Handbook of Clinical Neurology, Vol.

129 (3rd series)

The Human Auditory System
G.G. Celesia and G. Hickok, Editors
© 2015 Elsevier B.V. All rights reserved

Chapter 37

Hearing and music in dementia

JULENE K. JOHNSON1* AND MAGGIE L. CHOW2
1
Institute for Health and Aging, University of California, San Francisco, CA, USA
2
School of Medicine, University of California, San Francisco, CA, USA

INTRODUCTION cognition, it is sometimes difficult to separate difficul-

ties in sound processing due to cognitive impairment ver-
Both music and speech are complex acoustic signals that
sus difficulties in sound processing due to an auditory
rely on a number of brain and cognitive processes to cre-
system-specific deficit.
ate the sensation of hearing. The transmission of audi-
The aim of this chapter is to review the current state
tory signals is supported by large-scale neural
of knowledge concerning hearing and music perception
networks. Changes in hearing function are generally
in persons who have a dementia as a result of a neurode-
not a major focus of concern for persons with a majority
generative disease. The fundamental questions of this
of neurodegenerative diseases associated with dementia,
chapter are: How do persons with a neurodegenerative
such as Alzheimer disease (AD). However, changes in
disease process comprehend music? Do persons with dif-
the processing of sounds may be an early, and possibly
ferent neurodegenerative diseases perceive and process
preclinical, feature of AD and other neurodegenerative
music differently? How is music used as a tool to better
diseases. For example, patients with semantic dementia
understand both the auditory system and neurodegener-
often present to a physician with difficulty comprehend-
ative diseases?
ing speech, in addition to difficulties with finding words
in conversational speech. Other persons with a dementia
OVERVIEW OF DEMENTIA
may have difficulty following multiple auditory streams
or following complex instructions. The frequency of Dementia is a general term that refers to a progressive
complaints about hearing difficulties differs by the type decline in cognition and behavior that impacts a person’s
and stage of the neurodegenerative disease. ability to function independently in everyday life
Persons with neurodegenerative diseases, however, (American Psychiatric Association, 2000). Dementia is
rarely present with significant deficits in the processing a common syndrome in older adults, and there are over
of music, compared with persons who have an auditory 50 different causes of dementia. For the purposes of this
agnosia or amusia, an acquired impairment in the ability chapter, we will focus on the most common causes of
to process music (see Chapters 32 and 34). In contrast, dementia (see Miller and Boeve, 2009; Ames et al.,
there are numerous anecdotal reports suggesting that 2010; Krishnamoorthy et al., 2010 for a comprehensive
the appreciation (and perception) of music often remains overview of dementia and neurodegenerative diseases).
preserved in persons with AD and possibly other neuro- AD is the most common cause of dementia in adults
degenerative diseases. over age 65 and accounts for approximately half of all
A key question is the extent to which the core cogni- dementia diagnoses (Alzheimer’s Association, 2012).
tive deficits associated with various neurodegenerative Impairment in memory is the most common cognitive
diseases contribute to difficulties in comprehending and often predominant deficit in AD, but deficits in
auditory information versus the extent to which changes other cognitive domains (language, executive function,
in central auditory processing may contribute to auditory visuospatial skills) are often present. Other neurodegen-
comprehension difficulties. In other words, because erative diseases can also cause dementia; the most com-
dementia, by definition, is a progressive impairment in mon non-AD dementias include dementia with Lewy

*Correspondence to: Julene K. Johnson, Ph.D., Institute for Health and Aging, University of California, San Francisco, 3333
California St., Suite 340, San Francisco, CA 94118, USA. Tel: +1-415-476-1106, E-mail: julene.johnson@ucsf.edu
668 J.K. JOHNSON AND M.L. CHOW
bodies (DLB), frontotemporal dementia (FTD), cortico- this reason, the chapter will focus primarily on AD.
basal degeneration, progressive supranuclear palsy, and However, the chapter will include information about
Huntington’s disease. Vascular cognitive impairment hearing function and music in non-AD dementias when
(also called vascular dementia), which is caused by vas- it is available.
cular disease in the brain, is another common cause of
dementia (Rincon and Wright, 2013). Many persons with HEARING FUNCTION IN
vascular dementia also have changes in the brain associ- NEURODEGENERATIVE DISEASES
ated with AD. Approximately 30–60% of persons with
Hearing sounds, including music, relies on both the
Parkinson disease also eventually develop cognitive dys-
peripheral and central auditory systems (see Chapters 1
function (Aarsland et al., 2003; Williams-Gray et al.,
and 2). Both the peripheral and central auditory systems
2007). There is often clinical overlap between Parkin-
undergo change with age. The section below will provide
son’s disease dementia and DLB.
a broad overview about hearing function in aging and
DLB is another common cause of dementia. It is
neurodegenerative diseases. (For further information
characterized by progressive cognitive and functional
about hearing function in aging and dementia, see
decline with at least two of the following additional
Grimes, 1995 and Weinstein, 2000.)
symptoms: (1) prominent visual hallucinations; (2) fluc-
tuations in alertness and attention; and (3) parkinsonian
Hearing impairment
motor symptoms (McKeith et al., 2005). Although
visual hallucinations are a prominent feature of DLB, Hearing loss is one of the most common chronic condi-
auditory hallucinations are rare. Corticobasal degener- tions in older adults (see Chapter 21). Hearing loss in the
ation and progressive supranuclear palsy are two more general population increases with age, and men have
rare neurodegenerative diseases that are classified as higher rates of hearing impairment than women.
atypical parkinsonian disorders (Armstrong et al., Approximately 40% of adults over age 65 have hearing
2013; Respondek et al., 2013). Huntington’s disease is loss (>30 dB loss in at least one ear), and approximately
another rare neurodegenerative disease that causes 50% of adults over age 85 have hearing loss (Gates and
involuntary motor symptoms (i.e., chorea), dementia, Mills, 2005). Age-related hearing loss (presbycusis) first
and psychiatric symptoms (Biglan et al., 2013). affects the high-frequency range, is progressive, and can
FTD is a common cause of early age-of-onset demen- be caused by damage to either the peripheral or central
tia (and is caused by significant atrophy in the frontal and auditory system (or both). Gates and Mills (2005) note
temporal lobes of the brain. FTD can be subdivided into that persons with hearing loss often have difficulty
two language-variant syndromes (progressive non-fluent understanding conversations and misperceive phoneti-
aphasia and semantic dementia) and one behavior cally similar words, such as “map” and “mat.” Family
variant, called behavioral-variant FTD (bvFTD) (Gorno- members or friends are often more aware of the change
Tempini et al., 2011; Rascovsky et al., 2011). The in hearing function than the older person with hearing
behavioral variant of FTD is characterized by changes loss. Hearing loss in older adults can also affect the abil-
in personality and social behavior (e.g., impulsivity, apa- ity to perceive and comprehend music, but few studies
thy, decreased empathy, and diminished insight). Persons have explored this topic.
with semantic dementia develop a progressive loss of the A number of studies have examined the relationship
meaning (semantics) for both verbal and non-verbal con- between hearing loss and cognitive decline in older
cepts, which is due primarily to atrophy of the temporal adults. Gennis and colleagues (1991) reviewed 15 studies
lobes of the brain. Persons who have progressive non- and concluded that hearing loss was more common in
fluent aphasia develop progressive difficulty producing persons with dementia, but there was considerable het-
language (e.g., hesitant and effortful speech). Logopenic erogeneity in the study designs, and the underlying
aphasia is another variant of primary progressive aphasia causes of the dementia were not always clear. Other
characterized by slow speech and naming deficits and is studies suggest that the hearing loss in persons with
thought to be caused by AD (Gorno-Tempini et al., 2008). dementia is more severe than older adults without cog-
Mild cognitive impairment (MCI) is a term used for nitive decline (Uhlmann et al., 1989; Lin et al., 2011).
the preclinical stage of dementia. MCI is associated with Recent studies also suggest that adults with hearing loss
mild declines in cognitive function, but the ability to per- are more likely to develop AD or other dementias over
form daily living skills is still relatively preserved. There time. For example, Lin and colleagues (2013) found that
is a high rate of progression from MCI to dementia hearing loss (pure-tone average >25 dB) was indepen-
(Petersen, 2011). dently associated with both increased rate of cognitive
The majority of research about hearing and music in decline and incident cognitive impairment in a large sam-
dementia has been done with persons who have AD. For ple of community-dwelling older adults.
 HEARING AND MUSIC IN DEMENTIA 669
Several recent studies suggest that adults with thresholds), pure-tone and speech audiometric testing,
Parkinson’s disease may have a higher prevalence of word recognition, and distortion product otoacoustic
age-related, high-frequency sensorineural hearing loss emissions testing to 10 mild to moderate patients with
relative to healthy adults. One recent study involving AD and matched controls. They found that the AD
118 patients with Parkinson’s disease found a higher patients had only slightly worse low-frequency thresh-
prevalence of age-dependent high-frequency hearing olds compared to the controls. Another study involving
loss than age- and sex-matched controls (Vitale et al., 33 patients with a diagnosis of AD, progressive non-
2012). Within this cohort, 26% had mild, 63% had mod- fluent aphasia, or logopenic aphasia found only small
erate, and 11% had severe hearing loss. The Parkinson’s differences on sound detection thresholds in the patient
disease patients with hearing impairment were older, groups compared to controls (Goll et al., 2011). Mahoney
more likely to be male, and had a later age at onset than and colleagues (2011) reported that 32% of patients with
the Parkinson’s disease patients with normal hearing. semantic dementia complained of tinnitus or hyperacu-
The authors also noted that the Parkinson’s disease sis, but peripheral hearing function was not examined.
patients were generally unaware of their hearing loss. A few other less common adult-onset neurodegener-
It is also important to remember that the patient with ative diseases occasionally involve the peripheral audi-
dementia may not complain of hearing loss symptoms. tory system. For example, one study documented a
Gates and Mills (2005) recommended an examination 71-year-old man who developed a rapidly progressive
of hearing function in any person with cognitive decline. dementia with features of DLB and also inflammation
They also note that tinnitus is a common comorbid con- of the cartilage of the pinna (Head et al., 2006). An
dition with hearing loss and should be queried in persons autopsy revealed inflammation-induced neurodegenera-
with cognitive decline. It is possible that hearing loss tion caused by relapsing polychondritis, an autoimmune
symptoms are underreported in persons with neurode- inflammatory disorder of cartilaginous tissues. There
generative diseases, as they may be regarded as second- are also a few other rare neurodegenerative diseases
ary to concerns about memory or are confused as or genetic mutations that can cause a dementia and sen-
memory or communication symptoms. It is also possible sorineural hearing loss (e.g., mitochondrial disease syn-
that dementia may be overdiagnosed in persons with dromes, adult-onset Friedreich’s ataxia). A few recent
hearing loss. studies have focused on cases of autosomal-dominant
hereditary sensory and autonomic neuropathy with
dementia and hearing loss (HSAN1) (Wright and Dyck,
Peripheral auditory system function
1995). Klein and colleagues (2011, 2013; U.S. Congress,
Persons with a neurodegenerative disease (with the diag- Office of Technology Assessment, 1992) described a pri-
noses discussed above) are generally thought to have an marily adult-onset hearing loss and neuropathy followed
intact peripheral auditory system and are only affected by memory decline or personality changes typical of FTD
by typical, age-related changes. That is, most neurode- in the 30s and 40s with a mutation in DNA methyltrans-
generative diseases do not directly damage the periph- ferase 1 (DNMT1). Autopsies in persons with a DNMT1
eral auditory system. Autopsy studies have not mutation in a case series from Japan revealed diffuse
detected neuropathologic changes associated with AD non-specific degeneration and glial activation especially
in the peripheral auditory system (Sinha et al., 1993). in the frontal, temporal, parietal, and occipital cortex,
However, only a few studies have been done, and the hippocampus, and thalamus, but the auditory system
majority of these autopsy studies focus on AD. The was not mentioned (Hojo et al., 2004).
peripheral auditory system is just beginning to be studied
in non-AD dementias.
Central auditory system
Early studies documented normal peripheral hearing
function in AD patients (Grimes et al., 1985; Eustache Because neurodegenerative diseases primarily affect the
et al., 1995; Gates et al., 1995). For example, Kurylo central nervous system, the majority of studies have
and colleagues (1993) investigated a comprehensive bat- focused on the central auditory system. The changes
tery of auditory function, including pure-tone thresh- to the central auditory system are thought to occur as
olds, sound localization, pitch perception of complex a result of the neurodegenerative diseases, in addition
tones, phoneme perception, timbre discrimination, and to age-related changes in the central auditory system.
tonal memory (from the Seashore Tests of Musical Abil- Histopathologic and morphometric studies have found
ities). There were no differences between patients with a number of neuropathologic changes in the central audi-
AD and matched older adults on the majority of these tory system in different neurodegenerative diseases. The
tests. Another study (Strouse et al., 1995) administered auditory system has been most extensively studied in
immittance tests (e.g., tympanograms, acoustic reflex persons with AD. Neuron loss, neuritic plaques, and
670 J.K. JOHNSON AND M.L. CHOW
neurofibrillary tangles, the classic neuropathologic impairment performed worse than matched controls
lesions of AD, have been identified in auditory system but better than the demented patients, even after control-
brainstem and midbrain nuclei, including the olivary ling for age, hearing threshold, and word recognition
nucleus, inferior colliculus, and medial geniculate body scores. However, the underlying diagnoses of the
(Ohm and Braak, 1989; Dugger et al., 2011). In addition, demented participants were not reported. Another study
plaques and tangles are also common in primary audi- also found that persons with MCI had an impairment on
tory and auditory association cortex in persons with a dichotic listening task that was intermediate between
AD (Sinha et al., 1993; Chance et al., 2011). Neuropatho- healthy adults and AD patients (Idrizbegovic et al.,
logic studies of the central auditory system are less com- 2011), again suggesting that deficits in central auditory
mon in non-AD dementias. A few studies suggest that an processing occur before the onset of dementia and get
accumulation of tau neuropathology in auditory brain- worse after the onset of dementia symptoms.
stem nuclei in persons with progressive supranuclear Impairments in central auditory function may also be
palsy (Dugger et al., 2011) and severe neuronal loss a risk for developing dementia. For example, one study
has been documented in the auditory cortex of persons recently found that older adults with severe central audi-
with FTD and primary progressive aphasia (Baloyannis tory dysfunction, particularly as measured by the
et al., 2011). These neuropathologic changes of the cen- Dichotic Sentence Identification test, were at increased
tral auditory system are thought to be related to the pro- risk for developing incident AD after 3 years (Gates
cessing of sounds. et al., 2011). The majority of those who developed AD
The majority of studies focus on the processing of also had lower memory scores, as measured by the mem-
verbal information, while studies about the processing ory subscale of the Cognitive Abilities Screening Instru-
of non-verbal information, including music and environ- ment. As discussed above, another recent study found
mental sounds, are less commonly done. This section will that hearing loss (pure-tone average >25 dB) was inde-
provide a brief overview of central auditory system dys- pendently associated with increased rate of cognitive
function in neurodegenerative diseases, and additional decline and incident cognitive impairment in a large sam-
information about the processing of music and other ple of community-dwelling older adults (Lin et al., 2013).
non-verbal sounds will be discussed in the following Some authors propose to frame auditory cognition
two sections. deficits in terms of “auditory objects” or “auditory scene
Early studies in the 1980s used dichotic listening par- analysis,” the ability to parse sound sources in the audi-
adigms (simultaneous presentation of different acoustic tory environment (Goll et al., 2010b). For example, Goll
signals to the right and left ears) and other basic auditory and colleagues (2012a) recently assessed auditory scene
perceptual tasks to study central auditory function in analysis of both verbal and non-verbal sounds in a cohort
persons with AD. For example, Grimes and colleagues of 21 persons with AD. The persons with AD performed
(1985) found that 81% of the patients with AD had abnor- much worse than matched controls on both auditory
mal scores on dichotic listening tasks. The dichotic listen- scene analysis tasks, but their performance was some-
ing scores correlated with performance on tests of what attenuated after accounting for visuospatial work-
cognition, volume of the temporal lobes on brain com- ing memory. They also found that performance
puted tomography imaging, and metabolism of the left correlated with brain volume in several posterior cortical
temporal lobe using positron emission tomography areas, using voxel-based morphometry of brain mag-
imaging. That is, lower scores on dichotic listening tasks netic resonance imaging (MRI).
correlated with lower cognitive scores, less brain vol- Central auditory processing deficits have also been
ume, and lower metabolism in the left temporal lobe. studied in a few non-AD dementias. For example, Goll
Other early studies using dichotic listening methods also and colleagues (2010a) found significant difficulties in
documented auditory processing impairments in AD the processing of complex non-verbal sounds in
patients (Grady et al., 1989; Mohr et al., 1990). 12 patients with progressive non-fluent aphasia and
Persons with MCI may also have central auditory 8 patients with semantic dementia. The authors used
function impairments. For example, Gates and col- several newly designed auditory tasks to assess early per-
leagues (2008) examined central auditory processing ceptual, apperceptive, and semantic levels of non-verbal
using a comprehensive battery (synthetic sentence iden- auditory processing. While patients with progressive
tification with ipsilateral competing message, dichotic non-fluent aphasia were particularly impaired on the
sentence identification, and dichotic digits) in a large early perceptual tasks, the semantic dementia patients
cohort of older adults who had mild memory impairment had particular difficulty with the processing of semantic
(but not demented) or dementia based on a cognitive aspects of non-verbal sounds.
screening test (Cognitive Ability Screening Instrument). In conclusion, impairments in the central auditory
The authors found that the persons with mild memory system are common in persons with various
 HEARING AND MUSIC IN DEMENTIA 671
neurodegenerative diseases. However, the majority of Acoustic Input

studies have focused on AD, while an interest in study-

ing central auditory function in non-AD dementias is
Acoustic analysis
increasing. Additional consideration of the central audi-
tory system processing of music and non-verbal sounds
can be found in the next two sections. Temporal
Pitch organization organization

Tonal Interval Contour

PROCESSING OF MUSIC IN
Rhythm Meter Acoustic to
encoding analysis analysis analysis analysis phonological

NEURODEGENERATIVE DISEASES
conversion

As discussed in the introduction, persons with neurode- Emotion

expression
Musical
lexicon
Phonological
lexicon
generative diseases rarely present with significant defi- analysis

cits in the processing of music, compared with persons

Vocal plan
Associative
who have an auditory agnosia or amusia, an acquired formation
memories
impairment in the ability to process music (see Chapters
32 and 34). In contrast, there are numerous anecdotal Singing Tapping Speaking

reports suggesting that the appreciation (and perception) Fig. 37.1. Cognitive model of music processing. Each box
of music often remains preserved in persons with AD represents a processing component, and arrows represent path-
and possibly other neurodegenerative diseases. How ways of information flow or communication between proces-
do persons with a neurodegenerative disease process sing components. A neurologic anomaly may either damage a
and comprehend music? Do persons with different neu- processing component (box) or interfere with the flow of infor-
rodegenerative diseases perceive and process music dif- mation between two boxes. All components whose domains
appear to be specific to music are in green; others are in blue.
ferently? How is music used as a tool to better
There are three neurally individuated components in italics –
understand both the auditory system and neurodegener- rhythm analysis, meter analysis, and emotion expression
ative diseases? analysis – whose specificity to music is currently unknown.
They are represented here in blue, but future work may provide
Framework for examining music perception evidence for representing them in green. (Reproduced from
in neurodegenerative diseases Peretz and Coltheart, 2003, with permission.)
As discussed in Chapter 11, there are both perceptual and
associative aspects involved in the perception of music. information processing between components. The
Basic-level perceptual hearing processes extract pitch, acoustic signal enters from the top of the model. In addi-
rhythm, timbre, and timing information, while higher- tion, Stewart and colleagues (2006) identified the most
order cognitive processes help store and associate music important brain areas implicated in disorders of music
sequences with long-term memories. All of these pro- listening. The schematic of the brain at the top provides
cesses facilitate recognition of a musical sequence as the anatomic areas involved in music listening, while the
meaningful or familiar. four schematics below identify specific aspects of music
One of the early music psychologists, Carl Seashore processing. The authors argue that this framework can
(1866–1949), provided a useful framework for under- be applied to both acquired and congenital disorders
standing how the physical aspects of sound (frequency, of music listening. It is important to keep in mind that
intensity, duration, and waveform) are mapped on to the this framework was developed from studies of patients
perceptual qualities of music (pitch, loudness, time, tim- with focal brain lesions (e.g., stroke); however, there are
bre). That is, the acoustic aspect of frequency (number no compelling reasons to think that the deficits in music
of waves per second) is associated with the perception processing observed in persons with dementia would not
of pitch; intensity (decibels) is associated with loudness; follow this framework (Fig. 37.2).
duration (time intervals) is associated with time/meter; The melody is often the most conspicuous aspect of
and wave form (tone quality from pure tone to noise) music, and many studies focus on the processing of
is associated with the perception of timbre. These basic familiar and unfamiliar melodies. For familiar melodies
physical components of musical sounds can be combined in western cultures, healthy adults store relatively pre-
to create music intervals, scales, harmonies, melodies, cise knowledge about the notes and timing that comprise
and musical compositions. Figure 37.1 depicts a com- the melody. Recognition of a melody as familiar
monly used contemporary cognitive model of music rec- depends on the ability to match the mental representa-
ognition, as proposed by Peretz and Coltheart (2003). tion/percept of the melody with a “musical lexicon,”
Each box represents a music-processing component, which includes all melodies known to the listener
while the lines between boxes designate the path of (Peretz and Coltheart, 2003). Recognition of familiar
672 J.K. JOHNSON AND M.L. CHOW

Fig. 37.2. Brain areas implicated in disorders of music listening. Critical brain substrates for musical-listening disorders across
studies. Five cartoons are shown, each depicting the brain in a schematic axial section that includes all key anatomic areas involved
in music listening (identified on the top cartoon); the corpus callosum (black), superior temporal plane (light gray), and middle/
inferior temporal gyri (dark gray areas, in exploded view) are colored for ease of identification. Musical functions analyzed in
Supplementary Table 1 (http://brain.oxfordjournals.org/content/129/10/2533.figures-only) have been grouped as follows: pitch
processing (pitch interval, pitch pattern, tonal structure, timbre); temporal processing (time interval, rhythm); musical memory
(familiar and novel material); and emotional response to music. Each group of functions is assigned to a separate cartoon; indi-
vidual functions are identified to the right of the corresponding cartoon. Raw data from Supplementary Table 1 have been thre-
sholded; the presence of a colored circle corresponding to a particular function in a region indicates that at least 50% of studies of
the function implicate that region. The size of each circle is scaled according to the proportion of studies of the function implicating
that region (see text). Meter is not represented as no brain area was implicated in 50% or more of cases. amyg, amygdala; aSTG,
anterior superior temporal gyrus; bg, basal ganglia; cc, corpus callosum; r, frontal; hc, hippocampal; HG, Heschl’s gyrus; ic, infe-
rior colliculi; i, inferior; ins, insula; l, lateral; m, medial; thal, thalamus; PT, planum temporale; TG, temporal gyrus. (Reproduced
from Stewart et al., 2006, with permission.)
 HEARING AND MUSIC IN DEMENTIA 673
music can be assessed using a variety of methods. Sev- a 71-year-old amateur trombone player who continued
eral studies asked participants to judge the familiarity of to play in a Dixieland jazz band after he developed
a melody to determine if the listener can discriminate dementia (later confirmed to be AD by autopsy)
familiar and novel melodies. Another method is to ask (Beatty et al., 1994, 1997). When patient T was in the mild
participants to listen to a melody and determine if the stages of dementia (with a Mini-Mental State Examina-
melody is correctly played or has an error (e.g., pitch, tion score of 20 out of 30), the authors made videotaped
rhythm). The Distorted Tunes Test (Drayna et al., recordings of his playing during a band performance and
2001) is one example of a pitch error detection task. asked raters to compare the quality of his playing at that
Brattico and colleagues (2006) suggest that the identifi- time with recordings of him playing from approximately
cation of errors in melodies occurs rapidly and automat- 30 years prior. The raters judged these two playing exam-
ically, even with unfamiliar melodies. Several studies ples as equivalent, suggesting that there had not been any
also ask participants to generate a title for a familiar mel- significant decline in his playing ability after the onset of
ody, but this type of task requires different cognitive dementia. Patient T was also asked to listen to 20 familiar
processes (e.g., verbal recall) compared with recognizing holiday songs and generate the titles. He recalled 80% of
melodies with errors. The processing of unfamiliar mel- the song titles, but his performance was slightly below a
odies can be assessed using a number of different para- group of healthy controls who recalled 95% of the titles.
digms. For example, both the explicit and implicit In another early case report, Crystal and colleagues
memory of unfamiliar melodies can be examined. The (Beatty and Greiner, 1998) described an 82-year-old
Montreal Battery for Evaluation of Amusia (Peretz music editor and pianist who was evaluated during the
et al., 2003) includes several tasks that require compar- MCI stage of AD. At that time, he was able to play, from
isons of unfamiliar melodies that may differ by notes, memory, 13 popular classic music compositions. How-
contour, or rhythmic patterns. ever, 3 years later, he was only able to play a few bars
The next sections will review the current literature of the same pieces. Several more recent case studies have
about how music, and melodies in particular, is pro- examined both music perception and production in more
cessed in persons who have a neurodegenerative disease. detail, including comparisons with non-AD dementias
It is important to keep in mind that performance on var- (Cuddy and Duffin, 2005; Hailstone et al., 2009;
ious music tasks can be affected by the type and severity Vanstone et al., 2009; Omar et al., 2010; Weinstein
of dementia. This often makes comparisons across stud- et al., 2011). Polk and Kertesz (1993) studied two persons
ies difficult. Performance on music tasks can also be with atypical presentations of AD (i.e., progressive apha-
affected by the amount of prior music training. The sia and posterior cortical atrophy).
majority of case studies reviewed below focus on per- After the early case studies in the 1980s, the examina-
sons who are either professional or amateur musicians, tion of music skills in persons with dementia eventually
while many of the group studies include persons with expanded. Subsequent research aimed to better under-
different levels of music background. Not all studies stand how music is processed by persons with AD,
report the music background of the participants. Similar and eventually, other types of neurodegenerative dis-
to the studies reviewed above, the majority of studies eases. In addition, a number of group studies were
about music have been done with persons with AD. How- conducted.
ever, recent studies focus more on the processing of Several studies have focused on the ability of persons
music in non-AD dementias. with AD to process both familiar and unfamiliar melo-
dies. Persons with AD are generally able to distinguish
melodies as familiar or unfamiliar (familiarity decision).
Alzheimer disease
This is often assessed by asking participants to listen to a
As mentioned in the introduction of this chapter, there melodic excerpt and decide if the excerpt is familiar or
are several case reports in the literature that document novel (new) or old. The findings with AD patients, how-
a relative preservation of music abilities in persons with ever, are somewhat mixed. In one study, the persons with
AD. These reports primarily focus on the preserved abil- AD performed slightly lower than healthy controls
ity to continue playing a musical instrument after the (Bartlett et al., 1995) when asked to discriminate familiar
onset of dementia. Table 37.1 summarizes these case and unfamiliar melodies, while other studies found no
studies and provides a short summary of the findings. differences between AD patients and controls (Cuddy
In several of the early case studies, Beatty and col- and Duffin, 2005; Hsieh et al., 2011). However, persons
leagues described the preserved music abilities of per- with AD may have difficulty with the explicit recognition
sons with AD who had music training (Beatty, 1988, of familiar melodies. One study presented eight familiar
1999; Beatty et al., 1994, 1999; Beatty and Greiner, melodies and then asked 15 persons with mild to moder-
1998; Cowles et al., 2003). For example, patient T was ately severe AD to if the melodies in the next set were old
674 J.K. JOHNSON AND M.L. CHOW
Table 37.1
Summary of case studies investigating music in persons with dementia

Study Case Background Diagnosis Main findings

Beatty et al. (1988) GW Music teacher and AD Preserved ability to play piano; impaired
pianist ability to name familiar music
Crystal et al. (1989) – 82-year-old music MCI due to AD Preserved ability to play piano; unable to
editor and pianist name title or composers
Polk and Kertesz CW 58-year-old guitar Primary progressive aphasia Preserved ability to play guitar and
(1993) teacher due to AD recognize familiar melodies; unable to
reproduce rhythms
Polk and Kertesz, MA 53-year-old piano Posterior cortical atrophy Preserved ability to name familiar tunes,
(1993) teacher due to AD discriminate melodies, identify pitch
errors, and reproduce rhythmic patterns;
impaired ability to play piano
Beatty et al. (1994) T 71-year-old amateur AD (pathologically Preserved ability to play trombone and name
Beatty et al. (1997) trombonist confirmed) familiar tunes
Johnson and DN 76-year-old non- AD Preserved ability to reproduce melodies and
Ulatowska (1996) musician rhythmic patterns and sing familiar
songs, which declined over 2 years
Beatty et al. (1999) ML 79-year-old amateur AD Preserved ability to play piano; difficulty
pianist learning new song and impaired naming
of familiar tunes and rhythm recognition
Miller et al. (2000) 4 49-year-old non- Primary progressive aphasia Compulsive whistling; composed songs
musician about his bird
Miller et al. (2000) 5 78-year-old non- Primary progressive aphasia New skill in composing classic music
musician
Miller et al. (2000) 6 71-year-old musician Primary progressive aphasia Composed songs that captured personalities
of his acquaintances
Tzortzis et al. MM 74-year-old pianist Primary progressive aphasia Preserved ability to compose and play piano.
(2000) and composer Impaired naming of nonmusical stimuli,
but preserved naming of musical
instrument sounds
Cowles et al. (2003) CL 80-year-old amateur AD Learned to play new song on violin;
violinist and preserved ability to play previously
pianist known tunes on violin and piano,
recognize familiar songs, and reproduce
rhythmic patterns
Cuddy and Duffin EN 84-year-old amateur AD (pathologically Generally preserved ability to recognize
(2005) pianist confirmed) familiar music
Vanstone et al.
(2009)
Fornazzari et al. – 63-year-old AD Preserved ability to read, interpret, and learn
(2006) professional new musical pieces
pianist
Hailstone et al. – 56-year-old non- Semantic dementia Correctly sang 63% of familiar melodies;
(2009) musician increased interest in music listening and
singing along
Matthews et al. JS 30-year-old non- Auditory agnosia due to Preserved affective response when listening
(2009) musician neurodegenerative to personal music; impaired performance
disease on majority of music-processing tasks
administered
Vanstone et al. VC 83-year-old amateur AD Preserved ability to recognize and sing
(2009) pianist familiar tunes; diminished ability to play
piano
Barquero et al. – 53-year-old music Frontotemporal dementia Preserved ability to recognize familiar tunes
(2010) critic (pathologically and process rhythm and music emotions;
confirmed)
 HEARING AND MUSIC IN DEMENTIA 675
Table 37.1
Continued

Study Case Background Diagnosis Main findings

impaired ability to judge quality of music

performance
Omar et al. (2010) BR 56-year-old Semantic dementia Preserved recognition of music and music
professional symbols; impaired recognition of music
trumpet player emotions and recognition of musical
instruments
Omar et al. (2010) WW 67-year-old music AD Preserved recognition of music emotions
librarian and and musical instruments; impaired
oboist recognition of music and music symbols
Weinstein et al. – 59-year-old Semantic dementia Preserved ability to play harpsichord and
(2011) harpsichordist learn new complex pieces

AD, Alzheimer disease; MCI, mild cognitive impairment.

or new (Bartlett et al., 1995) AD patients performed format. While some studies found that AD patients were
worse than matched controls, suggesting that the explicit able to generate a similar number of titles as controls
memory for familiar melodies may not remain preserved (Hsieh et al., 2012), the majority of studies found that
in AD. Hsieh and colleagues (2011) found that the recog- AD patients generated fewer song titles for familiar
nition of familiar tunes correlated with the volume of the tunes than healthy controls (Crystal et al., 1989;
right anterior temporal lobe. Bartlett et al., 1995; Cuddy and Duffin, 2005), including
Persons with AD appear to retain the ability to recog- several case studies of musicians with AD (Beatty et al.,
nize pitch or rhythmic errors in familiar tunes (e.g., 1994; Cowles et al., 2003; Omar et al., 2010). However,
wrong notes). For example, patient EN, who was in the when given a multiple-choice format, the AD patients
severe stages of AD (Mini-Mental State Examination may be able to improve their score to the level of the con-
score of 8), was able to correctly identify familiar mel- trols (Cowles et al., 2003; Johnson et al., 2011), suggest-
odies with wrong notes (pitch errors) for 25 out of ing that the knowledge about the tunes may be intact but
26 tunes (Cuddy and Duffin, 2005). In another group the ability to access the verbal labels (titles) may be
study, Johnson and colleagues (2011) examined the abil- impaired.
ity of mildly demented patients with AD to detect pitch It also appears that AD patients are generally able to
errors in highly familiar melodies. The AD patients per- discriminate two short, unfamiliar melodic excerpts that
formed similarly to matched controls, and, as expected, may differ in a number of melodic aspects, such as pitch
the key-violating pitch errors were easier to detect than or rhythm. For example, two studies used the Scale subt-
key-preserving pitch errors for both groups. Perfor- est from the Montreal Battery for the Evaluation of
mance on this familiar melody pitch detection task cor- Amusia, which asks participants to listen to two unfamil-
related with gray-matter volume in the right temporal iar melodies and determine if the second melody was the
cortex, as measured by voxel-based morphometry anal- same as or different from the first melody. Half of the
ysis of brain MRI. Another recent study found variabil- second melodies in the Scale subtest have an alteration of
ity (ranging from 35% to 100% correct) in the ability of one pitch (note). Both studies found that mildly
moderate to severely impaired AD patients to detect demented AD patients performed similarly to healthy
errors in familiar tunes (Vanstone and Cuddy, 2010). controls, suggesting that AD patients are able to process
Several studies have evaluated the ability of persons novel melodic information that is presented in relatively
with AD to generate a title for familiar tune (i.e., name brief formats (Hsieh et al., 2011; Johnson et al., 2011).
that tune) as another way to assess knowledge about Omar and colleagues (2010) examined other aspects of
familiar melodies. As discussed above, generating a title unfamiliar melody processing in their case report of
for a familiar melody requires a different type of cogni- WW, who scored below controls on tasks that required
tive process (e.g., verbal recall) compared with recogniz- the processing of interval and timbre in unfamiliar mel-
ing melodies with errors. After listening to an excerpt odies. In contrast, WW was able to discriminate unfamil-
from a familiar melody, participants are asked to gener- iar melodies that differed by alterations in scale,
ate the title or select the correct title in a multiple-choice contour, and rhythm.
676 J.K. JOHNSON AND M.L. CHOW
In several other studies, the explicit short-term mem- 2 months (Cowles et al., 2003). Raters judged the quality
ory for unfamiliar melodies was examined in persons of his violin playing as “slightly better than that of a good
with AD. One study required participants to listen to high school violinist.” Another reported that a profes-
eight unfamiliar melodies (presented twice) and then sional pianist in the severe stages of AD was able to learn
make old/new judgments about a new set of melodies and recall a new eight-bar composition (Fornazzari et al.,
(half of which were novel) (Halpern and O’Connor, 2006). However, reports like these are quite rare, and it is
2000). Persons with AD performed similarly to controls, not yet known if the ability to learn a new musical com-
but worse than younger adults, on the explicit music position is common in more than just a few exceptional
memory task. However, both AD and age-matched con- cases of AD.
trols performed near chance. Two other studies found There has been a recent interest in studying “auditory
that AD patients scored lower than controls on a task objects” in persons with dementia. Auditory objects can
requiring explicit memory for unfamiliar melodies be defined as a “collection of acoustic data bound in a
(Bartlett et al., 1995; Quoniam et al., 2003). Implicit common perceptual representation an disambiguated
memory for unfamiliar melodies may also be impaired from the auditory scene” (p. 617) (Goll et al., 2010b)
in persons with AD. Implicit memory for unfamiliar These studies often consider basic levels of musical
music was examined by asking persons with AD to listen sound processing in addition to higher levels of sound
to unfamiliar melodies over several trials and rate their conceptualization. For example, Goll and colleagues
preference, with the idea that preference ratings increase (2011) completed a systematic study of non-verbal sound
after more exposure to the melodies (“mere exposure processing, including music, in 21 persons with AD (and
effect”). One study found that the preference ratings other neurodegenerative diseases, also discussed below).
increased with the number of presentations for AD They found that AD patients scored lower than controls
patients (Quoniam et al., 2003), while another study on timbre and pitch perception; however, after adjusting
did not find this pattern (Halpern and O’Connor, for performance on a spatial working-memory task, the
2000). The studies included patients with different AD patients performed similarly to controls. As dis-
dementia severity, and the tasks were slightly different, cussed below, patients with progressive non-fluent apha-
so it is difficult to make comparisons. sia and logopenic aphasia had difficulty with timbre
Other aspects of music processing, such as pitch dis- perception. In contrast, the AD patients had a dispropor-
crimination, recognition of major versus minor tonality tionate impairment on a task that required recognition of
(e.g., scale, chords), timbre and meter perception, are degraded sounds based on perceptual rather than seman-
rarely examined in detail. However, a few studies sug- tic information, even after adjustment for spatial
gest that the the processing of basic music components working-memory performance. On this task, partici-
may remain relatively intact in persons with AD. For pants were asked to decide whether a degraded sound
example, several studies report intact pitch discrimina- was more like an animal calling or a tool being used.
tion (Johnson et al., 2011; Goll et al., 2012a), meter per-
ception (Cowles et al., 2003), tonality discrimination
Frontotemporal dementia
(Mohr et al., 1990), and timbre perception (Goll
et al., 2010b). Although the initial studies about music and dementia
Only a few studies have examined the auditory pro- focused on persons with AD, more recent studies have
cessing of rhythmic information in music with persons examined music abilities in persons with non-AD demen-
with AD. Two case studies administered a modified ver- tias, including the variants of FTD. Several case studies
sion of the Seashore Rhythm subtest from the Seashore of persons with semantic dementia have recently been
Test of Musical Talent. Both ML and SL were able to published. For example, a 56-year-old professional trum-
complete this task, which requires participants to judge pet player and music teacher (BR) completed an exten-
whether two rhythmic patterns are the same or different sive battery of tests to examine his music abilities after
(Beatty et al., 1999; Cowles et al., 2003). The recognition developing semantic dementia (Omar et al., 2010). On
of meter (waltz vs march) was intact in patient SL tests of music perception (from the Montreal Battery
(Cowles et al., 2003). However, additional studies are for the Evaluation of Amusia), he scored lower than con-
needed to make more general conclusions about rhythm trols on the recognition of melodic contour (shape of the
perception in persons with AD. melody), intervals, and timbre. He also had difficulty
There are a few case reports documenting the ability recognizing emotions in music and identifying the
of persons with AD to learn new music. One case report sounds of musical instruments. He was, however, able
described an 80-year-old amateur violinist (SL) with to play familiar pieces from memory after music cueing
moderately severe AD who was able to learn a new, mod- and continued to play his trumpet (non-professionally).
erately difficult violin composition over six sessions over As another example, a 64-year-old semiprofessional
 HEARING AND MUSIC IN DEMENTIA 677
harpsichordist diagnosed with semantic dementia was performed in public (despite the lack of prior training
able to perform technically demanding compositions in music composition). The third patient was a skilled
and generate appropriate stylistic embellishments 5 years musician who also composed songs. Tzortzis and
after the onset of semantic dementia (Weinstein et al., colleagues (2000) performed a comprehensive examina-
2011). However, additional tests of music perception tion of music abilities of a professional pianist and
were not administered with the harpsichordist. composer with a 9-year history of progressive aphasia.
There have also been a few group studies involving They administered a series of tests that focused on
patients with semantic dementia (who are mostly non- receptive music skills (e.g., pitch error detection, identi-
musicians). These studies suggest that, while several fication of chords and musical styles) and expressive
aspects of music knowledge can remain preserved in music skills (e.g., playing music from memory, reading
semantic dementia, they may have difficulty processing an unfamiliar musical score). They found a consistent
familiar melodies. When examining the recognition of preservation of both receptive and expressive music
familiar melodies, two studies found that patients with skills, and the patient continued to compose music.
semantic dementia had difficulty in either detecting The famous French composer, Maurice Ravel, is another
“wrong notes” (pitch errors) in familiar tunes or judging example of a musician who developed a progressive
if a tune was familiar or novel (Hsieh et al., 2011; Johnson aphasia and apraxia but was able to compose for a time
et al., 2011). Patients with semantic dementia also had after the onset of symptoms (Amaducci et al., 2002). The
significant difficulty generating titles for familiar melo- progression symptoms, however, eventually affected his
dies or selecting the famous title from a four-item ability to compose, although Ravel reported that he
multiple-choice format. However, Omar and colleagues could “hear” the music in his head. Additional studies
(2010) found that their 56-year-old trumpet player with are needed to better understand the effect of progressive
semantic dementia could match titles to several famous aphasia on music skills.
melodies. It is important to keep in mind, however, that
the majority of case studies involve persons who have a
Parkinson’s disease
background in music, while most of the group studies
involve non-musicians with varying degrees of involve- Only a few studies to date have focused on the percep-
ment in music. tion of music in persons with Parkinson’s disease. Most
Several other studies have documented an increased studies have focused on rhythmic auditory cueing (using
interest in music after developing semantic dementia music) to improve gait in Parkinson’s disease (e.g., Thaut
(Miller et al., 2000; Boeve and Geda, 2001; Hailstone et al., 2001). One study examined rhythm discrimination
et al., 2009) and a change in music taste (new interest in 15 persons with Parkinson’s disease (with Hoehn and
in pop music) in a person with FTD (Geroldi et al., Yahr stages 1 or 2) (Grahn and Brett, 2009). The authors
2000). Barquero and colleagues (2010) studied a administered a series of rhythm recognition tasks with
53-year-old music critic whose first symptom was a com- and without a clear beat. The results suggested that
plaint about trouble evaluating the “quality of a musical the patients with Parkinson’s disease had difficulty per-
performance.” Although her neurologic and neuropsy- ceiving the beat structure, compared with matched con-
chologic examinations were normal, she had difficulty trols. However, the patients performed similarly to
differentiating renditions of music performed by either controls in the non-beat conditions. Another study found
a professional or a beginner music student. It appears that patients with Parkinson’s disease had difficulty rec-
that her ability to recognize various music elements ognizing fear and anger in music (van Tricht et al., 2010).
(e.g., melodies, pitch errors, rhythm, and meter) was pre- In this study, participants were asked to listen to
served at that time, although the specific tasks and 32 music excerpts and determine whether they expressed
results are not available. She later developed a progres- happiness, sadness, fear, or anger. Interestingly, the per-
sive dementia syndrome and was diagnosed with FTD sons with Parkinson’s disease were able to correctly iden-
caused by a novel progranulin mutation. An autopsy tify happiness and sadness in the music but had more
revealed ubiquitin-positive inclusions, particularly in difficulty identifying anger and fear (Fig. 37.3). The
the frontal, temporal, and parietal cortices. authors argued that the patients did not have deficits
A few studies have focused on persons with progres- in the processing of music, as they performed similarly
sive aphasia. For example, Miller and colleagues (2000) to controls on two subtests from the Montreal Battery
studied three individuals with progressive language for the Evaluation of Amusia (i.e., melodies, rhythm).
symptoms (variants of primary progressive aphasia). The difficulty identifying fear and anger in music was
One non-musician developed compulsive whistling and consistent with other studies suggesting that persons
composed songs about a bird, and the other non- with Parkinson’s disease have difficulty recognizing
musician began composing classic music that was emotions.
678 J.K. JOHNSON AND M.L. CHOW
Emotion recognition in PD patients and healthy controls persons with either premanifest or manifest Hunting-
ton’s disease (Saft et al., 2008). The authors found
8 reduced activation of basal ganglia-thalamic circuits in
premanifest Huntington’s disease, but persons with clin-
7 + +
ically evident Huntington’s disease had hyperactivation
6 of the same structures when listening to a sequence of
Number correct

tones. The authors suggested that this pattern reflected

5
functional reorganization of brain areas in an attempt to
4 + maintain auditory function.
The basal ganglia has been an area of interest in inves-
3
tigations of sound processing because of its role in
2 attention-dependent temporal processing (Buhusi and
Meck, 2005; Langers and Melcher, 2011). In particular,
1
this region interacts with the supplementary motor area
and the cerebellum for the temporal processing of
Anger Fear Happiness Sadness
sounds Macar et al., 2006; Ivry and Schlerf, 2008;
Fig. 37.3. Identification of emotions in music by persons with
Coull et al., 2011). Apart from these few studies, there
Parkinson’s disease (PD). Box plot of the scores on the four
subtests of the emotion recognition task in PD patients (black
does not appear to be any further systematic studies
lines, gray boxes) and controls (gray lines, white boxes). On of music processing in persons with Huntington’s
the happiness subtest all subjects obtained the maximum score, disease.
except two subjects (+). For the fear recognition subtask, none
of the controls scored below 5, therefore the downward error
Recognition of emotions in music
bar is absent. (Reproduced from van Tricht et al., 2010, with
permission.) The link between music and emotions has been debated
for centuries. An interest in how humans perceive the
emotional content in music or how an emotional
Huntington’s disease
response to music is generated has increased in recent
Woodie Guthrie (1912–1967) is perhaps the most famous years (Juslin and Sloboda, 2010). There are a number
musician to have developed Huntington’s disease. Guth- of cues that convey emotions in music. For example, a
rie performed during the early stages of the disease, but listener may visually perceive the gestures of a per-
it eventually affected his music career and ability to sing former that reflect emotions. Listeners might also hear
and play (Arevalo et al., 2001; Innes and Chudley, 2002). musical cues, such as tempo or tonality of a piece, that
His impact on the genre of folk music resulted in his convey emotional information. For the purposes of this
induction into the Rock and Roll Hall of Fame in 1988. chapter, we will focus on the recognition of emotions
The impact of Huntington’s disease on the music abili- while listening to music in persons with dementia.
ties of Guthrie was never formally studied, but a few Several recent studies have examined the recognition
studies have examined the processing of music in per- of emotions in music in persons with both AD and non-
sons with Huntington’s disease. For example, Beste AD dementias. Hsieh and colleagues (2011) studied the
and colleagues (2011) examined the brain response (using recognition of emotions in music with 11 persons with
functional MRI) to three types of auditory stimulation semantic dementia, 12 with AD, and 20 healthy controls.
(music, tones, and syllables) in persons with either pre- They administered 40 unfamiliar music excerpts that
manifest Huntington’s disease or manifest Huntington’s represented four emotions (happy, peaceful, sad, or
disease. The music condition included listening to a scary). The participants were asked to listen to the
piano piece by French composer Charles-Valentin Alkan excerpt and select the emotion that best represented
(“Barcarole”). Compared to controls, the persons with the music. Both semantic dementia and AD patients
Huntington’s disease had increased activation in the cer- scored lower than controls in identifying the emotions
ebellum and medial prefrontal cortex and reduced activ- associated with the music, but the semantic dementia
ity in the left parahippocampal gyrus and right fusiform patients performed substantially worse than the AD
gyrus when listening to a musical composition. In addi- patients. The authors also found that the semantic
tion, the authors found that the processing of music was dementia patients had particular difficulty when identi-
correlated with the severity of the movement disorder. fying negative (sad or scary) compared to positive emo-
Another study used an auditory stimulation paradigm tions (happy or peaceful) in the music. In addition, both
(sequence of tones) and functional MRI methods to AD and semantic dementia patients had more difficulty
examine the basal ganglia-thalamic brain circuits in identifying emotions in music than emotions in faces.
 HEARING AND MUSIC IN DEMENTIA 679
there are mechanic and environmental sources of sounds
(Griffiths and Warren, 2004; Engel et al., 2009). There
have been a number of studies that examine how non-
verbal (non-musical) sounds are processed in neurode-
generative diseases.
In one of the early studies about non-verbal sound
processing in AD, Rapcsak and colleagues (1989) used
a sound–picture-matching task to evaluate the proces-
sing of non-verbal sounds in AD. The authors found that
patients with mild to severe AD had considerable diffi-
Fig. 37.4. Correlation between performance on music emo-
culty selecting the correct picture that corresponded to
tions task and brain atrophy. Voxel-based morphometry ana-
lyses showing brain regions that correlate with recognition of the non-verbal sound. In contrast, the AD patients had
musical emotions (top left: Montreal Neurological Institute no difficulty selecting the correct picture when the
(MNI), x ¼ 46, y ¼ 12, z ¼ 46; top right: MNI, x ¼ 40, examiner verbalized the names. Other studies have also
y ¼ 6, z ¼ 48). Colored voxels are significant at P < 0.001 documented difficulty with selecting pictures to match
uncorrected. (Reproduced from Hsieh et al., 2012, with non-verbal sounds in persons with AD (Eustache et al.,
permission.) 1995; Brandt et al., 2010).
A few studies have examined the processing of envi-
ronmental sounds in non-AD dementias. For example,
A similar pattern was observed in two case studies, one Bozeat and colleagues (2000) used 48 sounds from six
with AD and the other with semantic dementia (Omar categories (domestic animals, foreign animals, human
et al., 2010). These initial studies suggest that persons sounds, household items, vehicles, and musical instru-
with AD and semantic dementia have deficits in recog- ments) to study non-verbal sound processing in
nizing emotions in music when it is just presented as 10 patients with semantic dementia. They asked the
an auditory stimulus. patients to match sounds to pictures, sounds to written
Hsieh and colleagues (2012) also examined the corre- words, and spoken words to pictures using an array with
lation between the performance on the music emotions 10 within-category items. They also administered a neu-
task with the amount of atrophy on the brain MRI using ropsychologic battery of general semantic knowledge.
voxel-based morphometry. They found that perfor- The semantic dementia patients performed below con-
mance on this task was correlated with brain atrophy trols on all the tasks involving the environmental sounds.
in the right anterior temporal pole, insula, and amygdala They also found significant correlations between the
(Fig. 37.4). That is, the patients who had the most diffi- environmental sounds tasks and verbal tests of semantic
culty identifying the emotions in the music excerpts had knowledge, suggesting that the semantic breakdown in
the most atrophy in these areas. Interestingly, there was patients with semantic dementia extends to both verbal
some overlap between the brain areas involved in per- and non-verbal information.
ceiving emotions in music and those involved in perceiv- In another study involving patients with two atypical
ing emotions in faces. Apart from these few studies with parkinsonian disorders (corticobasal degeneration, pro-
AD and semantic dementia, the recognition of emotions gressive supranuclear palsy), AD, and FTD, Chow and
in other types of neurodegenerative disorders is largely colleagues (2010) examined the naming sounds gener-
unexplored. ated from both manipulable (e.g., hammer) and non-
manipulable objects (e.g., train). An item was considered
manipulable if the action required to make the sound
PROCESSING OF NON-VERBAL SOUNDS
required manual manipulation by the hand. They found
IN NEURODEGENERATIVE DISEASES
that the patients with corticobasal degeneration or pro-
In addition to the studies involving music reviewed gressive supranuclear palsy named significantly fewer
above, there are a number of other studies that have sounds than controls or patients with AD or FTD, who
examined the processing of non-verbal (non-musical) typically do not have prominent motor symptoms. In
sounds in persons with neurodegenerative diseases. Sev- addition, the corticobasal degeneration and progressive
eral authors have provided a framework for categorizing supranuclear palsy patients had a disproportionate
non-verbal sounds that occur in the environment. Taken impairment in the ability to name the sounds from
broadly, there are sounds produced by both living (bio- manipulable objects. Interestingly, action naming and
logic) and non-living (non-biologic) agents. Within the verb production are often impaired in patients with cor-
living category, there are sounds produced by both ticobasal degeneration and progressive supranuclear
humans and animals; within the non-living category, palsy (Bak et al., 2006; Cotelli et al., 2006). These
680 J.K. JOHNSON AND M.L. CHOW
findings suggest that the ability to physically manipulate Left hemisphere Right hemisphere
an object is related to the ability to name an object and
6
suggest a link between the auditory system, cognition,
5
and the motor system. Chow and colleagues (2010) also

Animal sounds
4
found a correlation between performance on naming

mSTG
sounds of manipulable objects and gray-matter volume 3

on MRI in the left, premotor areas and left dorsolateral 2

prefrontal cortex. 1

% signal change
As discussed above, Goll and colleagues (2012a) 0

recently assessed auditory scene analysis, the ability to 3

parse sound sources in the auditory environment, of both 2

pLaS
verbal and non-verbal sounds in a cohort of 21 persons 1
with AD. The persons with AD performed much worse 0

Tool sounds
than matched controls on both auditory scene analysis −1
tasks, but the performance was somewhat attenuated 3
after accounting for visuospatial working memory. They 2
also found that performance correlated with brain vol-

pMTG
1
ume in several posterior cortical areas, using voxel-
0
based morphometry of brain MRI. The temporal lobe Control
SD −1
has also been implicated in the central auditory dysfunc-
tion of patients with other neurodegenerative diseases. Fig. 37.5. Category-specific contrast effects sampled at previ-
Patients with semantic dementia showed differential ously specified foci of category-specific semantic sound pro-
activation of the temporal lobe when listening to animal cessing. Bars show mean effect sizes (proportionate to percent
and tool sounds in a functional MRI paradigm (Goll blood oxygen level-dependent (BOLD) signal change) for the
control and semantic dementia (SD) patient groups separately
et al., 2012b) (Figs 37.5 and 37.6). The paradigm involved
for the category-specific semantic contrast at prespecified
the perceptual processing of spectrotemporally complex
foci of category-specific auditory processing (based on
but meaningless sounds and for the semantic processing Lewis et al., 2005); 95% confidence intervals are also dis-
of environmental sound category (animal sounds versus played. The upper panels show effects at foci previously asso-
tool sounds). Thus, anterolateral temporal cortical mech- ciated with animal sound processing in the contrast assessing
anisms may be necessary for the representation and dif- category-specific semantic processing favoring animal
ferentiation of sound categories. sounds, [(mful_a – mless_a) – (mful_t – mless_t)]; whilst
The processing of non-verbal auditory signals has the lower panels show effects at foci previously associated
also been studied using electrophysiology and other with tool sound processing in the reverse contrast assessing
brain-imaging methods in persons with neurodegenera- category-specific semantic processing favoring tool sounds,
tive diseases. For example, event-related potentials [(mful_t – mless_t) – (mful_a – mless_a)]. Asterisks above
bars indicate significance levels for the control and SD groups
(ERPs) can be measured on the scalp (after stimulus
separately; asterisks above brackets indicate significance
onset) and can provide estimates of the activity of spe-
levels for between-group comparisons. *P < 0.05; **P <
cific brain areas involved in the processing of sensory 0.01; ***P < 0.001; mSTG, middle superior temporal gyrus;
information. With auditory stimuli, electrical potentials pLaS, posterior lateral sulcus; pMTG, posterior middle
can be measured beginning in the brainstem (as with temporal gyrus; SD, semantic dementia. (Reproduced from
brainstem auditory evoked potential) up to brain net- Goll et al., 2012b, with permission.)
works involved in both primary and secondary auditory
cortices (P50, N100, N200) as well as association cortex
(N200, P300). These scalp recordings are often recorded Although the various potentials have been studied in
(using electroencephalograph (EEG) electrodes) when persons with dementia, the P300 brain potential is
participants perform a behavioral task. The oddball task thought to be important in the study of AD, particularly
is commonly used in electrophysiologic studies of neuro- in the early stages. Again, the majority of studies have
degenerative diseases. The oddball task requires subjects been done in persons with AD. Persons with AD have
to listen to a sequence of repeating tones (e.g., 1000 Hz) long been known to exhibit prolonged peak P300 latency
with a constant speed and press a button when they hear and decreased P300 amplitude (Polich et al., 1990; Holt
an oddball or deviant tone (e.g., 2000 Hz). In this oddball et al., 1995; Polich and Pitzer, 1999) compared with
paradigm, the deviant tones elicit a series of electric healthy controls. The differences in amplitude and
potentials that can be measured over time using EEG latency may be used to help differentiate between
methods. healthy individuals and those with preclinical or early
 HEARING AND MUSIC IN DEMENTIA 681

Fig. 37.6. Statistical parametric maps showing activation profiles for perceptual and semantic processing of environmental sounds
in healthy controls and patients with semantic dementia. Statistical parametric maps show clusters (formed at whole-brain uncor-
rected height threshold P < 0.001) that are significant at extent threshold P < 0.05, family-wise error-corrected for multiple com-
parisons over the whole brain. Maps are rendered on a composite mean normalized structural brain image; the left hemisphere is
shown on the left for all coronal and axial sections. For sagittal and coronal sections the plane is indicated using Montreal Neu-
rological Institute (MNI) coordinates. All axial slices are tilted parallel to the superior temporal plane to show key auditory regions;
the anatomic plane of view is indicated. SD, semantic dementia; STP, superior temporal plane; STS, superior temporal sulcus.
Panels a and b: the color bar (left) codes voxel-wise T scores for contrast (meaningless sounds > silence). Panel c: all clusters
showing a significant interaction with group (patient > control) for the contrast (all meaningless sounds > silence) are depicted
in either magenta or cyan. Magenta codes voxels in which controls alone showed greater activation in the reverse contrast (silence
> meaningful sounds) than the forwards (meaningless sounds > silence) contrast, indicating that the group interaction within these
voxels may be driven by greater activation for controls compared to patients in the reverse contrast. However, remaining voxels,
coded in cyan, are likely to be driven by greater activation for patients compared to controls in the forwards contrast. Panels d and e:
green codes significant clusters in the contrast assessing the category-specific semantic processing favoring animal sounds,
[(mful_a–mless_a) – (mful_t–mless_t)]; blue codes significant clusters in the contrast assessing category-specific semantic pro-
cessing favoring tool sounds, [(mful_t – mless_t) – (mful_a – mless_a)]. Panel f: all clusters showing a significant interaction with
group (patient > control) for the contrast assessing category-specific semantic processing favoring animal sounds are depicted in
either magenta or cyan. Magenta codes voxels in which controls alone showed greater activation in the reverse contrast (category-
specific semantic processing favoring tool sounds) than the forwards (category-specific semantic processing favoring animal
sounds) contrast, indicating that the group interaction within these voxels may be driven by greater activation for controls com-
pared to patients in the reverse contrast; however, remaining voxels, coded in cyan, are likely to be driven by greater activation for
patients compared to controls in the forwards contrast. (Reproduced from Goll et al., 2012b, with permission.)

AD (Polich and Pitzer, 1999; Golob et al., 2002, 2007). ERP measures may also be helpful in differentiating
In another study, Golob and colleagues (2007) found dementia etiologies. For example, the P300 latency, ampli-
significantly larger P50 and N100 amplitudes (using an tude, and topography may differ between individuals with
auditory oddball task) in amnestic MCI patients who DLB and AD (Bonanni et al., 2010). These measures may
eventually converted to AD, compared with those who also help distinguish between patients with Parkinson’s
remained stable. The P50 and N100 amplitudes were also disease with and without cognitive impairment
larger in the MCI converters than those with mild AD, (Nojszewska et al., 2009). Although few in number,
suggesting that these potentials may reflect the neural ERP methods have also been used to study non-verbal
activity during the transition from MCI to AD. auditory processing and attention in other non-AD
Figure 37.7 shows the P50 and N100 results for each of dementias, such as Huntington’s disease (Uc et al.,
the groups studied (young adults, older adults, MCI sta- 2003; Beste et al., 2008), vascular cognitive impairment
ble, MCI converters, and mild AD). P300 latency was (Muscoso et al., 2006), and primary progressive aphasia
also increased in MCI converters, but the P300 did not (Onofrjet al., 1994). Thus, auditory potentials may differ
differentiate the MCI converters from the mild AD according to the degree of cognitive impairment and also
patients. help distinguish dementia etiologies.
682 J.K. JOHNSON AND M.L. CHOW
The early evidence for the positive impact of music on
persons with dementia came out of the music therapy
and nursing literature in the 1980s. These studies focused
on using music activities to manage behavioral symp-
toms and increase alertness in persons who were in the
severe stages of dementia (Norberg et al., 1986;
Millard and Smith, 1989). Since these early studies, the
number of studies examining the effect of music inter-
ventions on persons with dementia has increased
steadily. However, it is important to keep in mind that
there are concerns about the methodologic quality of
many of these studies, as articulated in the most recent
Cochrane Collaboration review (Vink et al., 2004), which
was updated in 2011 again with the statement, “There is
no substantial evidence to support nor discourage the
use of music therapy in the care of older people with
dementia” (Vink et al., 2011). The studies have been crit-
icized with regard to the research design, small sample
sizes, short length of interventions, and presentation
of results. Keeping these limitations in mind, however,
the section below will review the primary areas of
research and promising leads about the effects of music
interventions for persons with dementia. There is clearly
a need for higher-quality studies about the therapeutic
effects of music on persons with dementia, particularly
because non-pharmacologic interventions, like music,
can be relatively low-cost to implement and easily trans-
lated in many different settings. There is also a need to
Fig. 37.7. P50 and N100 results for five subject groups. Event-
improve the tools for assessing the effect of music on
related potentials to non-targets during the baseline session in all
older subjects (A), mild cognitive impairment (MCI) subtypes
persons with dementia. This area of inquiry remains of
(B), and young and older controls (C). (D) P50 amplitudes from high interest, which can be inferred by the publication
individual MCI subjects (MCI single domain (MCI-SD) and of several recent reviews (Wall and Duffy, 2010;
MCI multiple domain (MCI-MD)). Mean  1 SD from controls McDermott et al., 2012; Raglio et al., 2012).
are also shown for comparison. Group comparisons of P50 (E) The majority of research about the therapeutic effects
and N100 (F) amplitudes. Note that in panel F negative poten- of music for persons with dementia has focused on using
tials are plotted upwards because the N100 is negative in polar- music to help reduce behavioral and psychologic symp-
ity. Vertical lines indicate stimulus onset. Asterisks show post toms, such as agitation, aggression, anxiety, and depres-
hoc tests indicating significant differences between pairs of sion. A number of studies have concluded that music
groups, shown by insert (*P < 0.05, **P < 0.01). (Reprinted interventions, such as music listening or group music
from Golob et al., 2007, with permission.)
therapy sessions, were associated with reduced agitation
in persons with dementia (Groene, 1993; Clark et al.,
1998; Gerdner, 2000; Sung et al., 2006; Janata, 2012).
It is important to note that the majority of these studies
enrolled persons who met criteria for dementia, but most
MUSIC AS THERAPY FOR DEMENTIA
studies did not stipulate specific dementia diagnoses. It
Music has also been used as a therapeutic intervention is likely that the effect of music on behavioral symptoms
for persons with dementia. The music activities range will differ depending on the dementia diagnosis. In a
from informal (e.g., background music in assisted-living recent study with an improved study design, Vink and
environments) to more formal approaches, such as with colleagues (2012) randomly assigned 77 persons with
music therapy – defined as the use of music to accom- dementia (34% AD, 21% vascular dementia, 35% other
plish specific therapeutic goals within a therapeutic rela- or missing) to either 4 months of music therapy (twice
tionship with a board-certified music therapist. weekly) or recreational activities (active control). Both
Additional information about the use of music with interventions were associated with a reduction in agitation
dementia can be found in Clair and Memmott (2008). from before to after the sessions (as measured by a
 HEARING AND MUSIC IN DEMENTIA 683
modified version of the Cohen-Mansfield Agitation therapy had positive effects on several motor outcomes
Inventory), but there were no significant differences (i.e., Berg Balance Scale, Timed Up and Go, and stride
between the effects of music or recreational activities length) but not the Unified Parkinson’s Disease rating
on agitation. motor scale (de Dreu et al., 2012). These results suggest
Several studies have also found a reduction in symp- that additional research is needed to explore the possible
toms of anxiety and depression after various music benefit of music-based movement therapy for persons
interventions. For example, Guetin and colleagues with Parkinson’s disease.
(2009) randomly assigned 30 mild to moderately severe
patients with AD in assisted living to either 4 months of
weekly music therapy sessions or a control group. The SUMMARY
patients with AD who completed the music therapy ses- This chapter provided a broad overview of hearing in
sions had significantly lower scores on Hamilton Anxi- persons with neurodegenerative diseases, with a partic-
ety Scale scores. This effect persisted another ular focus on the auditory processing of music as one
2 months after the music therapy sessions ended. Other type of auditory stimulus. The literature suggests that
studies also report a reduction in anxiety and depression the processing of music information differs by dementia
after various music interventions (Ashida, 2000; Han etiology. Impairments in the central auditory system are
et al., 2010; Sung et al., 2010, 2012). common in persons with various neurodegenerative dis-
Several studies have also attempted to examine the eases. A number of case reports document a relative
possible effect of music interventions on cognitive func- preservation of music abilities in persons with AD, par-
tion in persons with dementia. For example, one study ticularly for playing a musical instrument, processing of
found improved spontaneous speech content and lan- basic aspects of music, and making judgments about
guage fluency (as measured by the Western Aphasia Bat- familiar melodies. However, persons with AD have dif-
tery speech subscale) in a group of mild to severely ficulty with the short-term memory for music excerpts.
impaired persons with dementia following 2 months of Studies with persons with semantic dementia suggest
music therapy, compared to conversation sessions. that aspects of music knowledge may remain preserved,
Another study examined the effect of a 12-week Sound although they may have difficulty processing familiar
Training for Attention and Memory and Dementia melodies. These studies are few and most include only
(STAM-Dem) program on persons with mild to severe musically trained individuals. Music-based movement
dementia compared to a usual-care group (Ceccato therapy may improve some motor function for persons
et al., 2012). The authors found that the group with with Parkinson’s disease, while it appears that they have
STAM-Dem training had significantly better pre–posttest difficulty with rhythm perception or recognizing some
scores on attention and prose memory but not the test of emotions in music. The processing of auditory stimuli
global cognition (Mini-Mental State Examination). Other in persons with Huntington’s disease appears to engage
studies also document a lack of improvement on the Mini- brain circuits involved in movement. The evidence for
Mental State Examination after various music interven- the positive effect of music on managing behavioral
tions (Groene, 1993; Raglio et al., 2008; Guetin et al., symptoms in AD is encouraging, but higher-quality stud-
2009). This is not surprising because it is unlikely that ies are needed. It is important to keep in mind that per-
global tests of cognition are sensitive enough to detect formance on various music tasks can be affected by the
possible effects of music on cognition. It is difficult to type and severity of dementia. This often makes compar-
know at this stage whether or not music interventions isons across studies difficult. Performance on music
are an effective tool for managing behavioral symptoms tasks can also be affected by the amount of prior music
of dementia, in particular, AD. Despite the limitations of training. The majority of case studies focus on persons
the studies, there appear to be promising trends that sug- who are either professional or amateur musicians, while
gest that music may be an effective therapeutic tool, and many of the group studies include persons with different
additional studies are needed. levels of music background. The studies about music
Music-based movement therapy (Thaut et al., 1996) processing in neurodegenerative diseases are also help-
has also been used to help improve gait and balance in ing improve the understanding about how the brain pro-
persons with Parkinson’s disease. This type of interven- cesses music information.
tion is based on the premise that the temporal structure in
music helps provide meaningful auditory cues that facil-
itate synchronization of movement, such as gait REFERENCES
(Madison et al., 2011). A recent meta-analysis of six ran- Aarsland D, Andersen K, Larsen JP et al. (2003). Prevalence
domized controlled trials involving persons with Parkin- and characteristics of dementia in Parkinson disease: an
son’s disease concluded that music-based movement 8-year prospective study. Arch Neurol 60 (3): 387–392.
684 J.K. JOHNSON AND M.L. CHOW
Alzheimer’s Association (2012). 2012 Alzheimer’s disease Biglan KM, Zhang Y, Long JD et al. (2013). Refining the diag-
facts and figures. Alzheimers Dement 8 (2): 131–168. nosis of Huntington disease: the PREDICT-HD study.
Amaducci L, Grassi E, Boller F (2002). Maurice Ravel and Front Aging Neurosci 5: 12.
right-hemisphere musical creativity: influence of disease Boeve BF, Geda YE (2001). Polka music and semantic demen-
on his last musical works? Eur J Neurol 9 (1): 75–82. tia. Neurology 57 (8): 1485.
American Psychiatric Association (2000). Diagnostic and Bonanni L, Franciotti R, Onofrj V et al. (2010). Revisiting
Statistical Manual of Mental Disorders, text revision, P300 cognitive studies for dementia diagnosis: early
4th ed. American Psychiatric Association, Washington, DC. dementia with Lewy bodies (DLB) and Alzheimer disease
Ames D, Burns A, O’Brien J (2010). Dementia. CRC Press, (AD). Neurophysiol Clin 40 (5–6): 255–265.
Boca Raton, Fl. Bozeat S, Lambon Ralph MA, Patterson K et al. (2000). Non-
Arevalo J, Wojcieszek J, Conneally PM (2001). Tracing verbal semantic impairment in semantic dementia.
Woody Guthrie and Huntington’s disease. Semin Neurol Neuropsychologia 38 (9): 1207–1215.
21 (2): 209–223. Brandt J, Bakker A, Maroof DA (2010). Auditory confronta-
Armstrong MJ, Litvan I, Lang AE et al. (2013). Criteria for the tion naming in Alzheimer’s disease. Clin Neuropsychol
diagnosis of corticobasal degeneration. Neurology 80 (5): 24 (8): 1326–1338.
496–503. Brattico E, Tervaniemi M, Naatanen R et al. (2006). Musical
Ashida S (2000). The effect of reminiscence music therapy scale properties are automatically processed in the human
sessions on changes in depressive symptoms in elderly per- auditory cortex. Brain Res 1117 (1): 162–174.
sons with dementia. J Music Ther 37 (3): 170–182. Buhusi CV, Meck WH (2005). What makes us tick? Functional
Bak TH, Yancopoulou D, Nestor PJ et al. (2006). Clinical, and neural mechanisms of interval timing. Nat Rev
imaging and pathological correlates of a hereditary deficit Neurosci 6 (10): 755–765.
in verb and action processing. Brain 129 (Pt 2): 321–332. Ceccato E, Vigato G, Bonetto C et al. (2012). STAM protocol
Baloyannis SJ, Mauroudis I, Manolides SL et al. (2011). The in dementia: a multicenter, single-blind, randomized, and
acoustic cortex in frontotemporal dementia: a Golgi and elec- controlled trial. Am J Alzheimers Dis Other Demen 27
tron microscope study. Acta Otolaryngol 131 (4): 359–361. (5): 301–310.
Barquero S, Gomez-Tortosa E, Baron M et al. (2010). Amusia Chance SA, Clover L, Cousijn H et al. (2011).
as an early manifestation of frontotemporal dementia Microanatomical correlates of cognitive ability and
caused by a novel progranulin mutation. J Neurol 257 (3): decline: normal ageing, MCI, and Alzheimer’s disease.
475–477. Cereb Cortex 21 (8): 1870–1878.
Bartlett JC, Halpern AR, Dowling WJ (1995). Recognition of Chow ML, Brambati SM, Gorno-Tempini ML et al. (2010).
familiar and unfamiliar melodies in normal aging and Sound naming in neurodegenerative disease. Brain Cogn
Alzheimers-disease. Mem Cognit 23 (5): 531–546. 72 (3): 423–429.
Beatty WW (1988). Preserved musical skill in a severely Clair AA, Memmott J (2008). Therapeutic uses of music with
demented patient. Int J Clin Neuropsychol 10: 158–164. older adults, 2nd edn. American Music Therapy
Beatty WW (1999). Preserved cognitive skills in dementia: Association, Silver Spring, MD.
implications for geriatric medicine. J Okla State Med Clark ME, Lipe AW, Bilbrey M (1998). Use of music to
Assoc 92 (1): 10–12. decrease aggressive behaviors in people with dementia.
Beatty WW, Greiner F (1998). Preserved musical and game- J Gerontol Nurs 24 (7): 10–17.
playing skill in dementia. Psychol Beitr 40: 66–84. Cotelli M, Borroni B, Manenti R et al. (2006). Action and
Beatty WW, Zavadil KD, Bailly RC et al. (1988). Preserved object naming in frontotemporal dementia, progressive
musical skill in a severely demented patient. Int J Clin supranuclear palsy, and corticobasal degeneration.
Neuropsychol 10: 158–164. Neuropsychology 20 (5): 558–565.
Beatty WW, Winn P, Adams RL et al. (1994). Preserved cog- Coull JT, Cheng RK, Meck WH (2011). Neuroanatomical and
nitive skills in dementia of the Alzheimer type. Arch neurochemical substrates of timing. Neuropsychopharma-
Neurol 51 (10): 1040–1046. cology 36 (1): 3–25.
Beatty WW, Brumback RA, Vonsattel JP (1997). Autopsy- Cowles A, Beatty WW, Nixon SJ et al. (2003). Musical skill
proven Alzheimer disease in a patient with dementia who in dementia: a violinist presumed to have Alzheimer’s
retained musical skill in life. Arch Neurol 54 (12): 1448. disease learns to play a new song. Neurocase 9 (6):
Beatty WW, Rogers CL, Rogers RL et al. (1999). Piano play- 493–503.
ing in Alzheimer’s disease: longitudinal study of a single Crystal HA, Grober E, Masur D (1989). Preservation of musi-
case. Neurocase 5: 459–469. cal memory in Alzheimer’s disease. J Neurol Neurosurg
Beste C, Saft C, Gunturkun O et al. (2008). Increased cognitive Psychiatry 52 (12): 1415–1416.
functioning in symptomatic Huntington’s disease as Cuddy LL, Duffin J (2005). Music, memory, and Alzheimer’s
revealed by behavioral and event-related potential indices disease: is music recognition spared in dementia, and how
of auditory sensory memory and attention. J Neurosci 28 can it be assessed? Med Hypotheses 64 (2): 229–235.
(45): 11695–11702. de Dreu MJ, van der Wilk AS, Poppe E et al. (2012).
Beste C, Schuttke A, Pfleiderer B et al. (2011). Music percep- Rehabilitation, exercise therapy and music in patients with
tion and movement deterioration in Huntington’s disease. Parkinson’s disease: a meta-analysis of the effects of
PLoS Curr 3, RRN1252. music-based movement therapy on walking ability,
 HEARING AND MUSIC IN DEMENTIA 685
balance and quality of life. Parkinsonism Relat Disord 18 subtype and conversion to dementia. Brain 130 (Pt 3):
(Suppl. 1): S114–S119. 740–752.
Drayna D, Manichaikul A, de Lange M et al. (2001). Genetic Gorno-Tempini ML, Brambati SM, Ginex V et al. (2008). The
correlates of musical pitch recognition in humans. Science logopenic/phonological variant of primary progressive
291 (5510): 1969–1972. aphasia. Neurology 71 (16): 1227–1234.
Dugger BN, Tu M, Murray ME et al. (2011). Disease specific- Gorno-Tempini ML, Hillis AE, Weintraub S et al. (2011).
ity and pathologic progression of tau pathology in brain- Classification of primary progressive aphasia and its vari-
stem nuclei of Alzheimer’s disease and progressive ants. Neurology 76 (11): 1006–1014.
supranuclear palsy. Neurosci Lett 491 (2): 122–126. Grady CL, Grimes AM, Patronas N et al. (1989). Divided
Engel LR, Frum C, Puce A et al. (2009). Different categories of attention, as measured by dichotic speech performance,
living and non-living sound-sources activate distinct corti- in dementia of the Alzheimer type. Arch Neurol 46 (3):
cal networks. Neuroimage 47 (4): 1778–1791. 317–320.
Eustache F, Lambert J, Cassier C et al. (1995). Disorders of Grahn JA, Brett M (2009). Impairment of beat-based rhythm
auditory identification in dementia of the Alzheimer type. discrimination in Parkinson’s disease. Cortex 45 (1): 54–61.
Cortex 31 (1): 119–127. Griffiths TD, Warren JD (2004). What is an auditory object?
Fornazzari L, Castle T, Nadkarni S et al. (2006). Preservation Nat Rev Neurosci 5 (11): 887–892.
of episodic musical memory in a pianist with Alzheimer Grimes A (1995). Auditory changes. In: R Lubinski (Ed.),
disease. Neurology 66 (4): 610–611. Dementia and Communication, Singular Publishing
Gates GA, Mills JH (2005). Presbycusis. Lancet 366 (9491): Group, San Diego, pp. 47–69.
1111–1120. Grimes AM, Grady CL, Foster NL et al. (1985). Central audi-
Gates GA, Karzon RK, Garcia P et al. (1995). Auditory dys- tory function in Alzheimer’s disease. Neurology 35 (3):
function in aging and senile dementia of the Alzheimer’s 352–358.
type. Arch Neurol 52 (6): 626–634. Groene RW (1993). Effectiveness of music-therapy 1/1 inter-
Gates GA, Anderson ML, Feeney MP et al. (2008). Central vention with individuals having senile dementia of the
auditory dysfunction in older persons with memory impair- Alzheimers type. J Music Ther 30 (3): 138–157.
ment or Alzheimer dementia. Arch Otolaryngol Head Neck Guetin S, Portet F, Picot MC et al. (2009). Effect of music ther-
Surg 134 (7): 771–777. apy on anxiety and depression in patients with Alzheimer’s
Gates GA, Anderson ML, McCurry SM et al. (2011). type dementia: randomised, controlled study. Dement
Central auditory dysfunction as a harbinger of Alzheimer Geriatr Cogn Disord 28 (1): 36–46.
dementia. Arch Otolaryngol Head Neck Surg 137 (4): Hailstone JC, Omar R, Warren JD (2009). Relatively pre-
390–395. served knowledge of music in semantic dementia.
Gennis V, Garry PJ, Haaland KY et al. (1991). Hearing and J Neurol Neurosurg Psychiatry 80 (7): 808–809.
cognition in the elderly. New findings and a review of Halpern AR, O’Connor MG (2000). Implicit memory for music
the literature. Arch Intern Med 151 (11): 2259–2264. in Alzheimer’s disease. Neuropsychology 14 (3): 391–397.
Gerdner LA (2000). Effects of individualized versus classical Han P, Kwan M, Chen D et al. (2010). A controlled naturalistic
“relaxation” music on the frequency of agitation in elderly study on a weekly music therapy and activity program on
persons with Alzheimer’s disease and related disorders. Int disruptive and depressive behaviors in dementia. Dement
Psychogeriatr 12 (1): 49–65. Geriatr Cogn Disord 30 (6): 540–546.
Geroldi C, Metitieri T, Binetti G et al. (2000). Pop music and Head E, Starr A, Kim RC et al. (2006). Relapsing polychondri-
frontotemporal dementia. Neurology 55 (12): 1935–1936. tis with features of dementia with Lewy bodies. Acta
Goll JC, Crutch SJ, Loo JH et al. (2010a). Non-verbal sound Neuropathol 112 (2): 217–225.
processing in the primary progressive aphasias. Brain 133 Hojo, Kawamata T, Tanaka C et al. (2004). Inflammatory glial
(Pt 1): 272–285. activation in the brain of a patient with hereditary sensory
Goll JC, Crutch SJ, Warren JD (2010b). Central auditory dis- neuropathy type 1 with deafness and dementia. Neurosci
orders: toward a neuropsychology of auditory objects. Curr Lett 367 (3): 340–343.
Opin Neurol 23 (6): 617–627. Holt LE, Raine A, Pa G et al. (1995). P300 topography in
Goll JC, Kim LG, Hailstone JC et al. (2011). Auditory object Alzheimer’s disease. Psychophysiology 32 (3): 257–265.
cognition in dementia. Neuropsychologia 49: 2755–2765. Hsieh S, Hornberger M, Piguet O et al. (2011). Neural basis of
Goll JC, Kim LG, Ridgway GR et al. (2012a). Impairments of music knowledge: evidence from the dementias. Brain 134
auditory scene analysis in Alzheimer’s disease. Brain 135 (Pt 9): 2523–2534.
(Pt 1): 190–200. Hsieh S, Hornberger M, Piguet O et al. (2012). Brain correlates
Goll JC, Ridgway GR, Crutch SJ et al. (2012b). Nonverbal of musical and facial emotion recognition: evidence from
sound processing in semantic dementia: a functional the dementias. Neuropsychologia 50 (8): 1814–1822.
MRI study. Neuroimage 61 (1): 170–180. Idrizbegovic E, Hederstierna C, Dahlquist M et al. (2011).
Golob EJ, Johnson JK, Starr A (2002). Auditory event-related Central auditory function in early Alzheimer’s disease and
potentials during target detection are abnormal in mild cog- in mild cognitive impairment. Age Ageing 40 (2): 249–254.
nitive impairment. Clin Neurophysiol 113 (1): 151–161. Innes AM, Chudley AE (2002). Genetic landmarks through
Golob EJ, Irimajiri R, Starr A (2007). Auditory cortical activ- philately: Woodrow Wilson ‘Woody’ Guthrie and
ity in amnestic mild cognitive impairment: relationship to Huntington disease. Clin Genet 61 (4): 263–267.
686 J.K. JOHNSON AND M.L. CHOW
Ivry RB, Schlerf JE (2008). Dedicated and intrinsic models of Millard KA, Smith JM (1989). The influence of group singing
time perception. Trends Cogn Sci 12 (7): 273–280. therapy on the behavior of Alzheimer’s disease patients.
Janata P (2012). Effects of widespread and frequent person- J Music Ther 26 (2): 58–70.
lized music programming on agiation and depression in Miller BL, Boeve BF (2009). The Behavioral Neurology of
assisted living facility residents with Alzheimer-type Dementia, New York Cambridge University Press.
dementia. Music and Medicine 4 (1): 8–15. Miller BL, Boone K, Cummings JL et al. (2000). Functional
Johnson JK, Ulatowska HK (1996). The nature of the tune and correlates of musical and visual ability in frontotemporal
text in the production of songs in Alzheimer’s type demen- dementia. Br J Psychiatry 176: 458–463.
tia. In: RR Pratt, R Spingte (Eds.), Music Medicine, MMB Mohr E, Cox C, Williams J et al. (1990). Impairment of central
Music, Saint Louis, MO. auditory function in Alzheimer’s disease. J Clin Exp
Johnson JK, Chang CC, Brambati SM et al. (2011). Music rec- Neuropsychol 12 (2): 235–246.
ognition in frontotemporal lobar degeneration and Muscoso EG, Costanzo E, Daniele O et al. (2006). Auditory
Alzheimer disease. Cogn Behav Neurol 24 (2): 74–84. event-related potentials in subcortical vascular cognitive
Juslin RN, Sloboda J (2010). Handbook of music and emotion. impairment and in Alzheimer’s disease. J Neural Transm
Oxford University Press, Oxford. 113 (11): 1779–1786.
Klein CJ, Botuyan MV, Wu Y et al. (2011). Mutations in Nojszewska M, Pilczuk B, Zakrzewska-Pniewska B et al.
DNMT1 cause hereditary sensory neuropathy with demen- (2009). The auditory system involvement in Parkinson dis-
tia and hearing loss. Nat Genet 43 (6): 595–600. ease: electrophysiological and neuropsychological correla-
Klein CJ, Bird T, Ertekin-Taner N et al. (2013). DNMT1 muta- tions. J Clin Neurophysiol 26 (6): 430–437.
tion hot spot causes varied phenotypes of HSAN1 with Norberg A, Melin E, Asplund K (1986). Reactions to music,
dementia and hearing loss. Neurology 80 (9): 824–828. touch and object presentation in the final stage of dementia.
Krishnamoorthy ES, Prince MJ, Cummings JL (2010). An exploratory study. Int J Nurs Stud 23 (4): 315–323.
Dementia: a Global Approach, Cambridge University Ohm TG, Braak H (1989). Auditory brainstem nuclei in
Press, Cambridge. Alzheimer’s disease. Neurosci Lett 96 (1): 60–63.
Kurylo DD, Corkin S, Allard T et al. (1993). Auditory function Omar R, Hailstone JC, Warren JE et al. (2010). The cognitive
in Alzheimer’s disease. Neurology 43 (10): 1893–1899. organization of music knowledge: a clinical analysis. Brain
Langers DR, Melcher JR (2011). Hearing without listening: 133: 1200–1213.
functional connectivity reveals the engagement of multiple Onofrj MFT, Malatesta G, Locatelli T (1994). Focal abnormal-
nonauditory networks during basic sound processing. Brain ities of P3 ERPs unveiled in patients with cortical lesions
Connect 1 (3): 233–244. and primary progressive aphasia by average reference
Lewis JW, Brefczynski JA, Phinney RE et al. (2005). Distinct recordings. Brain Topogr 6 (4): 311–322.
cortical pathways for processing tool versus animal sounds. Peretz I, Coltheart M (2003). Modularity of music processing.
J Neurosci 25: 5148–5158. Nat Neurosci 6 (7): 688–691.
Lin FR, Ferrucci L, Metter EJ et al. (2011). Hearing loss and Peretz I, Champod AS, Hyde K (2003). Varieties of musical
cognition in the Baltimore Longitudinal Study of Aging. disorders. The Montreal Battery of Evaluation of
Neuropsychology 25 (6): 763–770. Amusia. Ann N Y Acad Sci 999: 58–75.
Lin FR, Yaffe K, Xia J et al. (2013). Hearing loss and cognitive Petersen RC (2011). Clinical practice. Mild cognitive impair-
decline in older adults. JAMA Intern Med 173 (4): 293–299. ment. N Engl J Med 364 (23): 2227–2234.
Macar F, Coull J, Vidal F (2006). The supplementary motor Polich J, Pitzer A (1999). P300 and Alzheimer’s disease: oddball
area in motor and perceptual time processing: fMRI stud- task difficulty and modality effects. Electroencephalogr Clin
ies. Cogn Process 7 (2): 89–94. Neurophysiol Suppl 50: 281–287.
Madison G, Gouyon F, Ullen F et al. (2011). Modeling the ten- Polich J, Ladish C, Bloom FE (1990). P300 assessment of early
dency for music to induce movement in humans: first cor- Alzheimer’s disease. Electroencephalogr Clin Neurophysiol
relations with low-level audio descriptors across music 77 (3): 179–189.
genres. J Exp Psychol Hum Percept Perform 37 (5): Polk M, Kertesz A (1993). Music and language in degenerative
1578–1594. disease of the brain. Brain Cogn 22 (1): 98–117, 027.
Mahoney CJ, Rohrer JD, Goll JC et al. (2011). Structural neu- Quoniam N, Ergis AM, Fossati P et al. (2003). Implicit
roanatomy of tinnitus and hyperacusis in semantic demen- and explicit emotional memory for melodies in
tia. J Neurol Neurosurg Psychiatry 82 (11): 1274–1278. Alzheimer’s disease and depression. Ann N Y Acad Sci
Matthews BR, Chang CC, De May M et al. (2009). Pleasurable 999: 381–384.
emotional response to music: a case of neurodegenerative Raglio A, Bellelli G, Traficante D et al. (2008). Efficacy of
generalized auditory agnosia. Neurocase 15 (3): 248–259. music therapy in the treatment of behavioral and psychiat-
McDermott O, Crellin N, Ridder HM et al. (2012). Music ther- ric symptoms of dementia. Alzheimer Dis Assoc Disord 22
apy in dementia: a narrative synthesis systematic review. (2): 158–162.
Int J Geriatr Psychiatry. Raglio A, Bellelli G, Mazzola P et al. (2012). Music, music
McKeith IG, Dickson DW, Lowe J et al. (2005). Diagnosis and therapy and dementia: a review of literature and the recom-
management of dementia with Lewy bodies: third report of mendations of the Italian Psychogeriatric Association.
the DLB Consortium. Neurology 65 (12): 1863–1872. Maturitas 72 (4): 305–310.
 HEARING AND MUSIC IN DEMENTIA 687
Rapcsak SZ, Kentros M, Rubens AB (1989). Impaired recog- U.S. Congress, Office of Technology Assessment (1992).
nition of meaningful sounds in Alzheimer’s disease. Arch Special care units for people with Alzheimer’s and other
Neurol 46 (12): 1298–1300. dementias, U.S. Government Printing Office,
Rascovsky K, Hodges JR, Knopman D et al. (2011). Sensitivity Washington, D.C.
of revised diagnostic criteria for the behavioural variant of Uc EY, Skinner RD, Rodnitzky RL et al. (2003). The midla-
frontotemporal dementia. Brain 134 (Pt 9): 2456–2477. tency auditory evoked potential P50 is abnormal in
Respondek G, Roeber S, Kretzschmar H et al. (2013). Huntington’s disease. J Neurol Sci 212 (1–2): 1–5.
Accuracy of the national institute for neurological disor- Uhlmann RF, Larson EB, Rees TS et al. (1989). Relationship
ders and stroke/society for progressive supranuclear palsy of hearing impairment to dementia and cognitive dysfunc-
and neuroprotection and natural history in Parkinson plus tion in older adults. JAMA 261 (13): 1916–1919.
syndromes criteria for the diagnosis of progressive supra- van Tricht MJ, Smeding HM, Speelman JD et al. (2010).
nuclear palsy. Mov Disord 28 (4): 504–509. Impaired emotion recognition in music in Parkinson’s dis-
Rincon F, Wright CB (2013). Vascular cognitive impairment. ease. Brain Cogn 74 (1): 58–65.
Curr Opin Neurol 26 (1): 29–36. Vanstone AD, Cuddy LL (2010). Musical memory in
Saft C, Schuttke A, Beste C et al. (2008). fMRI reveals Alzheimer disease. Neuropsychol Dev Cogn B Aging
altered auditory processing in manifest and premanifest Neuropsychol Cogn 17 (1): 108–128.
Huntington’s disease. Neuropsychologia 46 (5): 1279–1289. Vanstone AD, Cuddy LL, Duffin JM et al. (2009). Exceptional
http://dx.doi.org/10.1016/j.neuropsychologia.2007.12.002. preservation of memory for tunes and lyrics: case studies of
Sinha UK, Hollen KM, Rodriguez R et al. (1993). Auditory amusia, profound deafness, and Alzheimer’s disease. Ann
system degeneration in Alzheimer’s disease. Neurology N Y Acad Sci 1169: 291–294.
43 (4): 779–785. Vink AC, Birks JS, Bruinsma MS et al. (2004). Music therapy
Stewart L, von Kriegstein K, Warren JD et al. (2006). Music for people with dementia. Cochrane Database Syst Rev 3:
and the brain: disorders of musical listening. Brain 129 CD003477.
(Pt 10): 2533–2553. Vink M, Bruinsma MS, Scholten RJ (2011). Music therapy
Strouse AL, Hall 3rd JW, Burger MC (1995). Central auditory for people with dementia. Cochrane Database Syst Rev 3:
processing in Alzheimer’s disease. Ear Hear 16 (2): 230–238. 1–47.
Sung HC, Chang AM, Abbey J (2006). The effects of preferred Vink AC, Zuidersma M, Boersma F et al. (2012). The effect of
music on agitation of older people with dementia in music therapy compared with general recreational activi-
Taiwan. Int J Geriatr Psychiatry 21 (10): 999–1000. ties in reducing agitation in people with dementia: a rando-
Sung HC, Chang AM, Lee WL (2010). A preferred music lis- mised controlled trial. Int J Geriatr Psychiatry 28:
tening intervention to reduce anxiety in older adults with 1031–1038.
dementia in nursing homes. J Clin Nurs 19 (7–8): 1056–1064. Vitale C, Marcelli V, Allocca R et al. (2012). Hearing impair-
Sung HC, Lee WL, Li TL et al. (2012). A group music inter- ment in Parkinson’s disease: expanding the nonmotor phe-
vention using percussion instruments with familiar music notype. Mov Disord 27 (12): 1530–1535.
to reduce anxiety and agitation of institutionalized older Wall M, Duffy A (2010). The effects of music therapy for older
adults with dementia. Int J Geriatr Psychiatry 27 (6): people with dementia. Br J Nurs 19 (2): 108–113.
621–627. Weinstein BE (2000). Geriatric Audiology, Thieme, New
Thaut MH, McIntosh GC, Rice RR et al. (1996). Rhythmic York.
auditory stimulation in gait training for Parkinson’s disease Weinstein J, Koenig P, Gunawardena D et al. (2011).
patients. Mov Disord 11 (2): 193–200. Preserved musical semantic memory in semantic dementia.
Thaut MH, McIntosh KW, McIntosh GC et al. (2001). Arch Neurol 68 (2): 248–250.
Auditory rhythmicity enhances movement and speech Williams-Gray CH, Foltynie T, Brayne CE et al. (2007).
motor control in patients with Parkinson’s disease. Funct Evolution of cognitive dysfunction in an incident
Neurol 16 (2): 163–172. Parkinson’s disease cohort. Brain 130 (Pt 7): 1787–1798.
Tzortzis C, Goldblum MC, Dang M et al. (2000). Absence of Wright A, Dyck PJ (1995). Hereditary sensory neuropathy
amusia and preserved naming of musical instruments in an with sensorineural deafness and early-onset dementia.
aphasic composer. Cortex 36 (2): 227–242. Neurology 45 (3 Pt 1): 560–562.