Table 4.
Clinical, genetic, CSF biomarker, and longitudinal information separately for CN, AD, and MCI subgroups based on latent class analysis
| CN | MCI 1 | MCI 2 | MCI 3 | MCI 4 | p | AD | |
|---|---|---|---|---|---|---|---|
| Clinical | |||||||
| CDR | .03(.13) | 1.42(.86)2 | 1.64(.88)2 | 1.76(.74) | 1.53(.81) | .010 | 4.36(1.6) |
| FAQ | .20(.7) | 2.6(3.8)2 | 3.9(4.4) | 4.1(4.4) | 3.4(4.8) | .010 | 12.8(6.9) |
| GDS | .86(1.1) | 1.7(1.4) | 1.7(1.4) | 1.6(1.5) | 1.6(1.2) | .931 | 1.64(1.4) |
| Attention | |||||||
| Digit Span forward | 8.73(2.0) | 8.4(2.0) | 8.0(1.9) | 8.4(2.2) | 7.2(2.6) | .271 | 7.5(1.9) |
| Digit Span backward | 7.14(2.1) | 6.2(2.0) | 6.0(1.9) | 5.3(2.2) | 7.0(3.3) | .244 | 4.8(2.1) |
| Executive function | |||||||
| Digit Symbol | 46.03(10.1) | 38.3(10.3) | 36.6(11.3) | 32.6(10.4) | 41.7(22.8) | .123 | 26.0(13.1) |
| Trails B | 85.09(42.8) | 100.7(51.7)2,3,4 | 135.1(78.6)1 | 146.8(73.8)1 | 149.3(79.1)1 | <.001 | 201.4(86.2) |
| Category naming | 34.68(8.1) | 27.4(7.2) | 26.9(7.3) | 26.8(8.0) | 28.5(1.8) | .677 | 20.1(6.9) |
| Memory | |||||||
| MMSE | 29.0(1.1) | 28.0(1.6)2,3 | 26.9(1.8)1,4 | 26.8(1.7)1,4 | 27.8(1.8)2,3 | <.001 | 23.12(2.0) |
| ADAS-cog | 5.8(2.8) | 9.3(4.3)2,3 | 11.2(4.2)1 | 11.8(11.9)1 | 10.9(5.5) | <.001 | 19.9(6.9) |
| RAVLT (sum of five trials) | 44.9(9.7) | 36.5(10.7)2,3 | 31.0(9.4)1 | 28.8(10.7)1 | 35.1(9.1) | <.001 | 22.8(7.4) |
| RAVLT 30 min | 3.73(2.7) | 4.6(2.5) | 4.5(2.3) | 4.6(4.5) | 4.8(5.8) | .905 | 4.4(1.8) |
| Logical Memory II | 13.1(3.3) | 6.5(3.4)2,3 | 4.4(2.9)1,4 | 4.5(3.3)1,4 | 5.9(3.4)2,3 | <.001 | 1.3(1.9) |
| Summary scores | |||||||
| Memory domain | 1.03(.56) | 0.32(.67)2,3 | −0.05(.60)1 | −0.21(.69)1 | 0.18(.64) | <.001 | −.87(.54) |
| Executive function domain | .76(.71) | 0.37(.76)2,3,4 | −0.06(.82)1 | −0.26(.79)1 | −0.06(.69)1 | <.001 | −.92(.85) |
| Imaging Biomarkers | |||||||
| Total brain Volume (cm3)* | 1050(70) | 1053(73)2,3 | 1005(72)1,3 | 940(76)1,2,4 | 1006(63)3 | <.001 | 975(68) |
| Ventricle volume (cm3)* | 33.4(18.0) | 34.7(19.4)3,4 | 40.3(19.7)3,4 | 75.9(31.8)1,3,4 | 56.4(22.5)1,2,3 | <.001 | 50.5(22) |
| WMH (Log cm3) | −.07(.8) | 0.05(.82)2,4 | −0.41(.76)1,3,4 | 0.22(.76)2,4 | 0.89(.72)1,2 | <.001 | .047(0.04) |
| Average FDG-PET of angular, temporal, and posterior cingulate | 1.32(.1) | 1.27(.13)2,3 | 1.21(.12)1 | 1.15(.12)1 | 1.21(.14) | <.001 | 1.06(.14) |
| CSF Biomarkers | |||||||
| Low Aβ1–42 (%) | 28.7(4.5) | 52.22 | 39.5 1 | 38.8 | 57.6 | <.009 | 64.2(4.8) |
| High Tau (%) | 12.4(3.3) | 27.9 | 22.1 | 13.8 | 23.0 | .153 | 45.7(5.0) |
| High P-tau181p (%) | 43.6(4.9) | 62.12,3 | 41.71 | 25.01,4 | 57.63 | <.001 | 64.2(4.8) |
| High P-tau/Aβ ratio (%) | 48.7(5.0) | 64.12,3 | 45.21 | 38.81,4 | 65.33 | <.001 | 66.2(4.7) |
| Longitudinal outcome | |||||||
| Incidence rate of conversion to AD** | 7.6 (6.4–9.2),2,3 | 12.3 (10.2–14.9)1 | 16.5 (10.3–26.1)1 | 12.3 (6.8–22.3)1 | <.001 | ||
| Rate of Reversion to CN** | 1.9 (1.3–2.8),2,3 | 0.9 (0.4–1.8)1,3,4 | 01 | 01 | <.001 |
Data summarized as mean and (SE) unless otherwise noted
P-values are representative of outcomes of ACNOVA with age, gender, education and MRI field strength as covariates and MCI subgroup membership as independent variable. Numbered superscripts denote significant post-hoc differences at p < 0.01 between each aMCI subgroup and the subgroup number indicated
*
Measures adjusted by total intracranial volume
**
rates are reported “per 100 person-years” with 95% confidence interval