The Relationship Between Menopause And Dementia

Statistics indicate that individuals assigned female at birth (AFAB) are twice as likely to develop dementia compared to individuals assigned male at birth (AMAB).¹ While some may attribute this to people AFAB having longer life expectancies, it is not entirely true when considering the disparity in dementia rates between the sexes. Based on multiple lines of research, it is clear that hormonal factors play a crucial role in addressing this inquiry. 

To better grasp the correlation between hormones and dementia, it is essential to understand the impact menopause has on the nervous system. This article aims to clarify what menopause and dementia are and how they are interrelated through hormonal factors.

Overview

Research shows that people with AFAB  who are in the post-menopausal stage for longer periods produce fewer brain molecules, such as brain-derived neurotrophic factor (BDNF) that are necessary for maintaining learning and memory functions. This decrease in brain molecules may increase the risk of developing neurodegenerative diseases, such as Alzheimer's disease. Although oestrogen replacement therapy is a potential treatment, it carries significant risks and may either improve or worsen cognitive functions. 

Menopause

Menopause marks the end of a person's AFAB’s reproductive years, typically 12 months after the last menstrual cycle. The transition to menopause (perimenopause) generally happens between the ages of 45 and 55 and can last, on average, for seven years, although it can stretch up to 14 years for some.² After this transition, the post-menopausal stage is entered. While menopause typically occurs naturally, it can also be triggered by a hysterectomy or surgical removal of the ovaries, leading to an immediate post-menopausal stage. 

Symptoms

The severity of menopause symptoms may differ according to an individual's lifestyle. These symptoms can be classified into two categories: mental and physical.³

Mental symptoms

• Mood swings
• Low self-esteem
• Anxiety
• Brain fog (difficulty with memory or concentration)

Physical symptoms

• Hot flushes
• Difficulty sleeping
• Heart palpitations
• Headaches
• Joint and muscle pain
• Weight gain
• Dry and itchy skin
• Lower sex drive
• Vaginal dryness and pain
• Recurrent urinary tract infections (UTI)

It is not uncommon to encounter physical discomforts such as hot flushes and night sweats during perimenopause. It is worth noting, however, that the mental symptoms may intensify as menopause progresses.

Risk factors

Unhealthy lifestyle choices and other underlying health conditions or procedures can lead to an early onset of menopause. It is essential to be aware of the risk factors that are associated with it, which include:

• Smoking - Studies indicate that individuals who smoke tend to experience menopause about two years earlier than those who do not smoke, with symptoms being more severe.
• Alcohol - Frequent alcohol consumption after the age of 30 can be associated with early menopause.
• Family history -  Individuals with a family history of premature menopause are more likely to experience it themselves.
• Chemotherapy or pelvic radiation treatment for cancer - Radiation-induced early menopause is predominantly observed in older individuals as this medical procedure can potentially damage the ovaries and hinder the menstrual cycle. Younger people with AFAB  are less likely to experience perimenopause after radiation exposure.
• Oophorectomy - Surgical removal of both ovaries can lead to immediate menopause with severe hot flashes and lower sexual desire.
• Hysterectomy - Surgical removal of the uterus. This procedure can stop the menstrual cycle and lead to immediate menopause. However, the ovaries can still produce hormones necessary for the reproductive system. Nevertheless, a hysterectomy is linked to early menopause within two years.
• Autoimmune diseases (e.g. thyroid disease and rheumatoid arthritis) -  In certain cases, the immune system may inadvertently target the ovaries, disrupting hormone production, despite their vital role in providing immunity against illnesses.
• HIV and AIDs - If the HIV or AIDs infection is not well controlled via prescribed medicine, it can lead to early menopause.
• Chronic fatigue syndrome - Sometimes also referred to as myalgic encephalomyelitis (ME). While it shares some symptoms with menopause, it is also linked to early-onset menopause.⁴

Oestrogen and menopause

Oestrogen is a steroid hormone primarily linked with developing and maintaining sexual characteristics and reproductive systems. Throughout life, oestrogen levels naturally fluctuate. For example, during puberty, it is common for oestrogen levels to increase, while they tend to decrease as menopause approaches. 

Dementia

Dementia is a term used to describe a range of cognitive difficulties that can impact one's memory, decision-making abilities, and thought processes, leading to challenges in performing daily tasks. Alzheimer's disease is the most common form of dementia. Although dementia can frequently occur in older individuals, it should not be mistaken as a natural part of the ageing process.

Types

Various medical conditions can result in cognitive challenges, although not all of these conditions are classified as types of dementia. The list below is the common type of dementia.

• Alzheimer’s disease - the most common cause of dementia
• Vascular dementia - second most common type of dementia, caused by the blockage or breakage of small blood vessels in the brain, depriving it of oxygen
• Dementia with Lewy bodies - caused by protein aggregation interfering with brain function 
• Frontotemporal dementia
• Young-onset dementia - with onset before the age of 65

Symptoms

Symptoms of dementia can vary depending on the type and severity of the condition. The most common early symptoms of dementia are:

• Memory loss
• Difficulty concentrating
• Difficulty performing familiar daily tasks
• Mood changes
• Confusion

These indications of cognitive decline are generally mild and tend to deteriorate over time gradually. It is commonly termed mild cognitive impairment (MCI) since the signs are not severe enough to be categorised as dementia.⁵ 

As the condition progresses, individuals with dementia may face significant difficulties with both memory and communication. The symptoms of later stages of dementia include: 

• Memory problems -  Individuals suffering from memory loss may experience difficulty recognizing close family and friends, as well as recalling their place of residence.
• Communication problems - In certain scenarios, individuals may experience a decline in their speaking capabilities. In such instances, resorting to alternative communication avenues such as non-verbal methods like facial expressions, touch, and gestures can prove to be beneficial.
• Mobility problems - Mobility may decrease, and people may become reliant on assistance such as a wheelchair. People may also become bedridden due to their limited ability to walk. Individuals may struggle with conscious actions, such as chewing and swallowing food (dysphagia), and unconscious actions, such as loss of bladder control and appetite.
• Behavioural problems - Many individuals may experience behavioural and psychological symptoms of dementia, which can include heightened agitation, symptoms of depression, anxiety, wandering, aggression, or occasional hallucinations.

Risk factors

Risk factors of dementia include:

• Age - the risk of dementia increases with age (65+)
• Genetics - those with a family history of dementia may be more at risk of onset
• Smoking and alcohol use - both cause inflammation that can affect brain tissue 
• Diabetes - inadequate glucose uptake can interfere with brain cell function 
• High cholesterol and atherosclerosis - can restrict blood flow to the brain

Prevention and management

 It is challenging to prevent dementia as the cause is often uncertain. However, those with dementia caused by a stroke can reduce the risk of further deterioration by lessening the risk of heart disease and stroke. Even if you do not have these known risk factors, incorporating these strategies can enhance your overall health.⁶

• Avoid smoking
• Maintain a healthy diet and weight
• Exercise
• Stay mentally alert (e.g., learning new hobbies, reading, solving puzzles)

Unfortunately, there is currently no cure for dementia. However, there are ways to slow down symptoms, such as mental and behavioural functions, from progressing further.

Medicine

• Donepezil
• Memantine
• Antidepressants

Alternative remedies

• Cognitive rehabilitation - A type of therapy aimed at improving brain function after an accident or disease onset. Rehabilitation aims to prevent further brain deterioration and improve independence and confidence in those with dementia.
• Reminiscence - Long-term memory typically remains more intact than short-term memory in those with dementia. Reminiscence therapy evokes memories from the patient’s past, usually with the help of music or visual aids, to improve recall and keep the brain stimulated.

The objective of continuous treatment for dementia is to maintain the person's safety at home for as long as possible and offer guidance and assistance to the caregivers. Regular follow-up appointments every 3 to 6 months are necessary to monitor medications and the individual's condition. Eventually, the family may need to consider relocating the person to a care facility that specialises in dementia care.

Relationship between menopause and dementia

Research has revealed a significant correlation between age after menopause and the levels of Brain-Derived Neurotrophic Factor (BDNF).⁷ BDNF is a vital molecule that contributes to the neural plasticity (brain’s ability to change) responsible for learning and memory. When such molecules decline, they can cause neurodegeneration that leads to dementia. 

Many studies demonstrate that the longer the post-menopausal period, the lower the production of BDNF. Therefore, the likelihood of developing dementia increases. In fact, low BDNF levels directly led to progressive atrophy (decreased size) of neurons in Alzheimer's disease.^8,9 It can be debated that the decline of BDNF levels can be solely attributed to the natural ageing process. However, a study examining the BDNF levels and memory scores of both sexes at the same age suggests other factors may be at play. The study discovered that post-menopausal individuals exhibit lower BDNF levels and memory scores than people of AMAB, with people with AFAB  having a memory score 56% lower than people of AMAB despite having higher memory scores in a similar study with younger samples.¹⁰ This suggested that menopause is a bigger key risk factor of dementia than old age itself. 

Ideally, it would be sensible to assume that dementia in post-menopausal people AFAB  can simply be improved by inducing oestrogen, as it has been shown to improve cognitive functions .^{11, 12, 13} However, hormonal replacement therapy is not a viable treatment or prevention method for dementia. This is because oestrogen replacement therapy is risky and complicated. Surprisingly, when used at the wrong time (i.e. too early or too late), it can worsen the symptoms or, in some cases, induce breast cancer.^14,15 

Each individual's body operates uniquely and is influenced by various factors such as dietary habits, genetics, underlying health conditions, and lifestyle. As a result, predicting the onset of menopause can pose difficulties, making it challenging to determine the most suitable treatment window, which makes hormonal replacement therapy far riskier and assumed not to be worth the risk.

Currently, the effects of oestrogen-induced therapy for treating dementia are yet to be fully understood. Therefore, it is recommended to follow a traditional treatment and management route.

Summary

While there is a strong correlation between the decline in oestrogen and cognitive decline in dementia, it is not recommended to use oestrogen replacement therapy as a treatment. This is because of the complex treatment window and the potential risks involved.