Inhibition impairment in frontotemporal dementia, amyotrophic lateral sclerosis, and Alzheimer's disease: clinical assessment and metabolic correlates

The ability to reject an automatic tendency, i.e. inhibition, has been linked to the prefrontal cortex, but its neural underpinnings are still controversial. Neurodegenerative diseases represent an interesting model to explore this issue, given its frequent impairment in these disorders. We investigated the inhibitory impairment and its neural basis using four different tests, which evaluate the presence of inhibitory dysfunction (Stroop test, Hayling test, and two graphical perseveration tests), and assessed their correlation with brain metabolism using F-18-fluorodeoxyglucose positron emission tomography in a group of 76 participants with behavioral variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and healthy controls (HC). Inhibition impairment was more frequent in bvFTD and AD, than ALS and HC. AD and bvFTD only differed in the strategy used in Hayling test, and the frequency of impairment in graphical perseveration tests. Correlation between inhibition tests was moderate. The Stroop test correlated with several regions of the frontal and parietal lobes, mainly on the left side. Hayling test correlated with almost all regions of the frontal lobe and, especially, with the orbitofrontal cortex. Some differences in the impaired regions in each disease were found. Inhibition ability was mainly impaired in bvFTD and AD, and it correlated with the bilateral frontal lobe metabolism. There were certain particularities according to the specific task and patients evaluated. These dissimilarities may support the concept of inhibition as a multidimensional construct, with the involvement of common and divergent neural mechanisms.