TABLE 2.
Statistical analysis results using longitudinal atrophy measures of the medial temporal lobe subregions, longitudinal cognitive and plasma NfL measures, adjusted for age, in discriminating patients from Aβ− control
| Measurement | Aβ− control (A− controls) | Preclinical AD | Early prodromal AD (A+ EMCI) | ||
|---|---|---|---|---|---|
| CSF p‐tau negative (A + T− controls) | CSF p‐tau positive (A + T+ controls) | Whole group (A+ controls) | |||
| Total n | 151 | 32 | 36 | 76 | 110 |
| Annualized volume change rate (%/year), SD in parentheses | |||||
| Anterior hippo | −0.51 (0.75) | −0.61 (0.74) | −1.10 (0.94) | −0.84 (0.88) | −1.02 (1.27) |
| n | 144 | 32 | 35 | 74 | 102 |
| F stats | <2.5 | 14.7 | 7.9 | 15.7 | |
| p value | >.1 | 8.9e−5 | 2.7e−3 | 4.9e−5 | |
| Cohen's d | 0.14 | 0.69 | 0.40 | 0.49 | |
| Posterior hippo | −0.52 (0.62) | −0.69 (0.73) | −1.11 (1.00) | −0.89 (0.91) | −1.06 (1.19) |
| n | 144 | 32 | 35 | 74 | 102 |
| F stats | <2.5 | 18.7 | 12.5 | 20.4 | |
| p value | >.1 | 1.8e−5 | 2.6e−4 | 5.0e−6 | |
| Cohen's d | 0.25 | 0.71 | 0.48 | 0.56 | |
| Whole hippo | −0.51 (0.62) | −0.65 (0.71) | −1.11 (0.90) | −0.87 (0.84) | −1.03 (1.19) |
| n | 144 | 32 | 35 | 74 | 102 |
| F stats | <2.5 | 19.9 | 12.1 | 19.8 | |
| p value | >.1 | 7.0e−6 | 3.1e−4 | 7.0e−6 | |
| Cohen's d | 0.21 | 0.76 | 0.48 | 0.55 | |
| ERC | −0.43 (1.12) | −0.45 (1.00) | −1.18 (1.25) | −0.79 (1.15) | −1.18 (1.47) |
| n | 150 | 32 | 36 | 76 | 110 |
| F stats | <2.5 | 12.2 | 5.0 | 21.7 | |
| p value | >.1 | 3.0e−4 | .013 | 2.5e−6 | |
| Cohen's d | 0.02 | 0.63 | 0.32 | 0.57 | |
| BA35 | −0.65 (0.89) | −0.80 (1.07) | −1.27 (1.43) | −1.05 (1.25) | −1.56 (1.38) |
| n | 150 | 32 | 36 | 76 | 110 |
| F stats | <2.5 | 11.1 | 7.7 | 41.2 | |
| p value | >.1 | 5.3e−4 | 2.9e−3 | 3.4e−10 | |
| Cohen's d | 0.15 | 0.52 | 0.37 | 0.78 | |
| BA36 | −0.49 (0.81) | −0.47 (1.07) | −0.83 (1.27) | −0.66 (1.13) | −0.95 (1.30) |
| n | 150 | 32 | 36 | 76 | 110 |
| F stats | <2.5 | 5.2 | 2.8 | 13.5 | |
| p value | >.1 | .012 | .049 | 1.5e−4 | |
| Cohen's d | 0.02 | 0.32 | 0.18 | 0.42 | |
| PHC | −0.45 (0.75) | −0.44 (0.73) | −0.91 (0.90) | −0.65 (0.84) | −0.87 (1.11) |
| n | 150 | 32 | 36 | 76 | 110 |
| F stats | <2.5 | 11.8 | 5.1 | 14.7 | |
| p value | >.1 | 3.6e−4 | .013 | 7.9e−5 | |
| Cohen's d | 0.01 | 0.56 | 0.25 | 0.45 | |
| Annualized change rates of other markers of neurodegeneration (/year), SD in parentheses | |||||
| Plasma NfL | −1.38 (5.23) | −2.63 (8.20) | −4.02 (9.05) | −2.86 (8.30) | −1.03 (5.38) |
| n | 141 | 29 | 33 | 70 | 99 |
| F stats | <2.5 | <2.5 | <2.5 | <2.5 | |
| p value | >.1 | >.1 | >.1 | >.1 | |
| Cohen's d | 0.18 | 0.36 | 0.21 | 0.07 | |
| Annualized change rates of cognitive measurements (/year), SD in parentheses | |||||
| PACC | 0.18 (1.38) | 0.05 (1.44) | −0.07 (1.24) | −0.05 (1.34) | −0.20 (2.21) |
| n | 151 | 32 | 36 | 76 | 108 |
| F stats | <2.5 | <2.5 | <2.5 | 2.9 | |
| p value | >.1 | >.1 | >.1 | .045 | |
| Cohen's d | 0.09 | 0.19 | 0.17 | 0.21 | |
| ADAS‐Cog | −0.16 (1.38) | −0.31 (1.35) | 0.03 (1.47) | −0.07 (1.43) | −0.06 (1.87) |
| n | 150 | 32 | 36 | 76 | 108 |
| F stats | <2.5 | <2.5 | <2.5 | <2.5 | |
| p value | >.1 | >.1 | >.1 | >.1 | |
| Cohen's d | 0.11 | 0.14 | 0.06 | 0.06 | |
Note: The preclinical AD was further dichotomized based on CSF p‐tau (threshold: 23 pg/mL). Bilateral measurements of each subregion were averaged. Negative change indicates the measurement change towards worse condition in follow‐ups. Measurements that survived Holm‐Bonferroni correction are highlighted in bold font. Number of measurements of anterior/posterior hippocampus and MTL cortical subregions are presented based on exclusions on some measures due to quality control (Supplementary S1.3). All the statistical tests are one‐tailed.
Abbreviations: AD, Alzheimer's disease; ADAS‐Cog, Alzheimer's Disease Assessment Scale‐Cognitive; BA35/36, Brodmann area 35/36; CSF, cerebrospinal fluid; EMCI, early mild cognitive impairment; ERC, entorhinal cortex; Hippo, hippocampus; NfL, neurofilament light chain; PACC, preclinical Alzheimer's cognitive composition score; PHC, parahippocampal cortex.