Postmenopausal Women With Increased Stress at Higher Risk of Alzheimer Disease
However, there is no association between cortisol and tau pathology.
Women who are postmenopausal with high midlife cortisol are at an increased risk of Alzheimer disease (AD), according to new data published in Alzheimer’s and Dementia. However, there is no association between cortisol and tau pathology.1
However, there is no association between cortisol and tau pathology. | Image Credit: pikselstock - stock.adobe.com
Our work shows that considering sex and hormonal status in understanding Alzheimer’s disease pathogenesis is important and suggests that stress reduction and hormonal interventions may hold promise for Alzheimer’s prevention, especially in at-risk women,” Sudha Seshadri, MD, founding director of the Biggs Institute at The University of Texas Health Science Center at San Antonio, said in a news release.2
AD is the most common cause of dementia, according to the Mayo Clinic. It is the buildup of protein called amyloid plaques in the brain, causing brain cells to die over time and the brain to shrink. Approximately 6.9 million people in the United States 65 years and older have AD, with 70% being 75 years and older. Worldwide, more than 55% of people are estimated to have dementia, and 60% to 70% are estimated to have AD.3
Investigators aimed to conduct a longitudinal analysis to determine the relationship between serum cortisol levels and cognitive impairment for middle-aged individuals. They also examined the sex-related differences, particularly for postmenopausal women. Blood samples from patients were taken in 3 different assessments: 2002 to 2005, 2008 to 2011, and 2016 to 2019. Individuals also included demographics, socioeconomic status, and clinical evaluations. Patients aged 32 to 75 years who completed the first and third exams also had MRI scans and were free of neurological conditions were eligible for PET imaging for the substudy.1
There are 305 individuals included in the study, with 48.5% being female and 23.8% being APOE4 positive. The median cortisol level was 13.2 µg/dL. Investigators found no association between serum cortisol levels and regional amyloid distribution volume ratio; however, there “was a statistically significant interaction between cortisol levels and sex in regional amyloid deposition in posterior cingulate (p = 0.018), precuneus (p = 0.009), and FLR [frontal, lateral, and retrosplenial] (0.024) cortices.” They added that there was no interaction between cortisol level and superior temporal sulcus (STS) amyloid.1
The highest tertile of serum cortisol in women was associated with higher amyloid deposition in the posterior cingulate cortex (PCC), precuneus (PC), and FLR regions of interest (ROIs) compared with the middle tertile, according to the study authors. The association was not seen for men. Investigators noted that the menopause status was associated with serum cortisol and amyloid PET burden in the PCC and FLR. There was an effect between menopause status and secondary ROI STS. Higher amyloid deposition in the PCC, PC, and FLR ROIs for postmenopausal women in the highest tertile for cortisol compared to those in the middle.1
“We observed a significant association between elevated serum cortisol in early midlife and increased amyloid deposition 15 years later, measured by PET imaging. This association was specific to post-menopausal women and was absent in men or in relation to tau deposition in either sex,” the study authors stated.1 “Although the effect size was modest, the association persisted even after controlling for age and other confounding variables. This finding aligns with the well-established increased risk and prevalence of AD in women, particularly following menopause.”
