Male gender is associated with greater cerebral hypometabolism in frontotemporal dementia: Evidence for sex-related cognitive reserve

Background: Neuropathological studies suggest that the association between neurodegenerative brain damage and clinical symptoms may be struinger in women than in men; therefore women are more likely to express neurodegeneration as clinical dementia. Furthermore, a recent ¹⁸F-FDG PET study explored gender differences in the regional cerebral metabolic rate of glucose (rCMRglc) in patients with Alzheimer's disease and found that, at the same level of severity of cognitive impairment, men showed a significantly greater hypometabolism than women. This suggests that men can compensate more pathology than women. Objective: To test the hypothesis that cerebral metabolic deficits due to neurodegeneration are more pronounced in men than in women with frontotemporal dementia (FTD), controlling for cognitive impairment. Methods: Twenty-nine patients with FTD (20 men, nine women) underwent an extensive clinical examination and ¹⁸F-FDG PET imaging at a university-based outpatient unit for cognitive disorders. An analysis of covariance (with age, total score of the CERAD neuropsychological battery, and years of school education as co-variates) was conducted to identify gender differences in glucose metabolism. Results: Frontal cortical regions were identified where rCMRglc was significantly reduced in men as compared with women. These regions were located in the left middle, superior, and inferior frontal gyri and the right anterior cingulate, and superior frontal gyri (p < 0.001 uncorrected for multiple comparisons). Conclusion: The same level of severity of cognitive symptoms is associated with a more pronounced functional brain damage in male than in female patients with FrD, suggesting a greater degree of cognitive reserve in men.