Menopause And Brain Health
It has been called the Menopause Brain. Women notice definite changes in their thinking abilities and speed. But what exactly does menopause do to the brain? Is brain health function changed and what happens in different parts of brain? How can we support and optimize brain health during menopause? Read on for more details.
In this blog you will learn:
- How menopause affects cognition & brain health
- What are the precise changes menopause causes in the brain
- Do the cognitive changes caused by menopause last forever?
Menopause marks the end of the reproductive years when menstrual cycles stop. It comes with symptoms like hot flashes, night sweats, sleep issues, weight gain, cognitive issues, sexual issues, metabolic body changes, cardiovascular disease risk, osteoporosis risk and potentially other symptoms.
Despite this, menopause does not necessarily have to be difficult. There is a lot we can do with lifestyle habits and diet. In this blog we will focus on how menopause affects cognition. In a future blog, we will look at how to support good brain health throughout menopause.
MENOPAUSE & COGNITION: WHAT HAPPENS TO THE BRAIN IN MENOPAUSE?
Menopause has a significant impact on the brain. It changes brain structure, connectivity and energy metabolism (Mosconi, 2021). Changes happen in brain regions responsible for high level cognitive processes. The changes are not related to chronological aging but instead to hormonal or menopausal endocrine aging. We can see this by looking at and comparing with the brains of same aged men (Mosconi, 2021).
Within the brain, different regions are responsible for different cognitive skills:
- Pre frontal cortex = planning, organizing, decision making
- Hippocampus = memory, learning, navigation
- Amygdala = memory, decision making, emotional responses, anxiety
COGNITIVE SYMPTOMS
Menopause can negatively affect cognition in different ways. It can impact attention, working memory, verbal memory and executive function (Ramli NZ, 2023). Specific neurological menopause symptoms include forgetfulness, insomnia, depression, memory loss, executive cognition skills and cognitive decline (Ramli NZ, 2023).
HOW DOES THE BRAIN CHANGE DURING MENOPAUSE?
The hormonal changes seen in menopause affect brain function (Ramli NZ, 2023). There are some key brain changes during menopause that are unfortunately not supportive of good cognitive function (Mosconi, 2021):
- Estrogen and progesterone levels decline
- Estrogen receptors become denser
- Grey matter volume declines
- Neuroinflammation increases
- Amyloid beta plaques form
- The brain molecule BDNF decreases
These changes are the result of falling estrogen levels (Mosconi L, 2024).
ESTROGEN LEVELS DECLINE
Estrogen is neuroprotective and important for brain health. Declining estrogen leads to cognitive issues (Mosconi L, 2024). Estrogen is involved in cell signaling, neuronal growth and synaptic organization. It stimulates brain-derived neurotrophic factor (BDNF) which is important for neuronal plasticity, learning and memory.
Estrogen supports higher cognitive functions in brain regions such as the prefrontal cortex and hippocampus. Many of estrogen’s effects on brain regions and signaling pathways happen via estrogen receptors (ERs).
Estrogen deficiency can increase mood and memory disorders (Baek DC, 2024). Issues with depression and memory struggles can happen in menopause. These result from estrogen deficiency, changes in neurotransmitter levels like serotonin, neuroinflammation and the dysregulation of signaling pathways (Baek DC, 2024).
Progesterone is also neuroprotective. It activates signaling pathways, inhibits excitotoxicity, promotes myelin repair and has anti-inflammatory effects (Ramli NZ, 2023).
ESTROGEN RECEPTOR DENSITY INCREASES
In the brain, estrogen regulates cognitive function, neurological aging and neural processes (attention, movement, perception, reasoning) (Mosconi L, 2024). To be active and effective, estrogen has to bind to estrogen receptors (ERs) in different brain regions. These ERs are quite influential on cognition (Baek DC, 2024).
Estrogen receptors and progesterone receptors are located in the hippocampus, the medial prefrontal cortex, the basal forebrain and the striatum, all of which are important brain regions for cognition (Ramli NZ, 2023). ERs modulate synaptic plasticity, neurogenesis, DNA repair and the expression of many genes (Mosconi L, 2024). ERs, especially in the hippocampus, are associated with memory.
Research has been done in mice to better understand ERs (Baek DC, 2024).
- Estrogen deficiency triggers neuroinflammation which is thought to involve ERs in microglia and astrocytes (types of brain cells with many functions).
- ERs contribute to regulating neural generation, proliferation and neuroinflammation.
- An ER can suppress the production and release of pro-inflammatory cytokines by microglia and astrocytes in research.
- In mice, disabling ERs in astrocytes led to hippocampal neuroinflammation and cognitive impairment.
- Reducing ER expression can significantly impair microglial functions, affecting their ability to respond to infection and injury.
- Mice without ERs showed increased anxiety-like behaviors.
- Rats treated with ER activators showed reduced anxiety- and despair-like behaviors (Baek DC, 2024).
ER density increases during menopause. Increased ER density worsens cognitive function. This is especially true for mood changes, memory issues and other cognitive symptoms after menopause (Mosconi L, 2024). In research, ER density predicts self-reported mood and cognitive symptoms in postmenopausal women (Mosconi L, 2024).
GREY MATTER VOLUME DECREASES
Menopause speeds up brain aging and affects the structure of specific brain regions (Ramli NZ, 2023). The hormonal changes cause a decrease in brain volume. More age-related brain volume decreases are seen in postmenopausal women vs pre−/perimenopausal women (Ramli NZ, 2023).
Grey matter (GM) volume differences and reductions happen in the frontal cortex, the hippocampus, the temporal cortex and the amygdala (Ramli NZ, 2023). These regions matter for behavioral, emotional and cognitive functions (Ramli NZ, 2023).
The hippocampus is vital for learning, memory and encoding new information into long-term memory. Damage or atrophy in the hippocampus negatively affects cognition (Ramli NZ, 2023). Poor memory is linked to smaller hippocampus volume (Ramli NZ, 2023).
Neurons in the brain have the ability to divide, grow and create new neurons. This is neurogenesis. Neurogenesis takes place in the hippocampus and is important for learning and memory. Research on rats with low estrogen levels reflect impaired hippocampal neurogenesis (Ramli NZ, 2023).
A decreased GM volume in the temporal brain region among menopausal women is associated with cognitive decline (Ramli NZ, 2023). The smaller volume in temporal regions is related to reduced cerebral blood flow and neuronal activity in postmenopausal women (Ramli NZ, 2023). A decrease in temporal volume affects visual perception, language comprehension, verbal fluency, speech, language function and social cognition (Ramli NZ, 2023).
Visuospatial ability is the ability to visually identify objects in space and interpret the relationship of objects in more than one dimension. Visuospatial problems can include difficulty recognizing faces, locating objects, reading, depth perception and navigating movements. Visuospatial skills are sensitive to changes in estrogen levels (Ramli NZ, 2023). Postmenopausal women have the greatest rate of decline in this skill compared to non-menopausal women and men (Ramli NZ, 2023).
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ALZHEIMER’S DISEASE RISK INCREASES
- Women are twice as likely as men to develop Alzheimer’s (O’Neal, 2024).
- Postmenopausal women make up 70% of all people with Alzheimer disease (Coughlan GT, 2023).
- Women going through menopause or in post menopause are at a higher risk of developing Alzheimer’s disease than men (Baek DC, 2024).
It has long been thought that this is due to the fact that women live longer than men and Alzheimer’s incidence increases with age. However, it is now clear that menopause and hormone changes may be the cause.
Low estrogen levels make the female brain more vulnerable to brain injury and neurodegenerative conditions. This is relative to both premenopausal women and to men of similar age (Mosconi L, 2024).
- Estrogen is neuroprotective. It supports neural plasticity and affects neurotransmitters.
- Low estrogen is linked to memory loss.
- Neurodegenerative conditions are influenced by ER dysregulation, which happens in menopause (Mosconi L, 2024).
- Amyloid beta plaque deposits in the brain indicate Alzheimer’s pathology and development. Amyloid beta plaque deposits form in the brain during menopause.
- Perimenopausal and postmenopausal women have more amyloid beta plaque deposits and neuronal volume loss compared to premenopausal women and men of similar age (Mosconi L R. A., 2018). The frontal cortex and PCC (posterior cingulate cortex) regions of the brain showed consistent abnormalities in peri- and postmenopausal women (Mosconi L R. A., 2018)
- These amyloid beta plaque deposits are more pronounced in peri-menopausal and post-menopausal women with the APOE-4 gene for Alzheimer’s compared to men with the APOE 4 gene (Mosconi, 2021).
NEUROINFLAMMATION INCREASES
Neuroinflammation is inflammation that occurs in the brain or spinal cord. It can damage nerve cells essential to cognitive function. When neuroinflammation becomes chronic, the repeated damage can disturb the brain’s communication and potentially lead to the amyloid beta plaque formation associated with Alzheimer’s.
Inflammatory brain disorders are higher in menopausal women compared to pre-menopausal women due to low estrogen (Baek DC, 2024). Estrogen inhibits the inflammatory response. Menopausal women have high proinflammatory cytokines which causes neuroinflammation (Baek DC, 2024).
Mice in a low-estrogen state have more inflammatory molecules in three brain regions (hippocampus, PFC and striatum) (Baek DC, 2024). Inflammation in the hippocampus is associated with depression-like behavior and cognitive impairment in mice.
Neuroinflammation from low estrogen can change hippocampal plasticity and estrogen receptors (ERs), which can worsen depressive symptoms and memory loss (Baek DC, 2024). Inflammation-related neuronal injury and neural circuits disruption are seen in the brains of postmenopausal women. This relates to cognitive impairment and depression (Baek DC, 2024).
Lower estrogen levels in menopausal women increase risk of depression by 2–5 times (Baek DC, 2024).
BDNF LEVELS DECLINE
BDNF is a brain molecule involved in neuronal growth and plasticity, learning and memory. Low estrogen, changes in estrogen receptors and specifically, the suppression of, estrogen receptors lead to decreased BDNF expression in three brain regions (hippocampus, PFC and striatum) (Baek DC, 2024).
The BDNF decreases suggest that neuronal growth and activity are vulnerable to estrogen deficiency (Baek DC, 2024). The change is significant in the hippocampus, center of learning, memory and mood regulation. With lower estrogen, BDNF decreases and microglial brain cells become over active which is inflammatory. Hippocampus serotonin levels also decrease (Baek DC, 2024).
Mice in menopause experience anxiety- and depressive-like behaviors and memory impairment, similar to humans. These symptoms are related to a suppression in ERs and increased neuroinflammation. All of these changes reduce BDNF, especially in the hippocampus, and activate microglia which increases inflammation.
Serotonin levels significantly decrease in three brain regions (hippocampus, striatum and raphe nuclei), with the lowest serotonin levels seen in the hippocampus. The memory impairment and depression seen in women in menopause are linked to these changes in ERs in six brain regions (Baek DC, 2024).
DOES THE BRAIN RECOVER AGAIN POST MENOPAUSE?
Interestingly, it seems that things stabilize again in post menopause. Brain-related symptoms, like memory lapses, appear to improve again over time. Research has yet to fully determine and understand how this works. But it seems that the negative effects of menopause on cognition are time limited and that the brain somehow transitions back after menopause (Ramli NZ, 2023).
Brain biomarkers stabilize post-menopause and gray matter volume (GMV) in key brain regions recovers (Mosconi, 2021). The recovery in grey matter volume and brain mitochondria ATP production helps to preserve cognitive performance post-menopause. This shows there is an adaptive process to compensate for menopause changes.
Studies indicate that decreased cognitive performance during perimenopause appears to normalize in post menopause (Ramli NZ, 2023). If this pattern of change in memory during menopause is valid and memory can recover despite estrogen remaining low, then declining estrogen is probably not the sole reason for the cognitive changes (Conde DM, 2021).
It seems that with time the brain adjusts for the loss of estrogen and estrogen receptor activity. This resetting of the brain may explain why hot flashes and other symptoms improve 2-7 years from their onset (Mosconi, 2021).
Neuroimaging shows that grey matter volume returns to normal in post-menopausal women (Mosconi, 2021). In fact, grey matter volume was similar to that of men of the same age (Mosconi, 2021). This is particularly true in areas related to memory and cognitive processing.
White matter volume falls during menopause and does not recover thereafter. However, compared to males, women undergoing or past menopause showed higher structural connectivity and myelination, which may indicate that the neural networks in these regions are more efficient following the onset of menopause (Mosconi, 2021). It seems that neurogenesis is restored after longer periods, which involves neurogenesis genes being upregulated (Ramli NZ, 2023). This neurogenesis that occurs years later might be related to preserving hippocampal volume in postmenopausal women (Ramli NZ, 2023).
There may be a mechanism that compensates for the negative effects of menopause. Researchers are currently developing a comprehensive menopause study that will better understand many aspects of menopause and cognition.
In future blogs in our Menopause Series, we will look at how can we support and optimize brain health during menopause. We will specifically recommend lifestyle factors like diet, exercise, sleep, stress management and others that can help manage menopause symptoms so please keep reading!
If you are suffering from menopause symptoms, then get in touch with us at the Medicine with Heart clinic. We can help to manage symptoms, optimize your menopause experience and get your health back on track!
SUMMARY
- In menopause, estrogen and progesterone levels drops quite dramatically. The drop in estrogen has multiple effects on the brain. These effects can cause cognitive issues with thinking, memory, language and other aspects of cognitive function.
- Specifically, low estrogen causes changes in estrogen receptors, reduces grey matter volume, increases neuroinflammation, raises the risk of Alzheimer’s disease and reduces BDNF, a necessary brain molecule.
- Combined, these changes in the brain cause a distinct decline in cognitive capacities experienced by women through the different stages of menopause.
- Research is starting to find that some of these brain changes improve again after menopause. This can relieve cognitive symptoms and restore some cognitive function that was lost during menopause.
