Introduction

Lewy body dementia (LBD) is a common subtype of dementia – a progressive brain disease that, over time, reduces the brain’s ability to function, affecting a patient’s memory and thinking skills. LBD is caused by a build-up of a protein called alpha-synuclein, which forms larger protein masses called Lewy bodies.¹ The build-up of these protein masses leads to changes in the brain that can alter a patient’s behaviour and mood. Age is a key risk factor for developing the disease, with LBD most commonly developing at age 50 or older.

LBD accounts for around 20% of all dementia cases, with around 100,000 people in the UK currently living with this condition. The behavioural changes this disorder causes can severely affect patients’ quality of life. Understanding the mechanisms behind these behavioural and mood changes is essential so that appropriate measures can be taken to treat symptoms.

Overview of behavioural and mood symptoms of LBD

There are several behavioural symptoms associated with LBD, with the main ones being:²

• Hallucinations 
• Delusions
• Decline in cognitive abilities (i.e. the ability to think and reason)
• Sleeping problems 

There are also some important mood-related symptoms, and these are thought to worsen the behavioural symptoms previously mentioned:²

• Depression
• Anxiety
• Apathy 
• Agitation 
• Emotional instability

Other symptoms of LBD include reduced regulation of body functions due to changes in the autonomic nervous system.³ This can cause a patient to experience: changes in body temperature, problems with blood pressure, dizziness, fainting, falls, sensitivity to heat and cold, and urinary incontinence.

Specific behavioural manifestations

The following are behavioural symptoms that are characteristic of LBD.

Hallucinations and delusions

• Can be visual or auditory and involves perceiving people or objects that do not exist⁴
• Individuals may strongly believe in hallucinations and delusions without evidence
• Paranoia is a common theme in delusions 
• May develop Capgras syndrome, where a person believes a familiar person is an imposter that has been replaced, sometimes paired with visual hallucinations
• Occur in around 80% of LBD cases

Cognitive fluctuations

• A decline in problem-solving and decision-making abilities
• Difficulty with concentration and memory 
• Difficulty in understanding visual information 
• Symptoms most common in LBD compared to other forms of dementia

Sleeping issues (REM sleep disorder)

• REM sleeping disorder which involves physically acting out dreams during sleep
• Individuals may exhibit violent behaviour during sleep as a result of REM sleep disorder, e.g.punching, screaming, etc.
• General changes in sleeping pattern, which may include insomnia
• May also show excessive sleepiness during the day

Mood disorders associated with LBD

Depression

• It can affect an individual’s ability to participate in activities they previously enjoyed⁵
• It can cause feelings of worthlessness and can result in self-neglect, e.g. not eating
• It can occur as a result of behavioural symptoms, e.g. hallucinations and cognitive decline may make individuals less likely to interact with loved ones, thus increasing the risk of depression
• It is often mistaken for apathy, but while there are overlaps in features, depression involves more negative feelings, e.g. sadness
• Individuals with LBD have a higher risk of developing depression if they have experienced depression before

Anxiety

• Individuals can experience restlessness and agitation, shown physically through fidgeting
• This can result in paranoia, e.g. asking multiple questions, showing fear in the absence of familiar faces
• Agitation and restlessness, exhibited physically through hand wringing, pacing, and sometimes wandering off at inappropriate times, e.g. at night while in a hospital

Apathy

• Apathy is the loss of motivation to do simple tasks or even activities they may have previously enjoyed
• Patients may lack interest in interacting with others and appear detached from events around them
• In comparison to other subtypes of dementia, apathy appears earlier in LBD

Mechanisms behind behavioural and mood changes

Role of Lewy bodies in the brain

LBD is caused by the build-up of Lewy bodies in brain areas associated with the control of mood and behaviour, which may explain the changes in behaviour observed in individuals with LBD. These brain areas include: 

• The cerebral cortex - responsible for the control of many functions, including information processing, perception, thought, and language
• The limbic system - plays a key role in emotions and behaviour
• The hippocampus - critical for forming new memories

In healthy individuals, alpha-synuclein, the protein found in Lewy bodies, is instrumental in communication between nerve cells called neurons, specifically at the synapse, where both neurons meet. 

The build of Lewy bodies in LBD results in a declining ability for neurons to properly function, eventually causing cell death, and damaging brain areas linked to mood and behaviour. More specifically, brain areas affected also involve chemical changes where certain brain areas have neurotransmitters (chemicals in the brain that help neurons communicate with each other) that are lost in Lewy body accumulation.

One such neurotransmitter is dopamine, and LBD results in a loss of dopamine, which is thought to reduce motor function and the ability to find pleasure in activities. Another neurotransmitter especially influential in emotions and cognitive functioning is acetylcholine (ACh). Therefore, a loss in ACh and dopamine levels can explain the behavioural and mood changes seen in LBD, such as apathy and a decline in cognitive ability.

There are disruptions in brain systems and pathways that occur following the decline in cells and chemicals such as ACh and dopamine in certain brain areas, most significantly an area of the brain called the substantia nigra, which is involved in movement and linked to areas in emotional regulation. This shows how Lewy body accumulation changes the mechanisms of mood and behaviour, resulting in an observed change in individuals with LBD.

Management of behavioural and mood symptoms

Pharmacological approaches

While treatment is not currently available to fully cure individuals with LBD due to the degenerative nature of the disease, there are treatments available to alleviate the mood and behavioural symptoms of LBD. Sometimes, a combination of drugs targeting different symptoms may be needed.

Certain drugs, known as cholinesterase inhibitors, may be prescribed. These drugs slow down the natural breakdown of acetylcholine (ACh), making more ACh available in the brain, which is needed for emotional regulation. Thus, they can help patients with symptoms of delusions and hallucinations.

Antidepressants can be prescribed to help improve low mood. Treatment for REM sleep behaviour disorder is also available through certain drugs like clonazepam. If these treatments have little effect, antipsychotics can be used, e.g. quetiapine, to treat symptoms associated with emotional instability and violence. However, such antipsychotics are used as a last resort due to side effects that can worsen other symptoms related to LBD, such as sleeping issues and drowsiness.

It is important to note that different patients respond to different medications and certain medications may worsen behavioural symptoms over time, meaning that other treatment methods may be needed.

Non-pharmacological strategies

Non-pharmacological methods can also be greatly beneficial in the management of mood and behavioural symptoms associated with LBD. For example, a sound support system that promotes social and leisure activities, in addition to personal carers can be greatly helpful in improving general quality of life and potentially alleviating symptoms of depression and apathy. Cognitive behavioural therapy (CBT) is a type of talking therapy that involves identifying and managing inaccuracies or negativity in an individual's thought patterns and can help treat anxiety and depression-related symptoms of LBD.

Role of multidisciplinary care

A multidisciplinary approach encompassing drug and non-drug approaches (e.g. talking therapy and an active support system) delivered by a team of different types of healthcare professionals can be particularly beneficial. Members of a multidisciplinary team can address both biological and psychological aspects of the disease which together can help alleviate behavioural and mood symptoms of LBD.

Summary

LBD influences the mood and behaviour of patients due to the build-up of alpha-synuclein in areas of the brain associated with emotional regulation and behavioural output. These behavioural symptoms can include hallucinations, cognitive fluctuations, and, in some cases, REM sleep behaviour disorder. Mood changes that may occur can also include anxiety, depression, and general apathy.

There are different methods to alleviate these symptoms, including prescribing drugs to tackle the decrease in certain chemicals in the brain linked to emotional dysregulation. However, CBT can also be used to help alleviate some behavioural symptoms. Nevertheless, a group of professionals that can tackle the biological and psychological symptoms may be the most efficient method that considers the well-being of the patient the best.