Table 2.
Subject characteristics
| Non-carriers | Presymptomatic carriers | Symptomatic carriersa | P | |
|---|---|---|---|---|
| n | 247 | 275 | 127 | – |
| GRN | – | 128 | 49 | – |
| C9orf72 | – | 102 | 54 | – |
| APT | – | 45 | 24 | – |
| Age | 45 (37–58) | 44 (35–54) | 63 (56–69) | <0.001e |
| Sex, male (%) | 109 (44%) | 105 (38%) | 75 (59%) | <0.001 |
| MMSEb | 30 (29–30) | 30 (29–30) | 25 (20–27) | <0.001e |
| CDR® + NACC FTLD-SBc | 0 (0–0) | 0 (0–0) | 9.5 (3.5–14) | <0.001e |
| Whole brain volumed | 80.4 (78.8–82.4) | 80.2 (77.7–81.9) | 71.6 (69.3–75.0) | <0.001e |
| Frontal lobe volumed | 12.5 (12.0–12.9) | 12.5 (11.9–13.0) | 10.6 (9.8–11.3) | <0.001e |
| Temporal lobe volumed | 8.5 (8.2–8.8) | 8.4 (8.1–8.7) | 7.5 (6.9–7.9) | <0.001e |
| Parietal lobe volumed | 6.6 (6.3–6.9) | 6.5 (6.2–6.9) | 5.7 (5.4–6.1) | <0.001e |
| Occipital lobe volumed | 5.1 (4.8–5.5) | 5.1 (4.8–5.3) | 4.8 (4.4–5.0) | <0.001e |
| CSF NfL, pg/ml | 422 (298–555) | 470 (315–731) | 2393 (951–4023) | <0.001e |
| Serum NfL, pg/ml | 7 (5–11) | 8 (5–8) | 40 (23–62) | <0.001e |
| Serum pNfH, pg/ml | 48 (21–101) | 42 (20–94) | 139 (80–326) | <0.001e |
| CSF NPTX2, pg/ml | 990 (604–1373) | 988 (633–1274) | 624 (291–872) | <0.001e |
| Plasma GFAP, pg/ml | 105 (80–144) | 109 (82–156) | 212 (131–310) | <0.001e |
| CSF C1q, ng/ml | 295 (208–397) | 265 (207–350) | 339 (279–464) | 0.002f |
| CSF C3b, ng/ml | 2634 (1730–3556) | 2456 (1786–3285) | 3296 (2612–4737) | 0.001g |
Continuous variables are shown as medians (interquartile range, IQR). All continuous variables were compared between groups using Kruskal–Wallis tests, and, in the case of statistically significant differences, post hoc tests with Bonferroni correction were applied. Sex distributions were compared using a Chi-square test. Regional grey matter volumes are expressed as a percentage of total intracranial volume. The sample size for each of the fluid biomarkers is reported in Supplementary Table 1.
Phenotypes: behavioural variant FTD (n = 93), primary progressive aphasia (PPA) not otherwise specified (n = 13), non-fluent variant PPA (n = 12), memory-predominant FTD (n = 3), corticobasal syndrome (n = 2), dementia not otherwise specified (n = 2), semantic variant PPA (n = 1), progressive supranuclear palsy (n = 1).
MMSE score available in 231 non-carriers, 263 presymptomatic and 111 symptomatic carriers.
CDR® + NACC FTLD-SB score available in 173 non-carriers, 205 presymptomatic and 85 symptomatic carriers.
Neuroimaging data available in 225 non-carriers, 255 presymptomatic and 79 symptomatic carriers.
Symptomatic versus presymptomatic carriers: P < 0.001; symptomatic versus non-carriers: P < 0.001.
Symptomatic versus presymptomatic carriers: P = 0.001; symptomatic versus non-carriers: P = 0.019.
Symptomatic versus presymptomatic carriers: P = 0.001; symptomatic versus non-carriers: P = 0.002.