Table 2.
Baseline descriptive statistics of measures for each genetic group at three epochs.
| Mutation Status | Outcome Measure | Disease Age Epoch | |||
|---|---|---|---|---|---|
| −40 to −10 YSO | −10 to 0 YSO | 0+ YSO | |||
| Age-Matched Controls | N (prop) at baseline | 229 (0.56) | 85 (0.21) | 98 (0.24) | |
| Mean Age (SD) at baseline | 36.8 (7.7) | 52.6 (6.7) | 61.6 (7.7) | ||
| Mean Raw Score (SD; Range) | CDR®+ NACC FTLD SB | 0 (0; 0–0) | 0 (0; 0–0) | 0 (0; 0–0) | |
| Trails A (Total time in Seconds) | 22.76 (8.03; 8–78) | 26.36 (9.39; 12–61) | 31.07 (14.67; 12–89) | ||
| Trails B (Total time in Seconds) | 53.81 (21.93; 19–187) | 62.06 (29.48; 27–202) | 73.63 (30.43; 31–167) | ||
| MINT (Total Correct) | 29.92 (1.75; 24–32) | 29.94 (1.62; 26–32) | 29.95 (1.92; 25–32) | ||
| MRI Frontal/TIV | 7.07 (0.48; 5.39–8.21) | 6.68 (0.41; 5.83–7.55) | 6.33 (0.45; 5.27–7.28) | ||
| MRI Temporal/TIV | 4.76 (0.29; 3.76–5.62) | 4.54 (0.22; 4.07–5.03) | 4.24 (0.28; 3.46–4.79) | ||
| MRI Medial Temporal (MTL)/TIV | 1.03 (0.06; 0.81–1.22) | 1.02 (0.06; 0.89–1.19) | 0.97 (0.07; 0.8–1.13) | ||
| NfL (log) | 1.67 (0.43; 0.38–3.27) | 2.05 (0.38; 1.06–2.94) | 2.42 (0.43; 1.71–3.76) | ||
| C9orf72 | N (prop) at baseline | 135 (0.39) | 63 (0.18) | 149 (0.43) | |
| Mean Age (SD) at baseline | 38.3 (8.8) | 54.6 (8.2) | 61.5 (9) | ||
| Mean Raw Score (SD; Range) | CDR®+ NACC FTLD SB | 0.19 (0.57; 0–3) | 0.31 (0.69; 0–3.5) | 8.32 (6.23; 0–22) | |
| Trails B (Total time in Seconds) | 58.92 (21.85; 28–151) | 84 (45.61; 23–300) | 168.25 (88.4; 35–300) | ||
| MRI Temporal/TIV | 4.58 (0.29; 3.95–5.22) | 4.16 (0.32; 3.43–4.71) | 3.76 (0.46; 2.29–4.78) | ||
| NfL (log) | 1.89 (0.48; 0.94–3.89) | 2.58 (0.6; 1.72–4.76) | 3.31 (0.85; 1.54–5.54) | ||
| Mean Standardized Units from Control (SD; Range) | CDR®+ NACC FTLD SB | --- | --- | --- | |
| Trails B | 0.23 (1; −1.18–4.43) | 0.74 (1.55; −1.32–8.07) | 3.11 (2.91; −1.27–7.44) | ||
| MRI Temporal/TIV | −0.62 (1; −2.79–1.56) | −1.75 (1.43; −5.04–0.76) | −1.71 (1.65; −6.92–1.94) | ||
| NfL (log) | 0.51 (1.11; −1.68–5.1) | 1.37 (1.57; −0.85–7.06) | 2.07 (1.96; −2.01–7.18) | ||
| GRN | N (prop) at baseline | 125 (0.44) | 72 (0.26) | 84 (0.3) | |
| Mean Age (SD) at baseline | 41 (10.3) | 58.2 (7.5) | 63.7 (8.8) | ||
| Mean Raw Score (SD; Range) | CDR®+ NACC FTLD SB | 0.08 (0.26; 0–2) | 0.31 (0.71; 0–3) | 9.19 (6.53; 0–24) | |
| Trails A (Total time in Seconds) | 25.37 (9.2; 9–63) | 30.57 (10.73; 16–81) | 72.12 (46.48; 23–150) | ||
| MRI Frontal/TIV | 7.03 (0.52; 5.39–8.93) | 6.4 (0.52; 5.25–7.48) | 5.15 (0.92; 2.62–7.77) | ||
| NfL (log) | 1.87 (0.43; 0.82–3.34) | 2.45 (0.56; 1.57–4.27) | 4.04 (0.65; 2.14–5.35) | ||
| Mean Standardized Units from Control (SD; Range) | CDR®+ NACC FTLD SB | --- | --- | --- | |
| Trails A | 0.33 (1.15; −1.71–5.01) | 0.45 (1.14; −1.1–5.82) | 2.8 (3.17; −0.55–8.11) | ||
| MRI Frontal/TIV | −0.08 (1.09; −3.49–3.89) | −0.68 (1.26; −3.46–1.92) | −2.59 (2.02; −8.18–3.18) | ||
| NfL (log) | 0.46 (1; −1.95–3.84) | 1.04 (1.45; −1.25–5.79) | 3.74 (1.49; −0.62–6.75) | ||
| MAPT | N (prop) at baseline | 69 (0.41) | 37 (0.22) | 62 (0.37) | |
| Mean Age (SD) at baseline | 34.1 (9.2) | 46.3 (9.5) | 56.1 (8.6) | ||
| Mean Raw Score (SD; Range) | CDR®+ NACC FTLD SB | 0.15 (0.48; 0–2.5) | 0.39 (0.76; 0–3) | 7.9 (6.51; 0–24) | |
| MINT (Total Correct) | 29.88 (1.8; 25–32) | 29.16 (3; 17–32) | 21.22 (8.04; 1–32) | ||
| MRI MTL/TIV | 1.05 (0.06; 0.87–1.16) | 0.98 (0.07; 0.77–1.08) | 0.72 (0.14; 0.46–1.04) | ||
| NfL (log) | 1.69 (0.45; 0.39–2.53) | 1.98 (0.55; 0.93–3.44) | 3.04 (0.55; 1.93–5.1) | ||
| Mean Standardized Units from Control (SD; Range) | CDR®+ NACC FTLD SB | --- | --- | --- | |
| MINT | −0.02 (1.03; −2.82–1.19) | −0.48 (1.85; −7.98–1.27) | −4.56 (4.2; −15.12–1.07) | ||
| MRI MTL/TIV | 0.41 (1.04; −2.7–2.15) | −0.69 (1.29; −4.46–1.15) | −3.33 (1.86; −6.87–1.04) | ||
| NfL (log) | 0.04 (1.03; −2.95–1.98) | −0.19 (1.45; −2.91–3.63) | 1.45 (1.26; −1.11–6.17) | ||
Note. Baseline raw and standardized values for several measures are displayed for controls and mutation carriers at three Disease Age Epochs. Each participant was assigned to a Disease Age epoch based on the estimated Disease Age at their first visit. Clinical and imaging measures were selected by choosing the “best” measure for each genetic group based on when they became elevated compared to controls and the rate of longitudinal change (descriptive statistics for all modeled measures are displayed in Supplemental Table S2 and S3). Raw imaging measures are presented as percentage of total intracranial volume to account for head size. Mean standardized units from controls indicates the number of standard deviations from the control group.
Abbreviations: Prop: Proportion; CDR®+NACC FTLD SB: Clinical Dementia Rating Scale plus National Alzheimer’s Coordinating Center’s Frontotemporal Lobar Degeneration Module Sum of Boxes; Trail B: Trail Making Test, Part B; MINT: Multilingual Naming Test; MRI: magnetic resonance imaging; TIV: Total intracranial volume; NfL (log): Log-transformed plasma neurofilament light chain