Analyses conducted in the full sample and the two prespecified subgroups all showed the same general pattern of results. The PSPRS required the fewest participants to detect a treatment effect, followed by the FTLD-CDR Sum of Boxes score. The MoCA total score also performed fairly well, with diminished success in the least impaired subsample (FTLD CDR global score ≤1, PSPRS ≤ 25).. Regarding cognitive measures, there was no clear strongest indicator, but Digit Span Backwards consistently performed the worst. Based on all samples, it may be best to administer both Trail making tasks (Trails A and Trails B) as well as all fluency tasks (Animals, Vegetables, Words (L) and Words (F) ). The total time for this administration is up to approximately 15 minutes, but will be much less in most cases. The UDS3EF-Restricted composite measure, formed from fluency items and Trails A, outperformed the UDS3EF, which also included Trails B and Digits Backwards. The UDS3EF-Restricted also performed better than some individual cognitive tasks, providing some support for it’s use in the sample. It can be calculated from the aforementioned cognitive tasks and does not add time to administration.
The first tab (dataset) provides descriptions of the data.
| Overall | |
|---|---|
| n | 65 |
| days_between_visit (mean (SD)) | 286.34 (82.04) |
| age_at_visit (mean (SD)) | 68.20 (7.42) |
| education (mean (SD)) | 15.69 (2.56) |
| sex_at_birth = M (%) | 37 (56.9) |
| ftldcdr_global (%) | |
| 0 | 1 ( 1.5) |
| 0.5 | 21 (32.3) |
| 1 | 28 (43.1) |
| 2 | 13 (20.0) |
| 3 | 2 ( 3.1) |
| genetic_status (%) | |
| MAPT | 2 ( 3.1) |
| NONE-Research genetic testing completed and no mutation identified | 48 (73.8) |
| OTHER-Variant of unknown significance | 3 ( 4.6) |
| Pending results | 12 (18.5) |
| moca_total (mean (SD)) | 21.32 (4.67) |
| psprs_totalcln (mean (SD)) | 29.64 (12.01) |
| ftldcdr_sob (mean (SD)) | 5.25 (3.88) |
| uds3_ef (mean (SD)) | -2.03 (0.80) |
| uds.ef.rest (mean (SD)) | -2.09 (0.94) |
| flu_animal (mean (SD)) | 11.59 (5.06) |
| flu_veg (mean (SD)) | 7.70 (3.49) |
| flu_fwords (mean (SD)) | 7.17 (4.24) |
| flu_lwords (mean (SD)) | 6.71 (3.71) |
| traila_ratio (mean (SD)) | 3.32 (2.41) |
| udsvertn (mean (SD)) | 13.91 (7.60) |
| trailb_ratio (mean (SD)) | 13.60 (14.74) |
| dig_back_sum (mean (SD)) | 4.36 (1.90) |
| 0 | 0.5 | 1 | 2 | 3 | p | test | |
|---|---|---|---|---|---|---|---|
| n | 1 | 21 | 28 | 13 | 2 | ||
| days_between_visit (mean (SD)) | NaN (NA) | 310.45 (99.82) | 270.92 (69.39) | 261.46 (56.47) | 407.50 (26.16) | 0.038 | |
| age_at_visit (mean (SD)) | 80.00 (NA) | 68.38 (6.89) | 68.04 (6.54) | 70.15 (6.56) | 50.00 (7.07) | NA | |
| education (mean (SD)) | 18.00 (NA) | 15.81 (2.46) | 16.07 (2.43) | 14.46 (2.90) | 16.00 (2.83) | NA | |
| sex_at_birth = M (%) | 1 (100.0) | 11 (52.4) | 18 (64.3) | 6 (46.2) | 1 (50.0) | 0.698 | |
| genetic_status (%) | 0.002 | ||||||
| MAPT | 0 ( 0.0) | 0 ( 0.0) | 1 ( 3.6) | 0 ( 0.0) | 1 (50.0) | ||
| NONE-Research genetic testing completed and no mutation identified | 1 (100.0) | 18 (85.7) | 18 (64.3) | 11 (84.6) | 0 ( 0.0) | ||
| OTHER-Variant of unknown significance | 0 ( 0.0) | 0 ( 0.0) | 2 ( 7.1) | 0 ( 0.0) | 1 (50.0) | ||
| Pending results | 0 ( 0.0) | 3 (14.3) | 7 (25.0) | 2 (15.4) | 0 ( 0.0) | ||
| moca_total (mean (SD)) | 23.00 (NA) | 23.24 (3.46) | 21.70 (3.89) | 18.20 (5.49) | 8.00 (NA) | NA | |
| psprs_totalcln (mean (SD)) | 22.00 (NA) | 23.62 (10.01) | 30.21 (10.23) | 39.50 (8.98) | 50.50 (21.92) | NA | |
| ftldcdr_sob (mean (SD)) | 0.00 (NA) | 2.14 (0.95) | 4.86 (1.52) | 9.50 (2.28) | 18.50 (0.71) | NA | |
| uds3_ef (mean (SD)) | -1.07 (NA) | -1.86 (0.98) | -2.03 (0.72) | -2.32 (0.61) | -2.87 (NA) | NA | |
| uds.ef.rest (mean (SD)) | -1.04 (NA) | -1.78 (0.99) | -2.09 (0.92) | -2.62 (0.69) | -3.11 (NA) | NA | |
| flu_animal (mean (SD)) | 13.00 (NA) | 14.33 (5.55) | 11.22 (4.17) | 8.00 (3.50) | 3.00 (NA) | NA | |
| flu_veg (mean (SD)) | 10.00 (NA) | 9.42 (3.55) | 7.22 (3.03) | 6.11 (2.93) | 0.00 (NA) | NA | |
| flu_fwords (mean (SD)) | 11.00 (NA) | 8.63 (3.74) | 7.33 (4.33) | 4.45 (3.59) | 1.00 (NA) | NA | |
| flu_lwords (mean (SD)) | 9.00 (NA) | 7.61 (4.19) | 6.67 (3.73) | 5.27 (2.80) | 5.00 (NA) | NA | |
| traila_ratio (mean (SD)) | 0.96 (NA) | 2.85 (1.42) | 3.30 (2.61) | 4.63 (3.19) | NaN (NA) | NA | |
| udsvertn (mean (SD)) | 20.00 (NA) | 16.44 (7.55) | 14.00 (7.73) | 9.73 (6.00) | 6.00 (NA) | NA | |
| trailb_ratio (mean (SD)) | 3.29 (NA) | 12.59 (12.88) | 12.94 (13.09) | 18.29 (22.03) | NaN (NA) | NA | |
| dig_back_sum (mean (SD)) | 5.00 (NA) | 4.42 (2.24) | 4.28 (1.67) | 4.67 (1.94) | 2.00 (NA) | NA |
Each analysis below is based on the change over time in the data set described above. A difference score was calculated (Visit 2 score - Visit 1 score). This difference was then annualized: [difference score / days between visits ] * 365. Therefore we have 2 variables of interest (and SD) based on units:
Raw score units: Difference (Diff SD)
Annualized units: Annualized decline (Ann. SD)
I calculated necessary sample size for each measure to detect a hypothetical drug effect that reduced decline by 30%. Power was set at .8 with an alpha of .05. Let me know if you want any other values here.
I completed analyses first in the full sample, then in sub samples that were closer to what would be in the actual trial. The tables below present the estimated sample sizes for:
Raw score units: SampleSize_RawUnits
Annualized units: SampleSize_ann
| Variable | Sample Size | Difference | Diff. SD | Annualized Decline | Ann. SD | SampleSize_rawunits | SampleSize_ann |
|---|---|---|---|---|---|---|---|
| PSPRS Total | 43 | 9.302 | 12.118 | 12.996 | 18.728 | 80 | 98 |
| CDR+FTLD Sb | 61 | 1.869 | 3.063 | 2.482 | 4.396 | 127 | 148 |
| MoCA Total | 49 | -1.857 | 4.021 | -2.299 | 5.402 | 222 | 261 |
| Trails A Ratio | 42 | 1.477 | 3.679 | 1.969 | 4.875 | 293 | 290 |
| Animals | 47 | -1.383 | 4.163 | -1.613 | 5.602 | 429 | 570 |
| UDS3EF-Restricted | 52 | -0.199 | 0.647 | -0.248 | 0.910 | 502 | 638 |
| Vegetables | 49 | -0.714 | 2.630 | -0.918 | 3.764 | 641 | 796 |
| Trails B Ratio | 31 | 2.191 | 8.352 | 2.662 | 11.102 | 687 | 823 |
| Words (F) | 50 | -0.880 | 3.420 | -1.121 | 4.730 | 715 | 841 |
| UDS3EF | 51 | -0.132 | 0.551 | -0.161 | 0.754 | 825 | 1032 |
| Backwards Digit Span | 47 | -0.404 | 1.861 | -0.601 | 2.534 | 1002 | 842 |
| Words (L) | 49 | -0.612 | 2.971 | -0.550 | 4.649 | 1113 | 3379 |
| Variable | Sample Size | Difference | Diff. SD | Annualized Decline | Ann. SD | SampleSize_rawunits | SampleSize_ann |
|---|---|---|---|---|---|---|---|
| PSPRS Total | 36 | 9.889 | 12.547 | 13.922 | 19.248 | 76 | 90 |
| CDR+FTLD Sb | 46 | 2.120 | 3.072 | 2.809 | 4.361 | 99 | 114 |
| Trails B Ratio | 27 | 3.273 | 7.056 | 4.315 | 8.768 | 220 | 195 |
| MoCA Total | 39 | -1.974 | 4.264 | -2.417 | 5.732 | 221 | 266 |
| Trails A Ratio | 37 | 1.413 | 3.577 | 1.719 | 4.121 | 303 | 272 |
| UDS3EF-Restricted | 42 | -0.235 | 0.683 | -0.277 | 0.959 | 401 | 568 |
| Animals | 39 | -1.410 | 4.399 | -1.508 | 5.828 | 460 | 706 |
| Words (F) | 41 | -1.098 | 3.639 | -1.425 | 5.029 | 520 | 589 |
| Vegetables | 41 | -0.707 | 2.695 | -0.878 | 3.688 | 686 | 835 |
| UDS3EF | 41 | -0.129 | 0.582 | -0.153 | 0.806 | 958 | 1305 |
| Words (L) | 40 | -0.675 | 3.214 | -0.482 | 5.004 | 1072 | 5100 |
| Backwards Digit Span | 39 | -0.231 | 1.898 | -0.350 | 2.528 | 3199 | 2463 |
| Variable | Sample Size | Difference | Diff. SD | Annualized Decline | Ann. SD | SampleSize_rawunits | SampleSize_ann |
|---|---|---|---|---|---|---|---|
| PSPRS Total | 14 | 11.357 | 10.846 | 15.271 | 16.048 | 8 | 10 |
| CDR+FTLD Sb | 18 | 1.472 | 1.898 | 1.696 | 2.058 | 15 | 13 |
| Animals | 15 | -2.067 | 4.728 | -1.685 | 6.066 | 46 | 113 |
| Trails A Ratio | 15 | 0.525 | 1.497 | 0.526 | 1.614 | 71 | 82 |
| Trails B Ratio | 11 | 1.683 | 7.251 | 2.078 | 7.712 | 161 | 120 |
| Words (L) | 16 | 0.688 | 3.497 | 1.574 | 5.479 | 225 | 105 |
| UDS3EF-Restricted | 16 | -0.152 | 0.878 | -0.061 | 1.127 | 290 | 2951 |
| Vegetables | 16 | -0.312 | 2.575 | -0.237 | 3.477 | 590 | 1863 |
| Backwards Digit Span | 16 | 0.188 | 1.870 | 0.359 | 2.197 | 864 | 326 |
| MoCA Total | 14 | -0.214 | 3.926 | -0.553 | 5.275 | 2915 | 792 |
| Words (F) | 16 | -0.188 | 4.262 | -0.086 | 5.459 | 4487 | 35299 |
| UDS3EF | 16 | -0.023 | 0.752 | 0.064 | 0.957 | 9233 | 1973 |