Longitudinal assessment of frontal cognitive impairment in patients with motor neuron disease (I8-4B)

Objective. To test the progression of frontal cognitive impairment in patients with motor neuron disease (MND). Background. Cognitive deficits in MND without dementia have been found in up to 50[percnt] of subjects. Little is known about their progression over time. Methods. 28 non-demented patients with recently diagnosed sporadic MND were followed prospectively with clinical and neuropsychological evaluation every 3 and 6 months respectively, for a maximum follow-up of 24 months. Cognitive assessment was performed using the MMSE, verbal fluency tests, and the Test of Attentional Performance (TAP). The TAP, which is administered through an automated computerized system, permits to investigate the whole spectrum of frontal involvement in ALS, reducing verbal and/or physical disability. Alertness (in terms of its intrinsic and phasic components), divided attention, sustained attention, behavioural control and interference tendency (in terms of stimulus-reaction incompatibility) were evaluated. Scores were analyzed in terms of performance speed and performance accuracy (valid responses and omissions). Longitudinal linear models were used to assess clinical and cognitive variable changes over time and the relationship between baseline clinical features and cognitive deterioration. Results. During follow up, MND patients experienced a progressive worsening of motor disability, with a statistically significant decrease over time of the ALSFRSR scale score (p<0.001), total MRC (p<0.001) and ALS severity scale (p<0.001), and increase of the upper motor neuron score (p<0.001). MND patients also showed a significant deterioration of the global cognition (p=0.04), semantic fluency (p=0.03), and several frontal measures (p ranging from <0.001 to 0.04). The TAP showed that sustained attention, behavioural control and interference tendency significantly decreased over time. The progressive cognitive decline was independent of baseline motor clinical characteristics. Conclusions. Longitudinal analyses using computerized-based, sensitive executive measures revealed a progressive cognitive decline which appeared relatively early in the course of MND. Funding: Italian Ministry of Health (#RF-2010-2313220).