The interplay among education, brain metabolism, and cognitive impairment suggests a role of cognitive reserve in Amyotrophic Lateral Sclerosis

Abstract

We tested the Cognitive Reserve (CR) hypothesis in Amyotrophic Lateral Sclerosis (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 the right anterior cingulate and bilateral medial frontal gyrus. In the IRCA in the ALS group, the medial frontal cluster metabolism 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 agree with the CR hypothesis. The negative correlation between the medial frontal cluster and the cerebellum found only in ALS patients might reflect cerebellar compensation.

Keywords: (18)F-FDG-PET; Amyotrophic lateral sclerosis; Cognitive reserve; Frontotemporal dementia.