To identify the metabolic changes related to the various levels of cognitive deficits in ALS using ¹⁸F-FDG-PET imaging. 

PET scanning using the ¹⁸F-2-fluoro-2-deoxy-D-glucose ligand (¹⁸F-FDG-PET) is a marker of neurodegeneration and neuronal injury in vivo.

 274 ALS patients underwent neuropsychological assessment and brain ¹⁸F-FDG-PET at diagnosis. According to the criteria published in 2017, cognitive status was classified as: ALS with normal cognition (ALS-Cn, n=132), ALS with behavioural impairment (ALS-Bi, n=66), ALS with cognitive impairment (ALS-Ci, n=30), ALS with cognitive and behavioural impairment (ALS-Cbi, n=26), ALS with Frontotemporal Dementia (ALS-FTD, n=20). We compared each group displaying some degree of cognitive and/or behavioural impairment to ALS-Cn patients, including age at PET, sex, and ALSFRS-R as covariates. 

We identified frontal lobe relative hypometabolism in cognitively impaired patients that resulted more extensive and significant across the continuum from ALS-Ci, through ALS-Cbi, to ALS-FTD. ALS-FTD patients also showed cerebellar relative hypermetabolism. ALS-Bi patients did not show any difference compared to ALS-Cn. 

These data support the concept that patients with cognitive impairment have a more widespread neurodegenerative process compared to patients with a pure motor disease: the more severe the cognitive impairment, the more diffuse the metabolic changes. Otherwise, metabolic changes related to pure behavioural impairment need further characterization.