRI measure | Cognitively normal | Mild cognitive impairment | Alzheimer-type dementia | F value | |||||
---|---|---|---|---|---|---|---|---|---|
Amyloid negative | Amyloid positive | Amyloid negative | Amyloid positive | Amyloid negative | Amyloid positive | Diagnosis | Amyloid | Diagnosis × amyloid | |
Hippocampus left | 3837 (39) | 3752 (58) | 3638 (46) | 3353 (47)††† | 3051 (340) | 3124 (61) | 32.0*** | 0.7 | 3.5* |
Hippocampus right | 3960 (53) | 3830 (66)# | 3760 (57) | 3389 (57)††† | 3905 (337) | 3172 (70)# | 19.7*** | 12.3*** | 5.4** |
Amygdala left | 1501 (36) | 1439 (40)# | 1405 (37) | 1294 (37)††† | 1604 (171) | 1188 (42)# | 9.2*** | 11.0** | 2.5 |
Amygdala right | 1567 (52) | 1535 (55) | 1522 (53) | 1398 (53)††† | 1612 (183) | 1290 (57) | 4.6** | 6.7** | 3.2* |
Thalamus left | 6834 (101) | 6614 (119)# | 6951 (107) | 6689 (108)† | 6187 (564) | 6787 (126) | 1.1 | 0.04 | 1.1 |
Thalamus right | 6388 (104) | 6320 (113) | 6419 (106) | 6173 (107)††† | 5600 (420) | 6185 (117) | 2.4 | 0.4 | 3.2* |
Caudate left | 3419 (67) | 3336 (80) | 3571 (71) | 3407 (71)† | 4151 (393) | 3387 (85) | 2.9 | 6.1* | 1.7 |
Caudate right | 3491 (88) | 3396 (98) | 3584 (91) | 3463 (91) | 4575 (407) | 3413 (103)# | 3.7* | 10.7** | 3.4* |
Putamen left | 4831 (105) | 4779 (117) | 4689 (108) | 4609 (109) | 4692 (478) | 4509 (122) | 2.1 | 0.4 | 0.1 |
Putamen right | 4627 (121) | 4607 (130) | 4659 (123) | 4461 (124)† | 4524 (444) | 4302 (134) | 0.6 | 0.9 | 1.5 |
Pallidum left | 1366 (32) | 1412 (37) | 1370 (33) | 1385 (33) | 1488 (168) | 1390 (39) | 0.3 | 0.05 | 0.6 |
Pallidum right | 1388 (26) | 1382 (31) | 1384 (28) | 1379 (28) | 1361 (148) | 1392 (33) | 0.02 | 0.01 | 0.03 |
Accumbens left | 465 (23) | 432 (24)# | 434 (23) | 411 (23) | 526 (79) | 375 (25) | 2.1 | 6.7** | 1.5 |
Accumbens right | 497 (22) | 467 (23)# | 466 (22) | 443 (22) | 425 (78) | 419 (24) | 2.3 | 4.0* | 0.6 |
Average CT | 2.29 (0.02) | 2.28 (0.02) | 2.27 (0.02) | 2.22 (0.02)††† | 2.22 (0.07) | 2.19 (0.02) | 5.3** | 1.6 | 1.5 |
CT Dickerson | 2.54 (0.02) | 2.52 (0.02) | 2.50 (0.02) | 2.45 (0.02)†† | 2.48 (0.09) | 2.38 (0.02) | 8.3*** | 3.5 | 1.6 |
CT Jack | 2.68 (0.03) | 2.63 (0.03)# | 2.63 (0.03) | 2.56 (0.03)††† | 2.67 (0.10) | 2.47 (0.03)# | 6.7** | 9.3** | 1.7 |
Multi-variable classifier results
Group | Sensitivity | Specificity | Accuracy | PPV | NPV | Threshold SVM |
---|---|---|---|---|---|---|
Optimized sensitivity and specificity | ||||||
Cognitively normal | 0.61 | 0.71 | 0.68 | 0.41 | 0.84 | 0.70 |
Mild cognitive impairment | 0.71 | 0.77 | 0.74 | 0.84 | 0.62 | 0.33 |
Whole sample | 0.75 | 0.79 | 0.77 | 0.80 | 0.74 | 0.48 |
80% sensitivity | ||||||
Cognitively normal | 0.80 | 0.55 | 0.62 | 0.41 | 0.88 | 0.77 |
Mild cognitive impairment | 0.80 | 0.64 | 0.74 | 0.79 | 0.66 | 0.47 |
Whole sample | 0.80 | 0.69 | 0.75 | 0.74 | 0.76 | 0.56 |
85% sensitivity | ||||||
Cognitively normal | 0.85 | 0.46 | 0.57 | 0.38 | 0.89 | 0.80 |
Mild cognitive impairment | 0.85 | 0.54 | 0.73 | 0.75 | 0.68 | 0.53 |
Whole sample | 0.85 | 0.59 | 0.73 | 0.69 | 0.78 | 0.64 |
90% sensitivity | ||||||
Cognitively normal | 0.90 | 0.36 | 0.51 | 0.35 | 0.91 | 0.84 |
Mild cognitive impairment | 0.90 | 0.46 | 0.73 | 0.73 | 0.74 | 0.60 |
Whole sample | 0.90 | 0.51 | 0.71 | 0.67 | 0.83 | 0.70 |
95% sensitivity | ||||||
Cognitively normal | 0.95 | 0.24 | 0.44 | 0.32 | 0.92 | 0.87 |
Mild cognitive impairment | 0.95 | 0.37 | 0.73 | 0.71 | 0.83 | 0.70 |
Whole sample | 0.95 | 0.40 | 0.69 | 0.63 | 0.88 | 0.79 |
100% sensitivity | ||||||
Cognitively normal | 1.00 | 0.11 | 0.36 | 0.30 | 1.00 | 0.91 |
Mild cognitive impairment | 1.00 | 0.08 | 0.66 | 0.64 | 1.00 | 0.87 |
Whole sample | 1.00 | 0.04 | 0.54 | 0.53 | 1.00 | 0.95 |