The Neuropsychology of Huntington’s Disease
Julie S Snowden
Greater Manchester Neuroscience Centre, Salford Royal NHS Trust, Salford, UK
Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
Address for correspondence:
Prof. Julie S. Snowden
Cerebral Function Unit,
Greater Manchester Neuroscience Centre
Salford Royal NHS Trust
Salford M6 8HD, UK
Tel. 44-(0)161-206-2561
Email: [email protected]
Running title: The Neuropsychology of HD
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Abstract
Huntington’s disease is an inherited, degenerative brain disease, characterized by
involuntary movements, cognitive disorder and neuropsychiatric change. Men and
women are affected equally. Symptoms emerge at around 40 years, although there is
wide variation. A rare juvenile form has onset in childhood or adolescence. The
evolution of disease is insidious and structural and functional brain changes may be
present more than a decade before symptoms and signs become manifest. The earliest
site of pathology is the striatum and neuroimaging measures of striatal change correlate
with neurological and cognitive markers of disease. Chorea and other aspects of the
movement disorder are the most visible aspect of the disease. However, non-motor
features have greatest impact on functional independence and quality of life, so require
recognition and management. The evidence-base for non-pharmacological treatments in
Huntington’s disease is currently limited, but recent intervention studies are
encouraging.
Keywords: Huntington’s disease; neuropsychology
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Introduction and Epidemiology
Huntington’s disease (HD) is an inherited degenerative disorder of the brain,
caused by an expansion in the number of CAG repeats in the huntingtin gene on
chromosome 4 (Huntington’s Disease Collaborative Research Group, 1993). The mode
of inheritance is autosomal dominant and is fully penetrant. Thus, children of an affected
parent, both male and female, have a 50% risk of inheriting the faulty gene and gene
carriers will develop symptoms of disease during a normal life span. The mean age at
which symptoms and signs appear is around 40 years (Harper, 1991), but there is wide
variation. In around 5% of cases onset is in childhood or teenage years, referred to as
juvenile HD (Quarrell, 2014). At the other extreme, people may remain symptom-free
until the seventh or eighth decade of life, referred to as late onset HD. The course of
disease is insidiously progressive, the duration of illness from diagnosis to death being
about 15-20 years. The insidious evolution of disease is important. Structural and
functional brain changes and subtle cognitive, behavioral and motor changes may begin
years before the characteristic physical symptoms and signs are sufficiently manifest to
warrant a clinical diagnosis of HD (Brandt, Shpritz, Codori, Margolis, & Rosenblatt,
2002; Paulsen et al., 2008; Paulsen, Smith, & Long, 2013; Stout et al., 2011; Tabrizi et
al., 2009; 2012; 2013). The term ‘manifest HD’ refers to ‘clinically evident’ HD, which is
not equivalent to ‘onset of the disease process’, which may be more than a decade
earlier.
HD occurs worldwide. The overall incidence and prevalence of disease is difficult
to determine with accuracy. Like any strongly genetic condition there is geographical
clustering so that epidemiological studies that sample from a limited geographical area
can result in underestimation or overestimation of overall prevalence. Nevertheless, it is
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clear that HD is most common in populations of European descent (Kay, Fisher, &
Hayden, 2014), and genealogical studies have identified founders from northern Europe,
particularly the United Kingdom (Harper, 1992). Current figures for the UK, where
prevalence has been most intensively investigated, suggest a prevalence rate in excess
of 10 cases per 100,000, with higher than average prevalence in Scotland and
northeastern England (Evans et al., 2013). The highest prevalence estimate reported in
North America is 13.7 per 100,000 in the Canadian province of British Columbia (Fisher
& Hayden, 2013), with substantially higher prevalence in Caucasians than in other
ethnic groups.
Neuropathology
HD is a degenerative brain disease, involving progressive atrophy of the brain.
The major and earliest site of pathology is the neostriatum, which encompasses the
caudate nucleus and putamen (Vonsattel & Figlia.,1998; Vonsattel, et al., 1985). The
mutated huntingtin protein – the CAG repeat mutation - is assumed to have a toxic
function causing neuronal death, the striatum being particularly vulnerable. More
widespread brain atrophy is found over the disease course, reflecting loss of structural
and functional connectivity between striatum and other parts of the brain. HD has
provided a model for understanding the role of the basal ganglia in cognition.
Clinical Characteristics
HD gives rise to a triad of clinical features: motor, cognitive and neuropsychiatric.
The movement disorder is distinctive and is the hallmark of the disease. The most
characteristic feature is chorea, rapid involuntary movements of the face, trunk and
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limbs. Until recent years HD was known as Huntington’s chorea, reflecting that aspect of
the movement disorder emphasized by the eponymous George Huntington in his
seminal description of the disease (Huntington, 1872). However, chorea is not the sole
motor characteristic (Roos, 2014). People with HD also show dystonia, slow twisting
movements of the limbs, as well as bradykinesia, slowed execution of movements, and
limb rigidity, akin to that seen in Parkinson’s disease. These different motor features
may co-occur, albeit with variable prominence in different individuals. Notably, juvenile
HD is more often associated with prominent bradykinesia than with chorea (Hayden,
1981; Van Dijk, van der Velde, Roos, & Bruyn,1986).
Choreiform movements may be striking to the external observer. Yet such
movements are rarely a source of complaint to people affected with HD. Indeed,
affected individuals report chorea to be less of a problem than do their caregivers
(Simpson, Lovecky, Kogan, Vetter, & Yohrling, 2016) and studies have consistently
shown reduced awareness of chorea in people with HD (Sitek et al, 2011; Snowden,
Craufurd, Griffiths, & Neary,1998; Vitale et al., 2001;).
The cognitive and neuropsychiatric characteristics of disease are less
immediately evident but their recognition is crucial. They contribute greatly to the
affected person’s loss of functional independence and they have greatest impact on
families (Beglinger et al., 2010; Hamilton et al., 2003; Marder et al., 2000; Mayeux,
Stern, Herman, Greenbaum, & Fahn,1986; Nehl, Paulson, & Huntington Study Group,
2004; Ready, Mathews, Leserman, & Paulsen, 2008; Rothlind, Bylsma, Peyser,
Folstein, & Brandt,1993; Simpson et al., 2016; Tabrizi et al., 2013). These features are
considered below.
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Neuropsychological features
The salient changes in HD are in the domains of psychomotor and executive
skills, memory, emotion processing and social cognition.
Psychomotor slowing
The earliest change and best predictor of disease progression is psychomotor
slowing (Snowden, Craufurd, Griffiths, & Thompson, 2001; Snowden, Craufurd,
Thompson, & Neary, 2002; Stout et al., 2011; Tabrizi et al., 2009; 2012; 2013). Slowing
is demonstrated most commonly on timed tasks such as Stroop, Digit symbol
substitution and Trail making (Snowden et al., 2001; Starkstein, Brandt, Peyser,
Folstein, & Folstein, 1992; Stout et al., 2012; Tabrizi et al., 2012; 2013). Cognitive
slowing is found in the ‘pre-manifest’ stages of HD (Foroud et al., 1995; Kirkwood et al.,
1999; Maroof, Gross, & Brandt, 2011; Snowden et al., 2002; Stout et al., 2012; Tabrizi et
al., 2012; 2013), and is reported to be a significant predictor of functional capacity in
daily life (Eddy & Rickards, 2015a). Interestingly, the word reading component of the
Stroop test is a more sensitive marker of change than the more demanding Interference
component (Snowden et al., 2001; Tabrizi et al., 2012), attributed to a failure to
‘automatize’ the simpler psychomotor task (Snowden et al., 2001). Psychomotor
slowing has considerable practical impact in daily life. It has been found, for example, to
be a significant predictor of driving cessation (Beglinger et al., 2012).
Executive skills
Executive difficulties in HD include problems in planning (Lawrence et al.,1996;
Unschuld et al., 2013; Watkins et al., 2000), organisation and sequencing (Snowden et
al., 2001), cognitive flexibility and set shifting (Lawrence et al., 1996; Paulsen et al.,
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1995b; Watkins et al., 2000). In early studies, the Wisconsin Card Sorting test was
commonly used to measure cognitive flexibility (Josiassen, Curry, & Mancall, 1983;
Paulsen et al., 1995b; Pillon, Dubois, Ploska, & Agid, 1991; Weinberger, Berman,
Iadarola, Driesen, & Zec 1988), although its use has diminished in recent years. People
with HD commonly also show reduced performance on verbal fluency tasks (Henry,
Crawford, & Phillips, 2005; Rohrer, Salmon, Wixted, & Paulsen,1999; Rosser and
Hodges, 1994). Cognitive slowing as well as executive difficulties in strategic search are
likely to contribute to low scores (Henry et al., 2005; Rohrer et al., 1999).
A common practical difficulty observed in HD is in multi-tasking. In keeping with
this, there is neuropsychological evidence of problems in attention (Georgiou,
Bradshaw, Phillips, Bradshaw, & Chiu, 1995; Sprengelmeyer, Lange, & Homberg,
1995). It is worth highlighting, however, that dual task difficulty in HD extends to tasks
that in healthy individuals would be considered relatively undemanding of attention, such
as bimanual motor tapping (Thompson et al., 2010) and walking concurrently with
carrying out a cognitive task (Delval et al, 2008). Such findings indicate that ostensibly
‘automatic’ tasks require more conscious attention in people with HD.
Memory
Memory difficulties are commonly reported in HD and may be noticed by the
affected person as well as by their relatives (Cleret de Langavant et al., 2013). Memory
studies have shown proportionally poorer free recall than recognition memory and cued
recall (Butters, Salmon, & Heindel,1994; Butters, Wolfe, Martone, Granholm, &
Cermak,1985; Lundervold, Reinvang, & Lundervold,1994; Pillon, Deweer, Agid, &
Dubois, 1993), more passive learning strategies in HD than controls (Lundervold et al.,
1994), problems in source memory (Brandt, Bylsma, Aylward, Rothlind, & Gow, 1995)
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and in prospective memory (Nicoll et al., 2014) and relative preservation of retention
from immediate to delayed recall. The profile of memory disturbances suggests a strong
executive contribution to memory failures, in keeping with disruption to striatal-frontal
pathways.
Aside from problems in declarative memory (i.e. explicit memory for material
previously presented), people with HD show problems in procedural memory (i.e. skill
and habit learning). Difficulties have been demonstrated on tasks involving motor skill
learning (Gabrieli, Stebbins, Singh, Willingham, & Goetz, 1997; Heindel, Butters, &
Salmon, 1988;), serial reaction time (Knopman & Nissen, 1991), and sequence learning
(Willingham & Koroshetz, 1993; Willingham, Koroshetz, & Peterson, 1996; Thompson et
al., 2010). Problems in procedural memory are consistent with the findings of difficulties
in simultaneous execution of relatively low level, ‘automatic’ tasks. The study of HD has
been key to understanding of the role of the basal ganglia in memory (Salmon & Butters,
1995).
Emotion processing and social cognition
There is substantial evidence that people with HD have difficulty processing facial
expressions of emotion. Early reports suggested that the difficulty was particularly
prominent for the emotion of disgust (Sprengelmeyer et al, 1996; 1997), although more
recent studies have found deficits at least as great for other negative emotions, in
particular anger and fear (Aviezer et al., 2009; Calder et al., 2010; Henley et al., 2008;
2012; Snowden et al., 2008). Impairments are cross modal, affecting recognition of
vocal as well as facial emotions (Calder et al., 2010; Snowden et al., 2008). Difficulties
in emotional expression as well as recognition have also been demonstrated (Trinkler,
Clert de Langavant, & Bachoud-Lévi 2013). Emotion processing is important in HD,
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firstly because deficits appear at a very early stage of disease, including the preclinical
phase (Johnson et al., 2007; Labuschagne et al., 2013; Tabrizi et al., 2009) and
secondly, because they potentially contribute to the social breakdown and reduction in
sympathy and empathy that are common features of HD. Social breakdown in daily life
encompasses difficulties with interpersonal relationships and reduced flexibility in
adapting to the needs of others as well as impaired regulation of behavior in accordance
with social conventions.
Other aspects of social cognition may also be compromised. People with HD
perform poorly on tests of ‘Theory of mind’ that require attribution of intentions, beliefs
and mental states (Allain et al., 2011; Brune, Blank, Witthaus, & Saft, 2011; Eddy, Sira,
& Rickards, 2102; 2014; Snowden et al., 2003), recognition of socially inappropriate
behavior (Eddy et al, 2012) and sarcasm (Philpott, Andrews, Staios, & Churchyard,
2016). The precise interpretation of these findings and relationship between social
cognitive and executive impairments is a subject of debate (Allain et al., 2011; Eddy et
al., 2012; Philpott et al., 2016; Snowden et al., 2003). Nevertheless, the presence of
such difficulties is likely to contribute to the social breakdown in HD. The practical social
implications are well illustrated by a study by Sprengelmeyer et al. (2016), which
showed that people with HD have difficulty perceiving character traits such as
trustworthiness and dominance. Some authors have demonstrated problems in social
cognition in the ‘pre-manifest’ stages of HD, before the development of motor symptoms
(Adjeroud et al., 2016; Eddy & Rickards, 2015b).
Other cognitive domains
The domains outlined above are the most important from the perspective of
characterizing the neuropsychological profile in HD. People with HD do not show frank
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aphasia, agnosia or apraxia. Nevertheless, speech production becomes progressively
less intelligible due to the motor disorder, they may have difficulty coping with complex
syntax and impairments on language tasks may arise secondary to other cognitive
difficulties (Podoll, Caspary, Lange, & Noth, 1988). In the visuospatial domain, people
with HD have difficulty on high-level perceptual discrimination (Brouwers, Cox, Martin,
Chase, & Fedio, 1984; Lawrence et al., 1996), perceptual integration (Bamford, Caine,
Kido, Plassche, & Shoulson,1989; Gomez Tortosa, del Barrio, Barroso, & Garcia Ruiz,
1996) and constructional (Bamford et al., 1989) tasks, which make executive demands.
Spatially, people with HD show problems on tasks involving mental rotation or
manipulation of information (Brouwers et al., 1984; Bylsma, Brandt, & Strauss,1992;
Mohr et al., 1991) and timed visual search (Labuschagne et al., 2016). Slowed visual
search has been shown in the pre-manifest stages of disease and impaired mental
rotation in people close to clinical onset (Labuschagne et al., 2016). From a practical
perspective, perceptual and spatial problems in HD have not been identified as specific
predictors of difficulties in activities such as driving, whereas psychomotor slowing is a
strong predictor of driving cessation (Beglinger et al., 2012).
Problems in executive function and cognitive decline have a detrimental effect on
everyday functioning and level of independence of people with HD (Mayeux et al., 1986;
Rothlind et al., 1993) and quality of life (Ready et al., 2008) and these problems have
been described by caregivers as having the greatest impact (Simpson et al., 2016).
Neuropsychiatric Features
Apathy, irritability and depression are the most common and problematic
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neuropsychiatric symptoms in HD (Craufurd & Snowden, 2014). These symptoms are
distinct and dissociable (Craufurd, Thompson, & Snowden, 2001; Kingma, van Duijn,
Timman, van der Mast, & Roos, 2008; Naarding, Janzing, Eling, van der Werf, &
Kramer, 2009; Rickards et al., 2011), and they follow different trajectories over the
disease course (Thompson et al., 2012). Broadly, loss of motivation and drive is an early
symptom, which becomes increasingly pervasive over the disease course. Irritability and
loss of temper control worsen initially but subside in late stage disease, likely subsumed
by apathy. Depressive symptoms may emerge at any time in the course of disease. The
presence of apathy correlates with motor, cognitive and functional markers of disease
progression (Baudic et al., 2006; Naarding et al., 2009; Thompson, Snowden, Craufurd,
& Neary, 2002) and therefore it provides a marker of disease progression, even if not
independent, whereas depression and irritability do not.
People with HD rarely complain of apathy. Nevertheless, this symptom has a
significant effect on functional disability and quality of life (Banaszkiewicz et al., 2012;
Hamilton et al., 2003; Read et al., 2013). Importantly, from the perspective of possible
intervention, loss of motivation, initiative and spontaneity in HD has been noted to be
situation-dependent, and may be reduced in the presence of stimulating input and
structure (Caine, Hunt, Weingartner, & Ebert, 1978; Caine & Shoulson, 1983).
Irritability and poor temper control are amongst the most troublesome behavioral
features of HD and are typically assessed using standardized self-report or informant-
based irritability scales (Craufurd et al., 2001; Reedeker et al., 2012). In one study
cohort (Craufurd et al., 2001), clinically significant irritability was reported in more than
50%, verbal outbursts of temper in 40% and threatening behavior or violence in 22%.
Studies have also shown higher levels of irritability in asymptomatic carriers of the HD
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gene compared to non-carriers (Berrios et al., 2002; Julien et al., 2007). In these latter
studies interviews were carried out prior to genetic testing so that differences could not
be attributed to gene carriers’ knowledge of their genetic status. An increased
frequency of irritability was seen up to 10 years before the onset of motor abnormalities.
Irritability and poor temper control inevitably has a damaging effect on personal
relationships, and so requires recognition and management. Treatment commonly
involves the use of selective serotonin reuptake inhibitors, although the potential value
of behavioral approaches to management is recognized (van Duijn, 2010).
Depressive symptoms, which may occur even in the prodromal phases of disease
(Epping et al., 2016; Julien et al., 2007; van Duijn et al., 2008), may exacerbate apathy
and social withdrawal, worsen cognitive performance (Smith, Mills, Epping, Westervelt,
& Paulsen, 2012), contribute to functional decline (Beglinger et al., 2010; Marder et al.,
2000; Mayeux et al.,1986) and further impair quality of life (Read et al., 2013),
exemplifying the need for recognition and treatment. Moreover, depressive symptoms
may be associated with suicidal ideation (Hubers et al., 2013). An increased risk of
suicide has been recognized since Huntington’s seminal description of the condition
(Huntington, 1872). A recent study of more than two thousand HD mutation carriers,
98% with physical symptoms of HD, reported suicidal ideation in 8% (Hubers et al.,
2013). Paulsen, Hoth, Nehl, Stierman and the Huntington Study Group (2005a)
identified two particularly critical periods of vulnerability: the prodromal phase of disease,
defined by the presence of mild neurological signs insufficient to make a firm diagnosis
of HD,,and when functional independence begins to diminish.
Neuropsychological Assessment Strategy
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With the advent of the genetic test, neuropsychological assessment now plays a
relatively minor role in differential diagnosis. A clinical diagnosis of HD is typically made
on the basis of family history of HD, presence of the characteristic movement disorder
and confirmed mutation on genetic testing. Nevertheless, neuropsychology has a
crucial role in the identification of cognitive changes in the early phases of disease, in
monitoring progression and in the evaluation of outcome of therapeutic interventions.
Ideally, an assessment protocol should include each of those key components
that have been found most sensitive to HD: psychomotor speed, memory, executive
skills and emotion recognition. However, consideration needs to be given to the
purpose of the assessment and stage of illness. People in pre-clinical phases of disease
may show only very subtle changes whereas people in the later stages of disease may
be unable to tolerate lengthy assessments. Timed tasks are particularly valuable
because they elicit the earliest detectable changes in pre-manifest HD and are also
most sensitive to change over the course of the disease (Snowden et al., 2001; 2002;
Stout et al., 2011; 2012; Tabrizi et al., 2012). In keeping with such findings, the
Huntington’s Disease Rating Scale (Huntington Study Group, 1996), a widely used
screening instrument for HD, incorporates a brief cognitive screen consisting of three
tests, all of which are timed: verbal fluency, symbol digit modality and Stroop. Similarly,
the European Huntington’s disease network (Euro-HD), a European-wide network for
research into Huntington’s disease, has adopted letter and category fluency, symbol-
digit modality and Stroop tests as ‘core’ components of their recommended
neuropsychological test battery, with additional elements where more extensive
assessment is feasible.
Some memory and executive measures are of value for cross-sectional
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assessment but show poorer sensitivity to change over time Bachoud-Lévi et al., 2001;
Snowden et al., 2001). One contributory factor is the effect of practice. It has been
found (Bachoud-Lévi et al, 2001) that the practice effect is greatest between first and
second assessment. In intervention studies, the confounding effect can be mitigated if
dual baseline assessments are introduced preceding the intervention.
An additional consideration in evaluating cognition in HD is the contribution to
performance of motor and neuropsychiatric/behavioral changes. Timed tasks that
control for motor slowing are valuable because they provide information about cognitive
speed that is independent of general slowing of motor responses. Apathy is a core
behavioral change in HD that correlates with executive impairment (Thompson et al.,
2002). The inclusion of informant-based behavioral measures, such as the Problems
Behavior Assessment (Craufurd et al., 2001) can assist interpretation of cognitive test
performance.
Laboratory and radiographic investigations
The genetic mutation responsible for HD was identified in 1993 (Huntington’s
Disease Collaborative Research Group, 1993). Since then a clinical genetic test has
become available to test for the CAG repeat expansion and is used routinely to confirm
the clinical diagnosis of people who show symptoms of HD. The test, along with genetic
counseling, is also available for ‘at risk’ family members (i.e. offspring of an affected
parent) who wish to know whether or not they have inherited the gene mutation. Some
people prefer the certainty of knowing their gene status because this affords control of
life choices, such as whether to have a family or to take promotion at work. On the other
hand, the knowledge can lead to a variety of practical and emotional difficulties, ranging
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from difficulty in obtaining insurance cover to breakdown in inter-personal relationships
with siblings who have a different genetic result from one’s own. The experience of
predictive testing may be stressful and adjustment to test results can be difficult
(Crozier, Robertson, & Dale, 2015; Meiser & Dunn, 2001). Around 80% of ‘at risk’
people opt not to know (Meiser & Dunn, 2001). There has not, thus far, been a notable
increase in uptake of the genetic test over the years that it has been available, and the
reverse has even been reported (Bernhardt, Schwan, Kraus, Epplen, & Kunstmann,
2009). Nevertheless, the situation may change in the future as clinical therapeutic trials
become available, for which confirmation of gene status may be a criterion for eligibility
(Nance, 2017).
The genetic test confirms whether an asymptomatic person will develop
symptoms of HD but not when those symptoms will first appear. There is an inverse
correlation between age at which disease becomes manifest and length of the CAG
repeat expansion and formulae have been produced to predict age of clinical onset i.e.
when overt symptoms will begin (Langbehn, Brinkman, Falush, Paulsen, & Hayden,
2004; Zhang et al., 2011). Such prediction is insufficiently accurate to be helpful at an
individual level for an asymptomatic person taking the genetic test. Nevertheless, it
provides a valuable proxy of clinical onset for research studies. Major large-scale
international research studies have been undertaken: the PREDICT-HD study in the
USA (Paulsen et al., 2008) and TRACK-HD in Europe (Tabrizi et al., 2009, 2012, 2013)
that have tracked people who have the HD gene mutation to establish the natural history
of the disease.
Brain imaging in HD shows atrophy, with structural and functional changes most
prominent in the striatum (caudate nucleus and putamen). Striatal changes are present
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even in pre-manifest HD, i.e. before the emergence of overt clinical symptoms and
signs, (Andrews et al., 1999; Antonini et al., 1996; Aylward et al., 2004; Tabrizi et al.,
2013), reinforcing the view that this is the earliest site of pathology. The availability of
the genetic test means that neuroimaging is not essential for clinical diagnosis of HD.
Nevertheless, it has been important in helping to understand the basis for the symptoms
and signs in HD, and the natural history of the condition. Psychomotor speed in HD has
been shown to correlate with measures of caudate atrophy (Bamford et al., 1989;
Starkstein et al., 1992). There is evidence too of a relationship between executive test
performance in HD and changes in the striatum, measured either by structural
(Peinemann et al., 2005) or functional (Backman, Robins-Wahlin, Lundin, Ginovart, &
Farde,1997; Lawrence et al., 1998) brain imaging. Interestingly, functional imaging
studies in HD have demonstrated increased cortical recruitment in cognitive tasks
(Georgiou-Karistianis et al., 2007), indicating compensation for reduced striatal function.
Treatment
HD is a relentlessly progressive disorder that is currently incurable. Treatments
have, until recently, largely comprised pharmacological symptomatic therapies for the
alleviation of motor and mood-based symptoms. Tetrabenazine is a well-established
treatment for involuntary movements, although it may increase the likelihood of
depression in pre-disposed people (Kenney, Hunter, Meijia, & Jankovic, 2006) so needs
to be used judiciously. SSRIs have been used for the treatment of irritability (Groves et
al., 2011).
Currently, the evidence-base for non-pharmacological interventions in HD is
limited. Assistive technology for cognition (ATC) refers to external aids that serve to
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compensate for a person’s cognitive difficulties. Two studies have shown that Talking
Mats improved communication in people with relatively advanced HD who had poorly
intelligible speech (Ferm, Sahlin, Sundin, & Hartlius, 2010; Hallberg, Mellgren, Hartelius,
& Ferm, 2013). Notwithstanding this encouraging finding, evidence for the benefit of
assistive technology use in HD remains scarce. Van Walsem, Howe, Frich and Andelic
(2016) carried out a review of assistive technology use in 158 people with HD. The
authors distinguished between self-generated, informal use of mainstream products
such as calendars, planners, cell phones and alarm clocks and formal use of computer
software, specifically designed to support people with cognitive impairment. Around a
third of participants used assistive technology, with informal use occurring mainly in
early-stage disease and formal use in moderate-stage disease. Notably, however, a
formal needs assessment for assistive technology had been carried out in only a third of
participants and even fewer had received formal training for its use. No association was
found between the use of assistive technology and improved quality of life. The study by
van Walsem et al. (2016) was a descriptive rather than efficacy study. The authors
highlighted the need for systematic investigation of the value of assistive technology in
HD and its association with health-related quality of life. There are a priori grounds for
thinking that assistive technology may be helpful. Memory inefficiencies, which include
problems in prospective memory (Nicoll et al., 2014), might potentially be alleviated by
use of external prompts and memory aids.
A potential rationale for cognitive intervention in HD comes from functional brain
imaging findings, which suggest that neural compensation takes place in preclinical HD
to preserve motor and cognitive performance. Cognitive interventions aim to support and
enhance that neural compensation (Andrews, Dominquez, Mercieca, Georgiou-
17
Kartistianis & Stout, 2015; Metzler-Baddley et al., 2014; Papoutsi, Labuschagne, Tabrizi,
& Stout, 2014). In a pilot study, Metzler-Baddeley et al, (2014) showed improved
executive functions and white matter microstructure in ten people at varying stages of
HD following a two-month intervention involving rhythm exercises. Busse et al. (2013)
too reported modest benefits from physical exercise training on cognition and mobility.
Cruickshank et al., (2015) reported a multidisciplinary nine-month intervention study,
involving a program of physical exercises combined with cognitive exercises of verbal
planning, memory and problem solving. The study group of 15 HD participants showed
increased gray matter volumes on brain imaging that correlated with improved verbal
learning performance at the end of the nine-month period. These findings offer a degree
of optimism that interventions have the potential for neural enhancement, which may
delay clinical decline. Nevertheless, randomized controlled trials of cognitive intervention
are required to establish the efficacy of this approach.
Interventions in HD need to address behavioral/neuropsychiatric as well as
cognitive problems. Apathy is a pervasive feature that impacts on quality of life. The
finding of improvement with stimulating input and structure (Caine et al.,1978; Caine &
Shoulson, 1983) mirrors clinical experience and has obvious implications for
management. People with HD can benefit from external prompts, encouragement to
participate in pleasurable activities and the provision of a structured environment.
Irritability is another troubling feature of HD. There may, however, be predisposing or
precipitating factors, and if recognized, aggressive outbursts can be circumvented.
Education of family members is an important aspect of management of people with HD.
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When embarking on interventions with people who have HD, an important
consideration is their reduced awareness of motor (Sitek et al., 2011; Snowden et al.,
1998), cognitive/behavioural (Ho, Robbins, & Barker, 2006; Hoth et al., 2007; Sitek,
Thompson, Craufurd, & Snowden, 2014), emotional and functional (Hoth et al., 2007)
changes.
Recommendations
Recommendations for neuropsychological assessment and intervention are
summarized in table 1. Timed psychomotor tasks need to be considered a core and
necessary component of the assessment, regardless of stage of disease or the purpose
of assessment. Executive, memory and emotion recognition tests are valuable,
particularly in manifest disease.
Aside from cognitive assessment, evaluation needs to take account of
behavioral/affective symptoms. Rating scales for behavioral symptoms of HD have
undergone a systematic critique by an International study group, commissioned by the
Movement Disorder Society (Mestre et al., 2016). ‘Suggested’ scales specifically
designed for use in HD include the Problems Behaviors Assessment for Huntington’s
disease (PBA) (Craufurd et al., 2001) and Unified Huntington’s Disease Rating Scale,
behavioral section (Huntington’s Study Group, 1996). The Apathy sub-scale of the PBA
has been recommended by Tabrizi et al. (2012) as a behavioral measure for use in
clinical trials.
Interventions in HD need to take account of a number of characteristics.
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People with HD require extra time to carry out everyday tasks.
People with HD are forgetful but do not have a classical amnesia. They have the
potential to benefit from memory aids.
Tasks, such as walking and talking, which under normal circumstances might be
regarded as relatively ‘automatic’, require more conscious attention in people with
HD. They are more demanding of attentional resources. It is important for people
with HD to focus on one activity at a time.
People with HD may not initiate activities but with encouragement can engage
successfully in them and experience enjoyment.
References
Adjeroud, N., Besnard, J., El Massiouri, N., Verny C., Prudean, A., Scherer, C., et al.
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