Table 3.
Characteristics of the studies on the relationship between MRI perfusion and MS cognitive performance.
| study | Group | Demographics | Clinical variables | NPS tests | MRI | Perfusion assessment approach | Relationship between perfusion metrics and cognitive assessment | |
|---|---|---|---|---|---|---|---|---|
| Assessed relationship/comparison | Regions | |||||||
| Ma et al., 2018 | CI-RRMS (n = 20) | Age: 48.1±4.7a 12 females (60.0%) Edu: 14.6±1.9a | EDSS: 2.5 (2–3)b dd: 11.6±4.9a | MACFIMS | DSC (3T) | ROI-based | Association between DSC-derived parameters and SDMT score: ○ Positive, significant (in the whole MS group, n = 84) |
WML |
| CP-RRMS (n = 19) | Age: 46.4±7.2a 15 females (79.0%) Edu: 16.1±1.3a | EDSS: 1.5 (1–2)b dd: 11.8±5.4a | ||||||
| CI-SPMS (n = 25) | Age: 55.8±10.7a 16 females (68.0%) Edu: 14.6±3.1a | EDSS: 6.5 (6–6.5)b dd: 21.6±11.7a | ||||||
| CP-SPMS (n = 20) | Age: 55.2±6.5a 11 females (55.0%) Edu: 15.1±2.6a | EDSS: 6 (6–6.5)b dd: 16.7±6.5a | ||||||
| HC (n = 19) | Age: 49±7.1a 14 females (73.7%) Edu: 16.9±2.9a | |||||||
| Vitorino et al., 2016 | CI-RRMS (n = 20) | Age: 48.1±4.7a 12 females (60.0%) Edu: 14.6±1.9a | EDSS: 2.5 (2–3)b dd: 11.6±4.9a | MACFIMS | DSC (3T) | Voxel-wise | CBF: ○CI-RRMS<CP-RRMS ○ CI-RRMS<HC ○ CP-RRMS<HC |
L middle frontal gyrus (BA 10, 11, 46), L superior frontal gyrus (BA 6, 10), caudate head, thalamus, R caudate body L middle frontal gyrus (BA 10, 11, 46), L superior frontal gyrus (BA 6, 10), R middle frontal gyrus L middle frontal gyrus, superior temporal lobe |
| CBV: ○CI-RRMS<CP-RRMS ○ CI-RRMS<HC ○CP-RRMS<HC |
L middle frontal gyrus (BA 10, 11, 46), L superior frontal gyrus (BA 6, 10), R lingual gyrus, R inferior parietal lobule, L fusiform gyrus, L inferior frontal gyrus L middle frontal gyrus (BA 10, 11, 46), L superior frontal gyrus (BA 6, 10), L parahippocampal gyrus L middle frontal gyrus | |||||||
| CP-RRMS (n = 19) | Age: 46.4±7.2a 15 females (79.0%) Edu: 16.1±1.3a | EDSS: 1.5 (1–2)b dd: 11.8±5.4a | MTT: NA | |||||
| HC (n = 19) | Age: 49±7.1a 14 females (73.7%) Edu: 16.9±2.9a | |||||||
| Hojjat et al., 2016c | CI-RRMS (n = 20) | Age: 48.1±4.7a 12 females (60.0%) Edu: 14.6±1.9a | EDSS: 2.58±0.67a dd: 11.6±4.9a | MACFIMS | pCASL (3T) | Voxel-wise | CBF: ○ CI-RRMS < CP-RRMS ○ CI-RRMS < HC |
L frontal lobe (BA 4, BA 6), L/R superior frontal lobe (BA 6, BA 10) L frontal lobe (BA 4, BA 6), R superior frontal lobe (BA 6, BA 10), L middle frontal lobe (BA 9, BA 10), L/R inferior frontal lobe (BA 11, BA46, BA 47), L/R limbic lobe, L/R parietal lobe, L/R temporal lobe, R putamen, L thalamus/pulvinar |
| CP-RRMS (n = 19) | Age: 46.4±7.2a 15 females (79.0%) Edu: 16.1±1.3a | EDSS: 1.79±0.71a dd: 11.8±5.4a | ○ No CP-RRMS-vs-HC differences | Whole brain | ||||
| HC (n = 19) | Age: 49±7.1a 14 females (73.7%) Edu: 16.9±2.9a | |||||||
| Hojjat et al., 2016a | CI-RRMS (n = 20) | Age: 48.1±4.7a 12 females (60.0%) Edu: 14.6±1.9a | EDSS:s 2.5 (2–3)b dd: 11.6±4.9a |
MACFIMS | DSC (3T) | ROI-based | CBF: ○ CI-RRMS < CP-RRMS ○ CI-RRMS < HC ○ CP-RRMS < HC |
NAGM, NAWM, WML NAGM, NAWM NAGM |
| CP-RRMS (n = 19) | Age: 46.4±7.2a 15 females (79.0%) Edu: 16.1±1.3a | EDSS: 1.5 (1–2)b dd: 11.8±5.4a | CBV: ○ CI-RRMS < CP-RRMS ○ CI-RRMS < HC |
NAGM, NAWM, WML NAGM, NAWM | ||||
| HC (n = 19) | Age: 49±7.1 a 14 females (73.7%) Edu: 16.9±2.9 a | MTT: ○ CI-RRMS > CP-RRMS ○ CI-RRMS > HC |
NAGM NAGM, NAWM | |||||
| Hojjat et al., 2016b | CI-RRMS (n = 20) | Age: 48.1±4.7a 12 females (60.0%) Edu: 14.6±1.9a | EDSS: 2.5 (2–3)b dd: 11.6±4.9a |
MACFIMS | DSC (3T) | ROI-based | CBF: ○ CI-RRMS < HC ○ CI-RRMS < CP-RRMS |
Cortical GM, WM Cortical GM, WM |
| CP-RRMS (n = 19) | Age: 46.4±7.2a 15 females (79.0%) Edu: 16.1±1.3a | EDSS: 1.5 (1–2)b dd: 11.8±5.4a | CBV: ○ CI-RRMS < HC ○ CI-RRMS < CP-RRMS |
Cortical GM, WM Cortical GM, WM | ||||
| HC (n = 19) | Age: 49±7.1a 14 females (73.7%) Edu: 16.9±2.9a | MTT: ○ CI-RRMS > HC ○ CI-RRMS> CP-RRMS ○ CP-RRMS > HC |
Cortical GM,WM Cortical GM, WM Cortical GM, WM | |||||
| Association between CBF and overall cognitive impairment: ○ Inverse, significant |
All brain lobes | |||||||
| Association between CBV and overall cognitive impairment: ○ Inverse, significant |
All brain lobes | |||||||
| Association between MTT and overall cognitive impairment: ○ Inverse, significant |
All brain lobes | |||||||
| Debernard et al., 2014 | RRMS (n = 25) | Age: 37.2±8.6a 22 females (88.0%) Edu: 13.5±2.7a | EDSS: 1.5 (0–4.5)c dd: 2.4±1.5a | MoCA Letter fluency |
pCASL (3T) | Voxel-wise | Association between CBF and memory: ○ Positive, significant |
Precentral gyrus, postcentral gyrus, cingulate gyrus, lingual gyrus, frontal gyrus, intracalcarine cortex, supracalcarine cortex, parietal areas, occipital areas, L/R accumbens, L/R putamen, L/R caudate, R thalamus |
| HC (n = 25) | Age: 35.2±10.3a 17 females (68.0%) Edu: 13.8±2.1a | Category fluency BVMT CVLT SCWT SDMT PASAT BJLO RCFT | Association between CBF andPASAT, SDMT, MSFC, MoCA, executive function, attention, working memory, visuospatial function: ○ Non-significant |
Whole GM | ||||
| Francis et al., 2013 | CI-SPMS (n = 25) | Age: 55 (47.5–61.5)b 16 females (64.0%) Edu: 14 (13–17)b | EDSS: 6.5 (6–6.5)b dd: 19 (12–28.5)b | MACFIMS | DSC (3T) | Voxel-wise | CBF: ○ CI-SPMS<CP-SPMS CBV: ○ CI-SPMS<CP-SPMS |
L/R thalamus (pulvinar), L/R caudate body, R caudate tail, L/R medial frontal gyrus (BA 9), R cingulate gyrus (BA 31) L/R thalamus (pulvinar), L/R caudate body, L caudate tail, L/R superior frontal gyrus (BA 6, BA9), corpus callosum |
| CP-SPMS (n = 20) | Age: 54.5 (49.3–62.3)b 11 females (55.0%) Edu: 15.5 (13–17.8)b | EDSS: 6 (6–6.5)b dd: 18.5 (10.5–20.8)b | MTT: NA |
|||||
| Association between CBF and all the neuropsychological test scores, except for CVLT ○ Significant (SDMT showed the strongest association) |
Areas of reduced perfusion | |||||||
| Association between CBV and all the neuropsychological test scores, except for CVLT ○ Significant (SDMT showed the strongest association) |
Areas of reduced perfusion | |||||||
| Papadaki et al., 2014 | CIS (n = 40) | Age: 33.9±10a NA females Edu: 13.4±2.7a | EDSS: 1.2±0.65a dd: 2.3±2.7a | WASI WMS-MD WMS-LM MTCF | DSC (1.5T) | ROI-based | Correlation between CBV and WMS-MD (digit reverse): ○ Negative, significant | L/R thalamus, L frontal NAWM, L/R periventricular NAWM, splenium |
| HC (n = 30) | NA | Correlation between CBV and immediate free recall scores of WMS-LM: ○ Negative, significant |
R thalamus, L/R caudate, L frontal NAWM, L/R periventricular NAWM, splenium | |||||
| D’haeseleer et al., 2013 | MS (n = 18) | Age: 50.2±5.7a 9 females (50.0%) Edu: NA | EDSS: 3.3 (1.5–6)b dd: 18±9a | PASAT | pCASL (3T) | ROI-based | Association between CBF and PASAT: ○ Positive, significant ○ Non-significant |
L centrum semiovale (in MS group) R centrum semiovale (NAWM), L/R frontoparietal cortex, L/R cerebellar hemisphere |
| HC (n = 10) | Age: 50.2±5.5a 5 females (50.0) Edu: NA | |||||||
| Aviv et al., 2012 | CI-SPMS (n = 18) | Age: 58±10a 12 females (66.6%) Edu: 15.5 (13-17.5)b | EDSS: 6.5 (6.13–6.5)b dd: 23±12a | MACFIMS | DSC (3T) | ROI-based | CBF: ○ CI-SPMS < CP-SPMS CBV: ○ CI-SPMS < CP-SPMS |
GM, WM GM, WM |
| CP-SPMS (n = 17) | Age: 55±6a 11 females (64.7) Edu: 16 (13-17.5)b | EDSS: 6 (6–6.5)b dd: 17±6a | MTT: ○ No CI-SPMS-vs-CP-SPMS differences |
GM, WM | ||||
| Association between CBF and overall cognitive impairment: ○ Non-significant |
Any lobes and sub-ROIs | |||||||
| Association between CBV and overall cognitive impairment:a ○ Inverse, significant |
All L/R lobes, L inferior frontal ROI, L middle frontal ROI, L/R medial superior frontal, L superior frontal ROI | |||||||
| Inglese et al., 2008 | RRMS [n = 18] | Age: 48 (31–71)d 12 females (66.7%) Edu: 18 (16–21)d | EDSS: 1 (0–6.5)c dd: 7.6 (1–34)d | RCFT D-KEFSVF CVLT-II DB WAIS-III SDMT | DSC (3T) | ROI-based | Correlation between CBF and RCFT-Copy: ○ Positive, significant (in PPMS) ○Positive, significant (in all MS) |
DGM DGM |
| PPMS [n = 14] | Age: 55 (29–75)d 7 females (50.0%) Edu: 17 (12–21)d | EDSS: 4 (3–7)c dd: 5 (1–19)d | PASAT-3secs D-KEFSI D-KEFSIS | Correlation between CBV and D-KEFSI: ○ Positive, significant (in all MS) |
DGM | |||
| HC [n = 11] | Age: 51 (29–65)d 7 females (63.6%) Edu: NA | |||||||
BA: Brodmann area; BJLO: Benton Judgment of line orientation test; BVMT-R: Brief Visuo-Spatial Memory Test-Revised; CBF: cerebral blood flow; CBV: cerebral blood volume; CI: cognitively impaired; CL: cortical lesions; COWAT: Controlled Oral Word Association Test; CP: cognitively preserved; CVLT-II: California Verbal Learning Test-II; DGM: deep gray matter; D-KEFS: Delis-Kaplan Executive Function System Sorting Test; D-KEFSI: D-KEFS Color Word Interference Test inhibition; D-KEFSIS: D-KEFS Color Word Interference Test inhibition Switching; D-KEFSVF: D-KEFS Verbal fluency; DB: Digit Backward portion of Digit Span subset of Wechsler Adult Intelligence Scale; dd: disease duration; DMN: Default Mode Network; DSC: Dynamic Susceptibility Contrast; EDSS: Expanded Disability Status Scale; ECN: Executive Control Network; Edu: education level; HC: healthy controls; GM: gray matter; L: left; MoCA: Montreal Cognitive Assessment; MS: multiple sclerosis; MTCF: Modified Taylor Complex Figure; MTT: mean transit time; NAGM: normal appearing gray matter; NA: not available; NAWM: normal appearing white matter; NPS: neuropsychological; PASAT: Paced Auditory Serial Addition Test; PPMS: primary progressive multiple sclerosis; pCASL: pseudo Continuous Arterial Spin Labeling; R: right; RCFT: Rey Complex Figure copy; ROI: region of interest; RRMS: relapsing remitting multiple sclerosis; SCWT: Stroop Color and Word Test; SDMT: Symbol Digit Modalities Test; WM: white matter; WML: white matter lesions; SN: Salience Network; SPMS- secondary progressive multiple sclerosis; WASI: Wechsler Abbreviated Scale of Intelligence; WMS-LM: Wechsler Memory Scale Logical memory subscale; WMS-MD: Memory for digit subset of Wechsler Memory Scale. aMean±SD; bmedian (IQR); cmedian (range); dmean (range). Age, dd, edu are expressed in years. MACFISM includes PASAT, SDMT, CVLT-II, BVMT-R, D-KEFS, BJLO, COWAT. Subjects tested with MACFISM were classified as CI according to (Benedict J NeurolSci 2006).