Aphasia is a term used to denote impairment in the ability to express one’s self and/or to comprehend language. Our understanding of aphasia has been traditionally based on the study of stroke patients. These observations have identified several regions as building blocks of the language network including Broca’s area, Wernicke’s area, the supramarginal and angular gyri. Similarly, the most commonly used classification of aphasia is also based on observation of stroke patients (summarised in Table 3.2). However, Mesulam argues that this classification is not helpful in understanding the impairment in the language network associated with neurodegenerative disease. This is mainly because damage in stroke is due to abrupt, complete destruction of neurons, and the regional distribution is dependent on blood vessel territory. In contrast, the pathological process in neurodegenerative disorders involves gradual, progressive, and selective loss of cortical neurons, and the preferential spread of pathology is believed to be governed by neuronal connectivity within brain networks. This leads to more complex and subtle dissociations and involves brain plasticity. In addition, the model based on stroke patients does not include the anterior temporal lobe (especially on the left hemisphere) which studies from neurodegenerative disorders have shown to be an important part of the language network.

Primary progressive aphasia (PPA) is the prototype of neurodegenerative conditions where the language network is involved. PPA is a heterogeneous group of clinical syndromes often classified under the umbrella of FTD. Although the classification of PPA is still in evolution, it is currently accepted that there are three clinical variants, Agrammatic/non-fluent variant (nfvPPA), the logopenic variant (lvPPA) and the semantic variant (svPPA).

The deficits in fluency of speech and grammar observed in nfvPPA are similar to those described in patients with stroke affecting Broca’s area. However, nfvPPA patients present in a slowly progressive (as opposed to a sudden) manner. Patients with nfvPPA usually have effortful, halting speech. The breakdown in grammar can include simplification, distorted word order, omissions of function words (such articles and propositions), and poor use of pronouns. These changes extend to writing abilities. Indeed tasks of written language production (such as picture description) are among the most sensitive tasks in early nfvPPA. Other important features of this condition include impaired comprehension of syntactically complex sentences, impaired motor speech production in the form of speech apraxia (described in more detail below), and loss of normal prosody.

Structural and functional imaging in these patients usually shows changes in left posterior fronto-insular region (i.e. inferior frontal gyrus, insula, premotor & supplementary motor areas).

Patients with lvPPA also often have poor fluency of speech associated with the hallmark features of hesitancy due to impaired word retrieval and anomia (difficulty in naming objects while knowing what they are). The fact that grammar is usually intact in these patents is highlighted by Mesulam as an example of the neuropsychological and anatomical dissociation of grammar and fluency observed in neurodegenerative disease but not stroke. In addition, lvPPA patients often have poor comprehension of long unfamiliar sentences lending support to the hypothesis that phonological short-term/working memory impairment is a contributory factor to the deficits observed in this variant. In lvPPA, neuroimaging usually shows structural and functional changes in the left posterior perisylvian tempero-parietal regions (posterior temporal, supramarginal, and angular gyri).

Impaired repetition is a key feature of lvPPA and repetition of long unfamiliar sentences is sensitive in accordance with a phonological working memory impairment. Some impairment in repetition may also be seen in nfvPPA particularly of grammatically complex sentences.

The clinical characteristics of svPPA are described below in the discussion of naming difficulties which form a crucial element of this syndrome.

Difficulties in naming and word retrieval are found across many neurodegenerative diseases and naming abilities are among the most commonly assessed components of language within NPA.

The process of naming objects starts with the initial perception of the object. Impairment at this level is modality specific. For example in visual apperceptive agnosia (discussed in Visuo-spatial skills section) the patient is unable to recognise visual stimuli such as a picture of a key, but can recognise a key via tactile exploration or via auditory modality (e.g. sound of keys jiggling). To exclude modality specific impairment, it is important to test naming using several modalities such as picture naming, or naming by description. After the initial perception, naming an item/object requires three main steps: (1) accessing the semantic knowledge relevant to the object; (2) accessing the lexical representation of that object; and (3) activation of the modality specific processes involved in producing the name of that object (e.g. motor speech production in case of spoken language, see Fig. 3.2). Problems can occur at each of these three levels.

Typical examples of naming difficulties due to impaired access to semantic knowledge can be observed in patients with the semantic variant of PPA (svPPA). Imaging svPPA shows abnormalities in both anterio-lateral temporal lobes (usually left greater than right), and it is now recognized that this region plays a key role in semantic memory. Clinical presentation is often with naming problems which may include semantic errors including replacement of low frequency nouns with high frequency nouns (e.g. “dog” for “boar) and the use of supra-ordinate categories as opposed to their specific exemplars (e.g. “animal” for “cow”). Patients also often suffer from surface alexia (discussed below). Sometimes, these patients may understand complex abstract concepts (e.g. is justice more important than mercy?) but not simpler questions dependent on semantic knowledge of common objects (e.g. do people ride pineapples to get to work?). (Please also refer to Chap.​ 7.)

The second process involved in naming is the modality-independent retrieval of an item’s lexical phonological representation or lemma. This is associated with activation of the occipto-temporal region, the left frontal operculum and insula. Impairments at this level of processing are manifest as an inability to name objects in the context of intact knowledge of what it is. This deficit is termed anomia and usually extends to both speech and writing. Clinically this presents as hesitancy, circumlocutions (e.g. that thing … that you put in food). The individual may describe knowing what they want to say, often feeling that the word is at the “on the tip” of their tongue but being unable “to get the words out”. Paraphasic errors can occur, most frequently phonemic in nature due partial lemma retrieval e.g. “octoput” for “octopus”.

Anomia is often the presenting feature of PPA. Indeed, it is often the most salient and disabling feature of the logopenic variant (lvPPA). However, anomia can be observed in other neurodegenerative disorders affecting the posterior temporal region including AD.

The final process involved in naming takes place once the lemma is retrieved and involves activation of a modality–specific process depending on whether the output is spoken or written language. Either process can be selectively impaired. In case of spoken language, the phonologic representation of the lemma (which includes the correct sounds for producing a specific word and their sequence) is activated and is maintained while motor articulation takes place. This involves complex planning and co-ordination of the muscles that move the tongue, vocal cords, lips and respiratory muscles. Impairment at this level results in errors in sound production which can include erroneous speech sound substitution, insertion, and transpositions. This is termed apraxia of speech and results in the production of spoken words that may have a different meaning (e.g. “horn” for “horse”) or have no meaning at all (e.g. “hammot” for “hammock”). This can be difficult to differentiate from phonemic errors observed in patents with anomia. However, patients with apraxia of speech are often aware of their mistake displaying repeated attempt to correct themselves, while patients with paraphasic errors due to anomia are often unaware of their errors. Apraxia of speech is often associated with nfvPPA.

Impairment in the ability to read (alexia) or write (agraphia) can have a peripheral or central cause.

Peripheral causes are those external to the central language centres. Peripheral causes of alexia are due to breakdown in the transmission of the visual image of the word to the language centres. Causes of peripheral alexia include reduced visual acuity, visual field defects, ocular motor apraxia, saccadic intrusions and hemi-spatial neglect alexia (due to difficulty perceiving one side of the page/word). Disconnection alexia (also called alexia without agraphia) occurs in lesions affecting the left occipital lobe and splenium of the corpus callosum. It is due to disconnection between the remaining intact primary visual cortex (on the right) and the intact language centres (which are in the left hemisphere). It is usually associated with right hemianopia and preserved writing (because of the intact connections between visual cortex and primary motor cortex). Peripheral causes of agraphia are due to problems in the planning or execution of the motor elements of writing, such as those observed in writing apraxia (often associated with dominant parietal lobe lesions), hemi-spatial neglect, and pyramidal, extrapyramidal, or cerebellar motor deficits.

Central alexia and agraphia are caused by damage to the central language regions, and their classification is based on the dual-route theory of reading and writing. This suggests that two separate mechanisms are involved in these processes. Through the lexical route, a skilled reader can visually recognize a “whole word” by sight alone using a mental database (the internal lexicon) without the need to resort to letter-by letter reading. Similarly, when attempting to write the word, pre-stored knowledge is used rather than attempting to spell it letter-by letter. The mental lexicon includes all the words an individual knows including words with irregular pronunciation such “yacht” or “cough”. The second route is the phonological one which is reliant on sounding the word letter by letter using a letter-sound system. This system is used to read/write newly encountered or made up words.

Surface alexia is caused by lack of access to the internal lexicon which forms part of one’s semantic knowledge. Patients can read letter by letter (using the phonological route) but struggle when confronted with irregular words. In these cases, patients tend to regularise words (e.g. reading “pint” as “peent”).

Similarly, surface agraphia is associated with an inability to spell orthographically irregular words due to lack of access to the internal lexicon. These deficits are caused by damage to the antero-lateral temporal lobes (especially on the left) such as that observed in svPPA.

Conversely, patients with phonological alexia or agraphia have a breakdown in phonological system resulting in complete reliance on the internal lexicon. A patient with phonological alexia can read previously encountered regular and irregular familiar words with similar ease but has significant difficulties reading non-words/pseudo-words (e.g. kjud). These deficits are usually associated with lesions affecting the perisylvian region including superior temporal lobe, angular gyrus, and supramarginal gyrus.

Deficits in patients with deep alexia or agraphia are similar to that observed in the phonological subtypes but there is usually co-existing errors (e.g. reading “horse” as “cow”). This type of language abnormality is usually seen in patients with more widespread left hemispheric damage.

Discourse is the term used to describe the complex process of conveying meaning in a concise and accurate manner. These include speech content and non-verbal cues such as prosody (changes in vocal pitch, loudness, and duration to convey emotion or meaning), facial expressions, and gestures. Dysfunctional discourse can cause vague, circumferential speech and poor expression and comprehension of non-verbal clues. The right hemisphere plays a dominant role in the production and comprehension of the different elements involved in effective discourse. Although discourse has rarely been assessed as part of the routine NPA, it can give important clues to the diagnoses and localisation of the cognitive impairment. For instance, poor discourse is commonly reported in patients with bvFTD, who usually have widespread right hemispheric involvement. Table 3.3 includes a summary of commonly used tests of language function.