Introduction 

Lewy body dementia (LBD) is caused by abnormal deposits of alpha-synuclein protein (Lewy bodies) in the brain. Like other types of dementia, LBD is a slowly progressing disease, with symptoms worsening over time. The most common symptoms are visual and other sensory hallucinations, unpredictable changes in concentration, attention, or alertness, and severe loss of cognitive abilities, such as poor judgement, problems with time management orientation, and difficulties with language and numbers. Difficulties with movement, such as muscle stiffness, shaking at rest, balance problems, loss of coordination, reduced facial expression, difficulty swallowing, or unusually small handwriting, are also common. 

LBD is also often accompanied by a REM sleep behaviour disorder, excessive daytime sleepiness, insomnia, or restless leg syndrome. Further, patients with LBD are more prone to depression, apathy, and a lack of interest in daily activities, a decrease in social interactions, anxiety, restlessness, paranoia, and delusions. 

Some other symptoms may also be present. These are problems with blood pressure, dizziness, sensitivity to temperature, sexual dysfunction, urinary incontinence, constipation,  or impaired sense of smell. As the disease has slow progress, it can take, on average, 5 to 8 years from diagnosis to death. This time depends on the speed at which the symptoms develop, which depends on overall health, age, and severity of the symptoms and thus, it is highly individual.¹

Generally, there are two types of diagnosis for LBD – dementia with Lewy bodies and Parkinson’s disease dementia. Both of these types of LBD develop similar symptoms and have the same underlying changes in the brain. They only differ in the timing of cognitive and movement symptoms.¹

Dementia with lewy bodies

Cognitive symptoms of dementia with Lewy bodies usually develop within a year after the development of movement symptoms. The decline in cognitive ability may appear similar to Alzheimer’s disease with symptoms of LBD appearing with time.¹

Parkinson’s disease dementia

Parkinson’s disease dementia differs from dementia with Lewy bodies in the fact that the cognitive symptoms develop later. Usually, it takes more than 1 year after the development of movement symptoms for cognitive symptoms to develop. As the name suggests, Parkinson’s disease, dementia, usually starts with a diagnosis of Parkinson’s disease-like symptoms such as muscle stiffness, tremors, or slowed movement. Changes in mood and behaviour develop over time.⁷

Pathophysiology of lewy body dementia 

To understand how LBD medications work and address the question of their effectiveness, it is crucial to understand the basic mechanisms of the disease.

Lewy bodies

Lewy bodies are clumps of alpha-synuclein protein that build up inside the neurones of patients with Parkinson’s disease and related disorders. The buildup of protein is an important factor causing the damage and death of neurones.²

Brain regions affected by Lewy body dementia

Brainstem

When Lewy bodies start affecting the substantia nigra, an important part of the midbrain, they affect dopamine production, causing a gradual loss of neurones that produce dopamine as the disease progresses.²

Dopamine is a neurotransmitter. Its main role is the control and coordination of movement. It is also involved in the brain’s reward system and motivation. Dopamine also helps regulate cognitive functions such as memory, attention, and problem-solving. Thus, the insufficient supply of dopamine is a cause for many symptoms of LBD.³

Forebrain

In later stages of LBD, the Lewy bodies can spread to the forebrain, as well as in sensory areas of the neocortex and prefrontal neocortex.²

Other regions

Lewy bodies can, in some cases, be found in other brain regions, such as the olfactory bulb or pontine nuclei.² 

In summary, the spread of Lewy bodies starts in the lower part of the brainstem and as the disease progresses, it spreads out to the rest of the brain, which slowly causes the development of further symptoms as more and more parts of the brain get affected.

Current treatment strategies for lewy body dementia

To this day, no effective treatment for LBD has been developed. However, some treatment strategies focus on symptom management, which can improve the quality of life of the patient.⁴

Treatment of cognitive symptoms

To treat cognitive symptoms of LBD, medications called cholinesterase inhibitors are used. Cholinesterase inhibitors improve thinking and memory. The most common cholinesterase inhibitors are rivastigmine and donepezil. However, these medications can have side effects, affecting patients' autonomic nervous system.⁵

Cholinesterase inhibitors target enzymes in the brain called cholinesterases. There are two types of these enzymes: acetylcholinesterase, which breaks down acetylcholine, important for memory and thinking, and butyrylcholinesterase, which also breaks down acetylcholine. Cholinesterase inhibitors block the activity of acetylcholinesterase and, therefore, prevent the breakdown of acetylcholine. This results in more acetylcholine remaining active in the brain, boosting memory and thinking. 

Treatment of psychiatric symptoms

As anxiety, depression, and other psychological conditions are common in patients with LDB, it would seem appropriate to address those with antipsychotic medications. However, this is in most cases not possible, as it can have life-threatening reactions in patients with LDB. The only psychiatric symptoms that can be safely treated are hallucinations and delusions, which can sometimes improve with cholinesterase inhibitor medications.⁴

The reason for avoiding most types of antipsychotic medication is the risk of worsening symptoms, potentially causing sedation, immobility, or neuroleptic malignant syndrome (NMS). NMS is a medical emergency characterised by high fever, rigidity, breakdown of muscle tissue, and, consequently, death.

Treatment of movement symptoms

As mentioned earlier in this article, most movement symptoms of LBD are related to or are similar to those of Parkinson’s disease and are most commonly treated by levodopa medications and physical therapy. However, treatment of movement symptoms by levodopa can also lead to worsening of psychiatric symptoms.⁶

Levodopa is a chemical that the human body can convert into dopamine. In patients with Lewy body dementia, Lewy body accumulation can block the production of dopamine, resulting in movement difficulties, therefore, levodopa medication can improve these problems by supplying the body with dopamine.

Medication for sleep disorders and other symptoms

As LBD also affects the autonomic nervous system, symptoms like constipation, urinary issues, or low blood pressure often occur and are addressed with specific treatment. Sleep problems related to LBD are most commonly managed by medications such as melatonin or clonazepam. 

Melatonin is a hormone in charge of controlling when and how a person sleeps,  therefore, the synthetic version is a common supplement for those with insomnia. Clonazepam can reduce the feeling of anxiety and overall cause calmness and relaxation, which can make a person more likely to fall asleep.^7,8

Other non-pharmacological interventions

Drug interventions can be accompanied or replaced by other interventions, such as training programs for carers, allowing a better understanding of the perspective of a dementia patient and guidance for a better approach to patient care. 

Also, modifications of the environment may be helpful. For example, reducing the amount of bright light can reduce hallucinations. Physical therapy can help with managing the moving symptoms of LBD. Some studies claim that non-pharmacological approaches are more effective than medication use.

Summary

In summary, there is no effective cure for Lewy body dementia as of now. Current treatment, therefore, focuses on managing symptoms. Cholinesterase inhibitors can treat cognitive symptoms but these can severely affect patients' autonomic nervous systems. Psychiatric symptoms of Lewy body dementia are usually not treated by medication, as that can potentially have life-threatening consequences. 

Difficulties with movement are often treated by physical therapy and levodopa medication. Sleep disorders related to Lewy body dementia are treated by melatonin and clonazepam. Other approaches, such as physical therapy, adaptation to the environment, or training programs for carers, are also recommended.