Background
Methods
Subjects
Laboratory determinations
Statistical analysis
Results
Characteristics of the study population
Controls (n = 66) | AD-dementia(n = 168) | MCI total(n = 197) | MCI-St(n = 74) | MCI-AD(n = 70) | |
---|---|---|---|---|---|
Gender (M/F) | 27/39 | 56/112 | 68/127 | 25/49 | 26/44 |
Age (years) | 58.8 ± 11.9 | 68.1 ± 8.8*** | 67.1 ± 9.4*** | 65.2 ± 9.3* | 71.0 ± 8.0***,§§ |
Age onset (years) | 64.6 ± 8.7 | 64.2 ± 9.3 | 60.5 ± 9.4 | 68.8 ± 7.7γ,§§§ | |
Education (years) | 5.5 ± 4.0 | 6.0 ± 3.8 | 5.7 ± 3.6 | 5.8 ± 3.9 | |
MMSE | 28.4±1.8 | 17.2 ± 5.9*** | 25.9 ± 4.0***,γγγ | 26.5 ± 4.9***,γγγ | 25.1 ± 3.3***,γγγ,§ |
MoCA | 10.5 ± 5.1 | 17.7 ± 5.6γγγ | 19.9 ± 4.9γγγ | 15.5 ± 5.3γγ,§§§ | |
ADAS-Cog | 26.0 ± 12.3 | 11.8 ± 6.1γγγ | 9.0 ± 4.3γγγ | 14.7 ± 6.3γγγ,§§§ | |
APOE-ε4 (%) | 46% | 42% | 28% | 60%§§§ | |
Aβ42 (pg/ml) | 928 ± 435 | 455 ± 225*** | 689 ± 322***,γγγ | 785 ± 309*,γγγ | 476 ± 180***,§§§ |
Aβ40 (pg/ml) | 10,055 ± 4314 | 9229 ± 3668 | 11,097 ± 4635γγγ | 10,916 ± 4379γγ | 10,157 ± 3381 |
Aβ42/40 ratio | 0.100 ± 0.034 | 0.055 ± 0.029*** | 0.070 ± 0.039***,γγγ | 0.083 ± 0.046*,γγγ | 0.050 ± 0.020***,§§§ |
t-Tau (pg/ml) | 196 ± 95 | 543 ± 363*** | 374 ± 269***,γγγ | 253 ± 151γγγ | 511 ± 307***,§§§ |
p-Tau (pg/ml) | 33 ± 15 | 64 ± 37*** | 50 ± 28**,γγγ | 38 ± 19γγγ | 62 ± 30***,§§§ |
t-Tau/Aβ42 | 0.22 ± 0.11 | 1.53 ± 1.36*** | 0.74 ± 0.73***,γγγ | 0.41 ± 0.39γγγ | 1.18 ± 0.85***,§§§ |
Aβ42/p-Tau | 32.0 ± 15.3 | 9.3 ± 8.2*** | 18.6 ± 14.2***,γγγ | 25.7 ± 16.3γγγ | 9.7 ± 6.6***,§§§ |
Establishment of a cutoff value for the CSF Aβ42/40 ratio
Characterization of MCI biomarker-based subgroups according to the core CSF biomarkers
Low-AD likelihood | High-AD likelihood | IAP | SNAP | |
---|---|---|---|---|
N (%) | 59 (29.9%) | 62 (31.5%) | 21 (10.6%) | 55 (27.9%) |
Gender (M/F) | 17/42 | 26/36 | 8/13 | 17/38 |
Age (years) | 62.7 ± 9.9 | 69.6 ± 7.7** | 66.3 ± 9.7 | 69.4 ± 8.9** |
Age onset (years) | 59.0 ± 10.3 | 66.4 ± 7.8** | 63.1 ± 8.1 | 67.4 ± 8.1** |
Education (years) | 6.5 ± 3.9 | 6.1 ± 4.1 | 5.1 ± 2.4 | 5.8 ± 4.1 |
MMSE | 27.6 ± 2.6 | 24.3 ± 4.2*** | 25.1 ± 6.0 | 26.3 ± 3.2 |
MoCA | 20.5 ± 5.0 | 16.4 ± 5.5** | 16.3 ± 6.9 | 17.3 ± 4.9 |
ADAS-Cog | 8.5 ± 4.6 | 12.7 ± 4.3** | 13.3 ± 7.5 | 13.5 ± 7.5* |
APOE-ε4 (%) | 26% | 64%*** | 24%γγγ | 39%γγ |
Aβ42 (pg/ml) | 918 ± 243 | 405 ± 109*** | 403 ± 123***,§§§ | 867 ± 282γγγ |
Aβ40 (pg/ml) | 9608 ± 3219 | 10,945 ± 4191 | 8006 ± 3082γ,§§§ | 14,247 ± 5219***,γγγ |
Aβ42/40 ratio | 0.105 ± 0.040 | 0.040 ± 0.017*** | 0.066 ± 0.024*** | 0.061 ± 0.037***,γγγ |
t-Tau (pg/ml) | 169 ± 42 | 545 ± 274*** | 159 ± 67γγγ,§§§ | 488 ± 250*** |
p-Tau (pg/ml) | 30 ± 9 | 68 ± 28*** | 28 ± 7γγγ,§§§ | 61 ± 27*** |
Follow-up time (years) | 4.0 ± 3.3 | 4.0 ± 2.5 | 4.2 ± 4.1 | 3.6 ± 2.7 |
Effect of including the Aβ42/40 ratio in MCI biomarker-based classification
Aβ42/40 ratio < 0.068 | Aβ42/40 ratio ≥ 0.068 | |
---|---|---|
LL (n = 59) | 10 (17%)—IAP | 49 (83%)—LL |
IAP (n = 21) | 14 (67%)—IAP | 7 (33%)—LL |
SNAP (n = 55) | 36 (66%)—HL | 19 (34%)—SNAP |
HL (n = 62) | 56 (90%)—HL | 6 (10%)—SNAP |
Longitudinal assessment of MCI patients
Conversion to AD in MCI biomarker-based subgroups
Using Aβ42, t-Tau and p-Tau for classification | Using Aβ42/40 ratio, t-Tau and p-Tau for classification | |
---|---|---|
LL | 4/40 (10%) | 3/38 (8%) |
IAP | 7/16 (44%) | 8/18 (44%) |
SNAP | 20/36 (56%) | 9/17 (53%) |
HL | 39/52 (75%) | 50/71 (72%) |