Introduction

Primary Progressive Aphasia (PPA) is a neurological syndrome that affects an individual's ability to communicate. It is a degenerative disorder so symptoms will worsen over time as the syndrome develops. 

There are three types of PPA: semantic dementia, progressive non-fluent aphasia, and logopenic aphasia. Symptoms vary between individuals but often manifest in complications with word-finding, word usage, word order, word comprehension, and spelling. 

In general, PPA is diagnosed in people under 65 years old and is classified as a type of frontotemporal dementia. The loss of tissue in the brain is called atrophy. Atrophy that affects the frontal, temporal or parietal lobes can significantly impact the areas of the brain responsible for speech and language. If we think of the parts of the brain responsible for speech and language as a dictionary, an individual with aphasia would have some of the pages disordered, damaged, and missing. 

In this article, we will look at the causes and symptoms of PPA and the current treatment and management available.

Causes of PPA

Neurological factors

Research shows that the vast majority of PPA patients present with tau-positive, ubiquitin/TDP43- positive frontotemporal lobar degeneration (FTLD) or Alzheimer’s disease (AD).¹ Abnormal proteins from AD or FTLD attack the regions of the brain associated with language, leading to the symptoms experienced in PPA. It is estimated that in 60-70% of cases of PPA, FTLD is responsible. Whereas, AD causes 30-40% of cases. 

Semantic dementia has been linked to FTLD and presents itself with a loss of vocabulary and single-word comprehension difficulties.²

Progressive non-fluent aphasia has been associated with tau-positive pathology and results in difficulty producing speech and impaired structuring of speech.²

AD is most commonly associated with logopenic aphasia and patients will struggle with word retrieval and phonological assembly.²

Genetics

Advancements in PPA genetics have identified a possible genetic component associated with the risk of developing PPA. PPA can be inherited in an autosomal dominant pattern.³ The mutation affects the gene encoding a protein called progranulin (PGRN) and reduces the level of functional PGRN. 

In the body, PGRN is most active in cells that divide rapidly and aids in the growth, division and survival of these cells.⁴ Therefore, reduced PGRN activity may result in the degeneration of brain tissue in the regions linked to speech and language. 

Other gene mutations, such as C9orf72 gene expansions and MAPT mutations may also be linked to an increased risk of PPA.⁵

Overall, if other members of your family have suffered from PPA, you are more likely to be at risk of developing it. 

Cortical atrophy

Evidence from anatomical studies of PPA has resulted in a set of distinguishable patterns of cortical atrophy in the three subtypes:⁶

• Semantic dementia: Greatest atrophy to the left anterior temporal lobe
• Progressive non-fluent aphasia: Maximal atrophy to left frontal and insular regions
• Logopenic aphasia: Peak atrophy to left posterior perisylvian temporal and parietal cortex

Symptoms of PPA

There are a range of symptoms associated with the different subtypes of PPA. These include symptoms related to language production, language comprehension, and cognitive and behavioural changes. 

Language Impairments

Anomia

Individuals have difficulty finding the right words to say, although they understand the meaning of words. This is a common symptom of logopenic aphasia. 

Impaired grammar and syntax

Their sentences are often grammatically incorrect with inappropriate word use. Patients with the non-fluent variant of PPA often exhibit this symptom. 

Reduced fluency

Speech is halting and requires more effort. Individuals know what they want to say but struggle to get the words to flow. Commonly seen in the non-fluent variant. 

Spoken or written language comprehension difficulty

Individuals won’t be able to understand the meaning of common words. For example, they may forget simple words and the names of familiar, everyday objects. Individuals displaying the semantic variant of PPA often present with this symptom. 

Cognitive and behavioural changes

Memory problems

As the disease progresses, individuals may lose their ability to recognise people and objects, use household appliances, and forget conversations that have been held.

Social withdrawal

Difficulties in understanding social situations can often make individuals withdraw from these interactions. 

Personality changes

Sudden mood changes are also exhibited in PPA. 

Treatment and management strategies

Unfortunately, no cure is available for PPA. The treatment and management strategies are mainly aimed at improving an individual’s ability to communicate. 

Speech therapy

Individualised speech and language training programmes have been shown to be helpful for patients with PPA. These programmes mostly aim to improve word retrieval, fluency, and grammar difficulties. A 2021 study demonstrated the positive effect of speech and language therapy on managing individuals with PPA.⁷ 

Medications 

Pharmacological interventions may be used to manage symptoms, not related to language, present in PPA. Antidepressants, antipsychotics, and antianxiety medication have shown some promise in managing the behavioural changes exhibited in PPA. 

Cholinesterase inhibitors (ChEIs) are currently used to prevent the loss of cholinergic neurones in AD. As logopenic aphasia is associated with AD, ChEIs may be able to improve the symptoms of this variant of PPA.⁸

Supportive care and strategies for communication

Here are some useful tips to help PPA sufferers communicate better:

• Using gestures, tone of voice, and facial expressions may be useful in helping those with the semantic variety understand more easily
• Creating a phrase book including common words and pictures
• Focusing on priority vocabulary and what is important to the patient

Research and future direction

A deeper understanding of the pathophysiology of PPA is required to improve the diagnosis and treatment. Advances in genetic research may offer a breakthrough for neurologists in understanding the pathology of PPA. State-of-the-art imaging techniques have significantly improved and will continue to improve the adequate diagnosis of PAA. 

FAQs

What is PPA?

PPA is a neurodegenerative disorder resulting in the progressive loss of speech and language abilities.

What causes PPA? 

The loss of brain tissue in the frontal and temporal lobes of the brain leads to the symptoms of PPA. Abnormal protein accumulation is a potential cause of the loss of brain tissue. Genetic mutations may be responsible for the abnormal protein levels.

Does PPA run in families?

Yes, studies have shown a strong familial link to the risk of developing PPA. Therefore, if you have a family history of PPA it is more likely that you will develop the disorder. 

What are the symptoms of PPA?

• Word-finding difficulty
• Lack of fluency
• Halted speech
• Incorrect grammar and spelling
• Lack of comprehension of common words
• Difficulty following conversations
• Changes in behaviour (i.e., frustration and depression)

Is there a cure for PPA?

Unfortunately, there is no cure for PPA. Speech therapy can be used to help aid in communication issues. Behavioural symptoms, such as depression, can be treated symptomatically and pharmacologically.

Summary

The breakdown of communication can be extremely difficult for an individual and their loved ones. PPA is a neurodegenerative disorder that affects one's ability to speak and understand speech. There are three subtypes of PPA which have their own set of symptoms with some overlap between the subtypes.

Scientists believe there is a strong genetic connection linked to the risk of developing PPA. Speech therapy, medication and supportive care strategies are the current frontline methods used in the management of PPA. If you are noticing changes in your (or your loved ones) speech and language ability, contact your GP and voice your concerns.