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Foley FW, Zemon V, Campagnolo D, et al. Multiple sclerosis intimacy and
sexuality questionnaire re-evaluation and development of a 15-item version with
a large US sample. Mult Scler. 2013;19:1197-1203.
Sanders AS, Foley FW, LaRocca NG, et al. Multiple sclerosis intimacy and
sexuality questionnaire 19 (MSISQ-19). Sex Disabil. 2000;18:3-24.
Quirk FH, Heiman JR, Rosen RC, Laan E, Smith MD, Boolell MD. Development
of the sexual function questionnaire for clinical trials of female sexual
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Abraham L, Symonds T, Morris MF. Psychometric validation of a sexual quality of
life questionnaire for use in men with premature ejaculation or erectile
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Symonds T, Boolell M, Quirk F. Development of a questionnaire on sexual quality
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C H A P T E R 1 8
Cognitive Function in
Multiple Sclerosis
Jeffrey G. Portnoy Frederick W. Foley
Introduction
Cognitive dysfunction is a common and impactful
manifestation of multiple sclerosis (MS). For decades, it has
been known that, despite the frequency with which cognitive
deficits tend to occur in the MS population, cognition is not
formally assessed as often as is necessary, leading to underdiagnosis of this critical disabling symptom. 1 Estimates of the
prevalence of cognitive impairment have fluctuated alongside
changes in diagnostic criteria, methodological approaches in
research, and instruments used to assess cognitive functioning.
Nonetheless, a general consensus has emerged that
approximately half of MS patients experience clinically
meaningful changes in cognition, with recent appraisals
ranging from 40% to 65%.
2-4
Impaired cognitive ability is one facet of the broader
neuropsychiatric symptomatology present in MS, which also
includes high comorbidity with depression, anxiety, and other
forms of mood disturbance. Multifactorial neuropsychiatric
disability is a primary detractor from health-related quality of
life in MS patients
5,6
and an important consideration when
planning treatment around patients’ changes in function and
ability to maintain their routines when disease status worsens.
Psychosocial Impact and Quality of Life
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Patients and their caregivers frequently describe changes in
cognitive function as a particularly intrusive element of the
MS disability profile, and its functional consequences can be
severe and far-reaching. The trend in diagnosing presence and
severity of neurocognitive disorders has shifted to emphasize
the impact of cognitive change on the performance of
everyday functions. It is therefore important to consider the
manner in which cognitive changes may negatively impact
patients’ normal activities in order to help them retain high
quality of life.
MS patients with cognitive impairment often experience
numerous changes in life circumstance that can present
additional sources of medical, emotional, and financial
hardship. Loss of employment occurs frequently, and although
physical disability undoubtedly plays a large role, patients also
frequently complain of reduced ability to complete workrelated tasks at the cognitive level preceding the onset and
worsening of their MS. It may be difficult for individuals to
pinpoint what exactly is different about their cognition or
when their changes in thinking began. Nonetheless, patients
and their families, friends, and coworkers may still implicitly
perceive neurocognitive changes. This potential salience of
patients’ deficits, despite the uncertainty of their origin or
nature, makes them an especially meaningful chronic stressor,
particularly when these yield changes in ability to work,
engage in normal social activities, or function independently.
Employment
Vocational status holds a central role as an element of patients’
self-efficacy, quality of life, and general sense of well-being.
Employment is notably disrupted among individuals with MS,
with cross-sectional and longitudinal studies estimating
unemployment upwards of 50% and documenting significant
trends in loss of employment over time.
7,8
Although the
complex nature of disability in MS suggests that multiple
etiological considerations are in play to explain change in
work status, cognition has been shown to be a strong
independent predictor of employment among MS patients.
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Instruments such as the Multiple Sclerosis Work Difficulties
Questionnaire can be used to examine the origin of patients’
employment-related concerns and their risk for change in work
status. 9 Both subjective and objective measures of cognitive
impairment have been shown to predict employment status
among MS patients. 10 In-depth examination of barriers to
maintenance of employment shows that patients relate the
changes in their cognitive functioning to specific aspects of
their ability to complete tasks at work and follow standard
protocols in line with company policy. 11 Unemployed
individuals perform worse than their employed counterparts on
neuropsychological tests,
12,13
and while general increase in age
and worsening of disease status are associated with both
cognitive decline and loss of employment, the results of
cognitive testing exist as independent predictors of change in
employment. 14 By contrast, patients with relative stability in
cognitive functioning and other elements of disease
progression show a significant ability to retain employment,
even in the context of the numerous life challenges associated
with managing a severe disease.
15
Social Functioning
Following diagnosis of an incurable disease, patients will have
an increased need for coping methods and mentally healthy
ways to consider the role of their illness. These new demands
can present inherent challenges to the maintenance of
interpersonal relationships. Social isolation can occur due to
physical and psychological barriers associated with primary
and secondary aspects of any chronic illness. In MS, this is
further complicated by the presence of cognitive risk factors
that may detract from patients’ ability to remain socially
involved. Given high rates of depression and the reliance of
MS patients on caregivers for functional and emotional
support, the consequences of loss of social relationships can be
devastating.
Research has related self-reported and objectively measured
cognitive functioning to various aspects of community
integration. Subjective impairment is associated with reduced
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participation in social activities both inside and outside the
home, and poorer performance on tests of cognition has been
linked to decreased social involvement. 16 Core cognitive
deficits in MS have been tied to difficulty participating in
important domestic events, such as the preparation of meals.
17
The influence of cognitive symptomatology on social
functioning is not limited to the patient. Cognitive decline is
accompanied by a decrease in maintenance of social contacts
and leisure activities, both among individuals with MS and
their caregivers. 18 Cognitive changes may prompt increased
levels of social isolation and lead to dissatisfaction and
conflict with family members. 19 Social relations can
misinterpret patients’ cognitive changes as emotional
instability or lack of desire to socially relate. This can be
compounded by the genuine neurobehavioral change
sometimes found in patients with certain forms of cognitive
dysfunction, including diminished motivation.
20
The
erroneous attribution of decreased social ability to volitional
changes in attitude, emotional dysregulation, or altered
personality can lead to a breakdown in social connectedness
that originates from the social contact rather than the MS
patient.
Overt dysfunction of social cognitive processes can also occur,
producing an expected set of problems with social relatedness.
Social cognitive deficits, such as decreased emotion
recognition and theory of mind, can be a manifestation of MS.
21
Deficits of this variety have been associated with disease
status and duration, 22 raising additional concerns about
implications on psychosocial health for more disabled
individuals. Alexithymia has been known to occur and
progress in MS
23,24
and is associated with higher levels of
personal distress and emotional reactivity, as well as difficulty
relating to others empathetically. 25 Alexithymia tends to occur
in the presence of poorer performance on other cognitive
tasks, further adding to the list of social challenges that
cognitively impaired patients with MS may be forced to
endure.
26
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Independence
The loss of independence associated with MS can be a source
of frustration for patients and caregivers, as well as a threat to
patient safety. Cognitively impaired MS patients have
difficulty completing instrumental activities of daily living
(IADLs) in real time compared with healthy individuals and
are frequently unable to participate in common daily activities
due to cognitive limitations.
17,27
Deficits in executive
functioning, such as organization and planning ability, directly
impact capacity to perform everyday activities and overall
functional status. 28 Longitudinally, a significant effect of
declining cognitive performance emerges as a predictor of
functional status independent of physical disability.
29
Increased reliance on others is an important social and
emotional change. Research has recommended preparing
patients and their caregivers for changes in independence
through education and awareness to aid transitions in daily
living and promote safety by helping patients understand and
acknowledge their limitations. 30 This includes monitoring of
changes in patients’ ability to drive 31 ; clean, organize, and
manage the home
32,33
; handle finances
34,35
; and make
appropriate medical decisions.
36
Nature of Cognitive Change
As might be expected in a disease that presents as
heterogeneously as MS, patients’ degree and type of cognitive
dysfunction varies widely. Many patients, even those who
have had MS for many years, may be cognitively
asymptomatic. Those with complaints may experience mild
changes in a single area of thinking or report significant
impairment across multiple domains. While some cognitive
functions are more frequently affected than others, the MS
disease process and its sequelae have the potential to manifest
in the form of cognitive impairment in effectively any area.
There is undoubtedly a connection between central nervous
system disease activity and cognitive changes, but the link is
not always clear-cut. Patients can have intact cognition even
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when disease is active in the areas of the brain corresponding
to those cognitive domains. By contrast, they can show highly
specific cognitive deficits associated with brain regions in
which there is little or no radiological evidence of
inflammation, demyelination, or volume loss.
Formal methods of assessing cognition in MS will be
discussed later in this chapter, but broadly, the neurocognitive
profile in MS is often subtle and difficult for the layperson,
including the patient, to identify or describe with accuracy.
6
Attempts to develop valid self-report measures of cognition
have not been successful to this point. 37 General intellectual
functioning and conversational language ability are relatively
preserved, emphasizing the need for increased awareness and
vigilance on the part of patients, clinicians, and family
members toward the possibility of cognitive changes. When
dysfunction is suspected, formal neuropsychological
evaluation is the best way to rule out or clarify the nature of
cognitive dysfunction. Examples of patient complaints in
relation to types of cognitive dysfunction are shown in Table
18.1.
Table 18.1
Common Symptoms Reported by Patients in Relation to Cognitive
Domains Affected by Multiple Sclerosis (MS)
Cognitive
Domain
Affected
Examples of Reported Symptoms
Processing
speed
Decreased speed of thinking
Taking longer to finish projects at work or home
Trouble understanding others or following conversations
Difficulty with word-finding or fluent speech
Poor ability to learn new information
Forgetfulness, or being told that they are repeating
questions
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Cognitive
Domain
Affected
Examples of Reported Symptoms
Attention
Distractibility
Decreased ability to multitask
Trouble keeping track of information at prior level
Difficulty sustaining effort
Requiring more frequent breaks
Changes in memory
Executive
functioning
Difficulty starting tasks or initiating behaviors
Problems following through once a task is started
Becoming stuck or fixated easily
Trouble performing routine functions at work
Inability to plan activities or efficiently solve problems
Demonstrating poor judgment or self-control
Visual-spatial
processing
Trouble navigating
Concerns about ability to drive, voiced by the patient or
by others
Failing to notice visual details in the environment
Difficulty recognizing objects or other visual
information
Memory
Problems learning new information at work
Being told they agreed to complete a task or chore but
failing to do so
Starting an activity but forgetting what they were doing,
or being unable to recall steps to routine activities
Forgetting information shortly after reading it, or
needing to reread information multiple times
Requiring additional time and effort to recall things
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Cognitive
Domain
Affected
Examples of Reported Symptoms
Language
Problems with word-finding
Circumlocution, verbosity, or inefficient communication
of ideas
Stopping mid-sentence to gather thoughts
Problems producing language, including tripping over
words
Incomplete or inaccurate understanding of others
Difficulty following conversations
Processing Speed
Information processing speed is the rate at which patients can
apply cognitive ability in real time. Dysfunction in processing
speed has implications for functional ability across many areas
of cognition. 38 Over the course of an individual’s life, he or
she naturally develops an internal cognitive rhythm that
enables effective employment of cognitive processes. Even
slight changes in the rate at which individuals can think or
react in certain areas can give the patient the feeling of
considerable alteration in overall cognition. In many respects,
decreased processing speed is the core cognitive deficit in MS,
where demyelination and reduced white matter integrity
directly affect the speed of neural signal propagation and
transduction.
39-41
Table 18.2
Common Neuropsychological Tests Administered in Multiple Sclerosis
(MS)
Neuropsychological
Test
Cognitive Abilities
Required
Description
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Neuropsychological
Test
Cognitive Abilities
Required
Description
Symbol Digit
Modalities Test
(SDMT)
Processing
speed
Attention
Behavioral
initiation
Ability to
sustain
performance
Visual
working
memory
Patients use a response key to
identify number-symbol pairings as
quickly as possible. Successful
performance requires several of the
cognitive functions that are
frequently affected by MS, making
it an effective screening and
monitoring tool.
Normative data are available for
written or oral administration to
allow for assessment of patients
with physical disability.
Paced Auditory
Serial Addition Test
(PASAT)
Attention
Auditory
working
memory
Ability to
sustain
performance
Patients hear single-digit numbers
read at consistent intervals and
must add each new number to the
number preceding it. Two
difficulty levels, determined by the
length of the interval between
numbers, can be administered
independently or together.
California Verbal
Learning Test,
Second Edition
(CVLT-II)
Verbal
learning and
memory
Use of cues
to
consolidate
and retrieve
information
Patients are read a list of words to
learn and recall. Subsequent trials
assess how patients benefit from
repetition and reminder cues,
susceptibility to learning
interference, and maintenance of
memory after a delay.
Selective
Reminding Test
(SRT)
Verbal
learning and
memory
Attention
and selfmonitoring
Patients are presented with a list of
words and asked to recall them. On
successive trials, they are reminded
only of the words that they did not
provide during the preceding trial,
measuring efficiency of learning
and memory.
Brief Visuospatial
Memory Test—
Revised (BVMT-R)
Visual
learning and
memory
Graphomotor
functioning
Patients are shown an array of
simple figures and required to
memorize their shapes and relative
locations. The test is repeated
several times and is subsequently
followed by delayed recall and
recognition trials.
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