TABLE 1.
Sample characteristics of A+T+ individuals classified using different neurodegeneration (N) biomarker.
| A. Neurodegeneration biomarker (N) = neurogranin (Ng) | ||||
|---|---|---|---|---|
| Controls n = 145 | A+T+N− n = 12 | A+T+N+ n = 143 | P value N+ vs. N− | |
| Age, years | 64.6 (8.6) | 71.6 (5.9) | 71.1 (6.8) | 0.798 |
| Female (%) | 83 (57.2) | 7 (59.3) | 80 (55.9) | 0.873 |
| Education, years | 13.2 (3.6) | 10.9 (3.1) | 12.4 (3.9) | 0.226 |
| APOE ε4 carriers (%) | 28 (24.1) | 6 (54.5) | 94 (67.1) | 0.395 |
| MCI diagnosis | / | 12 (100.0) | 97 (67.8) | 0.019 |
| MMSE | 28.9 (1.2) | 26.3 (3.1) | 26.6 (2.8) | 0.749 |
| Memory, Z score | 0.2 (0.9) | −1.0 (1.5) | −1.9 (1.4) | 0.798 |
| CSF Aβ40, Z score | 0.3 (1.2) | −1.0 (1.1) | 0.1 (1.8) | 0.025 |
| CSF Aβ42, Z score | 0.5 (1.3) | −1.6 (0.4) | −0.9 (1.2) | 0.031 |
| CSF Aβ42/40 ratio, Z score | 0.9 (1.0) | −1.7 (0.6) | −1.7 (0.8) | 0.808 |
| CSF p‐tau, Z score | −0.4 (0.5) | 0.99 (0.43) | 1.8 (1.3) | 0.049 |
| CSF t‐tau, Z score | −0.3 (0.5) | 0.8 (0.7) | 1.6 (1.3) | 0.050 |
| CSF Ng, Z score | −0.3 (0.7) | −0.9 (0.3) | 0.6 (1.1) | <0.001 |
| CSF NfL, Z score | 0.0 (1.5) | 0.6 (1.8) | 1.3 (4.0) | 0.530 |
| HCV, Z score | 0.1 (1.3) | −0.7 (1.5) | −1.7 (0.7) | 0.151 |
| B. Neurodegeneration biomarker (N) = neurofilament light (NfL) | ||||
|---|---|---|---|---|
| Controls n = 145 | A+T+N− n = 33 | A+T+N+ n = 123 | p‐value N+ vs. N− | |
| Age, years | 68.1 (6.9) | 72.0 (6.5) | 0.003 | |
| Female (%) | 26 (78.8) | 61 (49.6) | 0.003 | |
| Education, years | 13.2 (4.0) | 12.1 (3.8) | 0.136 | |
| APOE ε4 carriers (%) | 19 (59.4) | 83 (69.2) | 0.295 | |
| MCI diagnosis | 13 (39.4) | 96 (78.0) | <0.001 | |
| MMSE | 27.1 (3.1) | 26.4 (2.8) | 0.212 | |
| Memory, Z score | −0.6 (1.4) | −1.0 (1.4) | 0.488 | |
| CSF Aβ40, Z score | −0.7 (0.8) | 0.2 (1.8) | <0.001 | |
| CSF Aβ42, Z score | −0.7 (1.0) | −1.0 (1.2) | 0.373 | |
| CSF Aβ42/40 ratio, Z score | −1.5 (0.7) | −1.8 (0.8) | 0.007 | |
| CSF p‐tau, Z score | 1.3 (0.9) | 1.8 (1.4) | 0.008 | |
| CSF t‐tau, Z score | 1.0 (0.9) | 1.7 (1.3) | 0.001 | |
| CSF Ng, Z score | 0.2 (0.8) | 0.6 (1.2) | 0.032 | |
| CSF NfL, Z score | −0.4 (0.7) | 1.7 (4.3) | 0.013 | |
| HCV, Z score | −1.0 (1.6) | −1.8 (1.7) | 0.018 | |
| C. Neurodegeneration biomarker (N) = hippocampal volume (HCV) | ||||
|---|---|---|---|---|
| Controls n = 145 | A+T+N− n = 55 | A+T+N+ n = 83 | p‐value N+ vs. N− | |
| Age, years | 68.8 (6.6) | 72.0 (5.9) | 0.004 | |
| Female (%) | 26 (47.3) | 49 (59.0) | 0.174 | |
| Education, years | 13.6 (3.8) | 12.0 (3.5) | 0.018 | |
| APOE ε4 carriers (%) | 32 (59.3) | 60 (74.1) | 0.070 | |
| MCI diagnosis | 21 (38.2) | 69 (83.1) | <0.001 | |
| MMSE | 27.8 (2.2) | 26.2 (2.9) | 0.001 | |
| Memory, Z score | −0.1 (1.2) | −1.4 (1.4) | <0.001 | |
| CSF Aβ40, Z score | 0.0 (1.6) | 0.3 (1.8) | 0.161 | |
| CSF Aβ42, Z score | −0.5 (1.3) | −1.0 (1.0) | 0.026 | |
| CSF Aβ42/40 ratio, Z score | −1.6 (0.9) | −1.8 (0.7) | 0.029 | |
| CSF p‐tau, Z score | 1.3 (0.9) | 2.0 (1.5) | 0.001 | |
| CSF t‐tau, Z score | 1.3 (1.0) | 1.9 (1.5) | 0.008 | |
| CSF Ng, Z score | 0.5 (1.0) | 0.6 (1.2) | 0.465 | |
| CSF NfL, Z score | 1.3 (5.4) | 1.1 (1.9) | 0.656 | |
| HCV, Z score | 0.1 (0.9) | −2.6 (1.2) | <0.001 | |
Notes: Controls were individuals with normal cognition and normal levels of Aβ42 and p‐tau. A+T+N− individuals were non‐demented (NC+MCI) individuals with abnormal levels of Aβ42 (A) and p‐tau (T) and normal levels of neurodegeneration marker (N, either Ng, NfL, or HCV). A+T+N+ individuals were non‐demented (NC+MCI) individuals with abnormal levels of Aβ42 (A), p‐tau (T), and neurodegeneration marker (N, either Ng, NfL, or HCV). Values represent mean (standard deviation) or number (percentages). Significant p‐values (< 0.05) are bold. The sample size was smaller for some variables: A total of 13 values are missing for education, 36 for APOE ε4, and 54 for memory. Twenty‐three values are missing for Aβ40, Aβ42, and HCV; 37 for NfL; 45 for Ng; and 74 for HCV. Aβ40, Aβ42, t‐tau, p‐tau, Ng, and NfL values are presented as Z scores with controls as a reference.
Abbreviations: APOE, apolipoprotein E; Aβ, amyloid beta; CSF, cerebrospinal fluid; HCV, hippocampal volume; MCI, mild cognitive impairment; MMSE, Mini‐Mental State Examination; NC, normal cognition; NfL, neurofilament light; Ng, neurogranin; p‐tau, phosphorylated tau; t‐tau, total tau.