TY - JOUR
T1 - Longitudinal Network Changes and Conversion to Cognitive Impairment in Multiple Sclerosis
AU - Huiskamp, Marijn
AU - Eijlers, Anand J.C.
AU - Broeders, Tommy A.A.
AU - Pasteuning, Jasmin
AU - Dekker, Iris
AU - Uitdehaag, Bernard M.J.
AU - Barkhof, Frederik
AU - Wink, Alle Meije
AU - Geurts, Jeroen J.G.
AU - Hulst, Hanneke E.
AU - Schoonheim, Menno M.
N1 - Publisher Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2021/8/24
Y1 - 2021/8/24
N2 - OBJECTIVE: To characterize functional network changes related to conversion to cognitive impairment in a large sample of patients with multiple sclerosis (MS) over a period of 5 years. METHODS: Two hundred twenty-seven patients with MS and 59 healthy controls of the Amsterdam MS cohort underwent neuropsychological testing and resting-state fMRI at 2 time points (time interval 4.9 ± 0.9 years). At both baseline and follow-up, patients were categorized as cognitively preserved (CP; n = 123), mildly impaired (MCI; z < -1.5 on ≥2 cognitive tests, n = 32), or impaired (CI; z < -2 on ≥2 tests, n = 72), and longitudinal conversion between groups was determined. Network function was quantified with eigenvector centrality, a measure of regional network importance, which was computed for individual resting-state networks at both time points. RESULTS: Over time, 18.9% of patients converted to a worse phenotype; 22 of 123 patients who were CP (17.9%) converted from CP to MCI, 10 of 123 from CP to CI (8.1%), and 12 of 32 patients with MCI converted to CI (37.5%). At baseline, default-mode network (DMN) centrality was higher in CI individuals compared to controls (p = 0.05). Longitudinally, ventral attention network (VAN) importance increased in CP, driven by stable CP and CP-to-MCI converters (p < 0.05). CONCLUSIONS: Of all patients, 19% worsened in their cognitive status over 5 years. Conversion from intact cognition to impairment is related to an initial disturbed functioning of the VAN, then shifting toward DMN dysfunction in CI. Because the VAN normally relays information to the DMN, these results could indicate that in MS normal processes crucial for maintaining overall network stability are progressively disrupted as patients clinically progress.
AB - OBJECTIVE: To characterize functional network changes related to conversion to cognitive impairment in a large sample of patients with multiple sclerosis (MS) over a period of 5 years. METHODS: Two hundred twenty-seven patients with MS and 59 healthy controls of the Amsterdam MS cohort underwent neuropsychological testing and resting-state fMRI at 2 time points (time interval 4.9 ± 0.9 years). At both baseline and follow-up, patients were categorized as cognitively preserved (CP; n = 123), mildly impaired (MCI; z < -1.5 on ≥2 cognitive tests, n = 32), or impaired (CI; z < -2 on ≥2 tests, n = 72), and longitudinal conversion between groups was determined. Network function was quantified with eigenvector centrality, a measure of regional network importance, which was computed for individual resting-state networks at both time points. RESULTS: Over time, 18.9% of patients converted to a worse phenotype; 22 of 123 patients who were CP (17.9%) converted from CP to MCI, 10 of 123 from CP to CI (8.1%), and 12 of 32 patients with MCI converted to CI (37.5%). At baseline, default-mode network (DMN) centrality was higher in CI individuals compared to controls (p = 0.05). Longitudinally, ventral attention network (VAN) importance increased in CP, driven by stable CP and CP-to-MCI converters (p < 0.05). CONCLUSIONS: Of all patients, 19% worsened in their cognitive status over 5 years. Conversion from intact cognition to impairment is related to an initial disturbed functioning of the VAN, then shifting toward DMN dysfunction in CI. Because the VAN normally relays information to the DMN, these results could indicate that in MS normal processes crucial for maintaining overall network stability are progressively disrupted as patients clinically progress.
UR - http://www.scopus.com/inward/record.url?scp=85114902401&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/WNL.0000000000012341
DO - https://doi.org/10.1212/WNL.0000000000012341
M3 - Article
C2 - 34099528
SN - 0028-3878
VL - 97
SP - e794-e802
JO - Neurology
JF - Neurology
IS - 8
ER -