Alzheimer’s disease - The linguistic deficit in patients with Alzheimer's Disease: is there a s

Alzheimer’s disease is a degenerative illness that affects the central nervous system. It is progressive and it cannot recede. It causes an increasing impairment of cognitive abilities that compromises daily life activities. Patients gradually lose autonomy in their everyday

life. The disease is age-related (Braak & Braak, 1997) as the risk for its onset sharply increases with age.

Alois Alzheimer (1964-1915) first describes the disease in 1906: Auguste D., a 51-year old female patient, shows symptoms of cognitive impairment. First, her memory is disturbed; second, she has unexpected behaviours: e.g., she cannot recognize and use common objects; she is confused and does not know where she is and what day it is; she moves things around with no reasons, among other symptoms. After her death, Alzheimer performs an autopsy and observes remarkable changes in the brain, mainly in the form of atrophy.

After this first case, many more were observed. In 2006, on the occasion of the 100^th anniversary of the first description of the disease, Braak & Del Tredici (2006) and Hyam (2006) describe the brain of patients affected by AD as showing signs of neural loss, tangles and plaques. Their formation is related to the presence of two proteins in the brain:

the Tau and the Beta amyloid proteins. PADs usually produce abnormal amounts of Tau.

The protein is present is the microtubules that transport substances within the brain cells.

When Tau is overproduced, microtubules collapse, twist and form tangles within the cells.

In turn, tangles disrupt intercellular functions. Cells characterized by tangles can survive for a long time (probably decades), but their death is nonetheless premature. When nerve cells die, tangles become extraneuronal and remain in the brain tissue.

Beta amyloids are protein fragments that surround nerve cells. Their function in the brain is not clear yet, but the human metabolism is usually able to break down fragments and eliminate them from the brain. This does not happen in PADs and beta amyloids tend to cluster and form plaques. These cause focal alterations in the synaptic organization.

In addition, neural loss increases to the point that PADs maintain only circa 50% of the neurons of a healthy brain (Gómez-Isla et al., 1997). The pace of the changes described above is very slow. According to Braak & Braak (1997), a small percentage of people (< 20%) develops the first neurofibrillary tangles already in their twenties, although the disease only very rarely manifests itself before the age of 55. Dementia emerges only after the brain has undergone sizeable changes due to neural loss, tangles and plaques (Hyman, 2006).

The distribution of lesions is rather consistent across patients (Braak & Del Tredici, 2006). Damages usually start from the transentorhonal region and subsequently spread to the entorhinal region and the hippocampus. This configuration corresponds to a pre-clinical period of AD, when changes start taking place in the brain, but patients do not show any symptoms (this stage can last decades). Later, damages harm the neo-cortex of the occipito-temporal lobes and eventually reach the frontal area. At this point, PADs start showing signs of mild cognitive impairment (Braak & Del Tredici, 2006).

Ultimately, higher associative areas are also affected and dementia becomes evident through a variety of symptoms.

Spinnler (1996) provides us with an overview of the symptoms of AD at the neuropsychological level. Indeed, PADs can develop forms of impairment in different areas. The first symptom to appear is usually an impairment at the anterograde episodic memory: PADs cannot acquire new memories anymore; for instance, they do not remember new events of their life (e.g., a new person they meet, a place they visit, what they eat, etc.). The impairment usually affects prospective memory too: PADs forget to perform actions or to take part in events scheduled at a precise moment in time (e.g., they forget about taking pills, deadlines, appointments, etc.). Episodic memory related to public events and famous faces also fades away. Progressively, semantic memory is also affected, while procedural memory seems to be spared longer (but not completely).

Autobiographical memory undergoes major disruptions too. In particular, PADs forget memories from more recent years and tend to transpose old memories to the present.

The supervisory attentional system is overall impaired, with negative effects on a variety of cognitive processes, such as: attentional control, inhibitions control, working memory, reasoning, etc.. The pool of executive resources that PADs can count on gradually decreases, such that task execution is quantitatively and qualitatively reduced too.

Also agnosia and apraxia are often associated to the disease. The former consists of the inability of recognizing familiar objects; the latter corresponds to difficulties at planning and carrying out actions and tasks.

All these forms of impairment deprive PADs of their autonomy in every-day life.

For instance, patients become unable to prepare meals, choose appropriate clothes for the

weather, find their way in areas they used to be familiar with, take care of personal hygiene, and much more.

Spinnler (1996) also describes symptoms of the psychiatric kind: emotional distress, depression, mania and hallucinations. Behavioural disorders are often caused by the inability of patients to recognize and accept the circumstances and the location where they are. For instance, anxiety may derive by the fact of not recognizing their own house, which makes them feel in danger and eager to go home (even though they already are in an environment they should be familiar with).

Finally, PADs also suffer from language impairment. The rest of the present chapter deals with it.

But before moving forward, a word of caution is necessary. Alzheimer’s disease can be diagnosed with absolute certainty only through a post-mortem inspection of brain tissues. While alive, patients receive a diagnosis of Probable Alzheimer’s Disease based on three elements. First, the patient must show signs of impairment in at least two of the following domains: memory, executive function, visuospatial performance, language, and behaviour (Carrillo et al., 2013). Second, specialists collect data through clinical tests.

This might include neuroimaging and blood tests. Neuroimaging techniques allow the monitoring of brain changes (i.e., lesions, atrophy). Blood tests allow the individuation of biomarkers for the presence of Beta amyloid and Tau proteins. Third, patients’ medical history and further clinical exams can be used to exclude other causes of dementia (e.g., alcohol abuse, previous head injuries, etc.). These criteria were first established by the National Institute of Neurologic and Communicative Disorders and Stroke (NINCDS) and the Alzheimer’s Disease and Related Disorders Association (ADRDA) in the Eighties, and have more recently been revised by the National Institute on Aging and the Alzheimer’s Association (Carrillo et al., 2013).

For the sake of simplicity and uniformity to previous studies, the present work uses the expression Patients of Alzheimer’s Disease (PAD) for persons who have received a diagnosis based on the criteria listed above. Nonetheless, it should be noted that a post-mortem diagnosis is not available for any of the enrolled patients in the studies presented in Chapters 4, 6 and 7. Unless specified differently, the same modus operandi is valid also for the studies reviewed below.

19 2.2 The linguistic impairment in PADs

The linguistic impairment of PADs is defined as a form of fluent aphasia, which is caused by major disruptions in the semantic and lexical domains. Consequently, their discourse is often described as empty, although their speech is fluent (Cummings et al., 1985;

Nicholas et al., 1985; Murdoch et al., 1987; a.m.o.). The majority of PADs does not show signs of impairment at the phonological and articulatory levels (Chertkow et al., 1989;

Chertkow & Bub, 1990; Patel & Satz, 1994).

Phonological and articulatory difficulties are only rarely detected. For instance, Croot, Hodges, Xuereb & Patterson (2000) report only ten cases of patients with such a form of impairment. By taking into account a variety of factors, the authors manage to point out that the phonological impairment appears more often in PADs that are characterized by at least one of the three following conditions: i) early onset of the disease (before the age of 65), ii) familial Alzheimer (at least one parent was demented), or iii) peculiar distribution of brain damages. As for the latter condition, they found out that patients with phonological impairment are characterized by early damages at the left temporal, parietal and frontal perisylvian areas (Croot et al., 2000:3003), while their hippocampus is relatively spared. This is precisely the opposite pattern of how damages spread in the majority of PADs. Following the results described above, we can assume that phonological and articulatory abilities are usually spared in PADs, unless specific conditions intervene.

Another frequent impairment among PADs is the progressive loss of reading and writing abilities (Platel et al., 1993; Patterson, Graham & Hodges, 1994; Harnish & Neils-Strunjas, 2008). Some authors ascribe it to the lexical loss in AD, especially for languages characterized by a low level of spelling transparency. However, inertia, apraxia and visuo-spatial impairments might also play a relevant role in the disruption of writing and reading skills. As for Italian, Luzzatti, Laiacona & Agazzi (2003) find high variability in writing proficiency across patients and cannot describe a predominant pattern. Overall, writing impairments are often observed, but the issue is far from being set. Given that the impairment is not relevant for the aims of the present study, I will set the problem aside.

In the following section, I will focus my attention on the three most interesting aspects of the linguistic competence of PADs, namely anomia, the dissociation between regular and irregular morphology and sentence processing.

20 2.3 Anomia

Relatives and caregivers often notice a specific difficulty at retrieving lexical items as one of the first symptoms of the disease. PADs increase their use of semantically empty words, like thing, it and do in order to substitute semantically specific nouns and verbs, thus failing at conveying the intended meaning. The deficit is known as anomia.

For instance, the affectionate readers of the British writer Iris Murdoch noticed her incapacity to use vocabulary properly in her final novel Jackson’s Dilemma published in 1995. The book overall received poor reviews from critics. Short after the publication, Murdoch showed clear signs of dementia and was diagnosed with Alzheimer. Garrard et al. (2005) analyse Murdoch’s final novel and compare it to two novels that the author had published earlier in her career. Their aim is to detect early symptoms of the disease in her writing. The lexical analysis they conduct reveals substantial differences between the two novels published earlier in her career and the last one. In particular, the range of vocabulary in use appears much more limited and the selected lexical items are characterized by higher frequency. In other words, the author resorts to a smaller pool of high frequency words in her final work. The observation is highly compatible with the diagnosis received by Murdoch and it represents a clear example of what PADs experience.

Two different sources of impairment could cause anomia. Some authors claim that PADs have difficulties at retrieving the target lexical items they need, despite their presence in the lexicon (Diesfelt, 1985; Nebes, Martin & Horn, 1984). The hypothesis overlooks the possibility of lexical disruption and calls into play factors related to impoverished cognitive abilities, e.g. the fast decay of lexical activation or the unsuccessful inhibition of alternatives.

Other authors claim that anomia is caused by a disruption in the lexical and semantic levels (Chertkow et al., 1989; Chertkow & Bub, 1990; Hodges et al., 1991, 1996; Almor et al., 2009, among others). In this case, it is not possible to retrieve lexical items precisely because they are not available in the lexicon of PADs anymore. Under this view, the disease progressively erases patients’ lexical knowledge.

Overall, studies show that the disruption of semantic knowledge plays a major role in causing anomia in PADs although difficulties at lexical retrieval are also relevant (Chertkow & Bub, 1990; Chertkow et al., 1990).

In the following sections, I present three different kinds of evidence that support the idea of a semantic knowledge loss in PADs: a item-by-item analysis (2.3.1), the relation between naming and knowing (2.3.1.1), and the error analysis (2.3.1.2). I will also consider the factors that influence anomia (2.3.1.3) and the dissociation between nouns and verbs (2.3.1.4). Finally, in section 2.3.2 I review studies that found signs of preserved semantic knowledge activation in PADs.

2.3.1 Semantic knowledge loss in PADs

The study of anomia in PADs developed at the beginning of the ‘80s. As anticipated, the discussion mainly concerns the source of impairment in PADs. In particular, authors evaluate the status of the semantic knowledge in PADs. Nebes, Martin & Horn (1984) and Diesfeldt (1985) initially claim that the semantic knowledge of demented patients is intact and that their anomia is the manifestation of a retrieval impairment. However, in the same years, Bayles & Tomoeda (1983) and Huff, Corkin & Growdon (1986) support the exact opposite, by pointing out an impairment at the semantic level, with major consequences on the lexicon. In particular, Huff, Corkin & Growdon (1986) notice that patients tend to make mistakes on the same nouns across different tasks and suggest that anomia should be studied through item-by-item analyses.

Starting from that idea, Chertkow, Bub and Seidenberg (1989) collect sound data in favour of the semantic impairment hypothesis. They use a battery of tests based on a list of 150 nouns: all selected nouns refer to concrete objects retrieved from different semantic categories (fruits, vegetables, animals and tools, among others). Six patients with a diagnosis of probable Alzheimer’s disease, who had previously undergone reading and visual tests in order to discard perceptual disorders as possible confounding factors, complete a naming and a word-to-picture matching task. As expected, their performance on both tasks is poorer in comparison to the one of healthy elderly speakers. Authors also compare data from the two tests and conduct an item-by-item analysis: results reveal that most patients either perform always correctly or always wrong on the same item in both tasks. In other words, if patients are able to match a word to the correct picture, they are also able to name the same object. In contrast, if patients fail the first task, they will most probably fail also the second one. The number of items on which patients perform well in one task, but wrong in the other one, is very narrow. The individual consistency across

tasks in patients’ performance suggests that lexical items can be either spared or disrupted in the lexicon of PADs. Successful activation seems not to depend on the activation route:

both visual and oral prompting lead to equivalent rates of successful retrieval.

In order to corroborate their results, Chertkow et al. (1989) repeat the naming test and ask patients twelve forced–choice questions concerning the attributes, the superordinate category and the functional characteristics of each element (e.g., for the word scissors: 'Is the tip made of metal or wood? ', 'Is it a tool or clothing? ', 'Do you cut things with it or lift with it?', etc.). Whenever a participant can answer correctly to at least nine questions, the item is classified as 'intact' in the subject’s lexicon, otherwise it is classified as 'degraded'. A cross comparison of results confirms patients’ consistency:

intact items are usually named correctly and recognized correctly in a sentence-to-picture matching task. In contrast, degraded nouns correspond to lexical items on which patients had failed both previous tests.

In a follow-up study, Chertkow & Bub (1990) enlarge their experimental group up to ten PADs and enrich their battery with new tasks: semantic cue, verbal fluency and on-line semantic priming. The semantic cue technique consists in helping participants when they cannot name a picture by providing a semantic information (e.g. 'it is similar to a tiger' when the participant cannot name the picture of a lion). The procedure is effective only with words which patients had previously shown to have intact knowledge of¹. For 'degraded' items, semantic cues are of no help for lexical retrieval.

Also results from verbal fluency pair the data presented so far: patients overall produce only 40% of the words² recalled by controls. Moreover, in the verbal fluency task they (almost) never spontaneously produce words that they had not been able to name previously. However, in verbal fluency tasks they do not recall all words that are otherwise classified as correct or intact in other tasks. In other words, they do not succeed at retrieving all the intact nouns that they had completed successfully in previous tasks.

1 As describe for Chertkow et al. (1989), 'intact knowledge' is defined in the study as the capacity of answering to at least 9 out of 12 questions concerning the object. All participants in Chertkow & Bub (1990) undergo this test in a separate session from the one in which naming and semantic cues are administered.

2 The mean number of words recalled in one minute highly varies across the prompted semantic category.

PADs are sharply more successful at retrieving nouns related to body parts and clothes, most probably because they use the visual cues in the context. In contrast, they make many mistakes on the vegetable and fruit categories, by mixing up items across the two.

Finally, the semantic priming test is performed through a lexical decision task.

Participants see a noun on the screen and must decide whether it is an existing word or not. Either a semantically related noun, an unrelated one or a pseudo-word precedes each experimental noun. Reaction times are recorded: patients are faster at answering to real words ('nail') when these follow semantically related nouns ('hammer'), than when they follow semantically unrelated nouns ('horse'). Authors conclude that semantic priming is spared in PADs, despite generalized slower reaction times.

In sum, Chertkow et al. (1989) and Chertkow & Bub (1990) succeed at showing that an item-by-item consistency across tasks exists in the performance of PADs. This can be explained in light of a semantic knowledge impairment. According to the author, lexical items are either intact in the lexicon, and can therefore be retrieved through different routes, or they are degraded. In the second case, the retrieval is never successful, independently of the technique in use. However, in the light of results from the last two tasks, namely verbal fluency and semantic priming, Chertkow & Bub (1990) must recognize that some retrieval difficulties are also at play. Verbal fluency shows that PADs cannot recall all the intact nouns they can count on in their lexicon, thus clearly showing an impairment in the retrieval process. Finally, the presence of enhanced priming effects in PADs indirectly speaks against the hypothesis of a semantic impairment, as it shows that the semantic knowledge network makes lexical activation flow through related items.

Authors explain the priming effect by assuming an asymmetry between automatic and explicit activation. Naming tasks, word-to-picture matching and semantic probe questions all require explicit activation of lexical items, while semantic priming favours automatic (thus implicit) lexical activation. The assumed asymmetry speaks in favour of a lexical retrieval impairment, which could play a role along with semantic impairment.

2.3.1.1 Naming & Knowing

In order to strengthen the hypothesis of a semantic deficit, it is useful to verify the information that patients retain for objects they can name, and for objects they cannot name anymore. For this purpose, Hodges, Patterson, Graham & Dawson (1996) enrol 51 PADs in two different tests: a picture naming task and a definition task. In the first task,

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