This is a promotional meeting, organised and funded by Sanofi Genzyme.

1. THINK COGNITION
Finding clarity in brain health
and MS management
Sunday 3rd November
17:45–18:30
Lakeside Suite
GZUK.MS.19.11.0504.
Date of preparation: November 2019This is a promotional meeting, organised and funded by Sanofi Genzyme.
Prescribing information is available at the end of the presentation.

2. SPEAKER AND DISCLOSURES
2
Dr Bronwen Bonfield,
Principal Clinical Psychologist, NHS
November 2019
Disclosures:
Presentation at Sanofi Genzyme’s symposium
Content has been created by Dr Bronwen Bonfield and reviewed by SGZ.
The views of the speaker are not necessarily that of SGZ.
Dr Bronwen Bonfield has received honorarium from SGZ for her involvement.

3. WHAT IS COGNITION?
Cognition is Thinking and Learning
(Malia and Branagan; 2006)
“the mental processes involved in activities
such as learning, understanding,
remembering, communicating, knowing,
awareness and judgement”
3

4. 4
• Attention and Concentration
• Memory
• Speed of Information
Processing
• Executive Functions- planning,
organising, initiating, problem
solving
• Verbal Fluency
• Visuospatial Awareness

5. FACTORS AFFECTING COGNITION
5
Fatigue
Overload Thoughts
Illness

6. FREQUENCY OF COGNITIVE CHANGE IN MS
• Cognitive Impairment between 43% – 70% (Chiaravalloti et al 2008)
• Cognitive function correlates with number of lesions and lesion area on MRI, as well as
brain atrophy (National Multiple Sclerosis Society Website, Zivadinov et al 2001)
• Greater decline with Progressive MS rather than Relapse Remitting MS, (Chiaravalloti et al
2008) but variability. Overall cognitive difficulties progress with time
• Evidence states that cognition can be impaired before (or without) physical symptoms
(Sumowski et al 2018)
• When clients report cognitive decline they are describing a change in function & important
to keep a context to each client e.g. previous function, change (not just whether impaired)
(Sumowski et al 2018)
• Cognitive difficulties increase with complexity – simple tasks can remain intact
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7. COGNITIVE CHANGE IN MS
7
Areas affected in MS Generally unaffected areas in MS
Difficulties seen in multiple domains
Slow information processing speed and
working memory – the most common
cognitive deficits in MS
Primary episodic memory problem is in the
initial learning of information
Executive functioning, verbal fluency and
visuospatial analysis also affected
General intellect
Long-term memory
Recognition memory
Conversational skill
Reading comprehension
However there is variability within individual presentation, with different effects on their lives

8. BRAIN HEALTH
8
1. Cognitive Reserve.
• High cognitive reserve – less cognitive impairment.
• Low cognitive reserve – greater cognitive impairment.
2. Brain Reserve (Brain Volume)
• Healthy adults – brain volume loss 0.27% per year.
• People with MS – brain volume loss 0.54% per year.

9. ADVICE AND EDUCATION
• Disease Modifying Therapy
• Physical exercise – aerobic, resistance & balance
• Healthy eating
• Avoidance of smoking
• Limiting the use of alcohol
• Intellectually enriching activities (education, reading, hobbies, creative
expression).
• Challenging thinking – variety in the way that tasks are approached

10. WHY ASSESS COGNITION?
Changes in cognition can affect an individual and their family’s ability to
engage in a life that is meaningful to them
It can affect:
Relationships: families, friends, work, healthcare professionals
Occupation: purposeful and pleasurable
Leisure: hobbies, family activities
Connections to Values & Choices: a loss of sense of self & feeling of being
connected
Emotional Well-being: mood, anxiety, motivation
What is important is understanding the meaning of the change in
cognition for each individual

11. MS AND ME
11
• Cognitive change & emotional well-being has to be placed within the context of the client and
the meaning on their lives.
• A framework that supports this view – The biopsychosocial model
Psychological
• The impact on thoughts, feelings and behaviours
• Feelings – shock, denial, anger, loss, fear, worry, low mood & depression
• Thoughts – affect our identify – who am I? loss of confidence, lowered self esteem
• Difficulties completing tasks and activities, withdrawal
Biological
• Physical abilities
• Emotional and behavioural control
• Cognition
• Communication
• Pain, appetite loss, sleeping disruption
• Reduce personal care abilities
Social
• Relationships with family,
friends, carers and their
reactions to diagnosis
• Occupational Role
• Leisure Activities
• Changing roles within
families – care giver
Biological
SocialPsycholog
- ical

12. HOW TO ASSESS COGNITION?
12
• Cognition can be assessed through many different means:
– Clinical interview: what does the client find difficult? What do family/friends/carers notice?
– Observation of function - when completing activities e.g. making a cup of tea can they do this
efficiently, what do you observe
– Formal Assessment – (including screening tools) Clinical Psychologists and Occupational
Therapists (this depends upon access from team to team)
– Have an understanding of the types of cognitive change experienced

13. SPEED OF INFORMATION PROCESSING
13
• Most common difficulty reported
• The time it takes a client to complete a task involving cognition ( not
purely motor)
• Clients often describe as not feeling as sharp and as on the ball – do
you feel as sharp and on the ball? Do you feel it takes you longer to
take in information?
• Taking longer to do the everyday things - Does it take you longer to
complete activities?
• Tasks take more time and effort to achieve them
• Cognitive/ Sensory overload can make these difficulties worse
• Can be influenced by many factors such as environmental, health and
emotional well-being.

14. ATTENTION
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• Focused – are individuals focused on what you are saying?
• Sustained – are individuals maintaining their attention over time?
• Selective – are individuals being distracted by environmental factors?
• Alternating – are the individuals able to switch from one task to another?
• Divided – are the individuals able to do two things at the same time?

15. MEMORY
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• Difficulties remembering new information:
• Can they remember information from the start to finish of a session?
• Do they frequently DNA appointments ?
• Do they remember strategies to put into place?
• Changes in visual and verbal memory

16. EXECUTIVE FUNCTIONS
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• Planning and organising activities – personal activities of daily living, work, home, leisure
activities, in pursuit of valued goals. Do you find it difficult to plan and organise your time?
• Monitoring own activities – self-regulation
• Initiation – do you have difficulties starting activities?
• Inhibition – being able to over-ride certain behaviours Do you find you say things before
thinking it through?
• Reason and solve problems – do you find it difficult to work through problems?
• Difficulties with decision making – do you find it difficult to make a decision ? Do you ask
others to make decisions for you?
• Getting fixed – do you get absorbed on one task and find it difficult to change plan?

17. VISUOSPATIAL AWARENESS & VERBAL FLUENCY
17
• How we perceive and interact with our visual world
• How we estimate the distance between objects e.g. when driving,
walking around objects Do you find you bump into things more often
at home?
• How we imagine objects and put an object together by locating its
components
• How we understand objects in relation to each other and to ourselves
• Word finding difficulties

18. IMPORTANT CONSIDERATIONS
18
• Cognitive skills are reliant on basic sensory registration (hearing, seeing,
touching, smelling, tasting).
• Cognitive skills are reliant on attention.
• Cognitive skills are inter-dependent, many tasks rely on more than one
domain
• Cognition should not be assessed in isolation – need to explore other
factors

19. COGNITIVE HINTS & TIPS
19
• Stop, think, observe, evaluate what you are seeing
• Formulate with the client and their relatives
• Introduce strategies or give information at a pace the client can manage – one or
two - don’t introduce cognitive overload!
• Could use session Summaries at the end of each session

20. HOLISTIC APPROACH TO REHABILITATION
20
• Effective Intervention requires:
– Supporting the clients understanding – through education relating to cognitive difficulties and
factors that affect cognition (sleep, meds, mood, fatigue)
– Feedback cognitive strengths to decrease difficulties in everyday life to individuals and support
system
– Aiding motivation – goals linked with their values
– Client compliance with the strategies – how to gain support
– Clinicians to be willing to take individualised rehab by unique circumstances of client
– Holistic rehabilitation should involve physical, cognitive, emotional and psychosocial aspects of
their lives (MDT approach)
Take time to figure out which strategies work best for your clients.

21. ENGAGING WITH THE CLIENT
“STEP INTO THEIR SHOES”
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Remember:
• MS is a new world to our clients – what seems everyday to us,
is not to them
• Try to understand their context
• Listen to patient’s views of their problem and what they want
from your care
• Reflective Listening – listen to what the person is meaning
Can be simple repetition.
Statement rather than question
• Use Accessible Language - adjust to clients and families
needs
Personal
history
MS
impact
External
resources

22. 22
ENGAGING WITH CLIENTS AND THEIR FAMILIES – CORE
SKILLS
• Summarising – use to link together and reinforce
information that has been discussed and to ensure you
have heard the client
• Consider different types of support – which is
appropriate for your client currently e.g. some like/need
emotional support, informational support, practical
support, positive distraction – social “chit chat”.
• Signpost – to appropriate services

23. 23
ENGAGING WITH CLIENTS AND THEIR FAMILIES – CORE
SKILLS
• Information giving
– Important to identify whether the client is ready for
information and/or wants it!
• Creating environment of openness, sharing and working
together.
• Acknowledgement of the difficulties & challenges
Empathise with how they feel

24. ENGAGING WITH CLIENTS AND THEIR FAMILIES
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• Identify priorities - at times it can feel
overwhelming for our clients and us – there
maybe many things raised and it can be difficult
to identify the starting point.
• Bubbles – can be useful – write in the bubbles
the areas that have been raised and then ask the
client to identify the starting point – leave some
bubbles blank for them to add
• Brings together the skills on previous pages but
enables client to take responsibility

25. MS Nurse perspective:
How do we as nurses
recognise and manage
cognitive difficulties?
GZUK.AUBA.19.10.0478
Date of preparation: November 2019This is a promotional meeting, organised and funded by Sanofi Genzyme.
Prescribing information is available at the end of the presentation.

26. Speaker and disclosures
• Elspeth Wolfenden is an MS specialist nurse working for Bucks
Healthcare NHS Trust
Disclosures:
- Ad board for Novartis, Biogen
- Presentation at Sanofi Genzyme’s symposium
Content has been created by Elspeth Wolfenden and reviewed by SGZ.
The views of the speaker are not necessarily that of SGZ.
EW has received honorarium from SGZ for her involvement.
26

27. RECOGNITION
• What do we do
–Appearance
–Presentation
–Relatives
27

28. DISCUSSION
• How do we address this?
– Question
– Probe
– Ignore
LACK OF RESOURCES
LACK OF TIME
LACK OF SUPPORT
28

29. MONITORING
• Do we do this?
– Why?
– Why not?
– How?
29

30. SUPPORT
• What support available?
• Response times
• Is this helpful in nursing management?
30

31. Cognitive deterioration appears to be related to brain volume loss
(atrophy) in early RRMS not treated with disease modifying drugs
Figure adapted from data in Zivadinov R, et al. J Neurol Neurosurg Psychiatry. 2001;70:773–80.
1. Zivadinov R, Sepcic J, Nasuelli D, et al. A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2001;70:77380.
2. Hohol MJ, Gutmann CRG, Orav J, et al. Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis Arch Neurol 1997;54:1018–25.
• The objective of the study was to
monitor the loss of brain parenchyma in
the early phase of the disease.
• The cognitively worsened patient group
had a greater change in BPV when
compared to the whole of the cohort.
31
• Zivadinov R demonstrated changes in BPV was significantly higher in cognitively worsened patients compared with
the whole of the cohort p=0.0031
• Additionally, Hohol et al also demonstrated that rapid development of brain atrophy determined substantial cognitive
decline
1
2

32. DMTs and BRAIN VOLUME LOSS
• Research has shown that early treatment
improves outcomes
• Various DMTs have data showing correlation
between treatment and reduction in brain
volume loss
32
DMT=Disease Modifying Therapies.
1,2
3
1. Popescu, V, Agosta F, Hulst HE, et al. Psychiatry 2013 ; 84:1062-1091.
2. Sormani MP, De Stefano N, Giovannoni G, et al. J Neurol Neurosurg Psychiatry, 2019 ; 90:38-43.
3. Radue E-W, Sprenger T, Gaetano L, et al. Teriflunomide slows BVL in relapsing MS. Neurol Neuroimmunol Neuroinflamm. 2017;4:1–9;

33. The example of AUBAGIO (teriflunomide):
AUBAGIO slows down Brain Volume Loss vs. placebo1
• A difference in brain volume loss favouring teriflunomide at Year 1 was maintained at Year 2
Annualised Change in Brain Volume
*Teriflunomide 14 mg versus placebo at Years 1 and 2. BPF=brain parenchymal fraction; MRIAP=MRI analysis package.
Blinded SIENA Analysis: Effects of Teriflunomide on Brain Volume Loss Versus Placebo.1
1. Radue E-W, Sprenger T, Gaetano L, et al. Teriflunomide slows BVL in relapsing MS. Neurol Neuroimmunol Neuroinflamm. 2017;4:1–9;
-1.4
-1.2
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
0 1 2
MedianPercentChange
FromBaseline
Year
Placebo
Teriflunomide 14 mg
36.9%
reduction*
P=0.0001
30.6%
reduction*
P=0.0001
TEMSO
Core
Post Hoc
Analysis
Both the primary end point (annualized relapse rate) and the key secondary end point (confirmed progression of disability for at least 12 weeks) in the phase III TEMSO trial were met.

34. 1. Wuerfel J, Macdonell R, Sormani MP, et al. Brain Volume Loss and Cognition in Teriflunomide-Treated Patients in TEMSO. Poster presented at AAN 2019. P2-058.
Reduction in Brain Volume Loss is correlated with improved
Cognition in Teriflunomide-Treated patients in TEMSO vs.
placebo-treated 1
• Treatment with AUBAGIO 14 mg was associated with improved cognition as well
as significant reductions in BVL, MRI lesions and relapses
• 44% of AUBAGIO’s effect on cognitive impairment accounted for BVL at Year 2
(Figure 4), 17% for new/enlarging T2w lesions and 7% for relapses
• This highlights the importance to look beyond just relapses.
TEMSO
Analysis
1
1

35. Getting ahead of cognition
• By understanding and
identifying the physical and
emotional signs of cognitive
deterioration, we can take the
first step in implementing an
effective management and
coping strategy.
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