Figure 1.

Coronal T1-weighted magnetic resonance imaging (MRI). Brain MRIs (coronal T1-weighted images) of the three familiar FTLD mutation carriers who progressed from the asymptomatic to the symptomatic stage are shown in the timeline with years before and after conversion. 0 indicates the actual symptom onset time point. (A) A male patient with MAPT N279K mutation whose first clinical manifestation was difficulties in remembering street names and people's names with Kokmen short test of mental status (36/38) at age 43. Two years after symptom onset, his forgetfulness progressed, with resting tremor in the left lower limbs, as well as some impulsivity and disinhibition, and was diagnosed with bvFTD and Parkinsonism. Five years after symptom onset, his cognitive function, parkinsonism, and behavior changes significantly worsened and mostly by motor impairment. Focal adjacent mesial temporal lobe atrophy mainly in the right side was observed 5 years before symptom onset and became bilateral hippocampal atrophy with generalized cerebral atrophy most marked in the bilateral parietotemporal regions. The structural brain change seems to be slower than his clinic symptom progression. (B) A male patient GRN mutation carrier whose first clinical manifestation was word-finding difficulties at age 68. Two years after symptom onset, his word-finding difficulties progressed, with additional executive dysfunction, forgetfulness, and tendency to repeat questions. He also had apathy, irritability, and dysphoria, and was diagnosed with mixed PPA/bvFTD syndrome. Asymmetrical (left greater than right) atrophy was observed 6 years before symptom onset, and became progressively asymmetric affecting the frontal, temporal, and parietal lobes as he aged. (C) A male patient C9orf72 mutation carrier whose first clinical manifestation was a change in motivation, spontaneity, and empathy at age 73 and was diagnosed as behavior MCI. After 4 years from symptom onset, his behavior change slightly progressed with subtleties in empathy, emotional blunting, irritability, and subtle apathy, still diagnosed as behavior MCI. While his clinic symptoms seem to be stable, the moderate parenchymal volume loss was observed 8 years before symptom onset most involved in the frontal and temporal areas, and progressed affecting the whole brain with greatest atrophy in the fronto-temporal regions as he aged.