Table 1
Demographic Characteristics.
| Age of Onset Groups | ALL | |||||||
|---|---|---|---|---|---|---|---|---|
| Young onset (20–29 years) | Typical onset (30–59 years) | Late onset (60+ years) | ||||||
| N | % | N | % | N | % | N | % | |
| TFC stage | ||||||||
| Stage I (11–13) | 191 | 31.31 | 1864 | 32.30 | 278 | 30.18 | 2333 | 31.95 |
| Stage II (7–10) | 198 | 32.46 | 2025 | 35.09 | 347 | 37.68 | 2570 | 35.20 |
| Stage III (3–6) | 139 | 22.79 | 1265 | 21.92 | 215 | 23.34 | 1619 | 22.17 |
| Stage IV (1–2) | 54 | 8.85 | 445 | 7.71 | 67 | 7.27 | 566 | 7.75 |
| Stage V (0) | 28 | 4.59 | 172 | 2.98 | 14 | 1.52 | 214 | 2.93 |
| TFC stage | ||||||||
| Early (Stage I & II) | 389 | 63.77 | 3889 | 67.39 | 625 | 67.86 | 4903 | 67.15 |
| Moderate (Stage III) | 139 | 22.79 | 1265 | 21.92 | 215 | 23.34 | 1619 | 22.17 |
| Advanced (Stage IV & V) | 82 | 13.44 | 617 | 10.69 | 81 | 8.79 | 780 | 10.68 |
| Sex | ||||||||
| Female | 319 | 52.12 | 2998 | 51.90 | 445 | 48.21 | 3762 | 51.46 |
| Male | 293 | 47.88 | 2778 | 48.10 | 478 | 51.79 | 3549 | 48.54 |
| Race | ||||||||
| Other | 41 | 6.70 | 335 | 5.80 | 39 | 4.23 | 415 | 5.68 |
| White/Caucasian | 571 | 93.30 | 5441 | 94.20 | 884 | 95.77 | 6896 | 94.32 |
| Has Mother Affected | 279 | 46.66 | 2660 | 47.75 | 365 | 45.23 | 3304 | 47.36 |
| Has Father Affected | 308 | 51.85 | 2602 | 47.12 | 278 | 34.71 | 3188 | 46.09 |
| Has Family History | 526 | 85.95 | 4866 | 84.25 | 788 | 85.37 | 6180 | 84.53 |
| Marital Status | ||||||||
| Married/Partnership | 199 | 32.52 | 3782 | 65.56 | 691 | 74.95 | 4672 | 63.97 |
| Single/Divorced/Widowed/Legally Separated | 413 | 67.48 | 1987 | 34.44 | 231 | 25.05 | 2631 | 36.03 |
| ISCED Education Level | ||||||||
| Less than or equal to 12th grade | 374 | 61.41 | 3217 | 55.96 | 541 | 58.87 | 4132 | 56.78 |
| Higher than 12th grade | 235 | 38.59 | 2532 | 44.04 | 378 | 41.13 | 3145 | 43.22 |
| Employment Status | ||||||||
| Employed | 129 | 21.11 | 1302 | 22.59 | 79 | 8.60 | 1510 | 20.70 |
| Not Employed | 482 | 78.89 | 4461 | 77.41 | 840 | 91.40 | 5783 | 79.30 |
| Rater’s Judgement of Initial Major Symptom | ||||||||
| Motor | 269 | 44.39 | 2966 | 51.51 | 631 | 68.36 | 3866 | 53.05 |
| Cognitive | 46 | 7.59 | 489 | 8.49 | 42 | 4.55 | 577 | 7.92 |
| Psychiatric | 165 | 27.23 | 1197 | 20.79 | 104 | 11.27 | 1466 | 20.12 |
| Oculomotor/Other/Mixed | 126 | 20.79 | 1106 | 19.21 | 146 | 15.82 | 1378 | 18.91 |
| Mean | SD | Mean | SD | Mean | SD | Mean | SD | |
| BMI | 24.32 | 5.43 | 25.03 | 5.03 | 25.02 | 4.31 | 24.97 | 4.99 |
| Age of clinical HD diagnosis | 29.83 | 6.25 | 48.27 | 8.72 | 67.92 | 5.57 | 49.22 | 11.99 |
| Larger research CAG allele determined from DNA | 49.81 | 4.67 | 43.59 | 2.49 | 40.75 | 1.19 | 43.75 | 3.34 |
[i] Missing values were encountered in 9 (0.12%) for TFC score, 335 (4.58%) for mother affected, 394 (5.39%) for father affected, 8 (0.11%) for marital status, 34 (0.47%) for education level, 18 (0.25%) for employment status, 24 (0.33%) for rater’s judgement of initial major symptom, 235 (3.21%) in BMI, and 140 (1.91%) in age of clinical HD diagnosis.
Table 2
Motor and Cognitive Variables by Age of Onset Groups and TFC Stages.
| TFC Score Category | Young | Typical | Late | P-value | ||||
|---|---|---|---|---|---|---|---|---|
| N | Median (Q1–Q3) or N (%) | N | Median (Q1–Q3) or N (%) | N | Median (Q1–Q3) or N (%) | |||
| Motor Symptoms | ||||||||
| UHDRS Motor score (TMS) | Early | 387 | 25.00 (15.00, 38.00) | 3871 | 27.00 (18.00, 38.00) | 619 | 30.00 (20.00, 39.00) | * <0.01 |
| Moderate | 139 | 56.00 (39.00, 67.00) | 1248 | 51.00 (38.50, 63.00) | 214 | 51.00 (39.00, 60.00) | 0.13 | |
| Advanced | 80 | 83.00 (70.00, 91.50) | 609 | 75.00 (63.00, 87.00) | 79 | 65.00 (53.00, 77.00) | * <0.01 | |
| Timed “Up and Go” Total time | Early | 190 | 8.75 (7.00, 11.00) | 1661 | 9.00 (7.40, 11.00) | 252 | 10.00 (8.80, 13.00) | * <0.01 |
| Moderate | 45 | 11.00 (9.00, 15.00) | 462 | 12.00 (9.50, 16.00) | 63 | 14.00 (11.00, 20.00) | * 0.02 | |
| Advanced | 10 | 14.00 (12.00, 21.00) | 72 | 15.50 (10.00, 23.00) | 12 | 17.00 (15.00, 26.50) | 0.47 | |
| Cognitive Symptoms | ||||||||
| Symbol Digit Modality Test Total correct % | Early | 384 | 100.00 (93.75, 100.00) | 3819 | 100.00 (95.00, 100.00) | 609 | 100.00 (93.33, 100.00) | * 0.02 |
| Moderate | 118 | 100.00 (86.67, 100.00) | 1104 | 96.23 (86.36, 100.00) | 187 | 95.00 (75.00, 100.00) | 0.13 | |
| Advanced | 52 | 0.00 (0.00, 87.78) | 398 | 0.00 (0.00, 94.74) | 45 | 50.00 (0.00, 100.00) | 0.16 | |
| Verbal Fluency Test Total correct % Category | Early | 384 | 100.00 (93.22, 100.00) | 3847 | 100.00 (90.91, 100.00) | 622 | 100.00 (90.91, 100.00) | * 0.01 |
| Moderate | 134 | 100.00 (87.50, 100.00) | 1227 | 100.00 (85.71, 100.00) | 210 | 100.00 (83.33, 100.00) | 0.41 | |
| Advanced | 65 | 85.71 (0.00, 100.00) | 491 | 85.71 (40.00, 100.00) | 67 | 100.00 (75.00, 100.00) | * 0.03 | |
| Verbal Fluency Test Total correct % Letter | Early | 300 | 95.45 (90.12, 100.00) | 3037 | 95.00 (88.89, 100.00) | 456 | 94.12 (87.50, 100.00) | 0.18 |
| Moderate | 92 | 94.28 (85.96, 100.00) | 854 | 92.98 (82.61, 100.00) | 155 | 90.00 (76.00, 100.00) | * <0.01 | |
| Advanced | 41 | 80.95 (0.00, 100.00) | 277 | 76.47 (50.00, 100.00) | 41 | 85.71 (61.54, 100.00) | 0.44 | |
| Stroop Color Naming Test Total correct % | Early | 381 | 100.00 (100.00, 100.00) | 3833 | 100.00 (100.00, 100.00) | 614 | 100.00 (100.00, 100.00) | 0.84 |
| Moderate | 133 | 100.00 (98.63, 100.00) | 1206 | 100.00 (98.08, 100.00) | 202 | 100.00 (97.50, 100.00) | 0.78 | |
| Advanced | 64 | 98.49 (0.00, 100.00) | 468 | 97.26 (0.00, 100.00) | 60 | 98.53 (64.38, 100.00) | 0.82 | |
| Stroop Word Reading test Total correct % | Early | 381 | 100.00 (100.00, 100.00) | 3831 | 100.00 (100.00, 100.00) | 614 | 100.00 (100.00, 100.00) | 0.18 |
| Moderate | 129 | 100.00 (100.00, 100.00) | 1187 | 100.00 (100.00, 100.00) | 200 | 100.00 (100.00, 100.00) | 0.65 | |
| Advanced | 63 | 96.67 (0.00, 100.00) | 457 | 100.00 (0.00, 100.00) | 60 | 100.00 (0.00, 100.00) | 0.19 | |
| Stroop Interference Test Total correct % | Early | 356 | 100.00 (96.08, 100.00) | 3511 | 100.00 (96.15, 100.00) | 548 | 100.00 (95.00, 100.00) | 0.24 |
| Moderate | 106 | 100.00 (88.89, 100.00) | 956 | 100.00 (87.50, 100.00) | 155 | 94.74 (76.92, 100.00) | * 0.02 | |
| Advanced | 38 | 95.00 (36.84, 100.00) | 281 | 88.24 (16.67, 100.00) | 33 | 84.62 (30.00, 100.00) | 0.53 | |
| Mini Mental State Examination (MMSE) score | Early | 270 | 26.00 (24.00, 29.00) | 2562 | 27.00 (25.00, 29.00) | 393 | 27.00 (25.00, 28.00) | 0.13 |
| Moderate | 80 | 24.00 (20.00, 26.50) | 725 | 23.00 (20.00, 26.00) | 128 | 23.00 (19.00, 25.00) | 0.08 | |
| Advanced | 34 | 17.00 (11.00, 22.00) | 252 | 17.00 (13.00, 21.00) | 37 | 18.00 (15.00, 22.00) | 0.68 | |
[i] * Significant at level p < 0.05.
Table 3
Behavioral Variables by Age of Onset Groups and TFC Stages.
| TFC Score Category | Young | Typical | Late | P-value | ||||
|---|---|---|---|---|---|---|---|---|
| N | Median (Q1–Q3) or N (%) | N | Median (Q1–Q3) or N (%) | N | Median (Q1–Q3) or N (%) | |||
| Behavioral Symptoms | ||||||||
| Has the participant ever abused drugs? Yes | Early | 389 | 77 (19.79) | 3883 | 385 (9.92) | 622 | 23 (3.70) | * <0.01 |
| Moderate | 139 | 27 (19.42) | 1262 | 84 (6.66) | 214 | 4 (1.87) | * <0.01 | |
| Advanced | 80 | 10 (12.50) | 613 | 23 (3.75) | 81 | 0 (0.00) | * <0.01 | |
| Has the participant had alcohol problems in the past? Yes | Early | 389 | 50 (12.85) | 3881 | 358 (9.22) | 622 | 28 (4.50) | * <0.01 |
| Moderate | 139 | 17 (12.23) | 1261 | 146 (11.58) | 214 | 15 (7.01) | 0.13 | |
| Advanced | 81 | 8 (9.88) | 612 | 64 (10.46) | 81 | 5 (6.17) | 0.55 | |
| HADS-SIS anxiety subscore | Early | 264 | 6.00 (3.50, 9.00) | 2417 | 6.00 (3.00, 9.00) | 365 | 4.00 (2.00, 7.00) | * <0.01 |
| Moderate | 62 | 4.00 (2.00, 8.00) | 604 | 5.00 (3.00, 9.00) | 100 | 5.00 (3.00, 8.00) | 0.28 | |
| Advanced | 24 | 4.00 (2.50, 8.50) | 172 | 5.00 (3.00, 9.00) | 25 | 4.00 (2.00, 6.00) | 0.40 | |
| HADS-SIS depression subscore | Early | 264 | 5.00 (3.00, 8.00) | 2416 | 5.00 (3.00, 8.00) | 365 | 4.00 (2.00, 7.00) | * <0.01 |
| Moderate | 62 | 5.00 (3.00, 8.00) | 602 | 7.00 (4.00, 10.00) | 99 | 8.00 (4.00, 11.00) | * <0.01 | |
| Advanced | 24 | 7.00 (3.00, 11.00) | 176 | 8.00 (5.00, 12.00) | 25 | 7.00 (6.00, 9.00) | 0.39 | |
| HADS-SIS irritability subscore | Early | 263 | 6.00 (3.00, 10.00) | 2413 | 6.00 (2.00, 9.00) | 365 | 5.00 (2.00, 7.00) | * <0.01 |
| Moderate | 62 | 5.00 (2.00, 8.00) | 601 | 5.00 (2.00, 9.00) | 100 | 5.00 (3.00, 8.00) | 0.52 | |
| Advanced | 25 | 4.00 (2.00, 8.00) | 174 | 5.00 (2.00, 8.00) | 25 | 4.00 (2.00, 7.00) | 0.88 | |
| HADS-SIS outward irritability subscore | Early | 263 | 4.00 (2.00, 7.00) | 2426 | 3.00 (1.00, 6.00) | 368 | 3.00 (1.00, 5.00) | * <0.01 |
| Moderate | 62 | 3.00 (1.00, 6.00) | 604 | 3.00 (1.00, 6.00) | 101 | 3.00 (1.00, 5.00) | 0.23 | |
| Advanced | 25 | 3.00 (1.00, 5.00) | 175 | 3.00 (1.00, 6.00) | 25 | 2.00 (1.00, 5.00) | 0.65 | |
| HADS-SIS inward irritability subscore | Early | 264 | 2.00 (0.00, 4.00) | 2421 | 2.00 (0.00, 4.00) | 365 | 2.00 (0.00, 3.00) | * <0.01 |
| Moderate | 62 | 1.00 (0.00, 3.00) | 603 | 2.00 (0.00, 4.00) | 100 | 2.50 (1.00, 4.00) | * 0.01 | |
| Advanced | 25 | 1.00 (0.00, 3.00) | 174 | 1.00 (0.00, 3.00) | 25 | 1.00 (0.00, 3.00) | 0.86 | |
| Total # of suicide attempts (C-SSRS BL and FUP) | Early | 27 | 1.00 (1.00, 2.00) | 142 | 1.00 (1.00, 2.00) | 13 | 1.00 (1.00, 1.00) | 0.55 |
| Moderate | 19 | 1.00 (1.00, 2.00) | 75 | 1.00 (1.00, 2.00) | 7 | 1.00 (1.00, 2.00) | 0.99 | |
| Advanced | 5 | 2.00 (1.00, 2.00) | 32 | 1.00 (1.00, 2.50) | 3 | 1.00 (1.00, 3.00) | 0.75 | |
| PBA-s Depression | Early | 388 | 4.00 (0.00, 9.50) | 3883 | 4.00 (0.00, 8.00) | 624 | 2.00 (0.00, 6.00) | * <0.01 |
| Moderate | 138 | 2.50 (0.00, 7.00) | 1257 | 3.00 (0.00, 8.00) | 215 | 4.00 (0.00, 8.00) | 0.50 | |
| Advanced | 71 | 2.00 (0.00, 8.00) | 545 | 2.00 (0.00, 8.00) | 78 | 2.50 (0.00, 8.00) | 0.88 | |
| PBA-s Irritability aggression | Early | 386 | 2.00 (0.00, 6.00) | 3885 | 1.00 (0.00, 4.00) | 624 | 0.50 (0.00, 4.00) | * <0.01 |
| Moderate | 138 | 1.00 (0.00, 6.00) | 1261 | 1.00 (0.00, 6.00) | 215 | 1.00 (0.00, 4.00) | 0.13 | |
| Advanced | 80 | 1.00 (0.00, 7.00) | 599 | 2.00 (0.00, 8.00) | 79 | 1.00 (0.00, 4.00) | 0.32 | |
| PBA-s Psychosis | Early | 386 | 0.00 (0.00, 0.00) | 3878 | 0.00 (0.00, 0.00) | 625 | 0.00 (0.00, 0.00) | 0.17 |
| Moderate | 137 | 0.00 (0.00, 0.00) | 1257 | 0.00 (0.00, 0.00) | 215 | 0.00 (0.00, 0.00) | 0.06 | |
| Advanced | 69 | 0.00 (0.00, 0.00) | 547 | 0.00 (0.00, 0.00) | 77 | 0.00 (0.00, 0.00) | 0.22 | |
| PBA-s Apathy | Early | 387 | 1.00 (0.00, 6.00) | 3884 | 0.00 (0.00, 4.00) | 624 | 0.00 (0.00, 4.00) | * <0.01 |
| Moderate | 138 | 3.00 (0.00, 8.00) | 1258 | 4.00 (0.00, 9.00) | 215 | 6.00 (0.00, 9.00) | 0.10 | |
| Advanced | 71 | 8.00 (0.00, 12.00) | 555 | 8.00 (0.00, 12.00) | 77 | 8.00 (1.00, 12.00) | 0.97 | |
| PBA-s Executive function | Early | 386 | 0.00 (0.00, 4.00) | 3874 | 0.00 (0.00, 4.00) | 623 | 0.00 (0.00, 4.00) | * <0.01 |
| Moderate | 137 | 4.00 (0.00, 9.00) | 1256 | 3.00 (0.00, 9.00) | 215 | 2.00 (0.00, 6.00) | 0.16 | |
| Advanced | 71 | 6.00 (0.00, 12.00) | 541 | 6.00 (0.00, 10.00) | 76 | 4.00 (0.00, 9.00) | 0.34 | |
| PBA-s Depressed mood frequency Present vs. Not Present | Early | 389 | 224 (57.58) | 3889 | 2064 (53.07) | 625 | 267 (42.72) | * <0.01 |
| Moderate | 139 | 60 (43.17) | 1265 | 623 (49.25) | 215 | 98 (45.58) | 0.28 | |
| Advanced | 82 | 45 (54.88) | 617 | 323 (52.35) | 81 | 45 (55.56) | 0.81 | |
| PBA-s Suicidal ideation frequency Present vs. Not Present | Early | 389 | 40 (10.28) | 3889 | 363 (9.33) | 625 | 39 (6.24) | * 0.03 |
| Moderate | 139 | 13 (9.35) | 1265 | 110 (8.70) | 215 | 21 (9.77) | 0.86 | |
| Advanced | 82 | 15 (18.29) | 617 | 100 (16.21) | 81 | 14 (17.28) | 0.88 | |
| PBA-s Anxiety frequency Present vs. Not Present | Early | 389 | 235 (60.41) | 3889 | 2225 (57.21) | 625 | 316 (50.56) | * <0.01 |
| Moderate | 139 | 69 (49.64) | 1265 | 691 (54.62) | 215 | 125 (58.14) | 0.29 | |
| Advanced | 82 | 48 (58.54) | 617 | 333 (53.97) | 81 | 36 (44.44) | 0.17 | |
| PBA-s Irritability frequency Present vs. Not Present | Early | 389 | 228 (58.61) | 3889 | 2124 (54.62) | 625 | 303 (48.48) | * <0.01 |
| Moderate | 139 | 72 (51.80) | 1265 | 690 (54.55) | 215 | 106 (49.30) | 0.33 | |
| Advanced | 82 | 49 (59.76) | 617 | 353 (57.21) | 81 | 46 (56.79) | 0.90 | |
| PBA-s Angry or aggressive behavior frequency Present vs. Not Present | Early | 389 | 129 (33.16) | 3889 | 1091 (28.05) | 625 | 135 (21.60) | * <0.01 |
| Moderate | 139 | 41 (29.50) | 1265 | 417 (32.96) | 215 | 49 (22.79) | * 0.01 | |
| Advanced | 82 | 29 (35.37) | 617 | 238 (38.57) | 81 | 24 (29.63) | 0.27 | |
| PBA-s Lack of initiative (apathy) frequency Present vs. Not Present | Early | 389 | 209 (53.73) | 3889 | 1944 (49.99) | 625 | 264 (42.24) | * <0.01 |
| Moderate | 139 | 88 (63.31) | 1265 | 884 (69.88) | 215 | 147 (68.37) | 0.27 | |
| Advanced | 82 | 63 (76.83) | 617 | 469 (76.01) | 81 | 62 (76.54) | 0.98 | |
| PBA-s Perseverative thinking or behavior frequency Present vs. Not Present | Early | 389 | 128 (32.90) | 3889 | 1493 (38.39) | 625 | 210 (33.60) | * 0.01 |
| Moderate | 139 | 76 (54.68) | 1265 | 759 (60.00) | 215 | 119 (55.35) | 0.25 | |
| Advanced | 82 | 53 (64.63) | 617 | 408 (66.13) | 81 | 50 (61.73) | 0.72 | |
| PBA-s Obsessive-Compulsive Behaviors frequency Present vs. Not Present | Early | 389 | 100 (25.71) | 3889 | 800 (20.57) | 625 | 96 (15.36) | * <0.01 |
| Moderate | 139 | 42 (30.22) | 1265 | 353 (27.91) | 215 | 49 (22.79) | 0.22 | |
| Advanced | 82 | 33 (40.24) | 617 | 207 (33.55) | 81 | 20 (24.69) | 0.11 | |
| PBA-s Delusions frequency Present vs. Not Present | Early | 389 | 26 (6.68) | 3889 | 198 (5.09) | 625 | 21 (3.36) | * 0.05 |
| Moderate | 139 | 13 (9.35) | 1265 | 124 (9.80) | 215 | 12 (5.58) | 0.14 | |
| Advanced | 82 | 24 (29.27) | 617 | 120 (19.45) | 81 | 10 (12.35) | * 0.02 | |
| PBA-s Hallucinations frequency Present vs. Not Present | Early | 389 | 6 (1.54) | 3889 | 47 (1.21) | 625 | 7 (1.12) | 0.82 |
| Moderate | 139 | 7 (5.04) | 1265 | 36 (2.85) | 215 | 1 (0.47) | * 0.02 | |
| Advanced | 82 | 17 (20.73) | 617 | 105 (17.02) | 81 | 6 (7.41) | * 0.05 | |
| PBA-s Disoriented Behavior frequency Present vs. Not Present | Early | 389 | 78 (20.05) | 3889 | 666 (17.13) | 625 | 104 (16.64) | 0.31 |
| Moderate | 139 | 54 (38.85) | 1265 | 534 (42.21) | 215 | 102 (47.44) | 0.23 | |
| Advanced | 82 | 49 (59.76) | 617 | 436 (70.66) | 81 | 58 (71.60) | 0.12 | |
[i] * Significant at level p < 0.05.
PBA-s = Problem Behaviours Assessment – Short, UHDRS = Unified Huntington’s Disease Rating Scale, HADS-SIS = Hospital Anxiety and Depression Scale – Snaith Irritability Scale.
Figure A
Average change in TFC score by age-of-onset groups. Young age of onset group shows markedly increased rate of decline compared to typical and late onset groups. Δ = difference in mean TFC score, BL = baseline.
Figure B
Average change in UHDRS Functional Assessment Independence Scale. Young age of onset shows markedly increased rate of decline compared to typical and late onset groups from baseline to second visit and third visit. Δ = difference in mean FA score, BL = baseline.