The doctor asks: 'Can you tell me a little about your background?'
The patient replies: 'That … I … ing- eng- engineer … long time.'
This is the most complex variant of primary progressive aphasia and is dominated by agrammatism and/or apraxia of speech.
Agrammatism means that the patient uses short sentences that lack function words and inflections. Subtle difficulties with grammar may be more obvious in writing than in speech. Grammatical comprehension is also impaired, particularly for long or complex sentences, negations, and passive constructions. Word comprehension and object knowledge, however, remain intact.
Apraxia of speech refers to difficulties with speech flow and pronunciation of speech sounds (12). Speech is strained and halting, with varying errors in speech sounds. Patients and relatives sometimes describe this as 'stuttering'. The patient tries several times to say the same word, with different pronunciation errors each time. Apraxia of speech also affects prosody (sentence melody) and word stress, such that speech appears monotonous ('robotic') or incorrectly stressed. The patient may have comorbid oral apraxia, meaning he or she is unable to perform actions such as smacking the lips, clicking the tongue, or coughing or blowing on command.
Patients who have apraxia of speech without agrammatism do not, strictly speaking, have aphasia, and it has been proposed that this should instead be classified as a separate diagnostic entity, 'primary progressive apraxia of speech' (4, 7).
The non-fluent/agrammatic variant of aphasia shows greater variation in terms of underlying pathology and further disease progression than the other variants. The most common underlying pathology is frontotemporal lobar degeneration with tau inclusions (52 %), followed by amyloid pathology of the Alzheimer's type (25 %) and TDP-43 pathology (19 %) (8). Some patients develop behavioural variant frontotemporal dementia, while others develop Parkinson-plus syndromes with general motor disturbances (such as corticobasal syndrome). Progression to Parkinson-plus syndromes is more common when the clinical picture is dominated by apraxia of speech (4).
Patients have atrophy and hypometabolism in the posterior frontal lobe, particularly in the dominant hemisphere (Figure 1, Table 2) (3, 8). Broca's area is usually affected. If the patient has apraxia of speech, the premotor and motor cortex may also be affected (4). Brain MRI has low sensitivity (29 %), but better specificity (91 %), whereas brain FDG-PET is reported to have 67 % sensitivity and 92 % specificity for the diagnosis (8). The pattern of dementia markers in cerebrospinal fluid varies depending on the underlying neuropathology.