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. [(18)F]-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.

Cerebral Hypoperfusion and Hypometabolism Detected by Arterial Spin Labeling MRI and FDG-PET in Early-Onset Alzheimer's Disease.

BACKGROUND AND PURPOSE: Early-onset Alzheimer's disease (EOAD) is frequently associated with atypical clinical presentations and its early detection remains a challenging issue. In this study, we used arterial spin labeling (ASL), a noninvasive perfusion MRI sequence, and [(18)F]-FDG-PET to detect the perfusion and metabolic features in patients with EOAD. METHODS: All patients were investigated in the French reference center for young-onset dementia and were assessed by MRI, including a pseudo-continuous ASL (pCASL) sequence, and [(18)F]-FDG-PET. Quantitative analyses and intermodality comparison with correlation analysis were made after data processing including correction of partial volume effects, cortical projection, and specific intensity normalization. RESULTS: We prospectively included 37 patients with EOAD with a mean age of 58.3 years. The areas of most severe hypoperfusion detected with ASL were located in the parietal lobes, the precuneus, the right posterior cingulate cortex, and the frontal lobes (P < .05). The areas of lowest glucose metabolism detected by [(18)F]-FDG-PET were identified in the temporoparietal cortex and the precuneus (P < .05). Hypometabolic regions were more extensive than hypoperfused regions on ASL maps whereas ASL highlighted alterations in the frontal lobes without apparent hypometabolism on [(18)F]-FDG-PET maps. CONCLUSIONS: ASL and [(18)F]-FDG-PET detected pathological areas of similar distribution mainly located in the inferior parietal lobules and local zones in the temporal cortex in patients with EOAD. Our preliminary study showed that ASL and [(18)F]-FDG-PET may have a complementary role in combination with structural MRI for the assessment of suspected EOAD.

Memory loss during lenalidomide treatment: a report on two cases.

BACKGROUND: There are many reports of cognitive dysfunction in patients receiving chemotherapy or targeted therapies. Many antineoplastic agents may be involved in the condition also known as "chemo brain" or "chemo fog". CASE PRESENTATION: Two male patients (aged 41 and 70) with multiple myeloma developed severe, rapidly progressing cognitive impairment (mostly involving episodic memory) and loss of independence in activities of daily living during lenalidomide-based treatment. On withdrawal of the drug, one patient recovered normal cognitive function and independence in activities of daily living, whereas mild cognitive impairment persisted in the other patient. The Naranjo Adverse Drug Reaction Probability Scale score was 6 out of 13 for the first patient and 5 out of 13 for the second, suggesting a probable causal relationship between the adverse event and lenalidomide administration. CONCLUSION: Lenalidomide may induce particular cognitive disorders (notably episodic memory impairments) in some patients. The drug's putative neurotoxicity is probably promoted by specific risk factors (such as previous chemotherapy, prior mild cognitive impairment, age and the presence of cerebrovascular lesions).