But where does women's (metabolic) advantage go?

Sex differences play a vital role in human brain structure and physiology. Previous reports have proposed evidence hinting at a metabolic advantage in female brains across adulthood. It remained to be determined whether this advantage would be maintained across the spectrum of cognitive impairment, up to and including dementia due to Alzheimer’s disease (AD).

In this work we used the concept of “metabolic brain age”. Metabolism here is assessed using PET fluorodeoxyglucose (PET FDG) imaging, a form of brain scans that tell us where in the brain energy is being consumed. The “brain age” part comes from our building a mathematical model comparing the PET FDG scan of an individual to a database of similar scans, using machine learning techniques. This comparison allows us to generate a “metabolic brain age” for any given brain; in other words, if a brain looked metabolically “younger” for its chronological age, the same, or “older”.

In our article by Iman (Beheshti), Scott (Nugent), Olivier (Potvin) and Simon (Duchesne), we set out to investigate whether this metabolic “youthfulness” advantage in females remained in the presence of neurodegeneration and cognitive impairment in mild cognitive impairment (MCI; a diagnostic state before dementia) and AD patients. We showed that although cognitively healthy females exhibited a significant metabolic brain age “youthful” advantage in adulthood, it disappeared in the presence of neurodegeneration and cognitive impairment.

This would imply that females undergoing neurodegeneration of an Alzheimer’s pathological nature have an accelerated rate of decline in brain metabolism, in order to age “faster” than males and obviate the earlier gap. Our findings could be a cue towards explaining the higher incidence of AD-related dementia in females, in support of the energy hypothesis.