CBI-R total and subscale scores at baseline and over time for at-risk family members by genetic group (no outliers included)
| Baseline* | Change score | |||||
| N | Estimate (95% CI) | P value | N | Estimate (95% CI) | P value | |
| Total score | 588 | 336 | ||||
| C9orf72 | 104 | 1.34 (0.78 to 2.31) | 0.29 | 0.28 (−1.42 to 1.97) | 0.75 | |
| GRN | 138 | 0.95 (0.52 to 1.73) | 0.86 | 0.38 (−0.8 to 1.56) | 0.53 | |
| MAPT | 52 | 1.96 (0.88 to 4.38) | 0.1 | 0.39 (−1.37 to 2.15) | 0.66 | |
| YEO | 1.02 (1 to 1.03) | 0.02 | 0.03 (−0.01 to 0.07) | 0.11 | ||
| Baseline score | – | – | −0.15 (−0.21 to −0.1) | <0.0001 | ||
| C9orf72*YEO | 1 (0.98 to 1.03) | 0.8 | 0.01 (−0.08 to 0.11) | 0.78 | ||
| GRN*YEO | 1 (0.97 to 1.03) | 0.87 | −0.02 (−0.08 to 0.05) | 0.63 | ||
| MAPT*YEO | 1 (0.96 to 1.05) | 0.85 | −0.01 (−0.12 to 0.1) | 0.86 | ||
| Memory and orientation | 588 | 334 | ||||
| C9orf72 | 104 | 0.88 (0.51 to 1.52) | 0.65 | 49 | −0.02 (−0.41 to 0.37) | 0.92 |
| GRN | 138 | 1.03 (0.56 to 1.89) | 0.92 | 85 | −0.03 (−0.3 to 0.25) | 0.85 |
| MAPT | 52 | 0.89 (0.39 to 2.03) | 0.78 | 33 | −0.01 (−0.42 to 0.41) | 0.98 |
| YEO | 1.03 (1.01 to 1.04) | 0.001 | 0.01 (0.002 to 0.02) | 0.02 | ||
| Baseline score | – | – | −0.18 (−0.23 to −0.13) | <0.0001 | ||
| C9orf72*YEO | 0.98 (0.96 to 1.01) | 0.29 | −0.003 (−0.02 to 0.02) | 0.74 | ||
| GRN*YEO | 1.01 (0.98 to 1.04) | 0.47 | −0.002 (−0.02 to 0.01) | 0.78 | ||
| MAPT*YEO | 0.99 (0.95 to 1.03) | 0.59 | 0.0003 (−0.02 to 0.03) | 0.98 | ||
| Everyday skills | 588 | 335 | ||||
| C9orf72 | 104 | 0.77 (0.09 to 6.56) | 0.81 | 50 | 0.07 (−0.01 to 0.14) | 0.09 |
| GRN | 138 | 0.71 (0.1 to 4.92) | 0.72 | 85 | 0.11 (0.05 to 0.16) | 0.0001 |
| MAPT | 52 | 1.08 (0.05 to 22.27) | 0.96 | 32 | 0.03 (−0.06 to 0.11) | 0.53 |
| YEO | 1.03 (0.97 to 1.09) | 0.34 | 0.001 (0 to 0) | 0.57 | ||
| Baseline score | – | – | −0.5 (−0.55 to −0.45) | <0.0001 | ||
| C9orf72*YEO | 1 (0.89 to 1.13) | 0.96 | 0.003 (0 to 0.01) | 0.21 | ||
| GRN*YEO | 1.05 (0.93 to 1.2) | 0.42 | 0.003 (0 to 0.01) | 0.07 | ||
| MAPT*YEO | 0.96 (0.82 to 1.11) | 0.57 | 0.0002 (0 to 0.01) | 0.95 | ||
| Abnormal behaviour | 588 | 334 | ||||
| C9orf72 | 104 | 2.16 (1.09 to 4.26) | 0.03† | 48 | −0.02 (−0.3 to 0.25) | 0.86 |
| GRN | 138 | 0.83 (0.36 to 1.91) | 0.67 | 86 | −0.03 (−0.22 to 0.15) | 0.73 |
| MAPT | 52 | 2.07 (0.8 to 5.38) | 0.14 | 33 | −0.02 (−0.3 to 0.26) | 0.89 |
| YEO | 1 (0.98 to 1.02) | 0.9 | 0.004 (0 to 0.01) | 0.19 | ||
| Baseline score | – | – | −0.23 (−0.28 to −0.18) | <0.0001 | ||
| C9orf72*YEO | 1.02 (0.98 to 1.06) | 0.37 | −0.006 (−0.02 to 0.01) | 0.47 | ||
| GRN*YEO | 1 (0.96 to 1.04) | 0.99 | −0.007 (−0.02 to 0) | 0.23 | ||
| MAPT*YEO | 0.99 (0.95 to 1.04) | 0.77 | −0.0033 (−0.02 to 0.01) | 0.71 | ||
| Mood | 587 | 334 | ||||
| C9orf72 | 104 | 1.22 (0.7 to 2.12) | 0.49 | 49 | −0.07 (−0.47 to 0.34) | 0.75 |
| GRN | 137 | 0.46 (0.23 to 0.93) | 0.03 | 84 | 0.18 (−0.11 to 0.47) | 0.2 |
| MAPT | 52 | 2.75 (1.29 to 5.89) | 0.01 | 33 | 0.38 (−0.05 to 0.81) | 0.08 |
| YEO | 1.01 (0.99 to 1.03) | 0.26 | −0.002 (−0.01 to 0.01) | 0.7 | ||
| Baseline score | – | – | −0.23 (−0.28 to −0.18) | <0.0001 | ||
| C9orf72*YEO | 1 (0.97 to 1.03) | 0.80 | −0.018 (−0.04 to 0) | 0.11 | ||
| GRN*YEO | 0.97 (0.94 to 1) | 0.05 | −0.003 (−0.02 to 0.01) | 0.73 | ||
| MAPT*YEO | 1.01 (0.97 to 1.05) | 0.58 | 0.0031 (−0.02 to 0.03) | 0.81 | ||
| Beliefs | 340 | |||||
| C9orf72 | 49 | −0.004 (−0.02 to 0.01) | 0.56 | |||
| GRN | 86 | −0.01 (−0.02 to 0.0014) | 0.097 | |||
| MAPT | 33 | −0.01 (−0.02 to 0.01) | 0.46 | |||
| YEO | 0.00007 (−0.0002 to 0.0004) | 0.62 | ||||
| Baseline score | −0.38 (−0.41 to −0.34) | <0.0001 | ||||
| C9orf72*YEO | −0.00017 (−0.0009 to 0.0005) | 0.64 | ||||
| GRN*YEO | −0.00017 (−0.0007 to 0.0004) | 0.52 | ||||
| MAPT*YEO | −0.0001 (−0.0009 to 0.0007) | 0.86 | ||||
| Eating habits | 588 | 335 | ||||
| C9orf72 | 104 | 0.61 (0.16 to 2.32) | 0.46 | 49 | −0.02 (−0.2 to 0.16) | 0.83 |
| GRN | 138 | 1.57 (0.46 to 5.39) | 0.47 | 86 | 0 (−0.13 to 0.1247) | 0.99 |
| MAPT | 52 | 0.68 (0.1 to 4.82) | 0.70 | 32 | 0.1 (−0.09 to 0.29) | 0.29 |
| YEO | 1.05 (1.01 to 1.09) | 0.01 | 0.0041 (0.0001 to 0.008) | 0.04 | ||
| Baseline score | – | – | −0.35 (−0.39 to −0.31) | <0.0001 | ||
| C9orf72*YEO | 0.96 (0.89 to 1.03) | 0.25 | −0.006 (−0.02 to 0.005) | 0.28 | ||
| GRN*YEO | 1 (0.94 to 1.07) | 0.91 | −0.00002 (−0.007 to 0.007) | 0.996 | ||
| MAPT*YEO | 0.95 (0.87 to 1.05) | 0.35 | 0.003 (−0.008 to 0.01) | 0.6 | ||
| Sleep | 588 | 334 | ||||
| C9orf72 | 104 | 1.4 (0.75 to 2.64) | 0.29 | 49 | −0.13 (−0.39 to 0.13) | 0.33 |
| GRN | 138 | 1.16 (0.56 to 2.39) | 0.68 | 86 | 0.05 (−0.14 to 0.23) | 0.62 |
| MAPT | 52 | 3.37 (1.46 to 7.74) | 0.004 | 32 | 0.02 (−0.26 to 0.3) | 0.89 |
| YEO | 1.03 (1.01 to 1.05) | 0.01 | −0.0009 (−0.007 to 0.005) | 0.76 | ||
| Baseline score | – | – | −0.28 (−0.33 to −0.22) | <0.0001 | ||
| C9orf72*YEO | 1.01 (0.97 to 1.05) | 0.56 | −0.008 (−0.02 to 0.006) | 0.25 | ||
| GRN*YEO | 1 (0.96 to 1.04) | 0.86 | 0.003 (−0.008 to 0.01) | 0.63 | ||
| MAPT*YEO | 1.03 (0.98 to 1.08) | 0.26 | −0.005 (−0.02 to 0.01) | 0.54 | ||
| Stereotypic and motor behaviours | 588 | 335 | ||||
| C9orf72 | 104 | 2.15 (1.05 to 4.39) | 0.04† | 49 | −0.12 (−0.42 to 0.18) | 0.44 |
| GRN | 138 | 1.07 (0.46 to 2.52) | 0.87 | 86 | 0.08 (−0.13 to 0.28) | 0.47 |
| MAPT | 52 | 1 (0.31 to 3.23) | 0.999 | 32 | 0.002 (−0.31 to 0.32) | 0.99 |
| YEO | 1.02 (1 to 1.05) | 0.05 | 0.0079 (0.001 to 0.01) | 0.02 | ||
| Baseline score | – | – | −0.3 (−0.37 to −0.24) | <0.0001 | ||
| C9orf72*YEO | 1.03 (0.98 to 1.07) | 0.23 | −0.01 (−0.03 to 0.007) | 0.23 | ||
| GRN*YEO | 1 (0.96 to 1.05) | 0.96 | 0.0001 (−0.01 to 0.01) | 0.99 | ||
| MAPT*YEO | 0.94 (0.89 to 1) | 0.05 | 0.002 (−0.02 to 0.02) | 0.86 | ||
| Motivation | 587 | 330 | ||||
| C9orf72 | 104 | 1.91 (0.72 to 5.06) | 0.19 | 49 | 0.093 (−0.19 to 0.38) | 0.52 |
| GRN | 138 | 0.93 (0.31 to 2.75) | 0.9 | 84 | 0.02 (−0.19 to 0.22) | 0.88 |
| MAPT | 52 | 3.68 (1 to 13.52) | 0.05† | 31 | 0.0004 (−0.3 to 0.3) | 1 |
| YEO | 1.05 (1.02 to 1.08) | 0.003 | 0.002 (−0.0047 to 0.008) | 0.62 | ||
| Baseline score | – | – | −0.26 (−0.33 to −0.19) | <0.0001 | ||
| C9orf72*YEO | 0.98 (0.93 to 1.04) | 0.51 | 0.005 (−0.0109 to 0.02) | 0.54 | ||
| GRN*YEO | 0.97 (0.92 to 1.02) | 0.26 | 0.006 (−0.0057 to 0.02) | 0.31 | ||
| MAPT*YEO | 0.97 (0.9 to 1.04) | 0.41 | −0.006 (−0.0247 to 0.01) | 0.49 | ||
Statistics are from the Solution for Fixed Effects table.
The model could not be run on some subscales after outliers were removed due to low symptom endorsement. At baseline, for the self-care subscale, three participants (three preclinical) had scores above zero after outliers were removed. At baseline, for the beliefs subscale, four participants (one preclinical, two non-carrier) had scores above zero after outliers were removed. For the change score, for the self-care scale, one non-carrier endorsed a change in symptom.
For the main effect of genetic group and Gene*EYO interaction=reference group are the non-carriers.
*Baseline data were modelled with a negative binomial distribution with a log link function. Estimates and CIs of fixed effects are exponentiated (base e) and indicate the incident rates. Estimates below one indicate an inverse relationship between the variable and outcome.
†Overall effect of genetic group was not statistically significant at p<0.05 (based on type III tests of fixed effects).
CBI, Cambridge Behavioural Inventory; C9orf72, chromosome 9 open reading frame 72; GRN, progranulin; MAPT, microtubule-associated protein tau; YEO, years from estimated onset.