Background
Methods
Literature search and study selection
Data extraction and analysis
Results
Study characteristics
Reference | Participants | Characteristics of patients with CSVD | MRI acquisition params | BOLD pre-processing | FC analysis | FC patterns associated with CSVD | Risk of bias (AXIS) | |
---|---|---|---|---|---|---|---|---|
Neuroimaging | Cognition | |||||||
[28] | 18 CSVD-CN 16 CSVD-MCI | WMH and lacunes (clinical diagnosis) | MMSE CN 28.9 ± 1.3 MCI 28.1 ± 1.4 | Philips Achieva, 3 T TR 2000 ms, TE 30 ms 64 × 64 × [] 3.6 × 3.6 × 4 mm3 220 volumes eyes open | DPARSF v2.0, SPM 5, REST [Confound regression] Motion scrubbing - Max motion > 1 mm/1° | PCC from external template SCA to define DMN Pearson correlation | ↓ FC in DMN in the left middle temporal gyrus, left ant. cingulate/left middle frontal gyrus, right caudate, right middle frontal gyrus, and left medial frontal gyrus/paracentral lobule ↑ FC in DMN in the right inf. temporal gyrus, left middle temporal gyrus, left precentral gyrus, and left sup. parietal lobule | High (2) |
[29] | 29 CSVD | WMH (clinical diagnosis) WMH volume VRF 0, 20.4 ± 19.3 VRF 1, 27.3 ± 21.5 VRF 3, 17.4 ± 19.5 | MoCA VRF 0, 25.8 ± 3.5 VRF 1, 22.0 ± 6.2 VRF 3, 21.0 ± 5.4 | Philips Achieva, 3 T TR 2000 ms, TE 30 ms 64 × 64 × 40 3.6 × 2.9 × 3 mm3 184–259 volumes, [eyes] | FSL v4.1 Confound regression - ICA Motion scrubbing - ‘relative motion’ > 1.5 mm | ICA to define DMN, SMN, medial-visual RSN Pearson correlation | FC in DMN ↗ cardiovascular reactivity | Moderate (4) |
[30] | 21 CSVD-CN 16 CSVD-MCI 13 SVaD | WMH (clinical diagnosis) | MMSE CN 28.9 ± 0.7 MCI 26.3 ± 1.0 SVaD 20.5 ± 2.3 MoCA CN 24.6 ± 2.9 MCI 20.6 ± 2.8 SVaD 15.1 ± 3.6 | Siemens, 3 T TR 2480 ms, TE 30 ms 64 × 64 × 36, 3 × 3 × 4 mm3 240 volumes eyes closed | SPM 8 [Confound regression] Motion scrubbing - Head motion > 2 mm/2° | AAL atlas Pearson correlation, (extended) maximal information coefficient SVM classification | None | High (3) |
[31] | 46 CSVD 41 CADASIL | WMH volume 0.3% [0.03, 3.1]% of intracranial volume Lacunes 0 (0) [0–20] | Siemens Skyra/Prisma, 3 T, 64-/32-channel head coils, multi-band × 8 TR 700 ms, TE 39 ms [matrix] 3 × 3 × 3 mm3 2.4 × 2.4 × 2.4 mm3 675–700 volumes eyes closed | FSL, ANTs, BRAMILA v2.0 Confound regression - ICA-AROMA non-aggressive - Linear trend, 6 motion params - GSR: CSF, WM Motion scrubbing - Volume censoring (FD > 0.5 mm, total time < 5 min) | Power atlas to define DMN, FPCN, hand-SMN, VN Pearson correlation graph theory | No association between WMH and FC Poor reproducibility of network measures in CSVD | Moderate (6) | |
[33] | 33 MCI with confluent (C) WMH 30 MCI with non-confluent (NC) WMH | Fazekas C-WMH 8.0 ± 2.4 NC-WMH 3.2 ± 1.2 WMH volume C-WMH 8.7 ± 9.2 ml NC-WMH 1.9 ± 1.5 ml | MMSE C-WMH 27.6 ± 1.5 NC-WMH 27.8 ± 1.7 | Siemens Trio, 3 T TR 2000 ms, TE 30 ms [] × []× 36, 3 × 3 × 3 mm3 240 volumes [eyes] | CONN 18b Confound regression - GSR: WM, CSF - Motion parameters Motion correction - Artefact Detection Tools - Spike regression (FD > 0.5 mm) | CONN atlas with 138 ROIs to define DMN, SMN, VN, DAN, FPCN language, and cerebellar networks Bivariate correlation coefficients | ↑ Interregional FC (C-WMH > NC-WMH) ↑ Intra-regional FC (C-WMH > NC-WMH) Few ↓ interregional FC (C-WMH < NC-WMH) | High (2) |
[34] | 29 CSVD with gait disorder (GD+) 29 CSVD without gait disorder (GD−) | Fazekas ≥2 WMH volume GD+, 6.12 mm3 GD−, 3.53 mm3 Lacunes GD+, 7.45 ± 4.01 GD−, 5.62 ± 3.35 | MMSE GD+, 25.14 ± 3.24 GD−, 25.69 ± 3.32 | GE Signa, 3 T, 8-channel head coil TR 2000 ms, TE 30 ms 64 × 64 × [] 3.75 × 3.75 × 4.6 mm3 240 volumes eyes closed | DPABI, SPM 8 Confound regression - Linear trend, 24p - GSR: CSF, WM Motion scrubbing - ‘displacement’ > 2.5 mm /2.5° | fALFF Pearson correlation VBM | ↓ FC between left SMA and temporal lobe (GC+ < GD−) ↗ gait speed fALFF in left SMA ↗ cadence | Moderate (4) |
Healthy controls and patients with CSVD without mandatory cognitive impairment | ||||||||
[35] | 12 CSVD 21 HC | Wahlund 8.3 ± 4.0 Lacunes 1.9 ± 2.4 | MMSE 27.6 ± 1.5 | [Scanner, field str.] TR 2300 ms, [TE] [matrix], 3 × 3 × 4 mm3 300 volumes [eyes] | FSL, AFNI, SPM B0 field map correction Confound regression - Linear/quadratic trend - 6 motion parameters - GSR: WM, CSF signal [Motion scrubbing] | Eigenvector centrality | ↓ FC in ventromedial PFC, MCC, and sup. parietal lobe ↑ FC in the cerebellar regions I–VI FC ↗ WMH in the middle temporal sulcus, inf. temporal gyrus, cerebellar lobules Crus II, VIIb, VIII FC ↘ WMH in ventromedial PFC, SMA, PCC, and sup. parietal lobe | High (1) |
[36] | 30 CSVD 26 HC | Fazekas 1–3 Lacunes excluded | MoCA 22.9 ± 3.4 (pooled) | Siemens, 3 T TR 2480 ms, TE 30 ms 64 × 64 × 36, 3 × 3 × 4 mm3 240 volumes, eyes closed | SPM 8 [Confound regression] Motion scrubbing - Head movement > 2 mm/2° | ICA to define SMN voxel-wise two-sample t test | ↓ FC in the right cingulate motor area, left posterior insula, and left ventral premotor area | High (2) |
[37] | 28 CSVD 30 HC | Fazekas 2.9 ± 1.2 | MMSE 27.9 ± 1.6 MoCA 25.7 ± 2.0 | Siemens Trio, 3 T TR 2000 ms, TE 30 ms 64 × 64 × [] 3.5 × 3.5 × 3 mm3 240 volumes [eyes] | SPM 8, DPABI, REST [Confound regression] Motion scrubbing - Head movement > 2 mm/2° | ALFF, SCA | ↓ ALFF in the left parahippocampus ↑ ALFF in the left inf. semi-lunar lobule and right frontal sup. orbital gyrus ↑ FC between right insula–right sup. orbitofrontal gyrus and right calcarine–left parahippoca. gyrus | High (2) |
[38] | 16 CSVD 13 HC | WMH (clinical diagnosis, Fazekas) | MMSE 23.7 ± 3.9 MoCA 18.3 ± 4.1 | Siemens, 3 T TR 2000 ms, TE 30 ms 64 × 64 × 35 3 × 3 × 3 mm3 230 volumes eyes closed | SPM 8 Confound regression - Linear trend Motion scrubbing - Head movement > 2 mm/2° | Regional homogeneity | ↓ ReHo in the left insula, right sup. temporal gyrus, Rolandic operculum, precentral gyrus, and cerebellum; bilateral ant. cingulate gyrus, ant. MCC, PFC, and SMA ↑ ReHo values in the left middle temporal gyrus, cuneus and sup. occipital gyrus, and the bilateral angular gyrus, precuneus, postcentral gyrus, inf. and sup. parietal gyrus | Moderate (5) |
[39] | 15 CSVD 15 HC | WMH (clinical diagnosis, Fazekas) | MMSE 23.7 ± 4.0 MoCA 18.6 ± 4.1 | Siemens, 3 T TR 2000 ms, TE 30 ms 64 × 64 × [] 3 × 3 × 4 mm3 230 volumes eyes closed | DPABI v2.1 Confound regression - Linear trend - 24p [40] - GSR: WM, CSF - Spike regressor (FD > 0.2 mm) Motion scrubbing - Mean FD > group mean + 2*SD | 36 ROIs representing DMN, DAN, FPCN, SMN, VN Pearson correlation Network-based statistics (NBS) [41] | ↓ AN-SMN network FC ↑ DAN-FPCN network FC ↓ Edge FC SMN-AN, SMN-VN, FPCN-AN and DAN-VN pairs, and within AN and VN ↑ Edge FC in DMN-AN, DMN-FPCN, and DAN-FPCN pairs | High (3) |
[42] | 26 lacunar stroke patients 19 HC | Fazekas ≥2 Lacunes 1–17 (6) WMH 33 ± 34 ml | History of lacunar stroke syndrome | Siemens Verio, 3 T, 32-channel head coil TR 2430 ms TE 1/2/3 13/31/48 ms 64 × 64 × 34 3.75 × 3.75 × 4.18 mm3 269 volumes, eyes open | SPM, CONN Confound regression - Motion parameters [details] - GSR: WM, CSF [Motion scrubbing] | Desikan–Killiany parcellation Pearson correlation Probab. tractography Graph theory | No difference in FC or brain network topology | Moderate (6) |
[43] | 36 CSVD 31 HC | Fazekas ≥2 | MMSE HC 28.4 ± 1.8 CSVD 26.4 ± 3.7 | Siemens Verio, 3 T, 12-channel head coil TR 2000 ms, TE 25 ms 64 × 64 × [z] 3.75 × 3.75 × 4 mm3 [volumes], [eyes] | DPARSF, SPM 8 Confound regression - 6 head motions params - GSR: global, WM, CSF Motion scrubbing - Head movement > 2 mm/2° | AAL 90 Pearson correlation Graph theory NBS | ↓ Global FC ↑ Characteristic path length ↓ Global efficiency | High (0) |
Healthy controls and patients with CSVD with mandatory cognitive impairment | ||||||||
[44] | 26 svMCI 28 HC | Wahlund ≥ 2 ± lacunes | Subjective complaints MMSE 25.7 ± 2.7 | Siemens, 3 T TR 2000 ms, TE 40 ms 64 × 64 × 28 4 × 4 × 5 mm3 239 volumes eyes closed | SPM 5 Confound regression - Linear trend - 6 motion profiles - GSR: WM, CSF Motion scrubbing - Head movement > 3 mm/3° | ALFF, SCA, FC density Pearson correlation (only positive) | ↓ ALFF in bilateral medial PFC ↑ ALFF in right PCC, precuneus, right hippocampus, right thalamus ↓ FC in DMN (PCC/precuneus, medial PFC, sup. frontal gyrus, inf. parietal lobule and hippocampus) and inferior/middle frontal gyrus | High (2) |
[45] | 21 svMCI 26 HC | Wahlund ≥ 2 ± lacunes | Subjective complaints MMSE 25.5 ± 2.7 | Siemens, 3 T TR 2000 ms, TE 40 ms 64 × 64 × 28 4 × 4 × 5 mm3 239 volumes eyes closed | SPM 5 and 8, REST, DARTEL Confound regression - Linear trend - 6 motion profiles - GSR: WM, CSF Motion scrubbing - Head movement > 3 mm/3° - Volume censoring (FD > 0.3 mm, < 3 min) | H-1024 parcellation Pearson correlation Graph theory | ↑ Characteristic path length, ↑ modularity ↑ Within-module degree in the medial PFC, left insula, and cuneus ↓ Within-module degree in the middle cingulate gyrus ↑ Participation coefficient in the left inferior/superior parietal cortex | High (1) |
[46] | 37 PiB+ AD 37 PiB− SVaD 13 mixed dementia 65 HC | Fazekas (severe) | MMSE PiB+ AD, 18.1 ± 4.2 PiB− SVaD, 21.5 ± 4.3 MD, 17.9 ± 4.9 HC, 28.9 ± 1.2 | Philips Achieva, 3 T, 8-channel head coil TR 3000 ms, TE 35 ms [matrix], 1.7 × 1.7 × 4 mm3 100 volumes, eyes open | AFNI Despiking [Confound regression] Motion scrubbing - Max FD > 0.3 mm - Head movement > 2 mm/2° | ICA to define DMN and FPCN W-score maps | ↓ FC in DMN in the left superior frontal gyrus ↓ FC in FPCN in the left insula | Moderate (5) |
[47] | 32 CSVD-CI 23 HC | Fazekas 2–3 ± lacunes | MMSE 23.8 ± 2.7 | GE Signa, 3 T TR 2000 ms, TE 30 ms 64 × 64 × [] 3.75 × 3.75 × 4.6 mm3 240 volumes eyes closed | SPM 8, DPARSF, CONN Confound regression - compCor - GSR: global signal [Motion scrubbing] | Medial PFC and thalamus from ext. template SCA Pearson correlation | ↓ FC between the left thalamus and right sup. temporal gyrus, left sup. frontal gyrus, left and putamen ↓ FC between the right thalamus and left inferior temporal gyrus ↑ FC between the bilateral thalamus and right inferior/middle frontal gyri ↓ FC between the med. PFC and bilateral SMA, thalamus, left sup. frontal gyrus, ACC, sup. parietal lobe, and hippocampus | High (2) |
[48] | 14 CSVD-CN 27 CSVD-MCI 12 SVaD 30 HC | Fazekas (cut-off not specified) | MMSE CSVD-CN 29.1 ± 1.0 CSVD-MCI 27.2 ± 2.4 SVaD 23.3 ± 3.4 | Siemens, 3 T TR 2000 ms, TE 30 ms 64 × 64 × 32, 4 × 4 × 3.7 mm3 [volumes], eyes closed | SPM 8 [Confound regression] Motion scrubbing - Head movement > 2 mm/2° | ICA to define DMN, SN, FPCN SCA from the right fronto-insular cortex | ↓ FC between SN-DMN ↑ FC between SN-FPCN and within SN | High (3) |
[49] | 36 CSVD 50 AD 55 HC | WMH volume svMCI 22.6 ± 6.1 ml SVaD 44.8 ± 10.1 ml Lacunes svMCI 6.5 ± 7.5 SVaD 7.4 ± 7.2 Microbleeds svMCI 13.4 ± 18.7 SVaD 26.0 ± 49.2 | MMSE svMCI 25.4 ± 3.7 SVaD 17.4 ± 4.2 | Siemens, 3 T TR 3000 ms, TE 35 ms [matrix] 3.4 × 3.4 × 3.4 mm3 200 volumes [eyes] | SPM 12 No smoothing Confound regression - Motion parameters - Linear trend - GSR: WM, CSF Motion scrubbing - Volume censoring (FD > 1 mm, > 30%) | Schaefer 400 atlas Pearson correlation AV1451 tau-PET | FC ↗ tau covariance, no associations with WMH | Moderate (7) |
[50] | 25 CSVD-CN 24 CSVD-MCI 36 HC | Fazekas ≥2 ± lacunes WMH CN 3.0 (0.76, 4.0) ml MCI 4.8 (0.76, 5.6) ml | MMSE CN 28.4 ± 1.3 MCI 27.8 ± 2.1 MoCA CN 26.1 ± 0.5 MCI 21.4 ± 0.5 | Philips, 3 T TR 2000 ms, TE 30 ms 64 × 64 × 35 3.75 × 3.75 × 4 mm3 230 volumes eyes closed | GRETNA v2.0, SPM 8 Confound regression - Linear trend, 24p - GSR: GS, WM, CSF Motion scrubbing - Head movement > 2 mm/2° | H-1024 parcellation Pearson correlation Graph theory to define DMN, FPCN, SMN, and VN | No robust associations | Moderate (4) |
[51] | 21 CSVD-CN 20 CSVD-MCI 25 HC | WMH volume CN 3.2 ± 3.0 ml CI 3.4 ± 4.1 ml ± lacunes | MMSE CN 28.5 ± 1.3 MCI 28.1 ± 1.3 MoCA CN 25.6 ± 1.9 MCI 22.2 ± 2.9 | Philips, 3 T, 32-channel head coil TR 2000 ms, TE 30 ms 64 × 64 × 35 3.75 × 3.75 × 4 mm3 230 volumes Eyes closed | DPABI Confound regression - 24p - GSR: GS, WM, CSF Motion scrubbing - Head movement > 3 mm/3° | PCC, dlPFC, IPS from external template SCA to define DMN, FPCN, and DAN | ↓ FC in DMN in the right thalamus, hippocampus, and precuneus ↑ FC in FPCN in the right inf. parietal lobule ↓ FC between PCC-FPCN in the left precentral gyrus and bilateral middle cingulate gyri ↓ FC between PCC-DAN in the bilateral paracentral lobule and precuneus ↓ FC between PCC-DAN in the bilateral PCC and right precuneus | Moderate (6) |
[52] | 14 CSVD + THA LAC 27 CSVD − THA LAC 34 HC | Fazekas 3–6 Lacunes LAC+, 5.6 ± 3.9 LAC−, 2.0 ± 1.4 | MMSE LAC+, 26.3 ± 2.8 LAC−, 28.1 ± 2.0 | GE Discovery, 3 T TR 2000 ms, TE 35 ms 64 × 64 × 36 3.4 × 3.4 × 4 mm3 210 volumes eyes closed | SPM 8 Confound regression - 6 motion parameters - GSR: WM, CSF Motion scrubbing - Head movement > 2 mm/2° | AAL 90 Pearson correlation Graph theory, Network-based statistics | ↓ FC in para-/limbic and subcortical regions | Moderate (5) |
[53] | 32 CSVD-MCI 20 SVaD 35 HC | Fazekas ≥1 | MMSE MCI 25.5 ± 1.8 SVaD 22.0 ± 2.0 MoCA MCI 22.2 ± 1. SVaD 17.4 ± 2.9 | Siemens Verio, 3 T TR 2000 ms, TE 30 ms 64 × 64 × 32 4 × 4 × 4.2 mm3 240 volumes eyes closed | DPARSF Confound regression - Linear/quadratic, 24p - GSR: WM, CSF Motion scrubbing - Head movement > 3 mm/3° | AAL atlas Pearson correlation Graph theory | ↓ Global FC ↓ Small-worldness | Moderate (4) |
[54] | 20 LA-VAD 32 LA-VCIND 35 HC | Not reported | MMSE HC 29.4 ± 1.1 LA-VCIND 27.9 ± 1.8 LA-VaD 23.0 ± 3.8 MoCA HC 26.0 ± 2.5 LA-VCIND 25.8 ± 2.0 LA-VaD 23.2 ± 2.8 | Siemens, 3 T TR 2000 ms, TE 30 ms 64 × 64 × 20 4 × 4 × 6 mm 250 volumes eyes closed | DPARSF Confound regression - 24p - GSR: WM, CSF Motion scrubbing - Head movement > 3 mm/3° | Group ICA (GIFT) Granger causality | Unclear; text and figures not consistent | High (2) |
Operationalisation of CSVD and associated cognitive impairment
Functional MRI acquisition and pre-processing
Connectivity analysis
Reference | Participants | Quantification of WMH load | rs-fMRI acquisition parameters | BOLD pre-processing | FC analysis | FC patterns associated with CSVD |
---|---|---|---|---|---|---|
[69] | 12 depression 12 HC | Fuzzy connected algorithm [70] | GE Signa, 1.5 T TR 2000 ms, TE 35 ms 64 × 64 × 26, 3.75 × 3.75 × 3.8 mm3 [volumes], eyes open | AFNI [Confound regression] [Motion scrubbing] | PCC from ext. template SCA to define DMN Pearson correlation | FC in DMN ↘ WMH in medial PFC |
[71] | 47 depression 46 HC | Not reported | Siemens Trio, 3 T TR 2000 ms, TE 32 ms 128 × 128 × 28, 2 × 2 × 2 mm3 150 volumes, eyes open | SPM 5 [Confound regression] [Motion scrubbing] | PCC from ext. template SCA to define DMN Pearson correlation | ↓ Association between DMN-FC and treatment response after controlling for WMH load |
[62] | 13 early AD 17 MCI 14 HC | Semi-automatic using FireVoxel [72] | [Scanner] TR 3000 ms, TE 30 ms [matrix], 3.3 × 3.3 × 3.3 mm3 140 volumes, [eyes] | [Confound regression] [Motion scrubbing] | Medial PFC and PCC from ext. atlas SCA to define DMN fALFF | Both increased WMH load and reduced DMN-FC in AD and MCI compared to HC |
[73] | 100 MCI | In-house automatic pipeline [74] | Philips Achieva, 3 T TR 2000 ms, TE 30 ms [matrix], [resolution] 200 volumes eyes closed | DPARSF Confound regression - 6 motion parameters - GSR: CSF, WM, global [Motion scrubbing] | SCA from the hippocampus and PCC | No association between WMH load and FC |
[63] | 43 MCI 24 HC | Histogram segmentation [75] | Training Philips, 3 T, 8-channel head coil TR 3000 ms, [TE] [matrix], 3.3 × 3.3 × 3.3 mm3 140 volumes eyes open Testing Siemens Verio, 3 T, 32-channel head coil TR 2580 ms, [TE] [matrix], 3.5 × 3.5 × 3.5 mm3 180 volumes eyes closed | DARTEL Confound regression - 6 motion parameters - GSR: CSF, WM [Motion scrubbing] | Whole-brain SCA Pearson correlation | No association between WMH and FC |
[65] | 90 MCI 140 HC | SPM Lesion Segmentation Tool [76] | Siemens Trio, 3 T TR 2300 ms, TE 30 ms [] × [] × 34, 3 × 3 × 4 mm3 [volumes] eyes closed | CONN, SPM 12 Confound regression - compCor - GSR: CSF, WM Motion scrubbing - Artefact Detection Tools - Spike regression (FD > 0.5 mm) | Preselected cognitive control networks (FPCN, SN) + DMN Pearson correlation Structural equation modelling | Weaker negative association between executive function/memory and WMH load in patients with high global FC |
[77] | 18 svMCI + depression 17 svMCI − depression 23 HC | Fazekas scale | GE MR750, 3 T TR 2000 ms, TE 35 ms 64 × 64 × 26, 4 × 4 × 4 mm3 240 volumes [eyes] | DPABI Confound regression - Linear and quadratic trends, 24p - GSR: CSF, WM, global Motion scrubbing - Head motion > 3 mm/3° - Volume censoring (FD > 0.5 mm) | VBM SCA from altered regions Pearson correlation | ↑ FC between right middle cingulate cortex and right parahippocampal gyrus |
[78] | 38 P w Sjogren syndrome 40 HC | Wahlund score | Siemens Trio, 3 T TR 2500 ms, TE 30 ms 96 × 96 × 40, 2.3 × 2.3 × 3 mm3 204 volumes eyes closed | Matlab, DPABI Confound regression - Linear trend - GSR: CSF, WM, global Motion scrubbing - Mean FD > 0.2 mm | SCA from hippocampi Pearson correlation | FC ↗ WMH left hippocampus and right inf. orbital and inf. temporal gyrus |
Healthy participants | ||||||
[79] | 76 healthy participants | Mixture model [80] | GE Signa, 1.5 T TR 2000 ms, TE 40 ms [] × [] × 24, [] × [] × 5 mm3 240 volumes [eyes] | REST Confound regression - Head motion parameters - GSR: CSF,WM, global Motion scrubbing - > 58 outlier volumes (> 1.5 mm/1.5°) | PCC from ext. template SCA to define DMN Pearson correlation | No association between WMH load and FC Episodic memory ↗ medial PFC–left inferior parietal cortex FC in patients with low grey matter volume |
[81] | 127 healthy (Harvard Ageing Brain Study) | Fazekas 0–1 vs. 2–3 | Siemens Trio, 3 T, 12-channel head coil TR 3000 ms, TE 30 ms 72 × 72 × [], 3 × 3 × 3 mm3 124 volumes eyes open | SPM 8 Confound regression - Realignment params + derivatives - GSR: WM, CSF, global Motion scrubbing - Mean FD > 0.15 mm - ≥ 20 outlier volumes (> 0.75 mm/1.5°) | PCC and medial PFC from external DMN template Partial Pearson correlation Probabilistic tractography | ↓ Association between PCC-medial PFC FC and mean diffusivity in cingulum bundle |
[82] | 186 clinically healthy (Harvard Ageing Brain Study) | Automated fuzzy-connected algorithm [70] | Simens Trio, 3 T, 12-channel head coil TR 3000 ms, TE 30 ms 72 × 72 × 47, 3 × 3 × 3 mm3 2 × 124 volumes eyes open | SPM 8 Confound regression - 12 motion parameters Motion scrubbing - ‘mean movement’ > 0.2 mm - > 20 outlier volumes (> 0.75 mm/1.5°) | Template-based rotation to define DMN and FPCN Pearson correlation | No association between WMH load and FC |
[83] | 51 healthy participants | SPM Lesion Segmentation Tool [76] | Phillips Ingenia, 3 T TR 2600 ms, TE 35 ms 128 × 128 × 35, 1.8 × 1.8 × 4 mm3 125 volumes, [eyes] | REST, GIFT [Confound regression] [Motion scrubbing] | ICA to define DMN, SN, FPN, VN | FC in DMN ↗ WMH in the mediotemporal complex FC in SN ↗ WMH in the right S1 and sup./inf. parietal cortex |
[84] | 1584 healthy participants (Rotterdam Study) | Tract-specific WMH load [85] | GE Signa, 1.5 T TR 2900 ms, TE 60 ms 64 × 64 × 31, 3.3 × 3.3 × 3.3 mm3 160 volumes, eyes open | FSL Confound regression - Low-frequency drifts - Motion components - ICA Motion scrubbing - Max FD > 0.5 mm, abs. motion > 3 mm | Desikan–Killiany parcellation Pearson correlation Probabilistic tractography | FC ↘ WMH both tract-specific and global |
[86] | 145 healthy participants | SPM Lesion Segmentation Tool [76] | GE MR750, 3 T TR 1500 ms, TE 27 ms 64 × 64 × 29, 3.75 × 3.75 × 4 mm3 162 volumes eyes open | FSL Confound regression - GSR: CSF, WM Motion scrubbing - FD > 0.5 mm | ICA to define DMN, SMN, FPCN Pearson correlation | No association between WMH load and FC |
[87] | 69 healthy participants | Coarse-to-fine in-house developed mathematical morphology method [88] | Phillips Achieva, 3 T TR 2050 ms, TE 25 ms 64 × 64 × 47, 3.2 × 3.2 × 3.2 mm3 210 volumes eyes open | CONN Confound regression - 6 motion parameters - GSR: WM, CSF [Motion scrubbing] | AAL atlas, DTI atlas Whole-brain SCA Intrinsic connectivity contrast | FC in the left cuneus and right sup. occipital cortex ↗ WMH in the right ant. corona radiata FC in the left superior occipital cortex ↗ WMH in the right superior corona radiata |
[67] | 400 healthy participants (Baltimore Longitudinal Study of Aging) | Multimodal supervised classification algorithm [89] | Philips Achieva, 3 T TR 2000 ms, TE 30 ms [matrix], 3 × 3 × 3 mm3 180 volumes [eyes] | Confound regression - 24 motion parameters - GSR: global, WM, CSF Motion scrubbing - ‘summary motion value’ > 0.2 mm - Volume censoring (FD > 0.5 mm, < 5 min) | Geodesic graph-based segmentation Regional homogeneity Sparse connectivity patterns | Pattern of advanced brain ageing characterised by both increased WMH burden and reduced FC compared to resilient agers |
[66] | 11 healthy participants | Siemens Trio, 3 T TR 2000 ms, TE 27 ms 92 × 92 × 43, 2.5 × 2.5 × 3 mm3 240 volumes eyes closed | SPM12 Confound regression - Linear/quadratic, 18 motion parameters - GSR: CSF, WM Motion scrubbing -> 3 mm max, > 3° max -> 24 spikes (FD > 1 mm) | Brainnetome atlas (228) Graph theory to define DMN Pearson correlation | No association between WMH load and DMN FC trajectories | |
[92] | 562 healthy participants | SPM Lesion Segmentation Tool [76] | Phillips Achieva, 3 T TR 2000 ms, TE 20 ms 112 × 112 × 37, 2 × 2 × 3 mm3 [volumes], [eyes] | [Confound regression] [Motion scrubbing] Mean FD as covariate in analysis | Desikan–Killiany parcellation FC measure not specified | No association between WMH load and FC |
[93] | 182 participants (UK Biobank) | BIANCA with manual correction [94] | Siemens Skyra, 3 T TR 735 ms, TE 39 ms 88 × 88 × 64, 2.4 × 2.4 × 2.4 mm3 490 volumes, [eyes] | FMRIB (FSL), ICA-FIX Confound regression - ICA [Motion scrubbing] | ICA, AAL atlas Pearson correlation Degree centrality | FC ↗ WMH in right orbitofrontal cortex |
[95] | 250 healthy (Harvard Aging Brain Study) | Automated fuzzy-connected algorithm [70] | Siemens Trio, 3 T TR 3000 ms, TE 30 ms [matrix], 3 × 3 × 3 mm3 2 × 124 volumes, eyes open | SPM 8 Template-based rotation method [Confound regression] [Motion scrubbing] | Template-based rotation to define DMN, SMN, DMN, and FPCN Pearson correlation | Association between WMH load and FC not investigated FC in DMN ↘ risk of progression to MCI |
Assessment of cognitive impairment
Cognitive domain | Reference | Instruments | |
---|---|---|---|
General | [47] | – | MMSE ↗ FC between the left thalamus–left orbitofrontal lobe |
[38] | – | MMSE ↗ ReHo in the right angular gyrus and precuneus MoCA ↗ ReHo in the bilateral angular gyrus, the right precuneus, medial/dorsolateral PFC, and supplementary motor area | |
[39] | – | MMSE ↗ FC right precentral–right calcarine fissure, left posterior inferior parietal lobe–left Heschl, right posterior inferior parietal lobe–right dorsolateral PFC MMSE ↘ FC right posterior inferior parietal lobe–left Heschl, left intraparietal sulcus–right superior temporal gyrus MoCA ↗ FC right posterior inferior parietal lobe–right anterior PFC, right posterior inferior parietal lobe–right dorsolateral PFC MoCA ↘ FC right posterior inferior parietal lobe–left Heschl, left intraparietal sulcus–right superior temporal gyrus | |
[53] | – | MoCA ↗ small-worldness | |
[33] | – | MMSE ↘ parieto-occipital FC in patients with confluent WMH | |
Executive function | [35] | CERAD battery [96] | Phonemic fluency ↗ FC in bilateral sup. parietal lobe, SMA, premotor cortex, MCC, and posterior superior frontal sulcus RTStroop, neutral ↘ FC in the bilateral premotor cortex, superior frontal sulcus, left inferior frontal sulcus, left SMA, left middle temporal sulcus, and right MCC RTStroop, neutral ↗ FC in the inferior parietal lobe and cerebellar lobules Crus II, VIIb, and VIII RTTMT-A ↘ FC in the bilateral premotor cortex, left posterior middle frontal gyrus, left inferior frontal sulcus, right superior parietal lobe, and left SMA RTStroop, incongruent ↘ FC in the left premotor cortex/posterior middle frontal gyrus RTStroop, incongruent ↗ FC in the cerebellar regions VI, Crus I, and Crus II |
[81] | Letter/category fluency, letter-number sequencing of the WAIS-III, Digit Span Backward of the WAIS revised (WAIS-R), Self-Ordered Pointing task, mod. Flanker task, and TMT A/B Confirmatory factor analysis [97] | Executive function ↗ FC-SC decoupling in DMN | |
[36] | Visuospatial/executive sub-score of MoCA | Executive function ↗ FC in the right cingulate motor area | |
[83] | Stroop test | Time interference index ↗ FC in anterior DMN and SN | |
[65] | TMT A/B, Stroop test Latent variables | Association (executive function ↘ WMH) attenuated in patients with high global FC in FPCN Associations (executive function ↘ WMH) and (memory ↘ WMH attenuated) in patients with high local FC in SN | |
[51] | TMT-A/B, Stroop test | RTTMT-A ↘ FC in FPCN in the right inferior parietal lobule RTTMT-A ↘ FC between the dorsolateral PFC and DMN between bilateral PCC and right precuneus | |
[43] | Semantic similarity test Stroop test | Mean FC ↗ similarity index Stroop C score ↗ path length, ↘ global efficiency | |
Memory | [45] | Auditory Verbal Learning Test [AVLT] [98] | Delayed recall ↘ participation coefficient left superior parietal lobule Recognition ↘ characteristic path length |
[65] | AVLT, structural equation modelling | Memory ↗ WML*global FC | |
[52] | AVLT | FC ↘ long recall between right olfactory–right rectus; ↘ short recall between right olfactory–left pallidum FC ↗ RTTMT-A between right olfactory–left pallidum |