FEMALES are more likely to develop Alzheimer’s disease (AD) than males, making up two-thirds of the population living with the disease. Researchers at Mass General Brigham, Boston, Massachusetts, USA, have recently shed light on the relationship between age at menopause, the use of hormone therapy (HT), and Alzheimer’s risk.
Rachel Buckley, Department of Neurology at Massachusetts General Hospital, Boston, USA, commented: “HT is the most reliable way to ameliorate severe menopause symptoms, but over the last few decades, there has been a lack of clarity on how HT affects the brain”.
Previously, the highest levels of tau, a protein involved in AD, were found in females reporting a long delay between menopause onset and the initiation of HT. Premature menopause, defined as menopause before the age of 40, or due to surgical intervention before 45, has been associated with an increased risk of AD. Whilst HT improves menopause symptoms, the seminal Women’s Health Initiative (WHI) found that HT was associated with a nearly two-fold higher incidence of dementia, compared to a placebo.
Researchers analysed the PET scans of 292 cognitively unimpaired adults from the Wisconsin Registry for Alzheimer’s Prevention to determine levels of amyloid and tau in seven brain regions. Tau levels were the main focus of the study, as they are known to be found in greater quantities in females compared to males in the included brain regions. Thus, levels may offer insight into the sex-specific aspects of Alzheimer’s disease, even before displaying symptoms of cognitive decline.
Results showed that females had greater levels of tau compared to males of the same age, and this association was strongest in cases where amyloid was also elevated. Importantly, researchers also found the association between abnormal levels of tau and amyloid to be stronger in females with early menopause onset. This association remained after adjusting for known causes of premature menopause, such as smoking and oophorectomy. Notably, tau levels were highest in the entorhinal and inferior temporal regions, located close to the memory centre of the brain, and known to be involved in the progression of Alzheimer’s disease. Whilst researchers were unable to confirm the association between hormone therapy and amyloid and tau levels, they confirmed that late initiation (>5 year delay in initiation) drove this relationship.
“Up to 10 percent of women experience premature or early menopause, and our findings suggest that earlier age at menopause may be a risk factor for AD dementia,” concluded Gillian Coughlan, Department of Neurology, Massachusetts General Hospital, before adding: “These observational findings support clinical guidelines that state hormone therapy should be administered close to menopause onset, but not several years after.”