Overview

Pernicious anemia is an autoimmune disease that is brought on by a vitamin B12 deficiency that prevents your body from producing enough red blood cells. This deficiency is caused by your body being unable to absorb vitamin B12. Vitamin B12 is needed for the normal functioning of the nervous system which is an essential system in our body that sends signals from your brain around your body to tell us how to function. 

Pernicious anemia can lead to serious medical issues, including severe damage to the nervous system.¹ This vitamin is also crucial in our neurological health, and if left untreated, it can lead to neurological and cognitive symptoms such as those seen in dementia and memory loss. This article will explore the relationship between pernicious anemia and cognitive function, focusing on how it can lead to dementia and memory loss and the role of vitamin B12 in this, in order for early diagnosis and prevention.

Causes of Pernicious Anemia

In pernicious anaemia, an autoimmune disease, your immune system creates antibodies that target nerve and stomach cells. This means your body is unable to absorb vitamin B12 properly, specifically due to a lack of intrinsic factor.² Intrinsic factor is an important glycoprotein produced in the stomach that carries vitamin B12 from your food to your small intestine. After being absorbed in the small intestine, vitamin B12 enters the bloodstream, where it travels throughout the body to support the proper functioning of the nervous system, as well as to your bone marrow to help make more red blood cells, which is vital for also transporting oxygen around your body to all your cells in order to function.^1,3 

Other causes and risk factors include:^1,2

• If you have had gastric bypass or stomach surgery
• If you have had partial/full removal of your small intestine
• In cases of small intestine bacterial overgrowth (SIBO)
• If you have endocrine autoimmune diseases such as thyroid diseases (hypoparathyroidism and Graves’ disease), Addison’s disease or vitiligo
• If you’re living with digestive system diseases such as celiac or Crohn’s disease
• If you take certain medications that affect vitamin B12 levels, such as antibiotics and seizure medication
• Having  type 1 diabetes (Certain diabetes medications can interfere with vitamin B12 absorption)
• If you follow a vegan or vegetarian diet or don’t eat foods that contain enough vitamin B12, such as meat, fish, and dairy
• A tapeworm infection can lead to vitamin B12 deficiency, as the parasite consumes the vitamin within your digestive tract

Symptoms of Pernicious Anemia

Pernicious anemia symptoms can often take a long time to show because your body stores vitamin B12 in the liver and uses it up slowly over time, and it takes several years to use up all your reserves. Pernicious anemia can affect the nervous system, digestive system, heart, and brain and leads to symptoms such as:^1,3

• Weakness
• Fatigue
• Lightheadedness
• Shortness of breath
• Loss of appetite
• Diarrhoea or constipation
• Weight loss
• Problems with taste and smell
• Uncontrollable muscle movements
• Heartburn
• Pale skin or mild jaundice
• Swollen and red tongue (glossitis)
• Bleeding gums

Long-term symptoms, if left untreated for too long, can also lead to psychological and neurological issues such as:¹

• Short-term memory loss/dementia-like symptoms
• Confusion
• Depression and anxiety
• Hallucinations
• Delusions
• Psychosis
• Loss of balance
• Numbness/tingling in hands and feet
• Problems concentrating
• Irritability
• Optic nerve degeneration leading to vision problems

Role of Vitamin B12 in Brain and Nerve Health

Vitamin B12 has important roles in red blood cell production and nervous system function, as well as having roles in maintaining our brain and nerve health and is essential for several processes.

One of its critical functions is in the synthesis of the myelin sheath, which is the fatty, protective layer that covers the axons of the nerve cells. Myelin allows for electrical signals to be efficiently transmitted between our neurons. Vitamin B12 also plays a role in the DNA synthesis of myelin-producing oligodendrocytes, which are the cells responsible for the formation and regeneration of myelin. This is needed especially after any nerve injury. Without vitamin B12, the production and repair of myelin stops, which leads to demyelination. If this occurs, our nerve impulses will slow down, which results in neurological symptoms such as numbness, tingling, lack of coordination and cognitive impairment.⁴

Vitamin B12 is also involved in neurotransmitter metabolism, energy production, fatty acid and nucleic acid synthesis, which are all important in our brain cell function. It also has a role in transmethylation processes, which are needed for producing compounds that help maintain communication between neurons. Vitamin B12 levels also affect the levels of the antioxidant reduced glutathione produced in the liver; without this, our cells are more exposed to oxidative stress, which damages our brain cells.⁴

Over time, a prolonged deficiency in vitamin B12 is also associated with and is a risk factor for brain shrinkage (atrophy) in regions such as the hippocampus, which is related to memory and cognition. This deterioration has been associated with a higher risk of developing dementia-like symptoms.⁵

Links of Pernicious Anemia to Memory Loss and Dementia

Vitamin B12 is involved in many important neurological pathways, and a deficiency in it can cause several different neurological and cognitive symptoms to appear before the other, more common physiological symptoms listed above. These can include short-term memory loss, confusion, difficulty concentrating, slowed thinking, mood swings, depression and in rare cases, paranoia and psychosis.

These cognitive and psychological symptoms closely resemble those of early dementia and other psychiatric disorders, and often conditions such as pernicious anemia are overlooked. This means people can be easily misdiagnosed as having dementia, a psychiatric disorder, depression, or just age-related cognitive decline, especially in older patients. An incorrect diagnosis leads to the delayed correct diagnosis of the actual condition, which leads to more damage to the brain and nervous system, which is why early detection and correct diagnosis are so important.⁶ There have been cases of patients who have suffered with confusion, memory issues, cognitive deterioration, depression and psychosis who did not get a diagnosis of pernicious anemia for several years, whose conditions started improving dramatically within days of appropriate treatment of intramuscular vitamin B12 injections.^6,7

Whilst a deficiency in vitamin B12 may cause dementia-like symptoms, it has not been found to be a cause of dementia. However, evidence has been found that vitamin B12 deficiency is potentially a cause of reversible dementia and can aggravate pre-existing dementia. Research studies have found a correlation between low levels of vitamin B12 and cognitive decline, and that patients with dementia-like symptoms had their cognitive impairments resolved within two weeks of treatment for pernicious anemia, further stressing the importance of correct diagnosis.⁸

Diagnosis and Tests

If you are presenting any symptoms of pernicious anemia, make an appointment with your GP. First, they will need to know about your symptoms and medical history, and then they will perform a blood test and as well as other tests which may include:¹

• Vitamin B12 level
• Complete blood count (CBC)
• Reticulocyte count
• Lactate dehydrogenase (LDH) test
• Serum bilirubin levels
• Methylmalonic acid (MMA) levels
• Homocysteine levels
• Upper endoscopy

You may still have the condition even if you have normal levels of vitamin B12, or you may have low levels of B12 but have no symptoms. They may also look for any signs of problems with your nervous system, and if you are presenting some neurological problems, in which case you may also have a neurological exam and cognitive screening tests. It is particularly important to get an early diagnosis of this condition to prevent lifelong neurological damage.

Treatment and Management

Since your body will still be unable to absorb vitamin B12. There is one main vitamin B12 replacement treatment that you will be prescribed with:²

• Intramuscular vitamin B12 injections (hydroxocobalamin) – this is the most common treatment and needs to be taken every other day for at least 2 weeks or until your symptoms improve, in some cases you may end up needing to take this injection every 2 months for the rest of your life, especially if you have lasting neurological symptoms

Other treatments can include:^1,3

• High doses of oral vitamin B12 replacement or sublingual supplements (such as a nose spray)
• Antibiotics – to get rid of any bacteria that might be preventing your body from absorbing vitamin B12
• Blood transfusions to treat serious cases
• With other causes of vitamin B12 deficiency, it is also best to add more foods that contain vitamin B12 to your diet, such as meat, fish, eggs, dairy products and other foods with added vitamin B12, like some cereals and vegetarian-based products

Symptoms may take months or even years to improve, you will need to monitor your vitamin B12 and blood levels and symptoms during this time. In some serious cases, especially if there is lasting damage to your nerves or brain, some symptoms such as numbness, tingling and short-term memory loss may not go away.

Summary

Pernicious anemia is an autoimmune condition caused by a deficiency in vitamin B12. Vitamin B12 is essential for maintaining the nervous system and brain function, particularly through its role in myelin production and neurotransmitter synthesis. If left untreated, this condition can severely affect nervous system function and neurological health, causing cognitive symptoms such as memory loss, confusion, dementia-like signs and even psychosis. These symptoms are often misdiagnosed, delaying proper treatment and creating further damage to the brain. Early detection, diagnosis and appropriate treatment management from intramuscular vitamin B12 injections and oral vitamin B12 supplements are crucial to prevent irreversible neurological damage, stressing the importance of understanding the link between vitamin B12 deficiency and cognitive decline.