Treatment And Management Of Frontotemporal Dementia: Current Approaches To Managing FTD Symptoms And Progression

Introduction

What is frontotemporal dementia?

Frontotemporal dementia (FTD) is a rare type of dementia, whereby damage to specific areas of the brain causes problems with certain cognitive and physical abilities.  

Dementia is an umbrella term used to describe disorders of the brain in which memory, language, problem-solving, and other cognitive skills are impaired, affecting the quality of life and ability to function independently. The most common types of dementia are Alzheimer’s disease and vascular dementia. 

How does frontotemporal dementia affect the brain?

FTD specifically affects the front and sides of the brain, known as the frontal and temporal lobes. The former is responsible for controlling your emotions, personality, movement, and judgement, whilst the latter processes sensory input and controls your memory and ability to understand language.¹ That is why FTD causes symptoms including:

• Behaviour and personality changes – acting impulsively, social withdrawal, loss of interest in things, inability to empathise
• Language problems – slow speech, loss of vocabulary, repeating words or phrases
• Problems with mental abilities – poor judgement, becoming easily distracted, difficulty recognising familiar people or objects
• Physical problems – slow movements, swallowing difficulties, loss of bladder or bowel control

[Above]: The lobes of the brain. From Wikimedia Commons; Licensed under the Creative Commons Attribution-Share Alike 4.0 International License (https://creativecommons.org/licenses/by-sa/4.0/deed.en); Author: Cancer Research UK. (File:Diagram showing the lobes of the brain CRUK 308.svg - Wikimedia Commons)

Types of frontotemporal dementia

There are several variants of FTD. They are:

• Behavioural variant (bvFTD) – this is the most common type of FTD and includes a gradual onset and progression of changes in behaviour and personality
• Primary progressive aphasia (PPA) – this is further subdivided into semantic (svPPA) and non-fluent (nfvPPA) primary progressive aphasia which have a slower progression than bvFTD and mainly affect speech
• Right lobe variant (rtvFTD) – this type can cause cognitive, behavioural and language impairments^2,3
• FTD associated with motor neurone disease (FTD-MND) – MND is a disorder that causes progressive muscle weakness and eventually leads to paralysis
• Cortico-basal syndrome (CBS) and progressive supranuclear palsy (PSP) – cause FTD-like symptoms, such as slow movements, slurred speech, and loss of balance

Current approaches to treatment

There is currently no specific cure for FTD so treatment focuses on managing symptoms and slowing the progression of the disease, to improve the patient’s quality of life as much as possible.

Symptom management is divided into pharmacological and non-pharmacological options. The former describes approaches which utilise medications, whilst non-pharmacological methods do not rely on medications.

Pharmacological treatment

Behavioural symptoms

Antidepressants

Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants which work by blocking the reuptake of serotonin, thereby increasing the levels of this chemical in the brain. Serotonin is a ‘feel-good’ hormone and transmits signals between nerve cells throughout the body to control functions like mood and cognition.⁴ Thus, SSRIs are useful for the disinhibition and depressive symptoms associated with FTD. Examples of SSRIs include paroxetine, sertraline, and fluoxetine.^1,3,5

Antipsychotics

For cases involving agitation or disruptive behaviour, a small dose of an antipsychotic medication can work. Trazodone dampens the arousal effects of neurotransmitters, like serotonin and noradrenaline to bring about a sedative effect. Alternatively, aripiprazole causes an antipsychotic effect owing to its ability to rebalance levels of serotonin and dopamine, another ‘feel-good’ hormone, in the brain.^1,3,5

Cognitive decline

Acetylcholinesterase inhibitors

An example drug in this class is Razadyne, known generically as galantamine. It treats FTD, as well as other types of dementia, by increasing the levels of a neurotransmitter called acetylcholine. This chemical is associated with the formation of memory and learning, so therefore helps to improve cognitive function. Galantamine has been shown to specifically help with progressive nonfluent aphasia.⁵ This is a condition in which your speech and language are impaired.

However, the use of acetylcholinesterase inhibitors is limited due to studies demonstrating that these drugs do not exhibit any improvement in cognitive performance, but actually exacerbate psychiatric symptoms instead.⁶

Motor symptoms

Tetrabenazine

This is a monoamine inhibitor which is typically used to treat depression by altering the levels of various chemicals in the brain. However, tetrabenazine also has implications in FTD treatment since it can help to improve tics and stereotypies.⁷ These are defined as rhythmic, repetitive moments such as body rocking, teeth grinding, and head banging.

Non-pharmacological treatment

Physical therapy

The aim of this is to improve your gait and balance so that you can remain as mobile as possible and avoid falls which are a common complication of FTD.¹

Techniques include:

• Doing exercises that impact your whole body or a specific part of the body, for example, if you have problems using your hands
• Learning how to use mobility aids, such as a walking stick
• Using manual therapy, which can have benefits including pain relief and improvement of blood circulation and general movement 

Occupational therapy and lifestyle modifications

If you are living independently, your household safety should be assessed to reduce your risk of sustaining damage from incidents, such as falls, burns, or poisoning. Help could also be offered if you have difficulty performing simple everyday tasks or those that require manual dexterity. Furthermore, it is important that you have regular support so as to maintain your emotional well-being, for example receiving visits from family and friends.^1,8,9

Behavioural therapy

This is usually in the form of cognitive behavioural therapy (CBT), which is a type of therapy that encourages you to consider how your thoughts and feelings can influence your behaviour. You are taught various techniques to help change your attitude towards certain problems, thus bringing about a positive overall benefit to your mental and physical well-being.

You may also receive social skills training and be taught management strategies for any behavioural difficulties that FTD causes you to experience, for example, social misconduct.⁵

Enjoying simple activities, such as doing puzzles and listening to your favourite music can be a distraction and may help attenuate any negative behaviour.⁹

Speech and language therapy

This is important to ensure that you can continue to communicate and interact with others, particularly caregivers. This treatment is especially beneficial for PPA since your speech and language is likely to be impaired.¹ Techniques include:

• Articulation therapy – this involves articulating words so that you can produce speech sounds correctly
• Oral motor therapy – this involves strengthening the muscles that control speech
• Language intervention therapy – this involves role-play to help you form coherent sentences
• Lee Silverman speech therapy – this helps you to speak more loudly and clearly

Slowing disease progression

Disease-modifying therapies

Tau is a protein that is usually found in neurons and helps to maintain their structure. This allows neurons to fulfil their purpose of sending and receiving information throughout the brain so as to coordinate specific functions in the body.

In some forms of dementia, including FTD, tau proteins become damaged and can aggregate to form amyloid fibrils. This causes neurons to die, thus chemical signalling in the brain becomes disrupted. This interference is what causes the symptoms of dementia, such as poor judgement and problems with movement.

Clinical trials are being conducted that use strategies to lower the accumulation of tau in neurons. One such strategy focuses on increasing the degradation and removal of tau, preventing its build-up.¹⁰

By altering levels of tau in the brain, it is hoped that the rate at which FTD causes behavioural and cognitive decline will reduce, allowing you to have a good quality of life for as long as possible.  

Palliative care

This involves support that is tailored to those with terminal illnesses who are in the last months or years of their life. Palliative care aims to make you as comfortable as possible by managing symptoms, such as pain. This type of care involves supporting your family and carers too.

When considering the ethics of an incurable illness, an advance decision, or living will, can be beneficial because it allows you to state how you wish to be supported and cared for in the event that your condition deteriorates and you lack the mental capacity to express this. If there is a specific type of treatment that you are not willing to receive you can declare this, allowing you to live with dignity towards the end of your life.

A living will also state where you wish to be treated during the final stages of your condition (i.e. home, hospice, hospital), and whether you consent to resuscitation and organ donation. 

Summary

FTD is a rare neurological condition that causes cognitive decline, behavioural challenges, and problems with movement. The most common type of FTD is the behavioural variant, although other types also exist, including primary progressive aphasia and the right lobe variant. When using medicines to treat FTD, antidepressants, antipsychotics, and acetylcholinesterase inhibitors may be recommended which target mood changes, agitation, and cognitive decline, respectively. Non-pharmacological treatments, such as physical, behavioural, and speech and language therapy can be beneficial too. To slow the progression of FTD, therapies that reduce the accumulation of tau protein may be effective since this molecule leads to neuronal damage and interrupted chemical signalling in the brain. Finally, palliative care is essential for supporting patients and carers alike towards the end stages of FTD.