Projects

Sex as a biological variable in declarative memory of night owls.

Sleep is important for hippocampal-dependent memory, an ability with a male advantage. Studies involving human participants typically include both sexes, but rarely address sex as a biological variable (SABV), including the contribution of hormonal state. Genzel and colleagues showed a male-specific benefit of napping on memory performance. When female participants were stratified by their menstrual cycle phase, those in the early-mid luteal phase (when hormones are moderate-high) also showed improved memory following napping. Those in menses, or the early follicular phase (when hormones are low) did not show any improvement. This was the first study to demonstrate both a sex and hormone effect on the benefits of napping. However, the cognitive benefits of sleep in this study may have been confounded by the use of memory tests that are prone to practice effects, and the time of day when performance was assessed. Indeed, cognitive performance follows a circadian rhythm, which is more pronounced in individuals with a delayed sleep-wake rhythm, also known as late chronotype. Late chronotype is associated with greater risk for certain neuropsychiatric and neurodegenerative diseases, and which may result from circadian disturbances due to their sleep-wake timing being adjusted to align with the societal clock. Given sex differences in many of these disorders, we wondered if this reflects greater sensitivity to circadian misalignment in one sex than the other.  

Female vulnerability to neurodegenerative disease: the role of ovarian hormones and X-linked genes in the UK biobank cohort.

Female sex is a biological risk factor for the development of late-onset Alzheimer’s Disease (AD), reflected by a greater lifetime risk and greater neural pathological markers. Two proposed female-specific risk factors that may contribute to this elevated AD risk are 1) menopause and 2) increased expression of X-linked genes. However, the role of genotypic sex remains understudied compared to studies addressing the role of phenotypic sex. An additional modifiable risk factor for AD is midlife sleep disturbance, reported by 40-60% of perimenopausal women. Sleep is important in maintaining brain health, while its disruption may contribute to the development of AD and peripheral inflammation. However, the combined contribution of sleep disturbances and hormonal and chromosomal sex on peripheral inflammation and AD risk remains unexplored. This project will determine if menopause and/or x-linked gene expression exacerbates sleep-loss specific effects on inflammation, cognition and brain structure.