Introduction
Patients and methods
Patients and controls
RA (total) | RA (MTX) | RA (biologic) | Controls | |
---|---|---|---|---|
n | 60 | 20 | 40 | 39 |
Age (years) | 60.7 ± 9.5 | 61.3 ± 9.1 | 60.4 ± 9.8 | 60.2 ± 6.7 |
Sex (females) | 60 | 20 | 20 | 39 |
Disease duration (years) | 11.6 ± 7.6 | 11.8 ± 8.6 | 11.6 ± 7.1 | – |
RF positivity (%) | 70% | 82% | 66% | – |
Anti-CCP positivity (%) | 65% | 75% | 64% | – |
Patients with erosions on hand/feet X-ray (%) | 54/60 (90) | 18/20 (90) | 36/40 (90) | |
MTX duration (years) | 6.7 ± 4.1 | 7.2 ± 4.9 | 6.4 ± 3.6 | – |
MTX dose (mg/week) | 14.9 ± 5.5 | 14.1 ± 4.4 | 15.3 ± 5.9 | – |
Biologic duration (years) | 4.0 ± 2.0 | – | 4.0 ± 2.0 | – |
mDAS28-ESRa | 2.50 ± 0.87 | 2.89 ± 0.80 | 2.30 ± 0.78 | – |
mESR (mm/h)a | 17.7 ± 15.9 | 20.3 ± 16.6 | 16.4 ± 15.7 | – |
hsCRP (mg/l) | 5.2 ± 7.7 | 8.5 ± 10.9 | 3.5 ± 4.7 | – |
Time at school (years) | 11.4 ± 3.0 | 12.5 ± 2.7 | 10.8 ± 3.0 | 12.3 ± 1.8 |
Smoking (%) | 10/60 (16.6) | 5/20 (25.0) | 5/40 (12.5) | 3/39 (7.7) |
Alcohol consumption (%) | 5/60 (8.3) | 2/20 (10.0) | 3/40 (7.5) | 10/39 (25.6) |
Current workability (%) | 9/60 (15) | 6/20 (30) | 3/40 (7.5) | 37 (95) |
Tests of cognitive function and depression/anxiety
Abnormala (↑ or ↓) | RA (total) | RA (MTX) | RA (biologic) | Controls | p (RA vs control) | p (MTX vs control) | p (biologic vs control) | p (MTX vs biologic) | |
---|---|---|---|---|---|---|---|---|---|
n | 60 | 20 | 40 | 39 | |||||
Cognitive function tests | |||||||||
MOCA total (n) | ↓ | 23.3 ± 3.8 | 24.6 ± 2.2 | 22.6 ± 4.2 | 25.6 ± 2.4 | 0.002 | 0.188 | 0.001 | 0.089 |
TMT-A time (s) | ↑ | 69.0 ± 26.3 | 57.9 ± 15.4 | 76.2 ± 29.7 | 53.1 ± 14.3 | 0.029 | 0.420 | 0.007 | 0.041 |
TMT-B time (s) | ↑ | 108.2 ± 48.4 | 98.4 ± 38.9 | 113.8 ± 56.7 | 76.3 ± 22.7 | 0.048 | 0.058 | 0.140 | 0.819 |
VST-A time (s) | ↑ | 20.6 ± 9.3 | 18.8 ± 7.9 | 21.6 ± 9.8 | 18.0 ± 10.1 | 0.040 | 0.450 | 0.019 | 0.232 |
VST-B time (s) | ↑ | 23.0 ± 9.6 | 20.7 ± 8.2 | 24.1 ± 10.1 | 19.3 ± 5.8 | 0.051 | 0.994 | 0.007 | 0.127 |
VST-C time (s) | ↑ | 36.9 ± 18.1 | 33.9 ± 13.9 | 38.4 ± 19.9 | 29.7 ± 9.3 | 0.075 | 0.308 | 0.069 | 0.504 |
WAIS total (n) | ↓ | 25.4 ± 13.3 | 28.0 ± 14.1 | 24.1 ± 12.9 | 28.5 ± 12.6 | 0.003 | 0.094 | 0.006 | 0.455 |
BVRT total (n) | ↓ | 6.58 ± 1.91 | 6.75 ± 1.87 | 6.50 ± 1.90 | 7.67 ± 1.98 | 0.005 | 0.074 | 0.006 | 0.662 |
BVRT error (n) | ↑ | 3.67 ± 0.93 | 3.50 ± 1.15 | 3.75 ± 0.81 | 3.54 ± 1.07 | 0.655 | 0.860 | 0.456 | 0.412 |
Depression/anxiety tests | |||||||||
STAIS (n) | ↑ | 45.5 ± 8.5 | 43.4 ± 9.0 | 46.6 ± 8.1 | 36.9 ± 9.1 | < 0.001 | 0.012 | < 0.001 | 0.134 |
STAIT (n) | ↑ | 48.0 ± 11.0 | 46.0 ± 11.6 | 48.9 ± 10.7 | 41.1 ± 9.0 | 0.004 | 0.183 | 0.002 | 0.384 |
BDI (n) | ↑ | 13.2 ± 8.8 | 12.3 ± 9.2 | 13.6 ± 8.7 | 8.9 ± 6.5 | 0.023 | 0.251 | 0.015 | 0.432 |
SF-36 test of general health status
Laboratory assessments and disease activity
Transcranial Doppler assessment
Carotid artery ultrasound examination
Brain MRI investigations
Statistical analysis
Results
Basic characteristics of RA patients and controls
Results of cognitive tests, depression and anxiety inventories
Correlations among cognitive function tests in RA patients
Correlations between cognitive function and SF-36 in RA patients
Correlations between cognitive function and other parameters in RA patients
Abnormala (↑ or ↓) | Age | Disease duration | mESRb | mDAS28b | School years | CRC (left) | CRC (right) | cIMT (right) | |
---|---|---|---|---|---|---|---|---|---|
Cognitive function tests | |||||||||
MOCA (n) | ↓ | R = 0.334 p = 0.009 | R = 0.445 p = 0.016 | ||||||
TMT-A time (s) | ↑ | R = 0.525 p = 0.002 | |||||||
TMT-B time (s) | ↑ | R = 0.492 p = 0.013 | |||||||
VST-A time (s) | ↑ | R = 0.366 p = 0.004 | R = 0.285 p = 0.027 | R = − 0.318 p = 0.013 | |||||
VST-B time (s) | ↑ | R = 0.424 p = 0.001 | R = − 0.398 p = 0.002 | ||||||
VST-C time (s) | ↑ | R = 0.486 p < 0.001 | R = − 0.345 p = 0.007 | ||||||
WAIS total (n) | ↓ | R = − 0.311 p = 0.001 | R = 0.456 p < 0.001 | R = − 0.291 p = 0.024 | |||||
BVRT total (n) | ↓ | R = 0.378 p = 0.003 | R = 0.342 p = 0.033 | ||||||
BVRT error (n) | ↑ | R = 0.290 p = 0.025 | R = − 0.369 p = 0.004 | ||||||
Depression/anxiety tests | |||||||||
STAIS (n) | ↑ | R = − 0.489 p < 0.001 | |||||||
STAIT (n) | ↑ | R = 0.354 p = 0.006 | R = 0.307 p = 0.018 | R = − 0.368 p = 0.004 | |||||
BDI (n) | ↑ | R = − 0.425 p = 0.001 | R = − 0.481 p = 0.008 |
Associations between cognitive function and vascular abnormalities in RA patients
Carotid plaque (right) | Carotid plaque (left) | MRI vascular lesions | MRI atrophy | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
+ | – | p | + | – | p | + | – | p | + | – | p | |
Cognitive function tests | ||||||||||||
TMT-A time (s) | 77.6 ± 28.7 | 58.6 ± 19.4 | 0.036 | |||||||||
VST-A time (s) | 24.5 ± 11.6 | 17.3 ± 4.3 | 0.032 | |||||||||
VST-C time (s) | 41.1 ± 20.7 | 31.7 ± 13.1 | 0.037 | 40.0 ± 16.5 | 33.8 ± 19.4 | 0.040 | ||||||
WAIS total (n) | 22.4 ± 11.3 | 29.0 ± 14.8 | 0.044 | 21.8 ± 11.3 | 28.9 ± 14.4 | 0.039 | 19.8 ± 11.4 | 28.0 ± 13.3 | 0.042 | |||
Depression/anxiety tests | ||||||||||||
STAIS (n) | 47.5 ± 8.4 | 43.2 ± 8.1 | 0.042 | 47.7 ± 8.5 | 43.3 ± 7.9 | 0.044 | ||||||
STAIT (n) | 50.4 ± 10.2 | 45.1 ± 11.4 | 0.038 | 51.2 ± 9.9 | 44.7 ± 11.3 | 0.025 | ||||||
BDI (n) | 15.2 ± 7.7 | 11.2 ± 9.4 | 0.015 |
Determinants of cognitive function in RA patients
Dependent variable | Independent variable | Univariate | Multiple | ||||||
---|---|---|---|---|---|---|---|---|---|
B | 95% CI | β | p | B | 95% CI | β | p | ||
Cognitive function tests | |||||||||
MOCA total | School years | 0.446 | 0.133 to 0.760 | 0.350 | 0.006 | 0.446 | 0.133 to 0.760 | 0.350 | 0.006 |
TMT-A time | Age | 1.763 | 0.717 to 2.809 | 0.525 | 0.002 | 1.798 | 0.831 to 2.764 | 0.536 | 0.001 |
Biologic vs MTX | 6.076 | − 0.012 to 12.163 | 0.343 | 0.030 | 6.345 | 1.252 to 11.432 | 0.359 | 0.016 | |
Carotid plaque (left) | 9.506 | 0.623 to 18.388 | 0.365 | 0.037 | 4.344 | − 3.891 to 12.580 | 0.167 | 0.290 | |
TMT-B time | Age | 3.007 | 0.949 to 5.064 | 0.492 | 0.006 | 3.007 | 0.949 to 5.064 | 0.492 | 0.006 |
VST-A time | Disease duration | 0.341 | 0.037 to 0.645 | 0.282 | 0.029 | 0.256 | − 0.108 to 0.619 | 0.193 | 0.163 |
MRI vascular lesions | 3.572 | 1.103 to 6.041 | 0.398 | 0.006 | 4.362 | 1.827 to 6.897 | 0.476 | 0.001 | |
VST-B time | Age | 0.308 | 0.058 to 0.559 | 0.308 | 0.017 | 0.493 | 0.155 to 0.830 | 0.385 | 0.005 |
School years | − 0.911 | − 1.722 to − 0.100 | − 0.283 | 0.028 | − 0.731 | − 1.539 to 0.078 | − 0.227 | 0.076 | |
VST-C time | Age | 0.819 | 0.369 to 1.268 | 0.432 | 0.001 | 0.819 | 0.369 to 1.268 | 0.432 | 0.001 |
School years | − 1.717 | − 3.252 to − 0.181 | − 0.282 | 0.029 | − 0.751 | − 2.004 to 1.101 | − 0.114 | 0.418 | |
Carotid plaque (right) | 4.709 | 0.119 to 9.298 | 0.260 | 0.045 | 1.414 | − 3.256 to 6.084 | 0.078 | 0.547 | |
WAIS total | Age | − 0.573 | − 0.907 to − 0.239 | − 0.411 | 0.001 | − 1.098 | − 1.705 to − 0.491 | − 0.604 | 0.001 |
School years | 2.042 | 0.995 to 3.089 | 0.456 | <0.001 | 0.574 | − 0.756 to 1.904 | 0.138 | 0.386 | |
cIMT (right) | − 144.84 | − 269.887 to 19.792 | − 0.291 | 0.024 | − 93.847 | − 204.589 to 16.895 | − 0.189 | 0.095 | |
Carotid plaque (left) | − 3.533 | − 6.883 to − 0.183 | − 0.267 | 0.039 | − 1.329 | − 4.501 to 1.844 | − 0.100 | 0.405 | |
BVRT total | School years | 0.286 | 0.142 to 0.430 | 0.372 | < 0.001 | 0.286 | 0.142 to 0.430 | 0.372 | < 0.001 |
MCA CRC (right) | 0.050 | 0.002 to 0.097 | 0.329 | 0.041 | 0.043 | 0.008 to 0.088 | 0.312 | 0.061 | |
BVRT error | Age | 0.029 | 0.006 to 0.051 | 0.247 | 0.014 | 0.019 | − 0.006 to 0.043 | 0.192 | 0.129 |
School years | − 0.132 | -0.204 to − 0.060 | − 0.348 | < 0.001 | − 0.132 | − 0.204 to − 0.060 | − 0.348 | < 0.001 | |
Depression/anxiety tests | |||||||||
STAIS | School years | − 1.410 | − 2.057 to − 0.763 | − 0.497 | < 0.001 | − 1.410 | − 2.057 to − 0.763 | − 0.497 | < 0.001 |
Carotid plaque (right) | 2.168 | 0.027 to 4.303 | 0.257 | 0.047 | 0.842 | − 1.255 to 2.940 | 0.100 | 0.425 | |
Carotid plaque (left) | 2.200 | 0.073 to 4.327 | 0.262 | 0.043 | 1.052 | − 1.022 to 3.126 | 0.125 | 0.314 | |
STAIT | School years | − 1.295 | − 2.205 to − 0.384 | − 0.350 | 0.006 | − 0.887 | − 1.800 to 0.026 | − 0.242 | 0.057 |
mESRa | 0.290 | 0.076 to 0.503 | 0.338 | 0.009 | 0.057 | − 2.980 to 0.413 | 0.076 | 0.749 | |
mDAS28a | 4.482 | 0.725 to 8.239 | 0.302 | 0.020 | 1.207 | − 3.090 to 5.503 | 0.089 | 0.576 | |
Carotid plaque (left) | 3.267 | 0.525 to 6.008 | 0.299 | 0.020 | 3.480 | 0.247 to 6.713 | 0.318 | 0.036 | |
BDI | School years | − 1.217 | − 1.922 to − 0.511 | − 0.413 | 0.001 | − 1.217 | − 1.922 to − 0.511 | − 0.413 | 0.001 |
MCA CRC (left) | − 0.246 | − 0.474 to − 0.019 | − 0.393 | 0.035 | 0.219 | − 0.455 to 0.016 | − 0.426 | 0.065 |