Table 3.
Demographics analyzed by initial diagnosis category.
| Variablesa | ALSP (n = 72) |
Frontotemporal dementia (n = 27)b |
Multiple sclerosis (n = 21) |
Cerebrovascular disease (n = 9) |
Familial leukoencephalopathy (n = 8) |
Alzheimer’s disease (n = 7) |
Adult-onset leukodystrophy (n = 5) |
Nonspecific neurodegeneration or dementia (n = 43) |
Other (n = 20)b |
Missing (n = 67)b |
p value |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age of onset | |||||||||||
| Mean (SD) | 44.1 (12.7) | 50.3 (8.5) | 33.4 (6.7) | 38.2 (11.5) | 48.6 (6.6) | 54.0 (15.3) | 36.8 (9.1) | 42.2 (10.6) | 45.7 (12.6) | 41.5 (10.3) | <0.001 |
| Median (min, max) | 42.5 (18.0, 86.0) | 50.0 (33.0, 71.0) | 36.0 (20.0, 47.0) | 40.0 (21.0, 57.0) | 49.0 (40.0, 60.0) | 52.0 (40.0, 78.0) | 42.0 (25.0, 45.0) | 43.0 (18.0, 63.0) | 43.8 (22.0, 67.0) | 40 (22.9, 70.0) | |
| ≤42 years | 36 (50.0) | 5 (18.5) | 20 (95.2) | 5 (55.6) | 2 (25.0) | 3 (42.9) | 3 (60.0) | 20 (46.5) | 10 (50.0) | 39 (58.2) | <0.001 |
| >42 years | 36 (50.0) | 22 (81.5) | 1 (4.8) | 4 (44.4) | 6 (75.0) | 4 (57.1) | 2 (40.0) | 23 (53.5) | 10 (50.0) | 28 (41.8) | |
| Sex | |||||||||||
| Female | 36 (50.0) | 10 (37.0) | 16 (76.2) | 6 (66.7) | 3 (37.5) | 3 (42.9) | 2 (40.0) | 21 (48.8) | 8 (40.0) | 32 (47.8) | 0.09 |
| Male | 36 (50.0) | 14 (51.9) | 2 (9.5) | 3 (33.3) | 5 (62.5) | 3 (42.9) | 1 (20.0) | 16 (37.2) | 9 (45.0) | 35 (52.2) | |
| Missing | 0 | 3 (11.1) | 3 (14.3) | 0 | 0 | 1 (14.3) | 2 (40.0) | 6 (14.0) | 3 (15.0) | 0 | |
| Family history | |||||||||||
| Yes | 39 (54.2) | 20 (74.1) | 10 (47.6) | 7 (77.8) | 7 (87.5) | 4 (57.1) | 1 (20.0) | 27 (62.8) | 14 (70.0) | 40 (59.7) | 0.046 |
| No | 29 (40.3) | 4 (14.8) | 8 (38.1) | 2 (22.2) | 1 (12.5) | 2 (28.6) | 4 (80.0) | 8 (18.6) | 2 (10.0) | 16 (23.9) | |
| Missing | 4 (5.6) | 3 (11.1) | 3 (14.3) | 0 | 0 | 1 (14.3) | 0 | 8 (18.6) | 4 (20.0) | 11 (16.4) | |
| Geographical region | |||||||||||
| Asia | 38 (52.8) | 4 (14.8) | 5 (23.8) | 3 (33.3) | 5 (62.5) | 4 (57.1) | 0 | 5 (11.6) | 4 (20.0) | 36 (53.7) | <0.001 |
| Europe | 9 (12.5) | 14 (51.9) | 9 (42.9) | 1 (11.1) | 3 (37.5) | 0 | 5 (100) | 18 (41.9) | 8 (40.0) | 27 (40.3) | |
| North America | 25 (34.7) | 9 (33.3) | 7 (33.3) | 5 (55.6) | 0 | 3 (42.9) | 0 | 20 (46.5) | 8 (40.0) | 4 (6.0) | |
| Mode of inheritance | |||||||||||
| Autosomal dominant | 32 (44.4) | 13 (48.1) | 8 (38.1) | 6 (66.7) | 5 (62.5) | 4 (57.1) | 1 (20.0) | 14 (32.6) | 9 (45.0) | 9 (13.4) | <0.001 |
| De novo | 34 (47.2) | 2 (7.4) | 6 (28.6) | 1 (11.1) | 0 | 2 (28.6) | 4 (80.0) | 7 (16.3) | 1 (5.0) | 5 (7.5) | |
| Maternal | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 (3.0) | |
| Unknown/missing | 6 (8.3) | 12 (44.4) | 7 (33.3) | 2 (22.2) | 3 (37.5) | 1 (14.3) | 0 | 22 (51.2) | 10 (50.0) | 51 (76.1) | |
| Exon number mutations | |||||||||||
| Exon (within 18–21) | 38 (52.8) | 16 (59.3) | 10 (47.6) | 5 (55.6) | 6 (75.0) | 3 (42.9) | 1 (20.0) | 25 (58.1) | 11 (55.0) | 42 (62.7) | 0.246 |
| Exon (outside 18–21) | 24 (33.3) | 4 (14.8) | 4 (19.0) | 1 (11.1) | 2 (25.0) | 1 (14.3) | 3 (60.0) | 7 (16.3) | 3 (15.0) | 15 (22.4) | |
| Intron | 6 (8.3) | 4 (14.8) | 4 (19.0) | 1 (11.1) | 0 | 1 (14.3) | 1 (20.0) | 1 (2.3) | 2 (10.0) | 3 (4.5) | |
| Missing | 4 (5.6) | 3 (11.1) | 3 (14.3) | 2 (22.2) | 0 | 2 (28.6) | 0 | 10 (23.3) | 4 (20.0) | 7 (10.4) | |
| Kinase domain mutation | |||||||||||
| Yes | 60 (83.3) | 24 (88.9) | 17 (81.0) | 7 (77.8) | 8 (100) | 4 (57.1) | 5 (100) | 31 (72.1) | 16 (80.0) | 60 (89.6) | 0.056 |
| No | 8 (11.1) | 0 | 1 (4.8) | 0 | 0 | 1 (14.3) | 0 | 1 (2.3) | 0 | 0 | |
| Missing | 4 (5.6) | 3 (11.1) | 3 (14.3) | 2 (22.2) | 0 | 2 (28.6) | 0 | 11 (25.6) | 4 (20.0) | 7 (10.4) | |
| Protein region mutations | |||||||||||
| Signal peptide | 1 (1.4) | 0 | 0 | 0 | 0 | 0 | 0 | 1 (2.3) | 0 | 0 | 0.441 |
| Ig-like domains | 3 (4.2) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Juxtamembrane domain | 1 (1.4) | 0 | 1 (4.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Tyrosine kinase domain 1 | 12 (16.7) | 3 (11.1) | 6 (28.6) | 2 (22.2) | 1 (12.5) | 0 | 2 (40.0) | 2 (4.7) | 3 (15.0) | 9 (13.4) | |
| Kinase insertion domain | 1 (1.4) | 0 | 0 | 0 | 0 | 1 (14.3) | 0 | 0 | 0 | 0 | |
| Tyrosine kinase domain 2 | 48 (66.7) | 21 (77.8) | 11 (52.4) | 5 (55.6) | 7 (87.5) | 4 (57.1) | 3 (60.0) | 29 (67.4) | 13 (65.0) | 51 (76.1) | |
| C-terminal domain | 2 (2.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Missing | 4 (5.6) | 3 (11.1) | 3 (14.3) | 2 (22.2) | 0 | 2 (28.6) | 0 | 11 (25.6) | 4 (20.0) | 7 (10.4) | |
| Initial symptoms c | |||||||||||
| Cognitive impairment | 49 (68.1) | 16 (59.3) | 11 (52.4) | 1 (11.1) | 7 (87.5) | 6 (85.7) | 4 (80.0) | 18 (41.9) | 11 (55.0) | 13 (19.4) | 0.007 |
| Behavioral and psychiatric | 26 (36.1) | 8 (29.6) | 11 (52.4) | 1 (11.1) | 1 (12.5) | 3 (42.9) | 2 (40.0) | 18 (41.9) | 3 (15.0) | 5 (7.5) | 0.047 |
| Extrapyramidal motor | 11 (15.3) | 1 (3.7) | 2 (9.5) | 2 (22.2) | 1 (12.5) | 0 | 2 (40.0) | 13 (30.2) | 4 (20.0) | 11 (16.4) | 0.020 |
| Pyramidal motor | 7 (9.7) | 0 | 6 (28.6) | 2 (22.2) | 0 | 0 | 0 | 8 (18.6) | 5 (25.0) | 6 (9.0) | 0.027 |
| Speech difficulty | 5 (6.9) | 1 (3.7) | 2 (9.5) | 2 (22.2) | 0 | 1 (14.3) | 0 | 6 (14.0) | 3 (15.0) | 13 (19.4) | 0.003 |
| Missing | 0 | 8 (29.6) | 2 (9.5) | 1 (11.1) | 0 | 0 | 0 | 6 (14.0) | 3 (15.0) | 40 (59.7) | N/A |
ALSP, adult-onset leukoencephalopathy with axonal spheroids and pigmented glia; Ig, immunoglobulin; SD, standard deviation.
a
Data are expressed as n (%) unless otherwise indicated.
b
Cases with missing age (n = 12) were not included in the analysis of variance.
c
Initial symptom categories do not add up to 100% because categories are not mutually exclusive.