Elevated Stress Hormones in Midlife May Increase Alzheimer's Risk for Postmenopausal Women

Recent research conducted by The University of Texas Health Science Center at San Antonio has revealed a concerning link between elevated levels of the stress hormone cortisol in midlife and an increased risk of Alzheimer's disease in postmenopausal women. This study, which analyzed data from 305 cognitively healthy participants in the Framingham Heart Study, has significant implications for understanding Alzheimer's disease risk factors.

The findings indicate that high cortisol levels, which are typically associated with stress, correlate with greater amyloid deposition in the brain of postmenopausal individuals. Amyloid proteins, when abnormally folded, can accumulate in tissues and organs, leading to the cognitive decline associated with Alzheimer's disease. By tracking cortisol levels over a 15-year period alongside indicators of Alzheimer's, researchers were able to propose that these levels might serve as a biomarker for the disease in women, especially in light of their menopausal status.

Notably, the study did not find similar associations in male participants or in relation to tau protein deposition, which is another biomarker linked to Alzheimer's. This raises important questions about gender-specific risk factors and the role of hormonal changes in Alzheimer's pathology. Dr. Arash Salardini, an associate professor of cognitive and behavioral neurology at the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, emphasized the significance of identifying early risk factors for Alzheimer's, particularly when biomarkers can be detected but cognitive impairment has not yet manifested.

The research highlights the urgency of addressing sporadic Alzheimer's disease, which is the primary cause of cognitive decline in older adults. This condition often features a prolonged asymptomatic phase that precedes noticeable cognitive decline, characterized by the accumulation of amyloid beta in the brain. Given that biological changes related to Alzheimer's can be well-established before symptoms appear, it is crucial to develop effective early interventions targeting risk factors during these preclinical stages.

Previous genetic studies have pointed to mutations in glucocorticoid signaling pathways, which are associated with an increased likelihood of developing Alzheimer's disease. Furthermore, multiple cross-sectional and longitudinal studies have suggested a connection between elevated blood cortisol levels and Alzheimer's risk. The current study sought to clarify these findings through a longitudinal analysis using data from the Framingham Heart Study, which has been ongoing since 1948.

Researchers assessed the serum cortisol levels of 305 cognitively healthy middle-aged individuals--48.5% of whom were female--with a mean age of approximately 39.6 years. They then analyzed the relationship between these levels and amyloid/tau burdens approximately 15 years later, utilizing positron emission tomography (PET) imaging and adjusting for various confounders in their analyses.

One of the key insights from the study is the importance of considering sex and hormonal status in Alzheimer's research. The findings suggest that hormonal changes after menopause may exacerbate the effects of cortisol on amyloid deposition, thereby increasing the risk of Alzheimer's among postmenopausal women. Future longitudinal follow-up of the cohort will be essential to determine if early amyloid changes correlate with clinical symptoms and to further elucidate the role of cortisol in Alzheimer's development.