My belief or yours? Differential theory of mind deficits in frontotemporal dementia and Alzheimer's disease

Theory of mind reasoning-the ability to understand someone else's mental states, such as beliefs, intentions and desires-is crucial in social interaction. It has been suggested that a theory of mind deficit may account for some of the abnormalities in interpersonal behaviour that characterize patients affected by behavioural variant frontotemporal dementia. However, there are conflicting reports as to whether understanding someone else's mind is a key difference between behavioural variant frontotemporal dementia and other neurodegenerative conditions such as Alzheimer's disease. Literature data on the relationship between theory of mind abilities and executive functions are also contradictory. These disparities may be due to underestimation of the fractionation within theory of mind components. A recent theoretical framework suggests that taking someone else's mental perspective requires two distinct processes: inferring someone else's belief and inhibiting one's own belief, with involvement of the temporoparietal and right frontal cortices, respectively. Therefore, we performed a neuropsychological and neuroimaging study to investigate the hypothesis whereby distinct cognitive deficits could impair theory of mind reasoning in patients with Alzheimer's disease and patients with behavioural variant frontotemporal dementia. We used a three-option false belief task to assess theory of mind components in 11 patients with behavioural variant frontotemporal dementia, 12 patients with Alzheimer's disease and 20 healthy elderly control subjects. The patients with behavioural variant frontotemporal dementia and those with Alzheimer's disease were matched for age, gender, education and global cognitive impairment. [F-18]-fluorodeoxyglucose-positron emission tomography imaging was used to investigate neural correlates of theory of mind reasoning deficits. Performance in the three-option false belief task revealed differential impairments in the components of theory of mind reasoning; patients with Alzheimer's disease had a predominant deficit in inferring someone else's belief, whereas patients with behavioural variant frontotemporal dementia were selectively impaired in inhibiting their own mental perspective. Moreover, inhibiting one's own perspective was strongly correlated with inhibition in a Stroop task but not with other subprocesses of executive functions. This finding suggests that self-perspective inhibition may depend on cognitive processes that are not specific to the social domain. Last, the severity of the deficit in inferring someone else's beliefs correlated significantly over all subjects with hypometabolism in the left temporoparietal junction, whereas the severity of the deficit in self-perspective inhibition correlated significantly with hypometabolism in the right lateral prefrontal cortex. In conclusion, our findings provided clinical and imaging evidence to support differential deficits in two components of theory of mind reasoning (subserved by distinct brain regions) in patients with Alzheimer's disease and patients with behavioural variant frontotemporal dementia.