Table 5.
Associations between neuroimaging biomarkers, cognitive dysfunction and APS or persistent aPL+
| Author and year | Sample (n) | Cognitive domain(s) affected | Statistical analysis | Cognitive dysfunction (exposure) and imaging biomarkers (outcome) | Imaging biomarkers (exposure) and aPL+ (outcome) | Cognitive dysfunction (exposure) and aPL+ (outcome) |
|---|---|---|---|---|---|---|
| Structural MRI (n = 16) | ||||||
| Arvanitakis et al. (2019) [20] | 956 | No specific domains reported | Linear regression, logistic regression | Association not assessed | Presence of brain infarcts and aPL+ (OR = 1.007, P = 0.97) | Global cognitive function and aPL+ (beta = −0.062, P = 0.203) |
| Homayoon et al. (2014) [21] | 1895 | No specific domains reported | Linear regression | Association not assessed | Hippocampal volume and aCL (IgG) (beta = −0.071, CI 0.013, 0.007, P = 0.003) | Global cognition and; aCL status (beta = −0.361, CI 0.666, 0.058, P = 0.020); aCL (IgG) (beta = −0.591, CI 1.058, 0.124, P = 0.01) |
| Erkan et al. (2010) [23] | 143 | No specific domains reported | χ 2 statistic (Fisher’s exact test) | Association not assessed | WM changes and high titer aCL (RR 2.03, CI 1.04, 3.94, P = 0.02) | Cognitive dysfunction and high titer aCL (P = 0.12) |
| Tektonidou et al. (2006) [31] | 60 (cases), 60 (controls) | Complex attention and verbal fluency | Logistic regression | Cognitive deficits and; WMLs (OR 4.18, CI 1.33, 13.11, P = 0.01); infarcts (OR 1.22, CI 0.35, 4.20, P = 0.76) | Association not assessed | Cognitive deficits and; aCL (IgG) (OR 1.92, CI 0.34, 10.78, P = 0.46); aCL (IgM) (OR 0.63, CI 0.22, 1.78, P = 0.38); LA (OR 2.38, CI 0.76, 7.40, P = 0.14); anti-β2GPI (OR 2.11, CI 0.74, 6.05, P = 0.16) |
| Kozora et al. (2014) [32] | 20 (SLE), 20 (aPL+) | Highest frequency of impairment in visual learning and memory, visuomotor speed and flexibility, verbal fluency, visuoconstruction and rapid auditory information processing | Spearman’s correlation | Cognitive impairment and abnormal/incidental MRI findings (P = 0.75) | Association not assessed | Cognitive impairment and aPL+ (P > 0.232) |
| Appenzeller et al. (2007) [34] | 75 (cases), 44 (controls) | General memory | t-statistic [SPM(t)] | Severe cognitive dysfunction and reduced WM and GM (statistical result not reported) | Reduced WM and GM and aPL+ (statistical result not reported) | Association not assessed |
| Appenzeller et al. (2005) [40] | 115 (cases), 44 (controls) | No specific domains significant | Linear regression | Cognitive dysfunction and reduced corpus callosum and cerebral volumes (P = 0.001) | Cerebral and corpus callosum volumes and aPL+ (P = 0.1) | Association not assessed |
| Tomietto et al. (2007) [35] | 52 (SLE), 20 (RA) | Memory, complex attention and executive function | Logistic regression | Severity of cognitive deficits and MRI severity (cerebral atrophy and ischaemic lesions) (OR 33.5, CI 3.23–348.3, P < 0.01) | MRI severity (cerebral atrophy and ischaemic lesions) (OR 7.9, CI 1.5, 4.1, P = 0.01); macro-ischaemic lesions (OR 8.8 CI 1, 76, P = 0.03); and aPL+ | Severity of cognitive deficits (OR 4.9, CI 1.2, 20.3, P = 0.03); executive function (OR 9.4, CI 1.1, 80, P = 0.02); complex attention (OR 6.22, CI 1.5, 25.6, P = 0.009); and aPL+ |
| Whitelaw et al. (1999) [25] | 69 | Intelligence, visual reproduction, learning, executive function, auditory verbal learning | Pearson’s correlation, | Association not assessed | VBRs and aPL+ (r = −1.01, P = 0.0004) | Intelligence (r = 0.72, P = 0.0007); visual reproduction (r = −0.63, P = 0.003); learning (easy) (r = −0.71, P = 0.0009); executive function (r = −0.32, P = 0.05); auditory verbal learning (r =−0.69, P = 0.001); and aPL+ |
| Sarbu et al. (2015) [26] | 108 | No specific domains reported | χ 2 statistic (Fisher’s exact test) | Cognitive dysfunction and WMH (P = 0.045) | WMH (P = 0.018); microbleeds (P = 0.002); cortical atrophy (P = 0.008); and LA | Association not assessed |
| Steup-Beekman et al. (2013) [37] | 155 | No specific domains reported | Descriptive statistics | Association not assessed | Association not assessed | Association not assessed |
| Abda et al. (2013) [28] | 34 | Attention, memory, problem solving, visual-spatial processing, psychomotor speed | χ 2 statistic (Fisher’s exact test) | No statistical differences cognitive deficits and MRI abnormalities | Association not assessed | Association not assessed |
| Zirkzee et al. (2012) [29] | 71 | No specific domains reported | χ 2 statistic | Association not assessed | Association not assessed | Association not assessed |
| Emmer et al. (2008) [37] | 52 | No specific domains reported | Linear regression | Cognitive dysfunction and; lower MTR histogram peak for brain parenchyma (beta = −0.435, R = 0.664, P < 0.001); WM (beta = −0.445, R = 0.647, P < 0.001); GM (beta = −0.306, R = 0.663, P < 0.01) | aCL on MTR histogram parameters (ns) | Association not assessed |
| Cho et al. (2007) [38] | 25 (NPSLE), 18 (NBD) | No specific domains reported | χ 2 statistic | Association not assessed | Association not assessed | n = 3 patients with cognitive dysfunction were aPL+ (association not assessed) |
| Roldan et al. (2006) [39] | 28 (SLE), 28 (controls) | No specific domains reported | Fisher’s exact test | Association not assessed | Old cerebral infarcts and aPL+ and aCL (P < 0.001) | Association not assessed |
| fMRI (n = 1) | ||||||
| Kozora et al. (2016) [22] | 40 (cases), 10 (controls) | Executive function, working memory | Wilcoxon rank-sum test | Higher activation in bilateral frontal, temporal and parietal cortices during working memory and executive function tasks (P < 0.001) | Higher activation in bilateral frontal, temporal and parietal cortices and aPL+ (P < 0.001) | Higher activation in bilateral frontal, temporal and parietal cortices during working memory and executive function tasks for aPL+ (P < 0.001) |
| TCD (n = 2) | ||||||
| Zamproni et al. (2013) [22] | 27 | Global cognition and executive function | Mann–Whitney U test | Worse global cognition and executive function with sRLS (P < 0.05) | Association not assessed | Association not assessed |
| Cantú-Brito et al. (2010) [30] | 109 | Memory, attention, visuospatial construction | χ 2 statistic, logistic regression | Cognitive dysfunction and MES (P = 0.036), cognitive dysfunction and MES (beta = 0.61, P = 0.19) | MES and aCL (IgG) (ns) | Association not assessed |
| EEG and CT (n = 1) | ||||||
| Chapman et al. (2002) [24] | 23 | No specific domains reported | Fisher’s exact test | Association not assessed | Association not assessed | Association not assessed |
| OCT (n = 1) | ||||||
| Shulman et al. (2017) [36] | 21 (cases), 11 (controls) | No specific domains significant | Pearson correlation | RNFL thickness and global cognition (r = −0.17, P = 0.45); memory (r = 0.08, P = 0.70); executive function (r = −0.25, P = 0.26); attention (r = 0.14, P = 0.53); information processing speed (r = −0.18, P = 0.46); visual spatial (r = −0.26, P = 0.26); verbal function (r = 0.19, P = 0.42); motor skills (r = −0.28, P = 0.21) | Association not assessed | Association not assessed |
Anti-β2GPI: anti-β2 glycoprotein-I antibody; beta: coefficient for a multiple linear regression; EEG: electroencephalogram; fMRI: functional MRI; GM: grey matter; MES: micro-embolic signals; MTR: magnetization transfer ratio; NBD: neuroBehçet’s disease; ns: not statistically significant; OCT: optical coherence tomography; OR: odds ratio; P: statistical significance probability; R: correlation between predicted and observed values; RNFL: retinal nerve fiber layer; RR: relative risk ratio; r: Pearson’s correlation; SPM: statistical parametric mapping; sRLS: significant right to left shunt; TCD: transcranial Doppler; VBR: ventriculo brain ratios; WM: white matter; WMH: white matter hyperintensities; WML: white matter lesions. Bold text indicates results statistically significant.