Cognitive Phenotypes in Multiple Sclerosis: Mapping the Spectrum of Impairment
Damiano Mistri1, Diana Biondi1, Nicolò Tedone1, Carmen Vizzino1, Elisabetta Pagani1, Paolo Preziosa2, Maria Rocca2, Massimo Filippi3
1Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 2Neuroimaging Research Unit, Division of Neuroscience; and Neurology Unit, 3Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit; Neurorehabilitation Unit; and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; and Vita-Salute San Raffaele University
Objective:
To identify cognitive phenotypes in MS patients, and describe their demographic, clinical and structural MRI characteristics.
Background:
Cognitive deficits in multiple sclerosis (MS) are common and heterogeneous, however available criteria rely on a dichotomous definition of impairment.
Design/Methods:
Two hundred and forty-three MS patients and 158 healthy controls underwent neuropsychological tests to assess memory, attention, and executive function. For each domain, mild impairment was defined as performing 1.5 standard deviations below the normative mean on two tests, while the threshold for significant impairment was 2 standard deviations. Patients were classified into cognitive phenotypes based on severity of the impairment (mild/significant) and number of domains affected (one/more).
Results:
Five cognitive phenotypes emerged: Preserved cognition (PC; 56%), Mild Single-Domain Impairment (DI; 15%), Mild Multi-DI (9%), Significant Single-DI (12%), Significant Multi-DI (8%). Compared with PC, patients with Mild Single-DI were older, had longer disease duration and higher T2-hyperintense lesion volume (LV; p≤0.02); patients with Mild Multi-DI were older had longer disease duration, higher disability, higher T2 LV and lower thalamic volume (p≤0.01); patients with Significant Single-DI had longer disease duration and lower gray matter cortical volume, thalamic, caudate, putamen and accumbens volumes (p≤0.04); and patients with Significant Multi-DI were older, had longer disease duration, higher disability and more extensive structural damage in all brain regions explored (p≤0.03), except white matter and amygdala volumes.
Conclusions:
We identified five cognitive phenotypes that represent a graded degree of impairment. These phenotypes were characterized by distinct demographic, clinical and MRI features, indicating potential variations in the neural substrates of dysfunction throughout disease stages.