Many women entering midlife notice changes in their memory, concentration, and mental clarity. Names seem harder to recall, multitasking feels more challenging, and episodes of “brain fog” become increasingly common. While these experiences can be frustrating, they are also incredibly common and they may be rooted in one of the most significant neurological transitions a woman will experience.

According to Dr. Kellyann Niotis, the years surrounding menopause represent a period of substantial change for the brain. Understanding what happens during this transition can help women better navigate symptoms, protect long-term brain health, and put concerns about cognitive changes into context.

The Brain During Perimenopause

Perimenopause refers to the transitional period leading up to and following menopause, which marks a woman’s final menstrual cycle. Dr. Niotis explains that “Perimenopause, which is a period of a woman’s life that spans seven maybe ten years or so, before and after menopause,” is characterized by major hormonal fluctuations, particularly involving estrogen. As estrogen levels begin to decline, the brain undergoes widespread remodeling. These changes affect how different brain regions communicate with one another, how the brain uses energy, and how it maintains healthy cellular function.

Dr. Niotis explains that “when that happens, it results in widespread remodeling of our brain, of how different brain regions are connected, of how our brain is utilizing energy.” At the same time, estrogen’s influence on Alzheimer’s-related proteins begins to change. Because estrogen plays a role in the accumulation and clearance of amyloid and tau, declining hormone levels may influence processes that are relevant to long-term dementia risk. One of the most noticeable consequences of this transition is brain fog. As Dr. Niotis notes, “a lot of women will start to complain of brain fog. That is probably the most common acute complaint that we’ll hear from women.” These symptoms are not simply imagined or psychological. They are linked to measurable changes in brain metabolism that occur as hormone levels fluctuate.

The Direct and Indirect Effects of Hormonal Change

The effects of perimenopause on the brain extend beyond hormones alone.

While hormonal fluctuations directly influence brain structure and function, they also create secondary challenges that can further affect cognitive health. Anxiety, depression, sleep disruption, and reduced energy often become more common during this stage of life.

Dr. Niotis explains that “while the brain is undergoing some of these structural changes, we’re also experiencing the secondary consequences of these hormonal shifts that can also negatively impact the brain.” These symptoms can create a ripple effect. Poor sleep and mood changes can reduce motivation to exercise, limit social engagement, and make it harder to maintain healthy routines—all of which are important contributors to brain health. As a result, the cognitive symptoms many women experience during perimenopause often reflect both the direct neurological effects of hormonal change and the indirect effects of lifestyle disruptions that accompany this transition.

Why Estrogen Matters for Brain Health

Researchers have become increasingly interested in estrogen because of its role as a neuroprotective hormone. The brain contains estrogen receptors throughout multiple regions, including areas heavily involved in memory and Alzheimer’s disease. As Dr. Niotis puts it simply, “Our brains like estrogen.” Regions such as the hippocampus and temporal lobe contain particularly high concentrations of estrogen receptors. During perimenopause, as circulating estrogen declines, the brain appears to compensate by increasing the number of receptors available.

Dr. Niotis explains that “the brain will start upregulating all of these estrogen receptors in efforts to kind of soak up as much circulating estrogen that it possibly can, because it’s protective.” This adaptation reflects the brain’s attempt to maintain normal function despite declining hormone levels. However, when estrogen becomes increasingly scarce, several important processes may be affected. Estrogen supports the formation of new neural connections, helps repair brain cells, and contributes to neuroplasticity—the brain’s ability to adapt and reorganize itself. It also appears to influence how amyloid and tau proteins accumulate and are cleared from the brain.

According to Dr. Niotis, “Estrogen seems to impact the accumulation and clearance of these proteins, which can impact someone’s risk for Alzheimer’s disease.”

Surgical and Medically Induced Menopause

While natural menopause involves a gradual hormonal transition, some women experience a much more abrupt change due to surgery or medical treatments. Dr. Niotis explains that “for women who’ve undergone surgically induced menopause or medically induced menopause, this really results in an abrupt decline in female reproductive hormones.” This sudden loss may be particularly challenging because the brain has less time to adapt. During natural perimenopause, estrogen levels fluctuate over several years, allowing the brain to gradually adjust. In contrast, surgical or medically induced menopause can remove that transition period entirely.

As Dr. Niotis notes, “the brain doesn’t have the opportunity to upregulate these estrogen receptors and to get more estrogen, because estrogen supply is immediately cut off.” Research has shown that women who undergo these forms of menopause may face a higher risk of dementia later in life, and some of the earliest studies linking menopause to Alzheimer’s disease emerged from these observations.

Looking Beyond Hormones

Although hormones are an important piece of the puzzle, Dr. Niotis emphasizes that they are far from the only factor influencing dementia risk. For women who are not candidates for hormone replacement therapy, or who have experienced medically or surgically induced menopause, focusing on other modifiable risk factors becomes especially important. “Hormones are not the whole story,” she explains. “They’re just one small piece of the puzzle.”

Cardiovascular health remains one of the most powerful predictors of future brain health. Managing cholesterol, blood pressure, insulin resistance, and other metabolic risk factors can have a meaningful impact on dementia risk.

Mental health is equally important. In fact, Dr. Niotis notes that “some would argue more important than hormonal health,” because the evidence linking cardiovascular disease and mental health to dementia risk is particularly strong. Sleep, exercise, nutrition, stress management, and social engagement also remain critical pillars of brain health throughout midlife and beyond.

Navigating the Transition

For many women, perimenopause can feel unsettling, especially when cognitive symptoms appear unexpectedly. But understanding the biological changes taking place can help put these experiences into perspective. Brain fog, memory lapses, and changes in concentration are often signs of a brain adapting to a major hormonal transition, not necessarily signs of future dementia. At the same time, this period offers an important opportunity to focus on the many factors that support long-term brain health.

As research continues to uncover the relationship between hormones, aging, and neurodegenerative disease, one message is becoming increasingly clear: supporting brain health during perimenopause involves far more than managing hormone levels alone. By paying attention to cardiovascular health, mental health, sleep, exercise, and nutrition, women can take meaningful steps to protect their brains during this important stage of life and beyond.

For more insights on the menopausal transition, watch our full conversation with Dr. Niotis in the video above.

By Alicia Barber Minteer, PhD