Table 3

Associations between brain structural MRI metrics, cognitive performance and other clinical features in SLE cohorts of previous studies

First author, year	Neurocognitive associations (L: left, R: right, ~: correlated with, correlation coefficient—r or standardised z-statistic or mean Δ, p value)	Other clinical associations (left, R: right, ~: correlated with)
Appenzeller, 2006	Baseline and follow-up: ↑ CD severity (r=0.9, p=0.001), ↓ composite (r not reported, p=0.015) and verbal (r not reported, p=0.010) memory, ↓ delayed recall (r not reported, p=0.010) ~ ↓ Hp volume	Baseline and follow-up (r, p from baseline only): ↑ Disease duration (r=0.89, p<0.001), number of CNS manifestations (r=0.65, p=0.01), past (but not active) CNS involvement (r=0.90, p<0.001), antiphospholipid Ab (r=0.50, p=06), cumulative steroid dose (r=0.74, p=01) ~ ↓ Hp volume
Appenzeller, 2007	Baseline (no follow-up): ↑ CD severity (z~>2.5, p<0.05), ↑ number of impaired domains (z~8.0, p<0.05) ~ ↓ total GM and WM volume ↓ Composite memory (z~10.0, p<0.05) ~ ↓ medial temporal and frontal lobe volume ↓ Attention (z~>10.0, p<0.05)~ ↓ parietal lobe volume	Baseline (no follow-up): ↑ disease duration (z~>6.5, p<0.05) ~ ↓ total GM and WM volume ↑ cumulative steroid dose (z, p not reported) ~ ↓ GM volume
Jung, 2012	Non-NPSLE: ↓ Overall cognitive function (z not reported, p=0.029) ~ ↓ FA in R external capsule NPSLE: ↓ Overall cognitive function (z not reported) ~ ↓ FA in L anterior Th radiation (p=0.004), CC - splenium/mid-body (p=0.006–0.022), L forceps major (p=0.02) and R forceps minor (p=0.049), R SLF (p=0.007–0.012), R anterior CR (p=0.031) ↓ Psychomotor speed (z not reported) ~ ↓ FA in L&R SLF (p=0.01–0.038), CC—splenium (p=0.037), mid-body (p=0.025), genu (p=0.046), L forceps major (p=0.028) and R forceps minor (p=0.042), L anterior Th radiation (p=0.019), R anterior (p=0.038) and L superior CR (p=0.044) ↓ Visual memory (z not reported) ~ ↓ FA in L IFOF (p=0.001), CC—R forceps minor, L SLF (p=0.027–0.038); ↓ Verbal memory (z not reported) ~ ↓ FA in L ILF (p=0.031) ↓ Attention (z not reported) ~ ↓ FA CC—splenium (p=0.007), mid-body (p=0.014) and L forceps major (p=0.049), R SLF (p=0.016) ↓ Executive skills (z not reported) ~ ↓ FA R SLF (p-0.04), L anterior Th radiation (p=0.018)	NR
Gitelman, 2013	CD-cSLE subgroup classification (NR correlations w/ cognitive domains) ~ ↓ total GM volume (mean Δ=81.2 cm³, p<0.001), ↓ lateral orbito-frontal, anterior cingulate and lateral temporal regions (not reported)	No correlations w/ disease duration or current/cumulative steroid dose in cSLE w/ CD
Cesar, 2015	↓ Executive skills ~ ↓ FA in CR, CC—superior body, SLF (NR effect measures, p<0.05)	NR
Bizzo, 2016	↓ Episodic memory ~ ↓ cortical thickness R superior A/P frontal and precentral regions (within SLE cohort, z not reported, p=0.0048)	NR
Bódi, 2017	↓ Overall cognitive function ~ ↓ CA1 Hp volume (r=0.62, p=0.005)	NR
Zimmerman, 2017	SLE w/ CD: no correlations between # of impaired domains and brain regions	NR
Wiseman, 2017	↓ Overall cognitive function ~ ↑ MD in WM (r=−0.31, p=0.03, not significant after age correction)	↑ Fatigue ~ ↓MD in WM (r=−0.35, p=0.01)
Cannerfelt, 2018	No correlation between any cognitive domain and Hp and CC volume ↓ composite (r=0.301, p=0.021), & verbal memory (r=0.404, p=0.001)~ ↑ WM lesion volume	NR
Corrêa, 2018	SLE w/ memory deficits vs SLE w/o memory deficits: no diffusion MRI brain differences	NR
Nystedt, 2018	SLE: ↓ psychomotor speed ~ ↓ FA R hippocampal Cg (r=0.334, p=0.010) NPSLE: ↓ cognitive flexibility (executive skills) ~ ↓ FA R subgenual Cg (r=0.357, p=0.038)	SLE: no correlations w/ depression or disease activity ↑ Fatigue ~ ↓ FA in CC—forceps minor (r=–0.229, p=0.038) ↑ disease duration ~ ↓ FA in CC—forceps minor (r=−0.372, p=0.003) NPSLE: ↑ Fatigue ~ ↑ MD in L hippocampal Cg (r=0.380, p=0.038)
Wiseman, 2018	↑ g (overall cognitive function) ~ ↑ all network metrics (r>0.32, p<0.05, except mean edge weight) ↑ g ~ ↑ density (r=0.48, p<0.01), strength (r=0.45, p<0.01), mean shortest path length (r=−0.34, p<0.05), global efficiency (r=0.35, p<0.05) and clustering coefficient (r=0.32, p<0.05) ↑ g ~ ↑ nodal strength in R Cd (r=0.55, p<0.05) and lingual regions (r=0.41, p<0.05), L precentral (r=0.50, p<0.05) and middle frontal regions (r=0.41, p<0.05) ↑ g ~ ↓ nodal strength in R Hp (r=−0.32, p<0.05)	↓ Disease duration ~ ↑ all network metrics (r<0.31, p<0.05 (except ↓ mean shortest path length; r=0.39, p<0.01) ↓ SLE damage ~ ↑ nodal strength in R Cd (r=−0.37, p<0.05), superior parietal (r=−0.38, p<0.05), superior temporal (r=−0.32, p<0.05), middle frontal (r=−0.36, p<0.05), lateral occipital (r=−0.31, p<0.05) and pericalcarine regions (r=−0.36, p<0.05)
MacKay, 2019	Baseline (no follow-up): ↑ spatial memory ~ ↑ FA in L&R paraHp (r=0.63, p<0.002)	Baseline (no follow-up): ↑ serum DNRAb titres ~ ↓ FA in bilateral paraHp (r=−0.64, p<0.002)
DiFrancesco, 2020	↓ Visual-spatial processing ~ ↑ D∗ × v_bw (perfusion) (r=−0.66, p=0.026) in middle posterior precuneus ↓ Psychomotor speed ~ ↑ D∗ × v_bw (r=−0.63, p=0.037), D∗ (r=−0.62, p=0.043) in middle posterior precuneus	↑ Disease activity ~ ↑ D∗ (r=0.58, p=0.061), ↓ v_bw (blood-water fraction) (r=−0.54, p=0.090) in middle posterior precuneus (marginally significant)
Mårtensson, 2021	SLE & HC: ↓ psychomotor speed ~ ↓ VBM volume in VIIIa area of L&R cerebellum (r=0.21, p=0.05)	NR
Qian, 2022	↓ Attention ~ ↑ FW in CC, fronto-parietal (anterior Th radiation) , fronto-temporal (SLF), fronto-occipital (IFOF) WM and Cg (r=−0.51, p=0.022, all significant regions evaluated together)	↑ Cumulative steroid dose ~ ↑ FW in callosal, fronto-parietal, fronto-temporal, fronto-occipital WM, Cg (r=0.63, p=0.0041, all significant regions evaluated together)
Julio, 2023	↑ Overall cognitive function ~ ↓ MD in whole CC (r=−0.207, p=0.03) and all CC parcels	↑ Age at disease onset (r=0.71, p<0.001), disease duration (r=0.481, p<0.001) ~ ↑ DTI metrics

Ab, antibodies; A/P, anterior/posterior; CC, corpus callosus; Cd, caudate; CD, cognitive domains; Cg, cingulum; CI, cognitive impairment; CR, corona radiata; D, Water diffusion coefficient; D*, perfusion coefficient; DTI, diffusion tensor imaging; EM, episodic memory; FA, fractional anisotropy; GM, grey matter; HC, healthy controls; Hp, hippocampus; IFOF, inferior fronto-occipital fasciculus; ILF, inferior longitudinal fasciculus; MD, mean diffusivity; NART, National Adult Reading Test; NP, neuropsychiatric; NR, not reported; SLF, superior longitudinal fasciculus; UF, uncinate fasciculus; VBM, voxel-based morphometry; v_bw, fraction of water molecules in blood; WB, whole brain; WM, white matter; Δ, difference.