1. MND, Cognitive change and Frontotemporal Dementia Eneida Mioshi Chair in Dementia Care Faculty of Medicine and Health Sciences

2. MND, Cognitive (and behavioural) change and Frontotemporal Dementia Eneida Mioshi Chair in Dementia Care Faculty of Medicine and Health Sciences

4. Case vignettes – Motor Neurone Disease
66-year-old male solicitor
Symptoms began in June 2011 (generalised weakness, respiratory disturbance)
ALSFRS-R = 28/48 in June 2012
72-year-old female teacher
Symptoms began in July 2006 (speech and swallowing) – prog bulbar palsy
ALSFRS-R score = 34/48 in July 2012
Jaye Ba**
58-year-old female Office Manager
Symptoms began in June 2011 (left hand weakness and cramps)
ALSFRS-R = 45/48 in November 2012

5. Frontotemporal Dementia (FTD)
Diagnostic criteria
(Simplified)
Possible: 3 of the 6: disinhibition, apathy/inertia,
loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality
and dysexecutive
neuropsychological profile.
2) Probable: functional disability and characteristic neuroimaging 
Then we have Frontotemporal dementia, or FTD
FTD is a devastating dementia of young onset, which is markedly characterised by changes in behaviour, such as disinhibition and loss of social skills.
In this talk I’ll be referring to FTD as the head of the elephant.

6. Case vignettes – dementia (Frontotemporal dementia)
FRSFTD Stage: MILD
“Problems preparing or cooking a meal on their own – needs supervision”
FRSFTD Stage: MODERATE
“lacks interest in doing things (old and new); lacks normal affection”
“increased sweet tooth”
“difficulties using cutlery; preparing meal alone (execution of it)”
FRSFTD stage: SEVERE
“confused/muddled in unusual surroundings”
“problems organizing finances and organizing preparation of meals”
“ lacks interest in doing new things, preparing a meal, personal affairs/finances”
Jaye Ba**

7. FTD MND 66-year-old solicitor
Symptoms began in June 2011 (generalised weakness, respiratory disturbance)
ALSFRS-R = 28/48 in June 2012
72-year-old teacher
Symptoms began in July 2006 (speech and swallowing) – prog bulbar palsy
ALSFRS-R score = 34/48 in July 2012
58-year-old Office Manager
Symptoms began in June 2011 (left hand weakness and cramps)
ALSFRS-R = 45/48 in November 2012
FRS stage: SEVERE
“confused/muddled in unusual surroundings”
“problems organizing finances and organizing preparation of meals”
“ lacks interest in doing new things, preparing a meal, personal affairs/finances”
FRS Category: MILD
“Problems preparing or cooking a meal on their own – needs supervision”
FRS Stage: MODERATE
“lacks interest in doing things (old and new); lacks normal affection”
“increased sweet tooth”
“difficulties using cutlery; preparing meal alone (execution of it)”
Jaye Ba**
FTD

8. MNDFTD spectrum FTD MND/ALS ALSFTD
Clinical, Genetics, Imaging, Pathological overlap
MND/ALS
ALSci
ALS-plus
ALSbi
ALSFTD
FTD
Strong et al, Frontotemporal syndromes in ALS:
consensus criteria for diagnosis, ALSFTD, 2009
Revised diagnostic criteria due 2016/2017

9. MNDFTD continuum: clinical
Cognitive tests
Neuropsychiatric ratings
MND/ALS
ALS-plus
bvFTD
Lillo et al, ALSFTD , 2012

10. MNDFTD continuum: imaging
FTD vs controls
FTDMND vs controls
MND vs controls
x = 0
x = 0
x = 0
y = -10
y = -10
y = -16 L L L
Lillo et al, PLOS One, 2012; Mioshi et al, Neurology 2013

11. What are these cognitive and behavioural changes?
Assessment
What are these cognitive and behavioural changes?

12. Cognitive deficits in MND/ALS MND/ALS All domains<controls Fluency
Language
Social cognition
Executive function
Memory
Beeldman et al, JNNP, 2016
systematic review: 44 studies included

13. I had the PEG inserted [he lifts his shirt to show it]
She lost the will to live; she doesn’t want to do much now…
Apathy
Disinhibition
ALS
Everything has to be done when she says so. She can’t wait and gets all worked up if we don’t do as she says
ALS-plus
ALSFTD
Rigidity
So we know more of the ALSFTD continuum these days – the elephant. Some patients present clinically with more prominent motor symptoms – ALS
Other patients present more with dementia-like symptoms – FTD. Some will present with both concomitantly, ALSFTD
But let me define neuropsychiatric symptoms first.
For this talk, when I refer to neuropsychiatric symptoms in ALS, I am referring to changes in behaviour (not deficits in cognition measured by neuropsychological tests).
In ALS these deficits are now recognised. Growing body of literature addressing this, and new measures have been validated.
[show call out balloons]
It is important for us to notice the different types of behaviours, and the gradient of behaviours in the ALSFTD spectrum. How they vary from FTD to ALS, via ALSFTD
And why is it important to investigate and understand these symptoms? Because there are major clinical implications.
IMPLICATIONS: Clinical decision making (as you would have seen this morning) AND carer burden
Our daughter was assaulted, and he didn’t care when she told us
FTD
Lack of empathy

14. Is apathy the most common symptom?
MiND-B
Apathy
Stereotypical behaviour
Disinhibition
Mioshi et al, ALSFTD, 2014

15. How late are neuropsychiatric symptoms in MND?
MiND-B
MND patients show early susceptibility to behavioural symptoms than motor symptoms
Mioshi et al, Neurology , 2014

16. What are the implications of the MNFTD continuum for
clinical care?
Why should we evaluate
these symptoms?

17. #1 Severe Apathy is associated with poor prognosis
Several studies have demonstrated that MNDFTD patients have worse prognosis
Caga et al, EJoN 2015

18. #2 Behavioural changes and
Disability in MND
Motor deficits
Apathy
Disinhibition +
DISABILITY
Mioshi et al, J Clinical Neurosci 2012

19. #3 Family carer burden 60% variance burden explained by model
Everything has to be done when she says so. She can’t wait and gets all worked up if we don’t do as she says
She lost the will to live; she doesn’t want to do much now…
Our daughter was assaulted, and he didn’t care when she told us
Caregiver burden
60% variance burden explained by model
Lillo et al, BMC Neurology, 2012

20. What happens to caregiver burden over time?
Significant increase over time
Hsieh et al, Journal of Alzheimer’s Disease 2015

21. Compliance to treatments?

22. ALS
How can we detect these cognitive and behavioural symptoms in a busy clinic?
ALS-plus
ALSFTD

23. Stereotypical Behaviour/Rigidity
MiND-B
Cognitive deficits in ALS: Mini ACE
1. Has temper outbursts
4 – Very rarely; or no change to 15 years ago
3 – A few times per month
2 – A few times per week
1 – Daily
0 – Constantly
2. Is uncooperative when asked to do something
3. Makes tactless or suggestive remarks
4 – Never; or no change to 15 years ago
4. Acts impulsively without thinking
5. Is rigid and fixed in his/her ideas and opinions
Neuropsychiatric symptoms in ALS: MiND-B
6. Repeatedly uses the same expression or catch phrase
4 – Never; or no change to 15 years ago
3 – A few times per month
2 – A few times per week
1 - Daily
0 – Constantly
7. Shows less enthusiasm for his/her usual interests
1 – Daily
8. Shows little interest in doing new things
9. Fails to maintain motivation to keep in contact with friends or family
Apathy
Disinhibition
Stereotypical Behaviour/Rigidity
For scoring:
Abn Beh. sub-score (1+2+3) = ……..
Ster Beh. sub-score (4+5+6) = ……..
Apa. sub-score (7+8+9) = ……...
Total MiND-B score = …………. (max 36)
Mioshi E,

24. Can the MiND-B discriminate Stereotypical Behaviour/Rigidity
ALS from ALS plus?
FTD
ALS
ALSFTD
ALS-plus
MiND-B SENSITIVITY SPECIFICITY
Cut off 35/ % %
Cut off 32/ % %
Stereotypical Behaviour/Rigidity
Apathy
Disinhibition
Available for free download from

25. Screening in a busy clinic
FTD
ALS
ALSFTD
ALS-plus
Screening in a busy clinic
M-ACE +
MiND-B
ECAS
Hsieh et al, J Ger Psych Neurol, 2014

26. Evaluating in more detail
ECAS
Evaluating in more detail
85% sensitivity, 85% specificity with published cut-offs
UK screen validated against gold standard extensive neuropsychology
Multidomain
MND-Specific functions (Executive, Language, Fluency)
MND Non-specific functions (Memory and Visuospatial)
Designed for physical disability
Written or spoken responses
Carer Behaviour Interview
Based on new bvFTD diagnostic criteria
University of Edinburgh
Courtesy of Prof Sharon Abrahams

28. Lack of empathy
All domains<controls
Fluency
Language
Social cognition
Executive function
Memory
Disinhibition
Rigidity
Apathy
ALS
How can we support patients who present with cognitive and behavioural symptoms in a busy clinic or home visit?
ALS-plus
ALSFTD
So we know more of the ALSFTD continuum these days – the elephant. Some patients present clinically with more prominent motor symptoms – ALS
Other patients present more with dementia-like symptoms – FTD. Some will present with both concomitantly, ALSFTD
But let me define neuropsychiatric symptoms first.
For this talk, when I refer to neuropsychiatric symptoms in ALS, I am referring to changes in behaviour (not deficits in cognition measured by neuropsychological tests).
In ALS these deficits are now recognised. Growing body of literature addressing this, and new measures have been validated.
[show call out balloons]
It is important for us to notice the different types of behaviours, and the gradient of behaviours in the ALSFTD spectrum. How they vary from FTD to ALS, via ALSFTD
And why is it important to investigate and understand these symptoms? Because there are major clinical implications.
IMPLICATIONS: Clinical decision making (as you would have seen this morning) AND carer burden
FTD

30. Take home message MND and FTD are on a disease spectrum
Early detection of cognitive and neuropsychiatric symptoms in MND/ALS is critical
…but symptoms are usually reported if you ask/evaluate/assess
MND is a multisystem disorder
Implications for treatment compliance; prognosis; disability and family carer burden
Research can lead to changes in practice
Clinicians change research

31. All research participants: patients and their family carers
Acknowledgements
All research participants:
patients and their family carers