Cognitive impairment and regional cortical atrophy in amyotrophic lateral sclerosis

Background: Patients with amyotrophic lateral sclerosis (ASL) show a cognitive impairment consistent with frontal-temporal dysfunction. In spite of histopathological evidence of cortical atrophy in parietal-frontal-temporal areas, data on brain MRI volume measures are discordant. Objective: To correlate cognitive profile with regional cortical volumes measured by voxel based morphometry (VBM)in ALS. Patients and Methods: Forteen clinically probable or definite ALS nondemented patients (El Escorial criteria) were examined.Age at observation was 57.85 ± 10.24 years and disease duration was 53.6 ± 35.5 months. Functional status was assessed by ALS functional rating scale (ALS-FSRS) and muscle strength by Manual Muscle Testing (MMT). Nine healthy subjects matched for age and educational level were assumed as controls. All subjects were tested by a neuropsychological battery including Mini Mental State Examination (MMSE), Prose Memory, Working Memory, Stroop Color Word Interference, Symbol Digit Modalities (SBM), Verbal Fluency and Beck depression inventory. MRI examination was performed by 1.5 Tesla GE. Coronal, axial T2 and 3D T1 weighted sequences were acquired. Total and regional brain atrophy was measured by VBM, a technique implemented in SPM99 consisting in a voxel-to-voxel parametric statistical test of 3D MR images after normalization, segmentation, smoothing and modulation. Results: In ALS the score of ALS FSRS was 28.7 ± 7.2 and MMT 7.82 ± 1.02. MMSE and neuropsychological tests evaluating temporal lobe functions did not differ in ALS and controls. Tests evaluating frontal lobe functions showed significant low scores in SBM test (ALS 27.85 ± 14.22 vs. controls 38.57 ± 10.66, p = 0.037) and pathological values were found in 10/14 ALS in comparison to 1/9 controls. T2-hyperintensity at subcortical white matter was found in 12/14 ALS and only in one control. T2 low signal intensity at the precentral gyrus was identified in 3 ALS patients. Total gray and white matter volumes did not differ in two groups. Compared to controls, ALS showed a decrease of gray matter volume in temporal-hippocampal gyrus bilaterally (p = 0.001), in right superior (p = 0.004) and medium (p = 0.008) frontal gyrus and in left inferior frontal gyrus (p = 0.009). A significant correlation was found between frontal-orbital volume and SBM test (p = 0.0001). Conclusions: This study shows more sensitivity of VBM analysis to detect a frontal and temporal dysfunction beyond the motor system.