Introduction
Material and methods
Study participants and clinical classification
CSF collection and analysis
Definition of amyloid profile
Measures of cognitive and functional impairment
APOE genotyping
Statistical analysis
Ethical approval and consent to participate
Results
Demographics and core CSF biomarkers
CN | AD | DLB | FTLD | Down | Others | ||
---|---|---|---|---|---|---|---|
N | 197 | 518 | 128 | 186 | 225 | 536 | |
AGE, years | Mean (SD) | 53.5 (12.5) | 73.1 (6.88) | 75.7 (5.49) | 70.8 (8.58) | 45.1 (10) | 70 (9.18) |
Median [IQR] | 55 [46–62] | 74 [69–78] | 76 [71–80] | 72 [66–77] | 48 [40–52] | 71 [65–77] | |
SEX, females/males (% females) | 132/65 (67%) | 311/207 (60%) | 64/64 (50%) | 77/109 (41.4%) | 103/122 (45.8%) | 310/226 (57.8%) | |
MMSE score | Mean (SD) | 29.2 (0.889) | 23.6 (4.52) | 24 (4.09) | 24 (5.08) | NAa | 25.4 (4.12) |
Median [IQR] | 29 [29–30] | 25 [22–27] | 24.5 [22–27] | 25 [21–28] | NAa | 27 [24–28] | |
Education, years | Mean (SD) | 15.6 (3.99) | 10.7 (4.72) | 9.18 (5.05) | 12 (5.13) | 15.3 (3.07) | 10.7 (4.93) |
Median [IQR] | 16 [12–20] | 10 [8–13] | 8 [7–12] | 12 [8–16] | NAa | 9 [8–13] | |
APOEε4, APOEε4−/APOEε4+ (%APOEε4+) | 46/151 (23.4%) | 254/251 (50.3%) | 33/93 (26.2%) | 37/139 (21%) | 44/177 (19.9%) | 115/413 (21.8%) | |
Follow-up, years | Mean (SD) | 2.02 (1.99) | 1.09 (1.49) | 3.33 (1.93) | 1.71 (1.47) | 1.76 (2.09) | 0.59 (1.23) |
Median [IQR] | 1.71 [0–2.82] | 0 [0–2.06] | 3.46 [2.07–4.52] | 1.52 [0.242–2.66] | NAa | 0 [0–0.383] | |
Aβ1–42, pg/ml | Mean (SD) | 1148 (397) | 562 (165) | 817 (399) | 938 (446) | 715 (417) | 1000 (500) |
Median [IQR] | 1118 [849–1371] | 556 [432–673] | 703 [542–1009] | 850 [569–1229] | 583 [430–892] | 896 [609–1323] | |
Aβ1–40, pg/ml | Mean (SD) | 11,694 (3595) | 12,790 (3781) | 11,506 (4189) | 10,806 (4357) | 11,673 (4678) | 11,399 (4390) |
Median [IQR] | 11,329 [9238–13,777] | 12,541 [10,125–15,122] | 10,885 [8882–14,234] | 10,140 [7710–13,334] | 11,035 [8346–14,594] | 10,638 [8112–13,986] | |
Aβ1–42/Aβ1–40 | Mean (SD) | 0.0991 (0.0181) | 0.0453 (0.0108) | 0.0727 (0.0263) | 0.0877 (0.0221) | 0.0615 (0.0226) | 0.0862 (0.0225) |
Median [IQR] | 0.104 [0.0986–0.109] | 0.0445 [0.0376–0.0514] | 0.0662 [0.0503–0.0996] | 0.0964 [0.0731–0.103] | 0.0562 [0.0422–0.078] | 0.0943 [0.0665–0.103] | |
tTau, pg/ml | Mean (SD) | 255 (152) | 748 (358) | 456 (334) | 387 (260) | 644 (520) | 334 (231) |
Median [IQR] | 230 [174–291] | 656 [488–915] | 361 [253–525] | 322 [222–456] | 489 [262–870] | 292 [213–378] | |
pTau181, pg/ml | Mean (SD) | 37.3 (27.3) | 122 (60.3) | 70.5 (55.5) | 49.9 (39.2) | 100 (96.8) | 45 (27.4) |
Median [IQR] | 31.6 [24.9–42] | 105 [78.7–145] | 51 [35.7–83] | 39.7 [29.2–54.1] | 63.6 [29.8–151] | 41 [29.3–52.7] | |
NfL, pg/ml | Mean (SD) | 475 (256) | 1330 (1824) | 1108 (570) | 2079 (1836) | 815 (773) | 1488 (1340) |
Median [IQR] | 458 [320–533] | 981 [791–1254] | 918 [719–1297] | 1412 [884–2767] | 614 [357–1014] | 1089 [595–1878] | |
Clinical stage, CN/MCI/dementia (% MCI) | 177/0/0 | 0/296/208 | 2/60/64 | 5/90/80 | NAa | 27/348/125 | |
Amyloid profile (Aβ1–42[−]Ratio[−]/Aβ1–42[−]Ratio[+]/Aβ1–42[+]Ratio[−]/Aβ1–42[+]Ratio[+]) | 165/13/11/8 | 4/154/2/358 | 50/29/7/42 | 120/8/23/35 | 61/37/13/114 | 345/45/47/100 |