Table 2.
Mean Annual Slopes of Within-Individual Longitudinal Change in Cerebrospinal Fluid Biomarkers During Middle Agea
| APOE ε4 Noncarriers (n = 108) | APOE ε4 Carriers (n = 61) | |||||
|---|---|---|---|---|---|---|
| Variable | Early (n = 26) | Mid (n = 44) | Late (n = 38) | Early (n = 19) | Mid (n = 17) | Late (n = 25) |
| Aβ40 | ||||||
|
| ||||||
| Estimated annual slope, mean (SE), pg/mL | −163.59 (80.50) | −153.82 (61.81) | −130.39 (77.20) | 30.63 (102.86) | 3.31 (107.75) | 110.77 (97.06) |
|
| ||||||
| Different from 0, P value | .04b | .01b | .09 | .77 | .98 | .26 |
|
| ||||||
| APOE ε4carriers vs noncarriers, P value | … | … | … | .14 | .21 | .05 |
|
| ||||||
| Aβ42 | ||||||
|
| ||||||
| Estimated annual slope, mean (SE), pg/mL | −14.81 (5.83) | −19.34 (4.48) | −22.80 (5.56) | −14.99 (7.42) | −29.22 (7.79) | −26.76 (6.99) |
|
| ||||||
| Different from 0, P value | .01b | <.001b | <.001b | .045b | <.001b | <.001b |
|
| ||||||
| APOE ε4 carriers vs noncarriers, P value | … | … | … | .98 | .27 | .66 |
|
| ||||||
| Aβ42 to Aβ40 ratio | ||||||
|
| ||||||
| Estimated annual slope, mean (SE) | 0.00027 (0.00042) | −0.00023 (0.00032) | −0.00068 (0.00042) | −0.00090 (0.00055) | −0.00202 (0.00057) | −0.00220 (0.00052) |
|
| ||||||
| Different from 0, P value | .52 | .47 | .10 | .10 | <.001b | <.001b |
|
| ||||||
| APOE ε4 carriers vs noncarriers, P value | … | … | … | .09 | .007b | .02b |
|
| ||||||
| Total tau | ||||||
|
| ||||||
| Estimated annual slope, mean (SE), pg/mL | 0.96 (3.44) | 2.84 (2.68) | 14.58 (3.08)c,d | 5.40 (4.20) | 22.28 (4.45)c | 18.45 (3.85)c |
|
| ||||||
| Different from 0, P value | .78 | .29 | <.001b | .20 | <.001b | <.001b |
|
| ||||||
| APOE ε4 carriers vs noncarriers, P value | … | … | … | .42 | <.001b | .43 |
|
| ||||||
| P-tau181 | ||||||
|
| ||||||
| Estimated annual slope, mean (SE), pg/mL | 0.23 (0.51) | 0.32 (0.40) | 1.84 (0.47)c,d | 1.08 (0.63) | 3.41 (0.67)c | 1.92 (0.58) |
|
| ||||||
| Different from 0, P value | .66 | .43 | <.001b | .09 | <.001b | .001b |
|
| ||||||
| APOE ε4 carriers vs noncarriers, P value | … | … | … | .30 | <.001b | .91 |
|
| ||||||
| Total tau to Aβ42 ratio | ||||||
|
| ||||||
| Estimated annual slope, mean (SE) | 0.0026 (0.0084) | 0.0081 (0.0066) | 0.0268 (0.0071)c | 0.0076 (0.0100) | 0.0538 (0.0106)c | 0.0478 (0.0088)c |
|
| ||||||
| Different from 0, P value | .76 | .22 | <.001b | .45 | <.001b | <.001b |
|
| ||||||
| APOE ε4 carriers vs noncarriers, P value | … | … | … | .70 | <.001b | .07 |
|
| ||||||
| VILIP-1 | ||||||
|
| ||||||
| Estimated annual slope, mean (SE), pg/mL | −0.18 (1.03) | −0.48 (0.80) | 2.39 (1.01)d | 0.79 (1.34) | 5.17 (1.39)c | 1.42 (1.27)d |
|
| ||||||
| Different from 0, P value | .86 | .55 | .02b | .55 | <.001b | .26 |
|
| ||||||
| APOE ε4 carriers vs noncarriers, P value | … | … | … | .56 | <.001b | .55 |
|
| ||||||
| YKL-40 | ||||||
|
| ||||||
| Estimated annual slope, mean (SE), ng/mL | 4.80 (1.29) | 4.26 (0.99) | 6.91 (1.27) | 6.25 (1.68) | 10.83 (1.75) | 4.90 (1.60)d |
|
| ||||||
| Different from 0, P value | <.001b | <.001b | <.001b | <.001b | <.001b | .002b |
|
| ||||||
| APOE ε4 carriers vs noncarriers, P value | … | … | … | .50 | .001b | .32 |
Abbreviations: Aβ, β-amyloid; P-tau181, tau phosphorylated at threonine 181; VILIP-1; visinin-like protein 1; YKL-40, chitinase-3-like protein 1; ellipses, not applicable.
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. Results for Aβ40,
Aβ42, Aβ42 to Aβ40 ratio, total tau, P-tau181, and total tau to Aβ42 ratio are from the improved INNOTEST enzyme-linked immunosorbent assay.
Statistically significant at P < .05.
Significantly different from early within the same APOE ε4 group (P < .05).
Significantly different frommid within the same APOE ε4 group (P < .05).