Table 1.
Baseline characteristics of the safety population
| Control 4 mg LMTM twice a day (n=354) |
75 mg LMTM twice a day (n=267) |
125 mg LMTM twice a day (n=264) |
Total (n=885) | |
|---|---|---|---|---|
| Age (years) | ||||
| Mean (SD) | 70·7 (8·5) | 71·0 (9·3) | 70·1 (9·3) | 70·6 (9·0) |
| Median (IQR) | 72·0 (65·0–77·0) | 72·0 (65·0–78·0) | 71·0 (64·0–77·0) | 72·0 (65·0–77·0) |
| Sex | ||||
| Male | 134 (38%) | 93 (35%) | 113 (43%) | 340 (38%) |
| Female | 220 (62%) | 174 (65%) | 151 (57%) | 545 (62%) |
| Ethnic origin | ||||
| Native American or Alaska Native | 2 (1%) | 3 (1%) | 2 (1%) | 7 (1%) |
| Asian | 41 (12%) | 32 (12%) | 30 (11%) | 103 (12%) |
| Black or African American | 3 (1%) | 3 (1%) | 4 (2%) | 10 (1%) |
| White | 307 (87%) | 226 (85%) | 225 (85%) | 758 (86%) |
| Other | 1 (<1%) | 0 | 2 (1%) | 3 (<1%) |
| Multiethnic | 0 | 3 (1%) | 1 (<1%) | 4 (<1%) |
| Years since diagnosis | 2·8 (2·4) | 2·9 (2·3) | 2·8 (2·2) | 2·8 (2·3) |
| Dementia severity (CDR score) | ||||
| 0·5 | 4 (1·1) | 1 (0·4) | 2 (0·8) | 7 (0·8) |
| 1 | 261 (73·7) | 209 (78·3) | 192 (72·7) | 662 (74·8) |
| 2 | 89 (25·1) | 57 (21·3) | 70 (26·5) | 216 (24·4) |
| MMSE score | ||||
| Mean (SD) | 18·6 (3·45) | 18·8 (3·44) | 18·5 (3·40) | 18·6 (3·43) |
| Median (IQR) | 18·0 (16·0–21·0) | 19·0 ((16·0–21·0) | 18·0 (15·0–21·0) | 18·0 (16·0–21·0) |
| MMSE severity | ||||
| MMSE score ≥20 | 134 (38%) | 105 (39%) | 98 (37%) | 337 (38%) |
| MMSE score <20 | 220 (62%) | 162 (61%) | 166 (63%) | 548 (62%) |
| ADAS-Cog score | ||||
| Mean (SD) | 27·2 (10·1) | 26·5 (9·4) | 26·7 (9·7) | 26·9 (9·8) |
| Median (IQR) | 26·3 (19·7–34·0) | 26·3 (18·7–32·7) | 26·3 (19·0–32·7) | 26·3 (19·3–33·0) |
| ADCS-ADL score | ||||
| Mean (SD) | 55·9 (12·7) | 58·0 (11·1) | 57·5 (12·7) | 57·0 (12·3) |
| Median (IQR) | 58·0 (48·0–65·0) | 58·5 (52·0–65·8) | 60·0 (48·0–67·9) | 59·0 (49·0–66·0) |
| Whole brain volume (cm3) | ||||
| Mean (SD) | 927 (108) | 922 (115) | 939 (101) | 929 (108) |
| Median (IQR) | 917 (847–1004) | 922 (848–993) | 934 (965–1005) | 925 (854–1002) |
| Lateral ventricular volume (cm3) | ||||
| Mean (SD) | 52 (23) | 52 (26) | 51 (23) | 52 (24) |
| Median (IQR) | 49 (35–66) | 44 (32–65) | 47 (34–62) | 47 (34–64) |
| Hippocampal volume (cm3) | ||||
| Mean (SD) | 2·3 (0·6) | 2·7 (0·6) | 2·9 (0·6) | 2·8 (0·6) |
| Median (IQR) | 2·7 (2·4–3·1) | 2·7 (2·3–3·1) | 2·8 (2·4–3·2) | 2·7 (2·4–3·1) |
| Alzheimer’s disease-approved comedications |
||||
| Acetylcholinesterase inhibitors only | 183 (52%) | 151 (57%) | 150 (57%) | 484 (55%) |
| Memantine only | 32 (9%) | 16 (6%) | 15 (6%) | 63 (7%) |
| Acetylcholinesterase inhibitors and memantine |
93 (26%) | 60 (22%) | 61 (23%) | 214 (24%) |
| Cerebrospinal fluid biomarkers (ng/L) | ||||
| Total tau | 143·9 (68·4; n=19) | 156·4 (72·5; n=15) | 113·2 (547; n=5) | 144·8 (68·2; n=39) |
| Phospho-tau | 59·2 (25·3; n=20) | 61·2 (20·3; n=15) | 58·1 (12·8; n=5) | 59·8 (21·9; n=40) |
| Aβ1–42 | 2647 (96·6; n=20) | 276·0 (85·9; n=15) | 235·8 (62·1; n=5) | 265·3 (88·0; n=40) |
| APOE genotype* | ||||
| ε4 allele present | 144/303 (48%) | 91/217 (42%) | 114/217 (53%) | 349/737 (47%) |
| ε4 allele absent | 159/303 (52%) | 126/217 (58%) | 103/217 (47%) | 388/737 (53%) |
Data are mean (SD), median (IQR), n (%), or n/N (%)· LMTM=leuco-methylthioninium bis(hydromethanesulfonate)· CDR=Clinical Dementia Rating· MMSE=Mini-Mental State Examination· ADAS-Cog=Alzheimer’s Disease Assessment Scale-Cognitive Subscale· ADCS-ADL=Alzheimer’s Disease Cooperative Study-Activities of Daily Living.
*
Denominator is the available sample.