Menopause and Hormone Therapy May Alter Risk of Alzheimer's Disease

Early age at menopause and delayed hormone therapy after menopause could be new risk factors for Alzheimer’s disease (AD), according to a new study published in JAMA Neurology. Alzheimer’s disease is the most common type of dementia, affecting 60 to 70% of people with dementia. However, there is a major gender difference among cases. Approximately two-thirds of people diagnosed with Alzheimers disease are women. The reasons for this gender disparity are likely related to hormonal changes, which play a role in the development of this neurological disorder.

Association of Age at Menopause and Hormone Therapy Use with Alzheimer’s Disease Risk

Premature menopause that occurs spontaneously before the age of 40 or due to surgical intervention before the age of 45, has also been associated with an increased risk of AD dementia. HT improves many severe symptoms related to menopause and has been hypothesized to also prevent cognitive impairment.

However, two decades ago, researchers found that HT use was associated with a nearly two-fold higher incidence of dementia compared to placebo among women aged 65 years and older, possibly due to the initiation of HT many years after menopause onset.

To better understand these findings, researchers used positron emission tomography (PET) neuroimaging to study how the presence of two proteins involved in AD dementia, β-amyloid, and tau, related to age at menopause and HT use.

While previous studies examined symptoms of cognitive decline in menopausal women, few investigations analyzed the biological factors underlying these changes, which may be at play in determining the risk of Alzheimer’s disease.

The previous study findings suggested that starting HT early in menopause, rather than late initiation, provides better outcomes for heart disease, cognitive function, and all-cause mortality — and this study suggests that the same is true for tau deposition.

Researchers analyzed PET scans from 292 cognitively unimpaired adults to determine levels of amyloid and tau in seven regions of the brain. Tau, which is known to be present in greater quantities in women compared to men in these brain regions, was the primary focus of the investigation.

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As expected, women had greater levels of tau compared to men of the same age, especially in cases where they also had elevated β-amyloid. But the researchers also found that the association between abnormal levels of β-amyloid and tau was much stronger in women who had earlier menopause onset.

Why the Timing of Hormone Therapy Too Matters

Notably, tau levels were high in the entorhinal and inferior temporal regions, which are located close to the memory center of the brain and are known to be involved in the progression of AD dementia. Given that many women who undergo premature menopause use HT, the researchers examined whether HT use was associated with β-amyloid and tau.

While they did confirm this association, they observed that late initiation of HT — five years or more after menopause — drove this relationship. Many women in the late-HT-initiation group began HT close to a decade after menopause.

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Going forward, the researchers are continuing to study sex-specific risk factors for AD dementia and are also to engage in efforts to understand the unique role that tau plays in women compared to men, its impact on the brain, and why earlier menopause and late HT initiation may be associated with increased tau, even in cognitively unimpaired women.

Hormone therapy can have negative effects on cognition, but only if initiated several years after the age of menopause. These observational findings support clinical guidelines that state hormone therapy should be administered close to menopause onset, but not several years after.



Source-Eurekalert