|Alzheimer's & Music|
|Looking at the impact of music in Alzheimer's|
Alzheimer’s disease (AD) is a neurodegenerative disorder that affects millions worldwide and is characterized by a progressive decline in cognitive functions, including the distinctive hallmark of deterioration of memory. Although the medial temporal lobes are a primary targeted brain area in this disease , it has been found that in even moderate to severe Alzheimer’s musical semantic and procedural memory, which are thought to involve the left temporal gyri, are often preserved . This inexplicable conservation of musical memory, coupled with the relatively poor tactics of treatments currently offered, make this wide-spread and impactful disorder a possible candidate for novel therapeutic strategies. Music therapy seems to be a promising alternative, offered in a variety of forms, providing a low cost and low risk approach for the possible prevention and treatment of Alzheimer’s, while perhaps also providing insight into the neural correlates of musical memory.
Table of Contents
|Cerebral Atrophy in AD|
|The general cerebral atrophy in AD (right) as compared to a healthy brain (left)|
Alzheimer's disease (AD) is characterized by behavioural, psychological and physiological changes that produce a significant impairment in functional ability. General cerebral atrophy and tau deposition have been associated with the cognitive deficits and emotional irregularities that are often associated with AD pathology . Some of the most common and well-documented symptoms include agitation, anxiety, forgetfulness, confusion, low mood and restlessness . These symptoms, especially in severity, pose a problem in terms of patient care and care-giver safety. Treatments are often pharmacological, and at later stages of the disease, include sedatives, neuroleptics or antidepressants . These methods of treatment are often inadequate and bear detrimental consequences to the patient. Alternative forms of treatment have become more and more prevalent in use and focus by the medical and scientific community, with an emphasis on low-cost, low-harm and more socially acceptable strategies in battling AD and improving patient’s quality of life.
|Musical Semantic Memory|
|PET activation during a musical semantic tasks of
the left (top) and right (bottom) hemispheres compared to rest.
Adapted from 
Neural Correlates of Musical Memory
Music processing and memory involves a diffuse brain system, differing from the cerebral organization for verbal or visual memory . A proposed model of musical memory includes a modular system of music processing , where the various aspects of music, such as pitch, rhythm, melody, and lyrics, all involve distinct brain regions for storage and retrieval. Musical memory can be categorized into explicit and implicit musical memory, where explicit musical memory can be further subdivided into semantic and episodic memory.
Musical semantic memory can be defined as the long-term storage of music that is associated with the ‘feeling of knowing’ of a melody, tune or a set of lyrics. Generally, musical semantic memory tasks produce a distributed bilateral activation in the temporal-prefrontal cerebral network. PET studies show musical semantic memory recruits the left anterior part of the middle temporal gyrus, the anterior temporal cortex, and the left inferior frontal gyrus. 
Musical episodic memory should be distinguished from musical semantic memory, and pertains to memory of specific musical events as well as the spatial and temporal context of acquisition. So far, studies have mainly focused on episodic memory in reference to language, with very little attention to musical episodic memory. However, it has been found that musical episodic tasks produce bilateral PET activations of the middle and superior frontal gyri, prominently on the right side .
These different patterns of PET activation during a semantic musical task versus episodic tasks suggest distinct neural correlates underlying the different components of explicit musical memory that could explain their dissociation in AD patients.
Musical Memory Preservation in Alzheimer’s
Certain individuals with AD have been shown to retain adequate abilities in a variety of musical tasks assessing memory in comparison to verbal or visual memory tasks. Others show a pattern of partial preservation, while some do not exhibit any preservation of musical memory . These highly variable results can be attributed to the heterogeneous nature of AD pathology, variability in individual performance abilities, and to the scarcity of methodological and reproducible experiments testing musical memory in AD in the literature. Despite this variability, the occurrence of musical memory preservation, compared to the common deterioration of verbal or visual memory, has been well documented both anecdotally and experimentally.
This apparent preservation in many AD patients can provide a possible explanation to the relatively successful nature of music therapy. Although, in order to take full advantage of music and its effects on Alzheimer’s, the different types of musical memory and the dissociable preservation of each with respect to Alzheimer’s must be examined.
Musical Explicit Memory
(1) familiarity decision-based tests which involve judging whether a musical excerpt is familiar, (2) recall of excerpt’s title or composer, (3) completion task that requires recall of the last pitch of the musical excerpt by singing, (4) presenting a series of melodies followed by yes/no recognition task, and (5) distorted tunes test which involves the recognition (sometimes through facial expression) of a distortion in familiar music.
The two main forms of musical explicit memory, semantic and episodic, demonstrate dissociation in their preservation in AD . Various studies implementing some of the methods of musical memory testing have shown a general preservation of musical semantic memory in Alzheimer’s patients . Memory for lyrics, tone and melody was found retained in individuals with mild, moderate and even severe stages of AD. These findings can be compared to the significant deficit in verbal and visual memory that is a common symptom in Alzheimer’s. Musical episodic memory, though, appears to be impaired in AD . Episodic memory loss is a hallmark of AD, and a major contributor to the loss of functional ability that is associated with this disease. The spatial and temporal context that is associated with memory acquisition is generally not retained in verbal, visual or musical memory in Alzheimer’s.
The case of the patient EN presents valuable insight into musical memory preservation in AD. EN was an 84-year old non-musician English woman diagnosed with severe AD. Cuddy & Duffin (2005) performed a variety of musical memory tasks on her to assess the level of musical memory that was preserved. EN received a perfect score in a music familiarity decision task, she scored near perfectly on a distorted tunes task, and in a famous melodies test, EN’s score for song melody recognition was 86% correct. Later autopsy revealed that this sparing of musical memory was not due to the preservation of her medial temporal lobes, which was a subject of debate among researchers, but in fact EN exhibited a common pattern of advanced advanced Alzheimer's disease with significant neuronal loss in the medial temporal lobe structure. In short, EN demonstrated significant explicit musical memory preservation, despite the diminishing of her various other cognitive functions such as verbal communication and general episodic memory.
Musical Implicit Memory
In contrast with explicit musical memory, implicit musical memory has received comparatively little research attention, especially in AD.
Though the findings are variable, generally studies show that the ‘mere exposure effect’ is observed in patients with AD . As well, procedural memory has been found to be preserved in some AD patients, especially with patients who are musicians.
Musical Therapy (MT) in Alzheimer's
|The Power of Music|
|Henry, a patient with severe Alzheimer's, reacts to music listening.|
Musical therapy has been an increasingly popular method of treatment for Alzheimer’s owing to its efficacy, low-cost, non-invasiveness, and it’s virtually non-existent side-effects. MT’s effectiveness may be due to the general observed preservation of musical memory in AD, though for the main part, it’s mechanism of action are still unknown.
MT’s success has been widely upheld by anecdotal evidence, though more and more studies are taking an experimental and quantifiable approach to studying MT’s effects in Alzheimer’s patients. A study examining the effect of music listening on AD patients showed an enhancing effect of music therapy on autobiographical memory and recall, proposing an anxiety-reducing mechanism . Other studies show a reduction of depression and agitation , with improvements in communication , recognition memory , positive participation , and various other cognitive functions. In contrast, Simmons-Stern et al. (2012) found that while recognition memory, which is a familiarity-based non-specific semantic memory, is enhanced, recollection, which is specific and qualitative, is unaffected by music therapy in AD.
Forms of MT Applications
|Group Music Therapy|
|A group instrument-playing music session with certified music therapists
leading a number of Alzheimer's patients
Direct and Indirect Techniques
Music therapy can be distinguished with a ‘musical condition’ by the involvement of one or more therapists and their interaction with one or more individuals . A common example of music therapy is group singing or group instrument playing. This method of musical therapy has been popular in care facilities, where both the music and the personal contact are critical in the treatment. Studies show the advantage of music on AD patients is augmented with the beneficial value of personal contact, as compared to an indirect music condition which does not involve social interaction . This synergism, however, has not been quantified. An indirect musical condition is often referred to as ‘music medicine’, and is usually effective on its own. It is often employed when music therapy is inefficient, such as during off-hours when therapists are unavailable.
Newer music therapy implementations have stressed the importance of patients playing an active role in regulating music stimulation through responses and interaction with assistive technology .
Active and Passive Techniques
Music therapy can come in a variety of forms and can involve active or passive conditions. In active conditions, patients undergo self-regulated stimulation such as instrument playing or singing. Passive techniques include forms of ‘music medicine,’ such as music listening, which are often employed with moderate AD cases .
MT in the Media
Proposed Mechanisms of MT Action
|The Implications of Sex Hormones in MT & Alzheimer's|
|The sex hormones estradiol and testosterone have been hypothesized to act as protective factors
in AD by acting on various brain factors such as NGF. They are also found to increase during MT application
on Alzheimer's patients. Adapted from 
Steroid hormones exert many vital effects on the brain and regulate a wide variety of functions such as brain development, neurogenesis, neuronal protection, memory and cognition. Estrogen plays a role in gene expression regulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) protecting the nerves and controlling cell proliferation. Testosterone has been attributed to decreasing the peptide β amyloid, a component of amyloid plaques, which has been associated with Alzheimer’s disease, by means of NGF and p75-NGF receptor elevation. 
Studies have found differing levels of steroid hormones in Alzheimer’s patients compared to healthy individuals. Age-related decreases in estrogen levels have been associated with cognitive dysfunction, learning and mood disorders. However, estrogen has been found to be markedly lower in Alzheimer’s outside of age-related effects. Low levels of estrogen may accelerate AD development by expediting β amyloid production and deposition. Estrogen replacement therapy has been administered to female Alzheimer’s patients where it has been shown to improve memory and attention. Likewise, optimal testosterone levels seem to be a vital aspect of normal cognitive function. Levels of testosterone have also been found to be lower in AD as compared to healthy counterparts, even within the elderly population. Testosterone administration is reported to improve spatial cognitive function in AD patients. Due to the importance of sex hormones and their roles in normal brain function, reductions in estrogen and testosterone pose as risk factors for AD. 
A study by Fukui, Arai & Toyoshima (2012) demonstrates that musical therapy increases estradiol and testosterone levels in Alzheimer’s patients, proposing a preventative value in music and a possible mechanism by which musical therapy has been found to be effective in this disease. Passive and indirect music application, such as listening to music, reportedly increases 17-β-estradiol levels, while direct music application termed “music therapy” showed the greatest increase. Music therapy also significantly increases testosterone in the same way.
Music has been widely associated with assuaging and lowering stress, observed both behaviourally and physiologically. Music’s effects on the body’s stress system had been attributed to reductions in cortisol in a sex independent manner. In AD, where the physical and mental stress associated with the disease is correlated with increased cortisol levels, music can help effectively suppresses stress responses in both genders. Other hormones apart of the stress/HPA axis, such as CRH (which promotes ACTH secretion) and ACTH (a hormone that in turn controls cortisol secretion), are also likely involved in music-mediated stress reduction. 
Several studies, as well as anecdotal observations, have linked music to positive adjustments in mood and sleep quality, through the modulation of hormones such as melatonin . Melatonin plays an important role in the regulation of monoamine activities, the HPA stress axis, sleep and behaviour. Its levels are negatively correlated with age, where these effects become exaggerated in disorders such as AD. After musical therapy conditions, patients with Alzheimer’s showed a significant increase in serum melatonin levels, as compared to various other hormones such as serotonin and prolactin, where this increase carried over and further increased 6 weeks following the musical therapy. 
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