By Dr. Priyom Bose, Ph.D.Aug 7 2022Reviewed by Benedette Cuffari, M.Sc.

According to recent reports, the number of individuals aged 65 years and older throughout the world is increasing at an exceptional rate. In 2008, about 506 million belonged to this age group; however, researchers estimate that this will increase to 1.4 billion by 2040. This predicted rise in elderly individuals suggests an increase in age-related health issues, particularly dementia and cognitive decline.

Study: Sex Hormones, Sleep, and Memory: Interrelationships Across the Adult Female Lifespan. Image Credit: Photographee.eu / Shutterstock.com

Background

The prevalence of dementia in people over 60 years of age appears to double every 20 years, with the number of dementia patients estimated to reach 115.4 million by 2050.

According to the World Health Organization (WHO), Alzheimer’s disease (AD) is the most common cause of dementia. Aging is a natural factor that contributes to the occurrence of sleep disturbances, memory deficits, and the risk of AD.

A recent study has determined an association to exist between sleep and cognitive impairment as demonstrated by the incidence of AD and related dementias (ADRD). This study also reported that greater fragmented sleep with either excessively short or long sleep durations increases the likelihood of ADRD. 

Several pathological findings of AD have been observed in sleep-deprived individuals. For example, sleep deprivation is associated with increased levels of interstitial fluid, the concentration of amyloid beta (Aβ) and tau in cerebrospinal fluid, and Aβ deposition in the brain, with Aβ accumulation likely to have a negative impact on sleep.

Biological sex also appears to have an important role in the incidence of AD, with women often at a greater risk of ADRD as compared to men of the same age. Furthermore, post-diagnosis of AD, women undergo faster cognitive decline than men.

Notably, one recent meta-analysis revealed that women are at a higher risk of sleep disturbances and inadequate sleep across their lifespan as compared to men.

In a recent Frontiers in Aging Neuroscience study, scientists describe the relationship between biological sex, memory, sleep, and hormones in relation to the risk of ADRD.

About the study

In the current study, the authors reviewed extensive literature to identify any evidence that linked female sex hormones with sleep and memory. Limited data were available on the influence of sex hormones on sleep and memory with regards to the menstrual cycle, menopause, and pregnancy.

Several controversial data were reported regarding the potential influence of fluctuating sex hormones on memory and sleep changes. For example, some studies reported that moderately increased levels of estrogen and progesterone are beneficial for memory and sleep. Conversely, other studies contradicted these findings and reported that sex hormones have no significant effect on memory and sleep.

The levels of estrogens and progesterone were found to strongly influence the pattern of sleep, with a strong correlation existing between sleep and memory. Sex hormone-induced changes in sleep also affect the relationship between sex hormones and memory. Furthermore, fluctuations in estradiol and progesterone levels at different phases of the menstrual cycle affect sleep and memory. 

Sleep spindles, which are defined as bursts of neural oscillations throughout the thalamus, affect long-term memory outcomes. This is because sleep spindles might increase prefrontal and hippocampal cortex synaptic plasticity and neurogenesis, which are key factors associated with the long-term maintenance of cognitive health and next-day memory performance. These factors are also influenced by fluctuations in estrogen and progesterone levels.

Another study revealed that a night of sleep deprivation reduced progesterone but not estradiol levels in women. However, this finding was contradicted in another study reporting that female sex hormones did not significantly change after sleep deprivation. A possible interaction between sex hormones and sleep that affects memory has also been postulated.

Several studies have linked sleep disturbances to clinical AD and ADRD biomarkers. These studies have further reported that the female sex is most susceptible to AD, with fluctuations in estradiol and progesterone being related to the incidence of ADRD. 

An association between several neuroprotective mechanisms, such as Aβ levels, glial cell function, and regulation of neuronal mitochondrial function, and a reduced risk of AD has been observed. For example, individuals belonging to older age groups exhibit lower levels of sex hormones that cause Aβ accumulation and neuroinflammation, both of which negatively impact sleep.

During menopause, hormonal changes affect sleep because of excessive neuronal activity. The difference in norepinephrine production between males and females may contribute to the increased risk of sleep disturbances among females and, consequently, AD.

Conclusions

The exact underlying mechanism behind the sex differences in sleep and memory, as well as their connection with ADRD, are not well understood. Thus, both longitudinal observational studies, as well as experimental studies using animals and humans, are needed to better understand the interrelationship between sleep, sex hormones, memory, and their implications on the incidence of ADRD.