Background
Methods
Subjects
Clinical assessment
CSF analyses
Genetic analyses
MRI analyses
Subject classification
Statistical analyses
Aβ − WMH− (n = 140) | Aβ − WMH+ (n = 39) | Aβ + WMH− (n = 63) | Aβ + WMH+ (n = 29) | |
---|---|---|---|---|
Baseline characteristics | ||||
Age, years | 61.7 (8.3)a,b,c,d
| 71.3 (7.7)b,d
| 66.7 (7.8)a,c,d
| 74.1 (5.0)b,d
|
Female sex, n
| 94 (67)b
| 23 (59) | 32 (51)d
| 16 (55) |
Education, years | 10.9 (3.1) | 11.9 (3.3) | 11.1 (3.1) | 10.3 (2.9) |
Hypertension, n
e
| 43 (34) | 9 (25) | 15 (25) | 9 (32) |
Obesity, n
e
| 15 (14) | 3 (11) | 4 (8) | 4 (21) |
Diabetes, n
e
| 16 (21) | 3 (15) | 3 (7) | 5 (28) |
APOE ε4 allele carrier, n
e
| 33 (51)a
| 5 (24)b,c
| 29 (62)a
| 10 (56)a
|
Diagnosis of MCI, n
| 70 (50)c
| 21 (54)c
| 40 (64) | 22 (76)a,d
|
Amnestic MCI, % within MCI group | 40 (57) | 15 (71) | 27 (68) | 17 (77) |
Nonamnestic MCI, % within MCI group | 30 (43) | 6 (29) | 13 (33) | 5 (23) |
CSF Aβ1–42, pg/ml | 973.6 (312.0)b,c
| 885.0 (242.0)b,c
| 404.3 (102.6)a,d
| 419.3 (97.2)a,d
|
White matter hyperintensitiesf
| 0.7 (0.5)a,c
| 2.3 (0.4)b,d
| 0.8 (0.4)a,c
| 2.4 (0.5)b,d
|
Follow-up characteristics | ||||
Follow-up duration, years | 2.1 (1.5) | 2.2 (1.3) | 2.1 (1.2) | 2.4 (1.2) |
Time to progression to dementia, years | 1.3 (0.5)a
| 2.0 (0.7)d
| 1.7 (0.7) | 2.1 (1.2) |
Progression to dementia, n
| 8 (6)a,b,c
| 9 (23)d
| 18 (29)d
| 11 (38)d
|
AD-type dementia, n
| 2 (1)a,b,c
| 7 (18)d
| 18 (29)d
| 10 (35)d
|
Vascular dementia, n
| 0 (0) | 2 (5) | 0 (0) | 1 (3) |
Frontotemporal dementia, n
| 4 (3) | 0 (0) | 0 (0) | 0 (0) |
Dementia with Lewy bodies, n
| 1 (1) | 0 (0) | 0 (0) | 0 (0) |
Dementia with unknown etiology, n
| 1 (1) | 0 (0) | 0 (0) | 0 (0) |
Neurodegeneration markers | Aβ − WMH− (n = 140) | Aβ − WMH+ (n = 39) | Aβ + WMH− (n = 63) | Aβ + WMH+ (n = 29) |
---|---|---|---|---|
MTA score | 1.2 (1.2)a,b,c
| 2.6 (1.6)c,d
| 2.1 (1.6)c,d
| 3.4 (1.8)a,b,d
|
MTA abnormal, n
| 62 (45)a,b,c
| 32 (82)d
| 41 (67)c,d
| 26 (93)b,d
|
p-tau, pg/ml | 54.5 (27.7)b
| 63.2 (29.3) | 77.0 (56.3)d
| 65.2 (38.2) |
p-tau abnormal, n
| 53 (38)b
| 22 (58) | 45 (71)d
| 15 (52) |
t-tau, pg/ml | 314.7 (202.0)a,b,c
| 438.4 (248.0)d
| 499.3 (413.8)d
| 426.2 (275.2)d
|
t-tau abnormal, n
| 36 (26)a,b,c
| 20 (53)d
| 36 (57)d
| 14 (48)d
|
Results
Cohort characteristics
Neurodegeneration markers
Baseline cognitive performance and cognitive decline
Aβ − WMH− | Aβ − WMH+ | Aβ + WMH− | Aβ + WMH+ | ||
---|---|---|---|---|---|
MMSE | No. of subjects | 140 | 39 | 62 | 27 |
Baseline | 27.79 (27.39, 28.19) | 27.52 (26.83, 28.21) | 27.20 (26.62, 27.78) | 27.40 (26.54, 28.25) | |
Slope | −0.01 (−0.15, 0.12) |
−0.29 (−0.55, −0.02)
|
−0.22 (−0.44, −0.01)
|
−0.31 (−0.62, 0.00)
| |
Memory delayed recall z-score | No. of subjects | 133 | 37 | 58 | 27 |
Baseline | −0.48 (−0.72, −0.24)b,c,d
| −1.04 (−1.48, −0.61)e
| −1.04 (−1.41, −0.68)A
| −1.33 (−1.86, −0.80)e
| |
Slope | 0.05 (−0.03, 0.13) | 0.02 (−0.12, 0.17) | 0.02 (−0.11, 0.14) | −0.07 (−0.24, 0.09) | |
Executive functioning z-score | No. of subjects | 130 | 37 | 60 | 24 |
Baseline | −0.48 (−0.76, −0.21) | −0.41 (−0.92, 0.09) | −0.78 (−1.18, −0.37) | −1.12 (−1.73, −0.50) | |
Slope | 0.06 (−0.02, 0.13) | −0.00 (−0.15, 0.15) | −0.03 (−0.16, 0.10) | −0.04 (−0.23, 0.15) |
Progression to dementia
Groups | HR | 95% CI |
p Value comparisons | |
---|---|---|---|---|
Aβ − WMH− | Reference | Reference | Aβ − WMH+ | 0.021 |
Aβ + WMH− | <0.001 | |||
Aβ + WMH+ | 0.036 | |||
Aβ − WMH+ | 3.30 | 1.21–8.98 | Aβ − WMH− | 0.021 |
Aβ + WMH− | 0.358 | |||
Aβ + WMH+ | 0.868 | |||
Aβ + WMH− | 4.84 | 2.03–11.51 | Aβ − WMH− | < 0.001 |
Aβ − WMH+ | 0.358 | |||
Aβ + WMH+ | 0.294 | |||
Aβ + WMH+ | 3.02 | 1.08–8.43 | Aβ − WMH− | 0.036 |
Aβ − WMH+ | 0.868 | |||
Aβ + WMH− | 0.294 |