The researcher hypothesis was that at an equivalent cognitive level, men would have greater white matter (WM) microstructural damage compared with women This might suggest that men have a greater degree of brain reserve than women as they are maintaining cognition at an equivalent level to their female counterparts despite the presence of greater WM damage. They also hypothesized that older women are at greater risk of developing mild cognitive impairment (MCI) as they may meet the criteria for this condition despite having significantly less WM microstructural damage than men with a comparable level of MCI. In the current study, tract based spatial statistics (TBSS) was used to assess sex differences in healthy older participants (24 women, 16 men) and participants with mild cognitive impairment (21 women, 12 men). All subjects enrolled underwent a brain diffusion tensor imaging registration. Results showed significantly lower Fractional Anisotropy (FA), and significantly higher radial diffusion (DR), axial diffusion (DA) and mean diffusion (MD) in MCI participants relative to healthy older controls. They also reported a significant main effect of sex which has not been previously noted. This significant main effect of sex demonstrated that men have significantly raised DR and MD, and significantly lower FA, relative to women, both within healthy older and MCI participants. Overall, these data suggest that the same degree of cognitive impairment is associated with greater structural damage in men compared with women.