Shrinkage of language-related brain regions
Primary progressive aphasia (PPA) encompasses a range of disorders where disturbance of speech and/or language is the earliest and most significant problem.
As the name suggests, forms of PPA are progressive over time and not caused by isolated brain insults like strokes, tumours or traumatic brain injury. Several underlying neurodegenerative disease processes can lead to PPA.
PPA is associated with progressive shrinkage in language-related brain regions. Depending on the subtype, this may involve a buildup of:
- abnormal tau or TDP-43 protein (related to frontotemporal dementia)
- amyloid and tau (when presenting as atypical Alzheimer’s disease).
What is primary progressive aphasia?
PPA is a condition in which language difficulty is the earliest and most prominent symptom. For a diagnosis of PPA, language must remain the main problem for at least the first two years, with other thinking skills relatively preserved during this time.
There are three recognised subtypes, each with a different pattern of language difficulty:
- logopenic progressive aphasia – difficulty finding words and repeating phrases or sentences, with word meaning and grammar relatively preserved. Speech is often hesitant, with frequent pauses as the speaker searches for words.
- progressive non-fluent aphasia – effortful, halting speech, with difficulty forming grammatically correct sentences. Speech may sound simplified or telegraphic, and word pronunciation can become difficult.
- semantic dementia – progressive loss of word and object knowledge, even though speech remains fluent. A person may use vague terms (eg ‘thing’ or ‘animal’) instead of specific words (eg ‘cat’) or lose the ability to recognise familiar objects.
Over time, PPA typically affects:
- word-finding, word meaning or grammar (depending on subtype)
- understanding spoken or written language
- reading and writing
- memory, behaviour and other thinking or daily living skills may also become affected later in the condition.
What happens in the brain?
PPA is associated with progressive shrinkage in the parts of the brain responsible for language, usually on the left side of the brain.
The underlying protein change depends on the subtype:
- logopenic progressive aphasia is usually associated with a build-up of amyloid and tau, the same protein changes seen in Alzheimer’s disease
- semantic dementia and progressive non-fluent aphasia are usually associated with a build-up of abnormal tau or TDP-43 protein, the same protein changes seen in frontotemporal dementia.
This means PPA is not a single disease, but a language-led way that different underlying brain diseases can first present.
What increases the risk of primary progressive aphasia?
Because PPA can arise from more than one underlying disease process, its risk factors largely overlap with those of the condition driving it – either frontotemporal dementia or Alzheimer’s disease – rather than forming a distinct, separate risk profile.
Factors that can’t be changed include:
- age – PPA most often presents in people in their 50s and 60s, making it one of the recognised causes of young-onset dementia, though it can occur at other ages too
- family history and genetics – where PPA is caused by underlying frontotemporal dementia, a family history and specific genetic changes (such as in the C9orf72, MAPT or GRN genes) are identified in a proportion of cases. Where PPA is caused by underlying Alzheimer’s disease, family history plays a smaller but still present role.
- underlying disease subtype – since semantic dementia and progressive non-fluent aphasia are usually linked to frontotemporal lobar degeneration, while the logopenic variant is usually linked to Alzheimer’s disease, the specific risk profile differs depending on which subtype is present.
Factors that may be modifiable are not well established for PPA specifically, given it is a less common condition and research into its risk factors is more limited than for Alzheimer’s disease or vascular dementia. General brain health measures (physical activity, cardiovascular health, cognitive engagement) are reasonable to encourage, consistent with broader dementia risk-reduction advice, but have not been specifically shown to reduce PPA risk.
Because of the genetic overlap with frontotemporal dementia in some cases, discussing family history with your GP or specialist is worthwhile, particularly if there is a strong family history of dementia or PPA.
Common patient questions
Not exactly. Two of the three PPA subtypes (semantic dementia and progressive non-fluent aphasia) are usually caused by the same underlying protein changes as frontotemporal dementia. The third subtype (logopenic progressive aphasia) is usually caused by the same protein changes as Alzheimer’s disease.
All three are grouped under the name PPA because they share a similar language-led pattern of symptoms.
Not usually, at least in the first two years. Memory and other thinking skills are often preserved early on, which is part of what defines PPA. Memory difficulties can develop later as the underlying condition progresses.
Yes, PPA often presents in people in their 50s and 60s, and is one of the recognised causes of young-onset dementia.
It depends on the underlying cause. Where PPA is linked to frontotemporal dementia, genetic factors play a larger role than in typical Alzheimer’s disease. Where it’s linked to Alzheimer’s disease, inheritance patterns are generally similar to typical Alzheimer’s disease, meaning most cases are not directly inherited.