Normalization method for relative cerebral blood flow influences sex and cognitive status effects in nondemented...

Cerebral blood flow (CBF) is lower in males than females in cortical gray matter, but these sex effects are unknown in the hippocampus. Potential interactions between sex and cognitive status on CBF, which may contribute to the greater risk for females to develop mild cognitive impairment (MCI), are also understudied. Moreover, these effects may vary when regional CBF is normalized relative to individual differences in reference region CBF (residual rCBF) compared to more common difference scores (traditional rCBF). The current study examined effects of sex, cognitive status, and their interaction on residual and traditional rCBF in the cortical lobes and hippocampus in 111 cognitively unimpaired older adults (CU; 61.3%) and 49 older adults diagnosed with MCI (46.9% female) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with T1-weighted and perfusion-weighted magnetic resonance imaging data. As expected, rCBF was significantly lower in males than females in the occipital lobe, p = 0.010, but was unexpectedly significantly higher in males than females in the hippocampus, p < 0.001, with the sex effect being larger for traditional rCBF in the occipital lobe and residual rCBF in the hippocampus, ps < 0.024. Cognitive status significantly interacted with rCBF metric and region, ps < 0.014, but yielded no significant between group difference for any metric in any region, ps > 0.06. There were no significant interactions between sex and cognitive status, ps > 0.10. Taken together, these findings indicate that effects of sex on rCBF are region specific, independent of cognitive status, and vary with rCBF normalization method in non-demented older adults.