Objective: To identify the metabolic signature of the various levels of cognitive deficits in amyotrophic
lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-D-glucose-PET (18F-FDG-PET).
Methods: A total of 170 ALS cases consecutively enrolled at the ALS Center of Turin underwent
brain 18F-FDG-PET and were classified as displaying normal cognition (ALS-Cn; n 5 94),
full-blown frontotemporal dementia (ALS-FTD; n 5 20), executive or nonexecutive cognitive
impairment not fulfilling FTD criteria (ALS-Ci; n 5 37), prevalent behavioral changes (n 5 9), or
nonclassifiable impairment (n 5 10) according to neuropsychological testing. Group comparisons
of 18F-FDG-PET pattern were carried out among the cognitive subgroups.
Results: We found a significantly reduced frontal and prefrontal metabolism in ALS-FTD as compared
to ALS-Cn, while ALS-Ci showed an intermediate metabolic behavior in frontal cortex,
being hypometabolic as compared to ALS-Cn, and relatively hypermetabolic as compared to
ALS-FTD. Hypometabolism in frontal regions was associated in all comparisons to hypermetabolism
in cerebellum, midbrain, and corticospinal tracts: the more severe the cognitive decline, the
larger the size of the cluster and the statistical significance of 18F-FDG uptake differences.
Conclusions: This study demonstrated in a large cohort of patients with ALS a continuum of frontal
lobe metabolic impairment reflecting the clinical and anatomic continuum ranging from pure
ALS, through ALS with intermediate cognitive deficits, to ALS-FTD, and showing that patients
with intermediate cognitive impairment display a characteristic metabolic pattern. Since
18F-FDG-PET allows us to estimate the cerebral lesion load in vivo in neurodegenerative diseases,
it might be helpful to investigate in ALS its association with neuropsychological testing along the
disease course to disclose the early metabolic signature of possible cognitive impairment.
