Cognitive Changes And White Matter Tract Damage In The Motor Neuron Disease Spectrum (P4.098)

OBJECTIVE: To assess the relationship between white matter (WM) tract abnormalities and cognitive changes in patients within the motor neuron disease (MND) spectrum using diffusion tensor (DT) MRI tractography. BACKGROUND: A detectable degree of cognitive involvement, which can vary in magnitude, appears in many patients with MND. DT MRI has the potential to provide an objective in vivo assessment of the extramotor brain damage in amyotrophic lateral sclerosis (ALS) and other MND. DESIGN/METHODS: Eighty-two MND patients (including 41 ALS, 31 primary lateral sclerosis/pure upper motor neuron, and 10 progressive muscular atrophy [PMA]) and 35 healthy subjects were studied. All patients underwent clinical evaluation, neuropsychological assessment, and DT MRI. To fulfill criteria for cognitive impairment, patients had to demonstrate impairment in at least 2 validated executive tasks. Using the same approach, The presence of non-executive cognitive impairment was also taken into account. DT MRI metrics were obtained from corpus callosum (CC), corticospinal tract and extra-motor tracts. Groups comparisons were assessed using age-adjusted linear regression models. WM tract damage contribution to cognitive deficits was assessed using Spearman correlation coefficients adjusted for age and ALSFRS-r. RESULTS: No PMA patients had cognitive impairment. In the remaining group, seven patients (9.7%) had frontotemporal dementia, six patients (8.6%) had an executive cognitive impairment, and non-executive deficits were found in two patients (2.8%). Relative to controls, ALS patients showed damage to motor and extra-motor tracts (p<0.001-0.49). PMA patients did not show tract damage. In the whole MND group, performances at tests assessing verbal fluency, attention and executive functions correlated with DT MRI measures of the CC, cingulum, inferior and superior longitudinal fasciculi, and uncinate bilaterally (R values from -0.47 to 0.47; p<0.001-0.049). Correlations remained significant adjusting for ALSFRS-r. CONCLUSIONS: Interhemispheric, limbic and major associative WM tract degeneration is associated with neuropsychological deficits in patients with MND. Study Supported by: Italian Ministry of Health (Grant #RF-2010-2313220).