Table 1.
Demographic characteristics
| HF | COD | VCI | Reference participants | Total | |
| n=153 | n=105 | n=154 | n=128 | n=540 | |
| Demographic and vascular risk factorsa | |||||
| Age, mean (SD) | 70.1 (9.7)‡§ | 66.1 (8.0)† | 68.8 (8.6)* | 65.7 (7.5)¶∘ | 67.9 (8.7) |
| Female, n (%) | 50 (32.7)* | 25 (23.8)∘§ | 58 (37.7)‡ | 60 (46.9)†# | 193 (35.7) |
| MMSE, mean (SD) | 28.5 (1.3)†# | 27.8 (2.1)† | 27.4 (2.7)¶§ | 28.8 (1.2)#∧ | 28.1 (2.0) |
| CDR, median (IQR) | 0 (0–0) | 0 (0–0.5) | 0.5 (0–0.5) | 0 (0–0) | 0 (0.0–0.5) |
| GDS, mean (SD) | 2.1 (2.5)∘§ | 2.4 (2.4)§ | 2.9 (2.7)†§ | 0.9 (1.3)¶#∧ | 2.1 (2.4) |
| Education, median (IQR) | 5 (4–6)* | 5 (4–6)* | 5 (4–6) | 6 (5–6)†‡ | 5 (4–6) |
| Systolic BP, mean (SD) | 134.7 (19.2)# ∘* | 152.3 (21.8)¶∘* | 142.0 (22.0)†‡ | 143.1 (19.2)†‡ | 142.2 (21.3) |
| Diastolic BP, mean (SD) | 76.2 (11.4)# ∘§ | 82.4 (12.2)¶ | 80.9 (11.1)† | 81.9 (10.2)¶ | 80.1 (11.4) |
| BMI, mean (SD) | 27.5 (4.6)* | 27.7 (3.9)* | 26.6 (4.5) | 26.1 (3.8)†‡ | 26.9 (4.3) |
| Creatinine in μmol/L, mean (SD) | 102.1 (42.0)#∧§ | 82.2 (32.1)¶ | 86.7 (23.6)¶ | 79.2 (29.4)¶ | 88.4 (33.8) |
| Hypertension, n (%) | 81 (53.3) | 80 (76.2) | 108 (70.1) | 33 (25.8) | 302 (56.0) |
| Hypercholesterolemia, n (%) | 71 (47.0) | 90 (85.7) | 102 (67.1) | 38 (29.7) | 301 (56.2) |
| Diabetes mellitus, n (%) | 27 (17.6) | 31 (29.5) | 17 (11.0) | 3 (2.3) | 78 (14.4) |
| Renal impairment, n (%) | 42 (27.5) | 10 (9.5) | 20 (13.0) | 5 (3.9) | 77 (14.3) |
| CSVD, mean (SD) | 0.84 (1.01)∧* | 1.15 (0.87)∘§ | 1.59 (1.29)¶‡§ | 0.45 (0.64)†#∧ | 1.01 (1.08) |
| CVA, n (%) | 9 (5.9) | 55 (52.4) | 62 (40.3) | 0 (0.0) | 126 (23.3) |
| TIA, n (%) | 16 (10.5) | 77 (73.3) | 36 (23.5) | 6 (4.7) | 135 (25.0) |
| Smoking, n (%) | 22 (14.4) | 30 (28.6) | 28 (18.2) | 9 (7.0) | 89 (16.5) |
| Myocardial infarction, n (%) | 81 (52.9) | 15 (14.3) | 18 (11.7) | 4 (3.1) | 118 (21.9) |
| Blood-based biomarkersb | |||||
| Aβ42/40 ratio, mean (SD) | 0.067 (0.014) | 0.067 (0.013) | 0.064 (0.012) | 0.067 (0.015) | 0.066 (0.013) |
| pTau181 in pg/mL, mean (SD) | 2.0 (1.2) | 1.7 (1.2) | 2.1 (1.2) | 1.7 (1.0) | 1.9 (1.2) |
| GFAP in pg/mL, mean (SD) | 113.9 (63.5) | 94.7 (44.5) | 127.9 (74.9)†§ | 91.3 (46.1)∧ | 108.8 (61.9) |
| NfL in pg/mL, mean (SD) | 25.1 (18.2)* | 27.8 (37.3)* | 26.8 (21.4)§ | 16.5 (7.2)†‡∧ | 24.1 (22.9) |
| Cognitive performancec (baseline z-score) | |||||
| Global cognition, β (SE) | –0.41 (0.05)§ | –0.52 (0.06)§ | –0.89 (0.10)§ | 0.00 (0.05) | –0.48 (0.04)§ |
| Memory, β (SE) | –0.48 (0.09)§ | –0.57 (0.11)§ | –1.44 (0.20)§ | –0.01 (0.06) | –0.67 (0.07)§ |
| Attention/psychomotor speed, β (SE) | –0.52 (0.07)§ | –0.85 (0.10)§ | –0.90 (0.11)§ | 0.01 (0.07) | –0.57 (0.05)§ |
| Language, β (SE) | –0.38 (0.06)§ | –0.34 (0.05)§ | –0.65 (0.09)§ | 0.00 (0.06) | –0.37 (0.04)§ |
| Executive functioning, β (SE) | –0.24 (0.06)§ | –0.33 (0.07)§ | –0.57 (0.08)§ | 0.01 (0.06) | –0.30 (0.04)§ |
BMI, body mass index; BP, blood pressure; CDR, Clinical Dementia Rating; COD, carotid occlusive disease; CSVD, cerebral small vessel disease; CVA, cerebrovascular accident; GDS, Geriatric Depression Scale; HF, heart failure; IQR, interquartile range; MMSE, Mini-Mental State Examination; TIA, transient ischemic attack; VCI, vascular cognitive impairment. aDemographic differences between groups were calculated with the analyses of variance (ANOVA) or Pearson χ2 test as appropriate. bRaw values of the plasma biomarkers are presented in the table. However, pTau181, GFAP, and NfL were log-transformed prior to analyses. Differences in plasma concentrations between groups were calculated using analysis of covariance (ANCOVA), adjusted for age, sex, and hospital site. Post-hoc analyses were performed, when between groups differences were significant in ANCOVA, to explore the differences between the included groups. Lower Aβ42/40 ratio indicate a more abnormal level, whereas it is inversed for pTau181, GFAP, and NfL, in which higher concentrations indicated a more abnormal level. cLinear mixed model included terms for time in separate models for each cognitive domain. The estimates (β±SE) of the intercept (estimated baseline z score) represent standardized baseline cognitive performance. Analyses were adjusted for age, sex, hospital site, and education. p-values represent a significant difference with reference participants. *p < 0.05 compared to reference participants; †p < 0.05 compared to HF; ‡p < 0.05 compared to COD; p < 0.05 compared to VCI; §p < 0.001 compared to reference participants; ¶p < 0.001 compared to HF; #p < 0.001 compared to COD; ∧p < 0.001 compared to VCI.