Table 1.
Demographic Characteristics and Baseline Cerebrospinal Fluid Biomarkersa
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APOE ε4 Noncarriers (n = 108)
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APOE ε4 Carriers (n = 61)
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|---|---|---|---|---|---|---|
| Variable | Early (n = 26) | Mid (n = 44) | Late (n = 38) | Early (n = 19) | Mid (n = 17) | Late (n = 25) |
| Baseline age, mean (SD), y | 50.1 (3.0) | 59.4 (2.9)b | 69.9 (3.5)b,c | 49.6 (2.9) | 59.3 (3.1)b | 69.4 (3.6)b,c |
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| Female, No. (%) | 17 (65) | 32 (73) | 22 (58) | 14 (74) | 11 (65) | 16 (64) |
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| Positive family history, No. (%) | 12 (46) | 22 (50) | 15 (39) | 15 (79)d | 13 (76) | 17 (68)d |
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| APOE genotype, No. | ||||||
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| ε2/ε2 | 0 | 1 | 1 | 0 | 0 | 0 |
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| ε2/ε3 | 3 | 8 | 6 | 0 | 0 | 0 |
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| ε3/ε3 | 23 | 35 | 31 | 0 | 0 | 0 |
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| ε2/ε4 | 0 | 0 | 0 | 2 | 2 | 2 |
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| ε3/ε4 | 0 | 0 | 0 | 14 | 12 | 20 |
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| ε4/ε4 | 0 | 0 | 0 | 3 | 3 | 3 |
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| Education, mean (SD), y | 16.1 (2.10) | 16.9 (2.27) | 15.6 (2.64)c | 15.8 (1.95) | 15.4 (3.45)d | 16.3 (2.23) |
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| Baseline MMSE score, mean (SD)e | 29.5 (0.65) | 29.3 (1.10) | 28.8 (1.22)b | 29.8 (0.38) | 28.9 (1.52)b | 28.9 (1.39)b |
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| Received ≥1 CDR >0 at follow-up, No.f | 0 | 1 | 4 | 1 | 3 | 5 |
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| Participants with 2/3/4 serial LPs, No. | 12/13/1 | 21/19/4 | 25/13/0 | 11/8/0 | 12/5/0 | 18/7/0 |
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| LP interval, mean (SD), mo | 3.3 (0.76) | 3.3 (0.91) | 3.1 (0.77) | 3.3 (0.73) | 3.6 (1.4) | 3.2 (0.77) |
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| Baseline biomarkers, mean (IQR) | ||||||
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| Improved INNOTEST ELISA | ||||||
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| Aβ40, pg/mL | 12 657 (10 461–14 480) | 14 319 (12 185–16 371) | 15 382 (12 417–17 906)b | 14 555 (12 984–16 638) | 13 103 (10 629–15 838) | 14 343 (12 199–16 748) |
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| Aβ42, pg/mL | 1293 (1046–1525) | 1340 (1132–1544) | 1270 (1021–1608) | 1306 (1193–1498) | 937 (671–1116)b,d | 970 (733–1225)b,d |
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| Aβ42 to Aβ40 ratio | 0.1052 (0.0900–0.1225) | 0.0972 (0.0800–0.1100) | 0.0871 (0.0700–0.1000)b,c | 0.0924 (0.0800–0.1000) | 0.0719 (0.0600–0.0850)b,d | 0.0709 (0.0550–0.0900)b,d |
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| Total tau, pg/mL | 202.3 (146.0–243.2) | 259.0 (182.6–278.7) | 324.3 (205.2–389.3)b,c | 257.7 (194.4–314.6) | 298.0 (210.2–391.6) | 321.4 (198.6–413.2) |
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| P-tau181, pg/mL | 39.8 (27.7–50.3) | 51.2 (37.2–55.4) | 58.8 (41.7–68.5)b | 47.7 (38.5–55.4) | 54.4 (37.9–67.8) | 55.4 (38.2–69.8) |
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| Total tau to Aβ42 ratio | 0.1541 (0.1200–0.1725) | 0.1908 (0.1400–0.2200) | 0.3054 (0.1500–0.3100)b,c | 0.1986 (0.1600–0.2300) | 0.4207 (0.1900–0.4550)b,d | 0.3816 (0.2150–0.5200)b |
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| EUROIMMUN ELISA | ||||||
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| Aβ40, pg/mL | 4857 (3525–6101) | 5408 (4305–6220) | 5569 (4347–6224) | 5535 (4816–6433) | 5266 (3966–7043) | 5257 (4119–5942) |
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| Aβ42, pg/mL | 616.1 (438.1–683.1) | 616.1 (495.9–741.8) | 590.1 (459.4–701.1) | 676.0 (462.3–797.6) | 449.5 (349.9–564.3)b,d | 487.5 (365.3–601.8)b,d |
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| Total tau, pg/mL | 254.7 (194.4–304.8) | 310.3 (230.3–344.6) | 362.5 (255.6–430.3)b,c | 299.1 (234.1–351.6) | 380.5 (313.6–469.6)d | 395.8 (274.1–487.4)b |
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| Total tau to Aβ42 ratio | 0.4050 (0.3341–0.4851) | 0.5022 (0.3900–0.5192) | 0.7023 (0.4065–0.6874)b,c | 0.4563 (0.3675–0.5390) | 1.073 (0.4680–1.1100)b,d | 0.9342 (0.5383–1.2250)b,d |
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| VILIP-1, pg/mL | 140.8 (102.3–169.8) | 154.4 (116.7–166.4) | 179.8 (133.6–218.9)b,c | 155.6 (128.8–175.4) | 153.2 (105.4–193.8) | 154.7 (117.0–180.2) |
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| YKL-40, ng/mL | 180.3 (124.2–220.3) | 231.3 (192.3–259.7)b | 301.1 (221.7–368.2)b,c | 188.4 (135.3–238.7) | 240.6 (165.5–297.9)b | 281.5 (201.8–353.8)b |
Abbreviations: Aβ, β-amyloid; CDR, Clinical Dementia Rating; ELISA, enzyme-linked immunosorbent assay; IQR, interquartile range; LP, lumbar puncture; MMSE,Mini-Mental State Examination; P-tau181, tau phosphorylated at threonine 181; VILIP-1; visinin-like protein 1; YKL-40, chitinase-3-like protein 1.
Age groups indicate the ages within middle age: early, ages 45 to 54 years; mid, ages 55 to 64 years; and late, ages 65 to 74 years.
Significantly different from early within the same APOE ε4 group (P < .05).
Significantly different from mid within the same APOE ε4 group (P < .05).
Significantly different from the same age group of the other APOE ε4 group (P < .05).
The MMSE scores can range from 0 to 30, with 30 as a perfect score.
A CDR of 0 indicates cognitively normal; a CDR higher than 0, cognitively abnormal.