MS and Cognitive Impairment: Dynamic Network Changes Cost More Energy

Patients with multiple sclerosis (MS) who are cognitively impaired require more energy to facilitate the dynamic network changes involved in normal cognitive processing, according to study findings published in Neurology.

Researchers conducted a cohort study to determine dynamic functional network trends relevant to cognitive impairment in patients with MS and explore whether these trends can be explained by modified energy costs.

Participants with available functional and diffusion magnetic resonance imaging (MRI) data who had clinically definite MS, were relapse-free, did not receive steroid treatment for 2 months prior to the study, and had no history of psychiatric or neurologic disease aside from MS were recruited from the MS Center Amsterdam between 2008 and 2012. On the same day as MRI examination, an expanded version of the Brief Repeatable Battery of Neuropsychological Tests was used to assess domains of executive functioning, verbal memory, information processing speed, verbal fluency, visuospatial memory, working memory, and attention. Performance was then compared with healthy control participants, resulting in the classification of participants as cognitively impaired, mildly cognitively impaired, or cognitively preserved. Linear mixed models were used in statistical analysis.

Complete functional MRI and neuropsychologic assessment data were available for 330 patients (mean age, 48; women, 68%; cognitively preserved, 54%; mildly cognitively impaired, 20%; cognitively impaired, 26%) and 95 healthy control participants (mean age, 46; women, 58%).

Based on area of highest centrality, the following 4 connectivity states were identified:

• Visual network (VIS) state;
• Sensorimotor network (SMN) state;
• Ventral attention network (VAN) state; and,
• Default-mode network (DNM) state.

Compared with cognitively preserved patients, patients with cognitive impairment transitioned between each state less frequently (β, -5.78; P =.038) and required more control energy to transition between states (β, 0.32; P =.007).

Total control energy in patients with cognitive impairment and mild cognitive impairment vs patients with preserved cognitive function and healthy control participants was increased (F(3413), 6.56; P <.001).

No significant between-group differences were observed for fractional occupancy in the SMN and VAN states.

Compared with healthy control participants, patients with MS at all cognitive function levels demonstrated higher fractional occupancy in the DMN state (F(3418), 5.55; P =.004) and lower fractional occupancy in the VIS state (F(3418), 9.38; P =.002). Patients with cognitive impairment transitioned less frequently from the DNM state to the VIS state (β, -0.02; P =.004).

Future studies are advised to use advanced diffusion protocols to generate more sensitive markers for cognitive dysfunction, such as higher b-values, more phase-encoding directions, and isotropic acquisitions.

“To further study the order of events leading to these network disturbances, future work should include longitudinal data across different disease stages,” the researchers concluded.

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.