Cognitive and MRI Profiles in Primary and Secondary Progressive Multiple Sclerosis
Damiano Mistri1, Laura Cacciaguerra2, Paola Valsasina1, Elisabetta Pagani1, Paolo Preziosa3, Maria Rocca3, Massimo Filippi4
1Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 2Neuroimaging Research Unit, Division of Neuroscience, 3Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, 4Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University
Objective:
We examined the neuropsychological profile of primary progressive (PP) and secondary progressive (SP) multiple sclerosis (MS) patients and investigated the relationship between cognitive functioning with structural and functional MRI abnormalities.
Background:
Studies comparing frequency and patterns of cognitive dysfunction between PPMS and SPMS have yielded conflicting results.
Design/Methods:
One-hundred eighty-three MS patients (60 PPMS and 123 SPMS) and 75 age- and sex-matched healthy controls underwent 3.0T MRI. MS patients were administered the Brief Repeatable Battery of Neuropsychological tests (BRB-N) and were classified as cognitively impaired if they scored below the 5th percentile of the normative sample on at least two tests. Four cognitive domain z-scores were determined from normative data, and then averaged to obtain a measure of global cognition (z-BRB-N). Using hierarchical linear regression analysis, the contribution of lesion volumes, normalized brain volumes, white matter fractional anisotropy (FA) and mean diffusivity (MD) abnormalities, and resting state (RS) functional connectivity (FC) alterations to global cognition in PPMS and SPMS was investigated.
Results:
Patients with PPMS and SPMS had similar z-scores in all investigated cognitive domains. Compared to PPMS, SPMS showed decreased FA and increased MD in the fornix, and lower RS FC within the basal ganglia network. The frequency of cognitive impairment was 31.7% in PPMS and 41.3% in SPMS (p=0.19). In PPMS, poorer cognitive performance (e.g., lower z-BRB-N) was associated with decreased FA of the medial lemniscus (ΔR2=0.11; p=0.011) and lower normalized gray matter volume (ΔR2=0.29; p<0.001). In SPMS, poorer cognitive performance was associated with decreased FA of the fornix (ΔR2=0.35; p<0.001) and lower normalized white matter volume (ΔR2=0.05; p=0.034).
Conclusions:
PPMS and SPMS had similar neuropsychological profile. Cognitive dysfunction in PPMS and SPMS was related to distinct patterns of structural MRI abnormalities and involvement of different white matter tracts, while RS FC alterations did not contribute to explain their global cognitive functioning.