When You Go Through Menopause May Affect Your Risk of Cognitive Decline

White matter helps different parts of the brain communicate. Damage in these areas, visible as bright spots on an MRI, has been associated with problems with attention, focus, planning, and how quickly the brain processes information.

“We could see an association between menopause age and white matter injury in women followed in their seventies and eighties — even decades beyond menopause — showing a lasting trace,” says the senior study author, Riley Bove, MD, the director of the UCSF Sex and Gender Enriched Program and Rosenberg Ach Family Endowed Professor in Neuroimmunology at the University of California in San Francisco.

While the study doesn’t prove that earlier menopause causes these brain changes, the observational findings add to existing evidence that the timing of menopause may be one factor that helps shape brain health later in life.

Study Tracked Brain and Thinking Changes Decades After Menopause

The study included 2,603 women enrolled in two long-running aging studies. Participants’ average age was 78 when they entered the study, and they were followed for as long as 18 years.

Everyone underwent yearly cognitive testing, and a smaller group of 774 women had repeated brain MRIs, allowing researchers to track changes in brain structure over time. Researchers had brain autopsy data for more than 1,200 women.

About two-thirds of the women had gone through menopause naturally, at a median age of 50. The remaining women reported surgical menopause, which happened at a median age of 43.

The researchers didn’t use one particular age to define “early menopause.” Instead, they looked at whether women who went through menopause at a younger age relative to other women in the study had differences in brain health and cognitive aging later in life.

Earlier Menopause Was Linked to Several Signs of Faster Brain Aging

Researchers found that earlier menopause was associated with several differences in brain and cognitive aging. Key findings included:

• Researchers estimated that a woman whose menopause occurred 10 years earlier would have about 1.8 fewer years without an Alzheimer’s diagnosis.
• Among women who went through menopause naturally, researchers estimated that menopause five years earlier was associated with about 15 percent more white matter injury over a decade.
• Earlier menopause was associated with a faster rate of decline in overall thinking ability and episodic memory.

Injury in the white matter becomes increasingly common as we age, says Dr. Bove.

“Along with aging itself, other conditions like hypertension, elevated blood sugar and cholesterol, and obesity can also contribute to this risk. Estrogen appears to provide some protection against these conditions, or against underlying brain vulnerability to injury, until it declines with menopause,” she says.

What This Adds to What We Know About Menopause and Alzheimer’s Risk

The new study helps fill an important gap by following changes within the same women over time, says Hadi Hosseini, PhD, a researcher and computational and cognitive neuroscientist and an associate professor of psychiatry at Stanford University in California who wasn’t involved in the study.

Most previous studies have just offered a snapshot of women’s brain and cognitive health, Dr. Hosseini says. This study followed women over time to see how age at menopause was related to changes in memory, thinking, and brain structure as they aged, he says.

Bove agrees that being able to follow the women over time allowed researchers to see “this lasting trace in women’s brains decades beyond their menopause — not just in the more immediate aftermath of menopause but over the rest of the lifespan.”

Why Might the Timing of Menopause Matter to the Brain?

While it’s not completely understood why earlier menopause might increase the risk of Alzheimer’s disease, the overarching theory is that sustained exposure to estrogen during the reproductive years may support resilience, says Bove.

Specifically, estrogen could help support communication between brain cells and the way those cells produce energy, and also general health, such as the risk of heart disease, which can contribute to brain injury and accelerated aging, she says.

“Women with earlier menopause have fewer total years of estrogen exposure and therefore may have fewer years in which to experience the neuroprotective effects of the reproductive hormones,” Bove says.

Strengths and Limitations of the Study

In addition to tracking cognitive changes for years, combining cognitive testing, Alzheimer’s diagnoses, MRI scans, and brain autopsy data also allowed researchers to look at menopause timing from several different angles.

But there are important limitations. Women reported their own ages at menopause, sometimes decades after the fact. More than 90 percent of participants were white, and the group was relatively highly educated, which may limit how broadly the findings apply.

Researchers also couldn’t distinguish between different types of surgical menopause, such as removal of both ovaries versus hysterectomy with the ovaries left in place.

Most important, the study was observational, and although the observed association between earlier menopause age and faster white matter injury accumulation in women with spontaneous menopause is important, it can’t be interpreted as causal evidence or an actionable individual effect, Hosseini says.

The study isn’t able to prove whether hormone therapy could prevent the brain changes linked with earlier menopause. Researchers explored whether menopausal hormone therapy (MHT) appeared to change the relationship between menopause timing and brain changes and found no significant effect.

There’s another problem with trying to answer the hormone therapy question using an observational study: Women who take MHT may differ from women who don’t in several ways, including healthcare access, health status, and medical conditions, Bove says.

What Should You Do if You Went Through Menopause Early?

The associations found in this study aren’t enough to prove that earlier age of menopause caused steeper decline in cognition or more accumulation of the white matter, and so they aren’t enough to change clinical recommendations, says Hosseini.

“However, earlier age at menopause may be regarded as one of several factors that could help identify women who may benefit from closer monitoring of their cognitive and brain health as they age,” he says.

“For now, women who undergo early menopause — especially if surgical — should stay on MHT until at least the typical age of spontaneous menopause, in the early fifties, unless there is a contraindication,” says Bove.

Women who notice cognitive symptoms during menopause should also bring them up with their doctor, she says. That includes word-finding problems, difficulty paying attention, or trouble retaining and working with new information.

“In most cases, these are transient changes and can stabilize once the hormones, sleep and mood do; sometimes, they warrant additional workup,” says Bove.

Perimenopause is also a window of opportunity during which women can comprehensively assess all their symptoms, including sleep, mood, joint pain, and bladder function, and aim for strong preventive care to support healthy aging, she says.

“This includes bone health, cardiovascular health, exercise and wellness, and cancer prevention, among others,” says Bove.