New research insights about menopausal women’s brain health was reported in March 2024 in a neuroscience research study led by Dr. Lisa Mosconi and co-workers of the Weill Cornell Medicine in New York City [1].  The research investigated the sex-specific relationship between serum cortisol levels and brain biomarkers associated with Alzheimer's disease risk. 

​Alzheimer's disease is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, with increasing evidence suggesting a link between stress-related hormones such as cortisol and the development of Alzheimer's Disease (AD). However, existing research has largely overlooked potential sex differences in these associations. 

​To address this gap, Dr. Mosconi and colleagues conducted a study involving 277 participants, to examine the relationship between serum cortisol levels and brain biomarkers of Alzheimer's risk, while considering sex-specific differences. The study included both male and female participants aged 35–65 years who have risk factors for late-onset AD such as a family history and/or the APOE4 genotype, and who were assessed prior to the study of having normal cognitive function. The research methods used advanced neuroimaging techniques to assess various brain biomarkers associated with Alzheimer's disease, such as amyloid-beta deposits and neurodegeneration. 

​The study revealed sex-specific associations between serum cortisol levels and brain biomarkers of Alzheimer's risk. Specifically, higher levels of serum cortisol were associated with increased amyloid-beta deposits in women but not in men. Amyloid-beta deposition is a hallmark pathological feature of Alzheimer's disease and is believed to contribute to the development and progression of the condition. The research findings suggests that elevated cortisol levels may exacerbate amyloid-beta deposition in women, thereby increasing their risk of developing Alzheimer's disease. 

​Furthermore, the study found no significant association between serum cortisol levels and neurodegeneration biomarkers in either men or women. Neurodegeneration is another critical aspect of Alzheimer's pathology, and is characterized by the progressive loss of neurons and brain tissue. The lack of association suggests that cortisol may have a more specific effect on amyloid-beta deposition rather than overall neurodegeneration, in the context of Alzheimer's disease risk. 

​The researchers did not observe reduced cognitive performance in women compared to men, nor did their study confirm the findings of a previous research study in 2018 that reported a stronger association of cortisol with memory in women compared to age-controlled men [2]. It was recommended that to advance this research, a broad range of cognitive tests might be needed to capture the subtle cognitive changes in men and women that are associated with cortisol levels.  

​In summary, Dr. Mosconi's study sheds light on the sex-specific associations of serum cortisol with brain biomarkers of Alzheimer's risk. The findings underscore the importance of considering sex differences in Alzheimer's research and highlight the potential role of stress-related hormones in the development and progression of the disease. Further research in this area may contribute to the development of personalized strategies and therapeutic interventions for Alzheimer's prevention and treatment.