Hot Flashes: Precursor to Alzheimer’s Disease?

PHILADELPHIA — Vasomotor symptoms during menopause — like hot flashes — were linked to worse Alzheimer’s disease biomarker profiles, the MsBrain study showed.

In a study of 274 postmenopausal women, vasomotor symptoms during sleep were associated with significantly lower plasma levels of Alzheimer’s biomarker amyloid beta 42/40 ratio (B = -0.001, P<0.05), indicating a higher number of amyloid plaques, reported Rebecca Thurston, PhD, of the University of Pittsburgh in Pennsylvania.

This association was significant even after adjustment for estradiol levels and actigraphy-assessed sleep duration, Thurston said during a presentation at the Menopause Society annual meeting

“A hot flash is not just a bothersome midlife symptom,” she noted. “Women’s quality of life absolutely matters, and the hot flashes deserve attention for their quality-of-life impacts alone.”

“However, we also are seeing that these hot flashes may be telling us much more about a woman’s health than we previously thought,” she added. “For example, in addition to these links between hot flashes and brain health, we see that women with more hot flashes also have poorer cardiovascular health.”

“We don’t want to just scare women. That’s not our goal here,” Thurston said. Instead, the goal is to improve the health of midlife women, she noted, though it’s too soon to tell if treating these vasomotor symptoms during sleep will reduce dementia risk.

Speaking with MedPage Today, Stephanie Faubion, MD, MBA, director of the Mayo Clinic’s Center for Women’s Health and medical director of the Menopause Society, agreed that we don’t yet know if quelling nighttime vasomotor symptoms can modify these biomarkers.

“Is it the other way around? Are women with these markers at greater risk of having vasomotor symptoms?” she posited.

There was also a trend towards a link between vasomotor symptoms while awake and lower amyloid beta 42/40 ratio, but this didn’t reach statistical significance, Thurston reported.

Although prior research has shown links between hot flashes and cognition and other indicators of brain health, Thurston told MedPage Today that it still surprised her to see that hot flashes were associated with this biomarker of Alzheimer’s risk.

“We were quite interested that the finding was primarily driven by sleep hot flashes, as we have seen sleep hot flashes associated with other markers of neurocognitive risk,” she pointed out. “In addition, the association between hot flashes and this Alzheimer’s disease biomarker was not explained by sleep or estrogen. Therefore, there is something specific to these sleep hot flashes for brain health that is not explained by poor sleep or estrogen levels.”

Asima Ahmad, MD, MPH, chief medical officer and co-founder of Carrot Fertility, told MedPage Today that it is still unclear if vasomotor symptoms during sleep can be used as a means of predicting risk of Alzheimer’s.

“Future studies, including studies following people with more [vasomotor symptoms] during sleep over time, may help further delineate if this is true,” she said.

The MsBrain study enrolled postmenopausal women who had a uterus and at least one ovary between 2017 and 2020. Mean age was 59, 81% were white, and 24.5% were APOE4 positive. No participants had a neurological disorder or recently used hormonal or non-hormonal treatments for vasomotor symptoms.

Vasomotor symptoms were measured by 24-hour ambulatory skin conductance monitoring, physical measures, an interview, 3 days of sleep actigraphy assessment, and a fasting blood draw for APOE genotyping and estradiol. The researchers also assessed other Alzheimer’s biomarker measures, including p-tau 181 and 231, glial fibrillary acidic protein, and neurofilament light, none of which had a significant association with vasomotor symptoms.

Thurston pointed out that women tend to underreport vasomotor symptoms, especially during sleep, which is why they opted to objectively measure these symptoms with a device instead. Women had a median of five physiologic measured symptoms during a 24-hour cycle: 2.8 during waking hours and 1.5 during sleep.

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