To determine whether participants who carry a genetic mutation associated with behavioral variant frontotemporal dementia (bvFTD) exhibit altered reward responses as they approach disease onset.

Twenty-six participants with bvFTD-associated mutations (including ten mildly symptomatic participants with Clinical Dementia Rating scale of 0.5) and a control group of thirty-five mutation-negative family members completed a reward paradigm involving pleasant and unpleasant odorants. Their physiological response to these different odorants, scaled ratings from 1-9 of each odor’s pleasantness and intensity, and the participants degree of motivation to obtain or avoid each odor were recorded and compared. The anatomic correlates of participants’ responses were determined by voxel-based morphometry.

Preclinical mutation carriers reported a smaller difference between their valence ratings of pleasant and unpleasant odors compared to mutation-negative family members (p < 0.05). The valence difference score was particularly low in the subset of mildly symptomatic participants. Low valence difference scores in mildly symptomatic mutation carriers were associated with increased atrophy within regions of the brain that have previously been associated with abnormal valence perception in bvFTD. On a test of motivated choice, preclinical mutation carriers also elected to pursue odors that are deemed unpleasant at an increased frequency compared to the mutation-negative group (p < 0.01).