Sub-threshold cognitive impairment in multiple sclerosis: the association with cognitive reserve.

Multiple sclerosis (MS) patients with high premorbid intellect have the advantage of cognitive reserve that may mitigate the effects of cognitive decline. A fall-off in cognition may nevertheless still occur, even should it fail to meet global impairment thresholds. The present cross-sectional study explores the neurologic and behavioral characteristics of this little known group of patients. A consecutive sample of 144 MS patients underwent neuropsychological testing with the minimal assessment of cognitive function in the MS (MACFIMS) battery. Premorbid IQ was assessed with the ANART reading test. A validated algorithm based on ANART errors and verbal fluency scores was used to predict whether current cognitive function matched premorbid estimates. Three MS groups were thus defined: cognitively intact (n = 53), impaired (n = 46) and cognitively intact on the MACFIMS, but falling short of premorbid predictions (n = 45). Patients who were cognitively intact on the MACFIMS but fell short of verbal fluency predictions had higher premorbid IQ (p = 0.007) and lower EDSS (p = 0.002) than cognitively impaired, but not intact patients. They outperformed impaired patients on every MACFIMS variable, but were more impaired than intact patients on the Paced Auditory Serial Addition Test-3 (PASAT-3) (p = 0.009). They were more likely to be employed (48.9%) than the impaired (26.1%) group (p = 0.025). We defined a group of MS patients deemed cognitively intact on conventional neuropsychological testing, but who, nevertheless, had deficits relative to premorbid intellectual abilities. The high premorbid IQ in this group does not prevent, but 'softens' the impact of cognitive decline. These findings provide novel evidence supporting cognitive reserve as a protective factor in relation to cognitive dysfunction in MS.