Preservation of Musical Memory Throughout the Progression of Alzheimer’s Disease? Toward a Reconciliation of Theoretical,Clinical,and Neuroimaging Evidence

Semantic Musical Memory

Episodic Musical Memory

Episodic Musical Memory Versus Episodic Verbal Memory

Some authors also investigated the nature of episodic verbal memory in relationship to episodic musical memory in patients at the mild stage of AD. They hypothesized that if episodic musical memory is often affected at a very early stage of the pathogenesis episodic verbal memory should also be. However, if this is the case, are they truly dissociable? To differentiate episodic verbal and episodic musical memories, Ménard and Belleville [47] carried out both verbal and musical recollection tasks in parallel paradigms to determine if either degrade differently in mild AD patients [47]. In the learning stage, patients memorized novel pseudo words (two syllables each) and novel melodies (lasting 10 seconds each). During the testing stage, a randomly assorted mix verbal and musical targets and distractors, stimuli were presented to patients (tests being performed separately). No significant difference was found between AD patients’ episodic verbal and musical memory. Even though both cognitive abilities were equally impaired in mild AD patients, their underlying mechanism may be independent since no significant correlation was found between AD patients’ performance in each task.

Semantic Musical Memory Versus Semantic Verbal Memory

Cuddy et al. proposed a battery of tests aiming at dissociating semantic musical memory and semantic verbal memory [40]. The first task aimed at evaluating semantic musical memory: after presenting an assortment of familiar and novel melodies, patients had to judge whether or not each melody was familiar. The second task aimed at evaluating semantic verbal memory, and followed the same principle, but with familiar and novel lyrics from songs instead. The third task evaluated semantic musical memory: after presenting a group of familiar melodies, patients had to determine whether each melody was correct or not (some were altered by one pitch, therefore not respecting the key). The fourth task evaluated semantic verbal memory, and was structurally the same as the third task, but with familiar lyrics. The fifth task tested the association between semantic verbal and semantic musical memory: patients had to attempt to sing the lyrics of the melodies they judged familiar in the second task, whether each melody was correct or not. The sixth task also aimed at evaluating verbal semantic memory, and required patients to complete famous proverbs. Tasks four and six were the only ones to test verbal semantic memory (besides task two which was heavily dependent on musical memory) and for which AD patients at a mild stage of the disease performed statistically below the range of controls. These results from Cuddy et al. suggest that musical memory may be spared at mild stage of the disease [40].

The study by Johnson et al. also sought to dissociate semantic musical memory from semantic verbal memory, and might have done so even more accurately [38]. The first recognition task required AD patients to determine if presented familiar melodies were correct, or if they contained a single pitch alteration. Although AD patients did perform slightly worse than controls on this task, no significant difference was found. It is also crucial to note that half of the distorted pitches in the first task of Johnson et al. [38] respected the key signature of the overall piece. That means that AD patients successfully committed to long-term semantic memory a specific melody, and did not use their general knowledge and musical intuition for Western Music harmonic structures to guide their decisions. This experimental paradigm contrasts with that of Cuddy et al. [40], who intentionally used words and tunes that do not respect grammar or tonal conventions in their distorted lyrics and tunes task. In the latter study, patients may have been recruiting cognitive abilities responsible for the intuitive and abstract laws and rules of grammar and music, rather than accessing the actual verbal or musical memory for the lyrics or melodies. The second recognition task of Johnson et al. [38] tested semantic verbal memory, asking patients to recall the title of the familiar melodies that were played. Patients performed statistically much worse on this semantic verbal memory task than they did on the semantic musical memory task, confirming again a possible dissociation. Kerer et al. [42] supplemented the findings of Johnson et al. [38] with another paradigm that addressed both semantic verbal and musical memories. Patients were first presented with a familiar melody. They were then asked to provide the name of the piece and whether one note in the melody had been altered in pitch, and finally if the piece was instrumental or vocal. Patients’ ability to recall the names of the pieces was worse than controls. Interestingly, patients’ ability to detect pitch errors in familiar melodies and to identify whether the piece was instrumental or vocal significantly exceeded that of controls. The authors hypothesized that AD patients’ superior performance was due to their focus on the musical tasks, as opposed to being unconsciously distracted by other verbal memories or associations that might have been evoked by the music (reflecting lost associative or multitasking abilities in AD patients). This argues in favor of two independents cognitive processes responsible for semantic verbal and musical memories, which could interact.

Despite their ultimate goal of stimulating recollection of autobiographical memories through associated musical memories, Basaglia-Pappas et al. [43] built on the semantic musical memory studies of Johnson et al. [38] and Kerer et al. [42]. AD patients were asked to hum a familiar song whose title was given. They performed significantly worse than controls. However, when patients were asked to identify from a fixed number of melodies the ones that were presented in the previous task, AD patients performed as well as controls, suggesting that AD patients’ verbal semantic memory retrieval may be impaired, whereas semantic musical memory would be preserved.

Overall, despite some variability, current results suggest that regardless of the method used, mild stage AD patients show classic deficits of episodic musical memory, but yet a partial preservation of semantic musical memory [57]. Studies also show dissociation between semantic verbal memory and semantic musical memory, effectively providing behavioral evidence that these two cognitive functions may be dissociated.

Procedural Musical Memory

One of the first case studies on long-term musical memory in moderate stage AD patients (16≤MMSE≤20; Table 2) was led by Beatty et al. on a professional jazz trombonist who met criteria for probable AD [58]. Two semantic verbal memory tests were conducted: 1) after explicit presentation of famous Christmas songs, the patient was asked to recall as many titles as he could; 2) the same task was performed using famous Dixieland jazz compositions. As expected, he performed well below the level of controls for both tasks. However, he obtains remarkable results on procedural musical memory task. Two audiotapes of the patient playing with his jazz band, one recorded in the late 1960 s (well before the onset of the AD pathogenesis) and one in 1993 (a year after his diagnosis), were played to a group of controls who were asked to judge the quality of his musical ability. Despite his hampered performance on the semantic verbal memory tasks (scoring 20 on the MMSE), and his disabilities to tie a necktie or put on his jacket (signs of serious procedural memory deficits for daily actions), he preserved his instrumental skills. That is, the listeners were not able to differentiate the quality of his performances. It is also worth noting that before his death, the patient required assistance with all daily living activities, yet when given a trombone, could still play a few notes and even tunes.

Semantic Versus Episodic Musical Memory

Bartlett et al. [59] performed the first battery of experiments which successfully dissociated episodic musical memory (first two experiments presented below) and semantic musical memory (third experiment below) in moderate stage AD patients [59]. The first experiment explicitly required patients to listen to a series of well-known familiar melodies. During the testing stage, a random assortment of familiar melodies they had just heard and familiar melodies that they had not heard were presented. Their task was to determine which familiar melodies had just been presented. The second experiment mirrored the first, but with completely novel melodies instead. Patients showed significantly lower performance for both experiments compared to controls, indicating an impaired episodic musical memory. The first experiment, on familiar melodies also garnered a statistically significant number of type I errors (false positive, or false alarms), suggesting that AD patients were wrongly guessing and assuming that the familiar tunes they were hearing had been presented in the experiment (despite being previously familiar well-known melodies). This might suggest that patients’ responses in the first experiment were elicited from a sense of familiarity for the musical excerpts, rather than a consciously controlled episodically driven memory retrieval process. The third experiment combined all previously played melodies (familiar and novel) into a random assortment. Patients were asked to determine which melodies were familiar (heard before the experiment) and which were novel (heard for the first time during the experiment). They were then asked to name the songs they deemed familiar to test their semantic verbal memories. A slight deficit in AD patients’ ability to successfully detect familiar melodies was observed. Patients also performed significantly worse in the semantic verbal memory test than for the semantic musical memory, further suggesting a behavioral dissociation between verbal and musical semantic memories. This is to our knowledge the first study to suggest dissociation between partial preservation of musical semantic memory and verbal semantic memory in late stage AD.

Samson et al. further extended the work done by Bartlett et al. to include a 24-hour retention period [62]. A preliminary task tested patients’ ability to judge familiarity for melodies: patients were presented with an assortment of familiar and unfamiliar melodies, and asked to determine which were familiar to them. No difference between patients and controls was observed, showing again preserved retrograde semantic musical memory. The first task presented the same mixture of familiar and novel melodies as in the preliminary task, but intertwined them with new familiar and new novel melodies (that they had not previously encountered in this battery of tests, hereafter foils). Patients were asked to determine which melodies (familiar or novel) had been presented in the preliminary task. The second task was the same as the first one, but the melodies were shuffled and new foils were included. The third task (identical in structure to the first and second tasks) was performed 24 hours after the second task, melodies were reshuffled and new foils were again included. For the three tasks, patients showed significantly lower recognition ability (lower hit rates and higher false alarm rates) than controls, albeit significantly above the level of chance confirming that the task was not too hard for the patients but rather that they suffer from impaired episodic musical memory. AD patients were not able to improve their performance over the course of the tasks, showing impaired episodic musical memory ability. The authors suggest that learning and remembering difficulties may underline patients’ inability to internalize prior knowledge relevant to the task. They claim that this is evidenced by the large amount of false alarms (type I errors) despite the patients receiving a continuous feedback on the accuracy of each response. This study clearly shows a dissociation between successful access to the Music Recognition Units (retrograde semantic musical memory) and impaired ability to retain spatio-temporal details of musical information (episodic musical memory) in moderate stage AD patients. Using the same paradigm as they did for mild stage AD patients, Moussard et al. [46] have highlighted with moderate AD patients an impairment on episodic musical memory only when explicit learning phase was proposed during episodic musical memory recollection tasks. Actually, they have shown a significant lower performance compared to controls on explicitly learned episodic musical memories [46]. However, patients showed no significant difference when compared to controls on incidentally learned musical episodic memories.

Procedural Musical Memory

Following up this methodology, Beatty et al. developed an innovative paradigm consisting of repeating a set of musical memory assessments over the course of three years, and documenting individual performance evolution of a female pianist with AD [64]. The assessment comprised various cognitive functions tests including language, attention, sequencing, and semantic verbal memory. A significant decline for the patient compared to controls over time was observed. To test her musical procedural memory, she was first recorded while playing a collection of familiar tunes. These recording were then played to impartial controls who empirically and numerically judged her performance. Interestingly, her piano playing skill showed only a slight (non-significant) decline in overall rated quality. This result demonstrates again a preserved ability to store and retrieve previously encoded musical procedural memories. Note, however, that the patient was unable to learn new songs, showing impairment in explicit encoding of new procedural musical memories.

In contrast, Cowles et al. carried out a case on a severe female AD former violinist patient who was still able to learn new pieces [69]. Prior to the musical procedural memory test, the patient carried out an extensive battery testing general memory, language, visuospatial construction, and attention abilities. As expected, he performed on average worse than controls. However, after a training period, the patient was not only able to play a newly learned melody from the sheet music, but also to retain significant portions of the melody for at least 10 minutes. With prompting from her teacher, the patient was nearly able to finish the piece from memory. With such a severe AD form and considering her impairments with other cognitive tasks (not to mention the difficulty of this musical task for non-musicians), her ability was remarkable. This case study clearly shows patient’s preserved ability to encode novel musical procedural memories. Fornazzari et al. published a similar case study on a severe stage AD patient with preserved ability to explicitly encode novel procedural musical memories: despite several key and pitch inaccuracies, the patient successfully learned a new melody on the piano [68].

Semantic Musical Memory

Semantic Musical Memory Versus Semantic Verbal Memory

Cuddy et al. [40] reported the latest group study on severe AD patients’ musical memory, showing varying results depending on the nature of the memory tasks. Patients performed the same tasks as those from the mild and moderate stage groups. Their performance on unfamiliar words or melodies judgment task, or on production of unfamiliar words, were significantly inferior to the controls, whereas performance for familiar words or melodies were significantly better, despite not being as high as mild and moderate stage AD patients.

These observations suggest that some long-term musical memory abilities, including semantic and procedural musical memories, are resistant to the AD pathology, as opposed to episodic musical memory or verbal semantic memory. Nevertheless, being able to use procedural memory to play an instrument at the later AD stages is not that surprising considering the areas of the brain that are at stake in playing a piece learned by heart (inferior-posterior areas such as basal ganglia or cerebellum). Indeed, these areas are well preserved even at these stages. However, results on anterograde semantic memory allow thinking that when a patient feels familiar with a recently learned musical excerpt or can reproduce a newly learned melody on an instrument, a new representation has been successfully encoded, stored, and retrieved from long-term musical memory. What, therefore, are the neural substrates underpinning these new representations? Furthermore, why can some long-term musical memories, as opposed to other kinds of musical memories and long-term verbal memories, be successfully formed and retrieved? The following brain imaging paradigms might provide pieces of an answer and clarify the neural components responsible for the preserved and lost musical memory processes in AD patients across all stages of the pathology.

Contribution of Neuroimaging Results

Both structural and functional neuroimaging data could complement the conceptual and behavioral mechanisms underpinning musical memory. To our knowledge, any research had directly studied the functional activations of musical memories on AD patients until an advanced stage. By comparing the AD anatomic pathogenesis (for review, see Veitch et al. [52]) with the functional activations of various long-term musical memories, we should be able to explain the peculiar pathological progression of long-term musical memories in AD patients across all stages. An important literature exists concerning the exploration of musical cognition [18 , 70–74] with neuroimaging methods. However, experimental works specifically focusing on musical memory are much scarcer [75 –77] and mainly done in healthy subjects. We emphasize the complementary results of four neuroimaging studies allowing assumptions on the underlying cerebral substrates organization of episodic and semantic memories and verbal and musical memories and their dissociations.

First, the brain imaging study led by Platel et al. provides a possible neural explanation uncovering the dissociation between semantic and episodic musical memories [20]. They proposed at healthy non-musician subjects two tasks (one episodic and one semantic musical memory task) in the PET scan. The authors highlighted activation of bilateral middle and superior frontal gyri and the precuneus for the episodic musical memory task, while the semantic musical memory task recruited bilateral medial and orbital frontal cortex, the left angular gyrus, and the left anterior middle temporal gyrus. These activations are consistent with the idea of one specific brain network existing for musical memory, rather than specialized networks engaged for each kind of long-term musical memory. Schwindt and Black follow up this experiment with a meta-analysis, and find similar activated neural networks [78].

The conceptual and behavioral dissociation between semantic musical verbal memories discussed in aforementioned studies is another important distinction, between language and music, which has gathered significant interest in the field [79 –83]. This led Isabelle Peretz [16, 17] to develop a cognitive model showing that semantic musical memory, by recruiting bilateral temporal and prefrontal lobe activations, engages a much larger neural network than verbal semantic memory does. As Isabelle Peretz suggests, we argue that this distributed nature of the substrates that are responsible for musical semantic memory across brain structures could be one factors explaining AD preserved semantic musical memory, in contrast to the vulnerability of their semantic verbal memories. Johnson et al. [38] confirmed this claim. They performed voxel-based morphometry (hereafter VBM) on all subject groups. The authors found a positive correlation between musical semantic memory performance (familiar melody pitch error detection task) and volume of the bilateral inferior and superior temporal gyri, and bilateral temporal poles. However, higher performance on the verbal semantic memory test (title recall task) correlated with greater volume in the bilateral inferior and middle temporal gyri, bilateral temporal poles, right frontal cortex, right inferior frontal gyrus (pars triangularis), and the hippocampus. Although some regions do overlap, a certain anatomical dissociation exists, further supporting the conceptual and behavioral dissociation between semantic musical memory and semantic verbal memory.

Groussard et al. propose a paradigm that dissociates the neural substrates of musical semantic memory and verbal semantic memory with functional magnetic resonance imaging (fMRI) [84]. Based on four tasks, neural imaging revealed for healthy non-musicians participants that both semantic verbal and semantic musical processes recruited the left inferior frontal and posterior middle temporal cortices. Semantic musical material however recruited the superior temporal gyrus bilaterally, while semantic verbal material the left middle and inferior gyri (Fig. 2). Thus, the implication of a larger and bilateral network for musical semantic memory is a possible explanation for their relative preservation in patients. These particular structures recruited during the semantic musical memory tasks are most of the time those that are later reached by the AD pathology [85].

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Fig.2

Results obtained by Groussard et al. [85]. Activation in the musical semantic contrast (in red), verbal semantic contrast (in blue) and conjunction analysis (in yellow) of musical semantic versus musical reference and verbal semantic versus verbal reference.

Jacobsen et al. [86] have proposed to compare the functional activation of healthy controls participants with patients suffering from cerebral atrophy in a long-term semantic musical memory task, to investigate brain areas responsible for long-term semantic musical memory and thus to understand why this function is preserved even in advanced AD patients. One hour before the 7T fMRI brain scanning, controls were presented with a series of unfamiliar melodies. During the scan, they were presented with an assortment of three kinds of melodies: familiar, recently heard, and completely novel. MRI scan subtraction of the recently learned music with the familiar music allowed to conclude that “semantic” musical memory task recruits significant activation in the caudal anterior cingulate and the ventral pre-supplementary motor areas. Neuroimaging of AD patients revealed a grey matter atrophy in the temporal, inferior parietal cortex, and the precuneus. No overlap was found between atrophied brain regions in AD patients and those associated with the musical recognition task in controls. In other words, this study provides a possible physiological explanation for the partial preservation of semantic musical memory in AD: the neural substrates that underpin their function would be targeted later in the AD pathogenesis.

Current neuroimaging data on long-term musical memories provides clues into the neural substrates responsible for long-term musical memories preservation in AD patients. It is nonetheless important to acknowledge the limitations of neuroimaging data. The differences in structure among each study’s behavioral paradigm could lend to recruitment of different neural substrates, and thereby activations of different brain regions. For example, although we have attempted to make conceptual and behavioral distinctions between the different kinds of musical memories, the memory retrieval tasks sometimes recruit both episodic and semantic mechanisms. In addition, while many semantic musical memories are effortlessly recognized, the data gathered from PET and fMRI indicate regions of higher metabolic activity that in turn are needed for deliberate and effortful cognitive processes. Therefore, these limitations and imprecisions emphasize the necessity for further investigations and clarifications of the mechanisms that underpin musical memories in AD patients with researches including AD patients with functional and structural neuroimaging investigation after learning phase of new song to identify cerebral areas permitted to encoded ones.

Limitations and Issues of the Literature

Overall, a couple of limitations can be brought up while studying musical memory in AD, which may account for the discrepancies among studies.

First, studies may rely on different theoretical basis. In the introduction, we gathered information from the literature in order to set up a coherent and inclusive theoretical framework of musical memory. To bypass this limitation, we defined and circumscribed memory systems involved in music processing regarding tasks used to evaluate them, and interpreted results according to this theoretical view. To our knowledge, no prior establishment of a rigorous theoretical background had been proposed regarding musical memory, and even if ours might be challenged, it is coherent with the recent memory literature and classical models, as well as results from the literature we presented. As such, it allows us to set the path for a more cohesive and inclusive way of studying musical memory for both AD patients and the general population.

From this perspective, episodic musical memory can be tested using humming, singing, or playing on an instrument a song that has been presented previously. Another evaluation way would be to propose a forced choice between two very similar pieces among which one has been previously played for the first time, referring to the retrieving sounds ability with their structural organization from a one-time event memory.

On the other hand, semantic musical memory, stripped away from its specific playing context (i.e., played with different instruments, or in a different key), can be revealed through the sense of familiarity or recognition of a musical piece. The contextual verbal information surrounding the piece are not musical memory per se, but verbal attributes attached to the music. Moreover, the two dimensions of semantic memory are to be contrasted: while retrograde musical semantic memory is well known to be resistant to AD, anterograde musical semantic memory should also be functional, but may rely on still unclear mechanisms. As promising clues, an important number of repetition (4 or more), incident encoding (without learning instruction) and pleasant settings seem to be the conditions in which new learning could be possible even at severe AD stage.

Finally, procedural memory can be evaluated by asking to play a song on a known instrument, either from memory or by reading/playing from ear. Whether memorized by heart or read, playing the music also involves a decoding process. However, playing a song from memory is a “pure” form of procedural memory retrieval.

Another limitation is the way most neuropsychological assessments are carried out. Using classical encoding/retrieval paradigms for testing musical memory in AD, especially in the latter stages, seems to have many limitations. Primarily, due to massive verbal memory impairments, testing musical memory with typical yes/no answers (or any other verbal only retrieval assessment) is challenging. Most of the time, patients are not comfortable with verbal production, so that assessing linguistic answer only does not provide enough information. Most AD patients at a late stage of the disease have speech impairments, which brings the necessity to revisit the way retrieval is assessed. Few studies have tried to investigate possibilities of adding behavioral cues, such as facial mimics or humming, with results showing a wider range of answers [87] along with further possibilities of investigating the answers. Moreover, carefully designed scales and double quotation may reduce the possibility of subjective assessment, and provide further evidence of preserved cognitive capacities in AD patients at a late stage, especially regarding music but also other forms non-verbal information learning.

Theoretical and Clinical Perspectives

In this review, important differences have been pointed out between studies regarding the AD patients included (number of patients, disease severity, socio-cultural level, and musical expertise), the processes studied and methods used (tasks, nature of the musical material used). The most consistent element is the noticeable strength of musical semantic memory mechanisms in AD patients, even at a severe stage. However, what was even more remarkable is the partial yet documented preservation of semantic memory encoding. This would suggest that the activation and mobilization of semantic musical memories, both retrograde and anterograde, is still possible regardless of the stage and should be prioritized for therapies. More work ought to be done to understand the disease pathogenesis and why some brain networks are preferentially spared, or targeted. Moreover, could engagement in tasks that activate the preserved brain areas of AD patients help to maintain not only the functions of those regions, but also other regions? Many papers suggest that musical training results in increased grey matter volume in some cortical regions and increased plasticity [88, 89], but does this truly delay the onset of the disease and promote better cognitive aging? Further research should seek to uncover this mechanism, and if any neural relationships exist with the partial preservation of semantic musical memory observed in AD.

It is also important to note that most of the current studies draw conclusions about musical memory abilities based on behavioral tasks (as mentioned above) that only test the retrieval stage. Although it is logical to verify the proper functioning of a system based on the quality of its final product, the same cannot be said when the final product is impaired: The deficits in episodic musical memory of AD patients does not mean that the whole processing system is impaired; there may well be solely encoding, storage, or retrieval deficits. Further work should seek to dissociate each step of the construction of musical memory to determine the neural mechanism that underpin each of them, and which one is first to be responsible for the impairment of episodic musical memories in AD patients. Furthermore, current semantic musical memory studies often assess retrograde musical memory, that is, correspond to the ability to have a sense of familiarity for well-known songs before the onset of the AD pathology. Further investigations should be done on severe stage AD patients’ ability to encode new semantic musical memories thanks to the sense of familiarity. It might then become interesting to compare the neural substrates recruited when retrieving music well-known before the disease, and music tunes learnt after the onset of the disease, to determine whether similar or different networks are engaged in semantic musical memory encoding, storage, and retrieval.

Many studies have also explored the strong associations between verbal and musical memory abilities in order to reveal the potential of music to be used as a mnemonic proxy to both decrease the difficulties of verbal learning, and increase the ability to retrieve otherwise inaccessible verbal semantic or even episodic memories [90 –95]. Some authors suggest that it merely provides an arousal effect, heightening our attention and priming our perceptual systems to encode and store the memories with more precision. However, this would suggest that any arousal means would have the same end, but it seems to be inaccurate: musically accompanied text is better retained than associated with non-musical sound or video [96].

The same can be said about the effect of emotions (especially pleasant emotions) on the musical information retention, which could explain why new musical information encoding would be facilitated [67 , 93]. The emotional factor is yet frequently put forward to explain the benefits of musical interventions in AD literature, as well as other dementias [4 –7]. Therefore, more work is definitely needed to understand the relationship between emotions and musical memory, and would provide the key to understand discrepancies between research works and fieldwork regarding musical memory. However, using music in experimental conditions may dispossess it of the emotions it conveys, which is one of its most important dimension [72, 97], and can largely influence memories attached to it [67]. To fix that important issue, alternative ways of testing music memory in more ecological settings should be developed to encompass every parameter of music listening, including emotions.

Through this review, we focused on AD, as the literature regarding other dementias or other neurological pathologies is scarcer, and could be the topic of another review by itself. However, work on semantic dementia [98 –101] and frontotemporal dementia [99 , 103] continue to emerge, and may provide additional proofs to get a better understanding of music processing for both the general population and patients suffering from neurological diseases.

Further investigations are also required to understand the preservation of technical knowledge related to music from experts (such as music theory, perfect pitch, rhythm reading, or finding the key to a piece). Although some studies show no effect of expertise in musical semantic memory [40], investigating music abilities that need both low and high expertise may be an interesting way of investigating musical knowledge’s effect on musical memory.

The studies’ results gathered in this literature review not only provide information on the neuropsychological underpinnings of musical memory in AD patients, but also a better understanding of how to develop greater cognitive stimulation techniques for patients based on their preserved semantic musical memories. To deepen this understanding, we need to continue seeking more information on the neural underpinnings of musical memories in both healthy subjects and AD patients, notably on a physiological level. Peck et al. begin to scrap the surface by observing a triangular interaction between music’s ability to enhance the default network connectivity, dopaminergic projections, and regulation of the autonomic nervous system [104]. One could wonder if this ability to globally activate brain regions and the vascular system is unique to music, or if we could develop other methods that can stimulate similar mechanisms. Either way, we can wonder if these interventions, musical or not, before or after AD diagnosis, have a long-term effect on slowing the progression of the pathology, or strengthening the brain against the onset of the disease [105 –107].

The numerous clinical case and group studies show us that for the majority of AD patients, both anterograde and retrograde semantic musical memory is still working partially. Thus, even though the literature is not always consensual, there are a few directions that can be useful for the health care professionals. First, on the mild and moderate stage of AD, semantic musical memory seems to be relatively well preserved, and can therefore provide an anchor for care. Indeed, valorization of patients is often a pillar of care for people with AD, and can be eased with participatory arts activities [108]. Therefore, using preserved semantic memory as a way to put patients in a situation of success can be easily achieved. By gathering information about patients’ tastes, it is possible to easily set up an activity where they can comment and evoke autobiographical memories about music or songs for example. During the AD severe stage, it becomes harder to find activities that are both suitable to patients and trigger positive emotions and behaviors. Music, however, can reaches both these goals when correctly used. In this review, we have highlighted the possibility of some music memory systems’ preservation in AD. As a result, relying upon semantic memory and creating a sense of familiarity seem to be the two most beneficial options whenever trying to use music with patients at severe stage of AD. Although traditional explicit testing is not suitable, behavioral cues provide enough evidence (as different or reliable may they be depending on the study) to promote the use of music in AD to create learning of new information [67 , 94]. It can also provide a concrete example to discuss the perception that is sometimes carried by people caring for AD patients that their interventions are useless, because immediately forgotten. Thus, this partial musical memory preservation may contribute to change care professionals’ and even family caregivers’ attitude toward AD, by focusing on preserved learning capabilities rather than deficits.