The Interplay Among Education, Brain Metabolism, and Cognitive Impairment Suggests a Role of Cognitive Reserve in Amyotrophic Lateral Sclerosis

We aimed at testing the Cognitive Reserve (CR) hypothesis in ALS enrolling 111 patients, using education as CR proxy, 18F-FDG-PET to assess brain damage, and ECAS to measure cognition. Education was regressed out against brain metabolism, including age, sex, spinal/bulbar onset, ALSFRS-R, and ECAS as covariates. Clusters showing a significant correlation were used as seed regions in an interregional correlation analysis (IRCA) in the ALS group and in 40 controls. In the ALS group we found a negative correlation between brain metabolism and education in right anterior cingulate and bilateral medial frontal gyrus. In the IRCA in the ALS group the metabolism of the medial frontal cluster positively correlated with that of frontotemporal regions (right>left), bilateral caudate nuclei, and right insula, and negatively correlated with that of corticospinal tracts, cerebellum and pons. In controls the IRCA showed significant positive correlations in the same regions but less extended. Our results are in agreement with the CR hypothesis. The negative correlation between the medial frontal cluster and the cerebellum that we found only in ALS patients might reflect cerebellar compensation.