Table 1.
Demographics of Enrolled Patients Harboring Cysteine‐Altering NOTCH3 Variants
| Variable | Total patients (N=246) | Patients without cognitive impairment (N=150)* | Patients with cognitive impairment (N=96)* | P value |
|---|---|---|---|---|
| Age, y | 62.7 (10.6) | 59.7 (10.1) | 67.4 (9.8) | <0.0001 |
| Male sex, n (%) | 132 (54) | 85 (49) | 47 (51) | 0.561 |
| Education, y | 11.2 (4.3) | 12.2 (3.7) | 9.4 (4.8) | <0.0001 |
| NOTCH3 variant position, n (%) | 0.990 | |||
| EGFR 1–6 | 18 (7) | 11 (7) | 7 (7) | |
| EGFR 7–34 | 228 (93) | 139 (93) | 89 (93) | |
| NOTCH3 p.R544C, n (%) | 209 (85) | 130 (87) | 79 (82) | 0.349 |
| APOE genotype, n (%) | 0.029† | |||
| ɛ3ɛ3 | 183 (74) | 120 (80) | 63 (66) | |
| ɛ2ɛ3 | 21 (9) | 9 (6) | 12 (13) | |
| ɛ3ɛ4 | 40 (16) | 19 (13) | 21 (22) | |
| ɛ4ɛ4 | 1 (0.4) | 1 (1) | 0 (0) | |
| ɛ2ɛ4 | 1 (0.4) | 1 (1) | 0 (0) | |
| MMSE score | 23.2 (7.1) | 28.0 (1.8) | 15.7 (5.5) | <0.0001 |
| Clinical presentations, n (%) | ||||
| Stroke | 150 (61) | 81 (54) | 69 (72) | 0.005 |
| Stroke type | ||||
| Ischemic stroke | 123 (52) | 64 (44) | 59 (65) | 0.001 |
| Hemorrhagic stroke | 38 (16) | 21 (14) | 17 (19) | 0.368 |
| Gait disturbance | 89 (36) | 39 (26) | 50 (52) | <0.0001 |
| Psychiatric symptoms | 49 (20) | 25 (17) | 24 (25) | 0.110 |
| Migraine | 13 (6) | 12 (10) | 1 (1) | 0.015 |
| Medical history, n (%) | ||||
| Hypertension | 132 (54) | 78 (53) | 54 (56) | 0.587 |
| Diabetes | 48 (20) | 25 (17) | 23 (24) | 0.175 |
| Dyslipidemia | 87 (35) | 58 (39) | 29 (31) | 0.169 |
| Smoking | 56 (24) | 37 (26) | 19 (21) | 0.415 |
| Alcohol | 37 (16) | 27 (19) | 10 (11) | 0.127 |
| Laboratory data | ||||
| Total cholesterol, mg/dL | 176.5 (38.9) | 179.2 (37.4) | 171.7 (41.1) | 0.209 |
| LDL cholesterol, mg/dL | 103.8 (34.5) | 104.9 (33.8) | 102.0 (35.9) | 0.579 |
| HDL cholesterol, mg/dL | 47.9 (12.3) | 49.1 (11.5) | 46.4 (13.2) | 0.303 |
| Triglyceride, mg/dL | 121.1 (69.3) | 120.9 (74.6) | 121.4 (60.8) | 0.962 |
| Fasting plasma glucose, mg/dL | 106.6 (30.4) | 107.6 (34.6) | 105.1 (22.7) | 0.605 |
| HbA1c, % | 5.89 (0.90) | 5.88 (0.91) | 5.90 (0.88) | 0.889 |
| Imaging characteristics‡ | ||||
| DWM hyperintensity score | <0.0001 | |||
| 1–1.5 | 21 (9) | 21 (14) | 0 (0) | |
| 2–2.5 | 82 (33) | 64 (43) | 18 (19) | |
| 3 | 143 (58) | 65 (43) | 78 (81) | |
| PVWM hyperintensity score | <0.0001 | |||
| 1–1.5 | 7 (3) | 7 (5) | 0 (0) | |
| 2–2.5 | 50 (20) | 44 (29) | 6 (6) | |
| 3 | 189 (77) | 99 (66) | 90 (94) | |
| MTA score | <0.0001 | |||
| 0–0.5 | 55 (22) | 52 (37) | 3 (4) | |
| 1–1.5 | 87 (35) | 59 (42) | 28 (33) | |
| 2–2.5 | 66 (27) | 26 (19) | 40 (48) | |
| 3–4 | 15 (6) | 2 (1) | 13 (16) | |
| Anterior temporal WMH, n (%) | 95 (43) | 52 (40) | 43 (47) | 0.341 |
Data are shown as mean (SD) unless otherwise indicated. DWM indicates deep white matter; EGFR, epidermal growth factor–like repeat; HbA1c, hemoglobin A1c; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; MMSE, Mini‐Mental State Examination; MTA, mesial temporal atrophy; PVWM, periventricular white matter; and WMH, white matter hyperintensity.
Cognitive impairment was defined by an MMSE score <24.
Comparison among APOE subgroups of the following: ɛ3ɛ3, ɛ2 carrier (ɛ2ɛ3), and ɛ4 carrier (ɛ3ɛ4 and ɛ4ɛ4).
DWM and PVWM hyperintensities were rated by the score of Fazekas et al,24 and MTA was rated by the score of Scheltens et al.23 Each semiquantitative score was presented as the average score from both hemispheres.