Transcript Les troubles cognitifs dans la maladie de Parkinson - unf

Webminar
Cognitive Impairment
in Parkinson’s Disease
Oury Monchi, PhD
Parkinson, Cognition, Action and Neuroimaging Laboratory,
Institut Universitaire de Gériatrie de Montréal,
Département de Radiologie, Université de Montréal
Disclaimer
This presentation is provided for
information purposes only and does not
represent medical advice.
If you have specific medically related
questions, you should speak with a
health care professional knowledgeable
about Parkinson's disease.
Introduction
James Parkinson
(1755-1828)
An essay on the
shaking palsy 1817
Introduction
 Even though symptoms like hallucinations and
dementia had been reported in some patients
with PD since 1882, the disease has been thought
as nearly exclusively a movement disorders and
the occurrence of cognitive deficit was
overlooked for the next 100 years or so.
 With the use of dopaminergic medication in the
1970’s, it was realized that ‘non-motor’ deficits can
also occur in the disease and in some cases
interfere significantly with the life of patients.
Plan of the presentation
 Different cognitive profiles found in Parkinson’s
Disease
 Neural origins of cognitive deficits
 Their evolution and possible occurrence of
dementia
 The interaction with depression
 The effect of dopaminergic medication on
cognition
 Some future avenues and practical suggestions
I. Different cognitive profiles
found in PD
 First important studies on cognition in PD were
published in the 1980’s (e.g. Taylor & Saint-Cyr,
1986), since then many others have been
published
 They suggest that most patients with PD exhibit
cognitive changes. However they are not
necessarily severe and can even be absent in
some patients.
I. Different cognitive profiles
found in PD
 Executive deficits:
‘higher order processes’ that are used when:
planning,
problem-solving
initiating a new task.
In daily life this may translate in finding it harder to
make a decision, or to plan daily or weekly activities
It helps to give clues
I. Different cognitive profiles
found in PD
 Attention difficulties:
Problems in focusing or dividing attention in
complex situations.
In real life, this may translate into difficulties in
resisting to distraction or to perform more than
one task at once.
It helps to focus on one goal or concept at a time
I. Different cognitive profiles
found in PD
 Visuo-spatial problems:
Problems in estimating distances,
discriminating and acting on visual information.
This can sometimes increase the risk of falls.
In real life this may translate in difficulties in orientation in
an environment with complex visual stimuli, such as
finding a specific isle in a supermarket.
 At the later stages of the disease, illusions or little
hallucinations are observed in some patients only.
I. Different cognitive profiles
found in PD
 Language dysfunction: word finding and naming deficits.
 Memory: Retrieving information that has already been
learned.
In PD the problem is mostly with recall, and not with pure
semantic or encoding like can occur in Alzheimer’s disease.
In PD patients with dementia these deficits are more severe.
Using a notepad can help
 IMPORTANT: Not all these symptoms are present in patients,
and great differences exist between them.
II. Neural origins of cognitive
deficits in PD
 The origins of cognitive deficits are not completely
understood
 Some cognitive deficits such as executive deficits are
more common and originate from PD pathology (i.e.
dopamine deficiency and fronto-striatal altered
function).
 The concept of bradyphrenia describes some
cognitive deficits observed specifically in PD. It refers
to a slowness in thinking and responding that could
share similarities with bradykinesia.
 Others such as memory problems are not necessarily
found in the majority of patients and might occur
from concurrent pathologies associated with aging.
II. Neural origins of cognitive deficits in
PD
SOURCE: Yin and Balleine
2008.
II. Neural origins of cognitive deficits in
PD
Since the 1990’s functional
neuroimaging techniques such as fMRI
(functional Magnetic resonance
Imaging) and PET (Positron Emission
Tomography) are helping us understand
better the origins of cognitive deficits
Neuroimaging Studies in our
laboratory
II. Neural origins of cognitive deficits in
PD
Wisconsin Card Sorting Task
fMRI WCST Results in Young
Controls: Shift-planning
Isolation of a cognitive cortico-striatal
loop
including the ventrolateral PFC in the
planning of a set-shift
Monchi et al., 2001: Journal of Neuroscience,
editor’s choice Science and Nature Reviews
Neuroscience
fMRI WCST Results in Young
Controls: Shift-execution
2ND ‘motor’ Cortico-BG loop (premotor cortex and
putamen) involved in the execution of a shift
Monchi et al., Journal of Neuroscience, 2001
fMRI WCST Results in PD-OFF and
matched Controls: Shift-planning
Controls
PD patients
Decreased activity in PD in the‘cognitive’
cortico-striatal loop during planning the set-shift
Monchi et al., Journal of Neuroscience 2004
Highlighted in ‘This Week in the Journal’
fMRI WCST Results in PD-OFF and
matched Controls: Shift-execution
Controls
Decreased activity in
PD in the‘motor’
cortico-striatal loop
during ‘executing’ the
set-shift
Monchi et al., Journal of Neuroscience 2004
Highlighted in ‘This Week in the Journal’
PD patients
III. Evolution of cognitive deficits
Dementia does not occur at the early
stages of Parkinson’s disease and usually
only occurs after many years following
diagnosis (if it does then it is another entity
Lewy Body Dementia)
 While age is the biggest predictor of
dementia in PD, its prevalence in PD is
higher than in the general population, and
it is estimated to affect approximately 30%
of PD patients
III. Evolution of cognitive deficits
 At the early stages of the disease one can distinguish
between patients with very little or no cognitive
impairments and those with so called ‘Mild Cognitive
Impairments’ MCI.
 Patients with MCI have cognitive deficits in one or
more domains of cognition, but they do not
significantly impair their daily life (unlike dementia).
 As a general rule deficits in only one domain of
cognition (such as executive function) is not
particularly predictive of dementia while deficits in
multiple domains may require more attention.
fMRI WCST MCI vs. NON MCI
OFF Shift Planning
NON MCI
MCI
T-stat
5
Vs.
2.5
Z = +4
Z = +4
fMRI WCST MCI vs. NON
MCI OFF Shift Execution
NON MCI
MCI
T-stat
5.5
vs Control Matching
3.5
Z = +30
Z = +30
IV. Depression in PD
 Depression is thought to be more common in
PD than in the general population (more than
twice the rate).
 However, in most patients with depression in PD
it is usually mild to moderate
 Furthermore it is not clear that PD is correlated
with all aspects of depression.
 In contrast to major depressive disorder, suicidal
tendencies or expressions of guilt and selfblame are rarely observed in PD patients.
IV. Depression in PD
 In PD depression can be confused with apathy or
fatigue which are common but distinct from
depression
 Apathy is a lack of motivation for goal-directed
behaviour, consisting in a loss of initiative, interest
and affect for goal-directed events.
 Similarly to the general population cognitive
deficits (especially those related to attention and
executive deficits) correlate with depression, and it
is not clear exactly what is their relationship.
V. Effect of dopaminergic
medication
 The effect of dopaminergic medication on
cognitive deficits are still controversial, unlike
for motor symptoms.
 Some studies find some improvement, others
find some worsening, and many find no
effects.
 We used neuroimaging to attempt to
understand further why this may be the case
fMRI WCST PD ON vs. OFF
Jubault
Jubault et al, 2009, PlosOne
Summary
et al. 2009, PLoS one
V. Effect of dopaminergic
medication
SOURCE: Yin and Balleine
2008.
fMRI Young healthy adults
Ventral striatum
Dorsal striatum
McDonald et al., 2011, Brain
Same task PD ON and OFF L-Dopa
McDonald et
al., 2011,
Brain
V. Effect of dopaminergic
medication
Other studies in literature
 L-Dopa (e.g. Sinemet) seems to correlate
with depression in PD but not
dopaminergic agonist (e.g. Mirapex)
 On the other hand it is possible to observe
Impulse control disorders (compulsive
buying, gambling, sexual disinhibition) after
prolonged use of agonists but less so with LDopa
V. Effect of dopaminergic
medication
These findings do NOT indicate that L-Dopa
induces depression or that agonists create
impulse control disorders
 They suggest that in patients with a
tendency for depression or for impulsivity,
the use of L-Dopa or agonists respectively
increase this trend.
V. Effect of dopaminergic
medication
The reason these studies are important is that
MD’s/Neurologists not only have to take into
account the evolution of the cardinal motor
symptoms, as well as the possible
occurrence of dyskinesia when determining
the relative dosage of L-Dopa vs. agonists
But also the patient’s cognitive and
behavioural profile
V. Effect of dopaminergic
medication
This is why patients with similar motor features
and advancement in the disease may have
different treatment
Studies are currently conducted in different
laboratories including our own to better
understand the complex relationship
between cognition, behaviour and
dopaminergic medications in PD
VI. Some future avenues and
practical suggestions
Different groups are looking longitudinally for
combinations of markers including anatomical and
functional brain imaging, neuropsychological tests,
and genotype that will help predict the possible
occurrence of dementia in specific patients
This is important as if we can identify these early
we can explore different therapeutic avenues to
slow down cognitive decline
VI. Some future avenues and
practical suggestions
These include different medication avenues
such as Rivastigmine and cholinesterase
inhibitor
BUT also non invasive stimulation Transcranial
Magnetic Stimulation and Transcranial Direct
Current Stimulation
And Programs of cognitive and physical
stimulation
VI. Some future avenues and
practical suggestions
 Most importantly: As much as possible: keep
active both mentally and physically, this will
help slowing down both motor and cognitive
decline
 This does not mean running a marathon or
solving advanced physics equations.
 For example: Walking, slow dancing, yoga or
Tai-Chi exercises, massages
 Reading, playing games, listening to music
 Regularity is more important than intensity
Collaborators and Funding
CRIUGM/PCAN
• Marie-Andrée Bruneau, MD, MSc
• Clotilde Degroot, MSc
• Benoît Kullmann, MD
• Kristina Martinu, MSc
•Atsuko Nagano, MD, PhD
• Christophe Beditti, MSc
• Beatriz Mejia, PhD
• Thomas Jubault, PhD
Toronto Western Hospital & CAMH
• Antonio P. Strafella, MD, PhD
MNI, McGill
• Anne-Louise Lafontaine, MD, MSc
• Alain Ptito, PhD
Université de Montréal
• Guy Rouleau, MD, PhD
• Sylvain Chouinard, MD, MSc
• Jean-Francois Gagnon, PhD