Transcript Parkinson’s disease and mood disorders

What is this all about and how do these
things go together?
What is a mood disorder?
 A collection of disorders that includes major
depression and anxiety disorder. They are all
characterized by major disruptions in patients' moods
and emotions, potentially caused from varying factors
PD and mood disorders
 Virtually all patients with PD experience some mood
disturbance during the course of the disease. Like any
other chronic condition, PD poses many challenges on
a daily basis that can be discouraging to both the
patient and their family. It is entirely normal to go
through periods of sadness and discouragement.
Huber SJ , Cummings JL , editors. Parkinson's Disease: Neurobehavioral Aspects. New York: Oxford University Press; 1992.
R. Pahwa and K.E. Lyons (Editors), Handbook of Parkinson’s Disease; 4th Edition, New York, Informa Healthcare Publishers, 2007.
R.F. Pfeiffer and I. Bodis-Wollner (Eds). Parkinson Disease and non-motor dysfunction, Humana Press; Totowa, New Jersey, 2005.
It is also entirely normal to experience worry and
anxiety about how you and your family are going
to cope with all the curve balls PD throws at you.
So sadness and anxiety are entirely normal
reactions to PD. What gets worrisome and
requires attention is when the sadness turns into
depression or when the anxiety becomes
persistent and interferes with daily functioning.
Huber SJ , Cummings JL , editors. Parkinson's Disease: Neurobehavioral Aspects. New York: Oxford University Press; 1992.
R. Pahwa and K.E. Lyons (Editors), Handbook of Parkinson’s Disease; 4th Edition, New York, Informa Healthcare Publishers, 2007.
R.F. Pfeiffer and I. Bodis-Wollner (Eds). Parkinson Disease and non-motor dysfunction, Humana Press; Totowa, New Jersey, 2005.
What does that have to
do with me ?
 Recent research has shown that mood changes, however
slight may actually be some of the first clinical non motor
signs of PD
 50-70% of patients diagnosed with Parkinson’s disease will
show symptoms of a mood disorder over time
 Up to 50% of PD patients experience major depression
during the course of the disease.
Huber SJ , Cummings JL , editors. Parkinson's Disease: Neurobehavioral Aspects. New York: Oxford University Press; 1992.
R. Pahwa and K.E. Lyons (Editors), Handbook of Parkinson’s Disease; 4th Edition, New York, Informa Healthcare Publishers, 2007.
R.F. Pfeiffer and I. Bodis-Wollner (Eds). Parkinson Disease and non-motor dysfunction, Humana Press; Totowa, New Jersey, 2005
 Depression can be effectively treated in PD with a
combination of psychotherapy and medication
 Between 30 and 40% of PD patients experience a
significant anxiety disorder during the course of the
illness. These anxiety disorders can be expressed as
panic, phobia(particular situations trigger the anxiety)
or generalized anxiety
Mood disorders commonly seen
with Parkinson’s disease
 Anxiety –
 A feeling of worry, nervousness, or unease, typically
about an imminent event or something with an
uncertain outcome
 A nervous disorder characterized by a state of excessive
uneasiness and apprehension, typically with compulsive
behavior or panic attacks
 This may manifest in physical symptoms such as nausea,
excessive sweating, racing heartbeat, headache, trouble
concentrating or sleeping, or lightheadedness.
Mood disorders commonly seen
with Parkinson’s disease
 Depression
 Feelings of severe despondency and dejection, typically felt
over a period of time and accompanied by feelings of
hopelessness and inadequacy
 A condition of mental distress characterized by such feelings
to a greater degree than seems warranted by the external
circumstances, typically with lack of energy and difficulty in
maintaining concentration or interest in life
 This too may manifest physically with body aching, fatigue,
daytime sleepiness, trouble sleeping, trouble multitasking or
staying on task.
Anhedonia
 A hallmark symptom of depression described as
 an inability to experience pleasure
 a decreased ability to enjoy previously pleasurable
activities.
Apathy
 Common mood symptom in PD
 State of indifference, suppression of emotions such as
concern, excitement, motivation and passion.
 Absence of interest in or concern about emotional,
social, spiritual, philosophical and/or physical life
 May lack a sense of purpose or meaning in their life
SO what can we do about it?
 Serotonin is the neurotransmitter we tend to think
of when it comes to depression, recent studies
have supported the hypothesis that major
depression, especially in PD, is associated with a
state of reduced serotonin AND decreased
dopamine transmission.
Most antidepressant treatments do not directly
enhance dopamine neurotransmission, which may
contribute to residual symptoms, including
impaired motivation, concentration, and pleasure
which are more controlled by dopamine release.
This may be evident in patient’s with treatment
resistant mood disorders that later go on to
develop PD symptoms.
The pathology of PD
 Neurons transmit messages
to other neurons via chemical
neuron
messengers, or neurotransmitters1,2
 One of the neurotransmitters
that helps control movement
dopamine
is dopamine1,2
 In PD, neurons lose the
ability to make and transmit
dopamine1,2
 Loss of dopamine leads to difficulty controlling movement1,2
 Dopamine can be affected by serotonin levels, becoming depleted when
serotonin is depleted. Likewise, dopamine levels can be elevated by
elevating the serotonin level.
1. What is Parkinson's disease (PD)? National Parkinson Foundation. Available at www.parkinson.org.
2. What is Parkinson's disease? Parkinson's Disease Foundation. Available at www.pdf.org.
Pathology continued…
 When the neurons start to malfunction, they start to
produce an waste products that they can’t get rid of
 Lewy bodies are the abnormal aggregates of protein
that develop inside neurons in Parkinson’s disease,
causing dysfunction within the nerve cell itself.
 Also found in other types of parkinsonism and the
location of the deposits determines the symptoms
caused. Frontal=emotional/cognitive effects, motor
cortex=motor effects.
An evolving picture of PD
The traditional
view, is that PD
begins in the
mid-brain, in the
substantia nigra
An evolving picture of PD
Adapted with permission from author (Braak H), taken from Braak H, Ghebremedhin E, Rub N, et al. Stages in the development of Parkinson’s
disease–related pathology. Cell Tissue Res. 2004; 318:121-134.
• A current hypothesis, called the Braak hypothesis, suggests PD begins
long before movement symptoms appear1
• PD begins in the lower brainstem and progresses to other parts of the brain1
• Some nonmotor symptoms appear before diagnosis1.
• It is thought that in stages 1 & 2 of disease progression, the serotonin supply
and reuptake is severely limited or affected, causing changes in dopamine
levels, leading to onset of mood symptoms even before motor symptoms show
in Stages 3 & 4
1. Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1S136.
Nonmovement (nonmotor)
symptoms of PD
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Depression and anxiety
Sleep problems
Pain
Slowed thinking
Memory difficulty
Constipation
Urinary problems
Fatigue
Reduced sense of smell
Loss of appetite
1. Symptoms. Parkinson’s Disease Foundation. Available at www.pdf.org.
2. Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology 2009;72(suppl 4):S1-S136
.
Mood changes and PD
 Mood changes are one of the first symptoms of
dopamine imbalance, but mood changes are not the
only indication that dopamine levels are not at optimal
levels. Dopamine affects thoughts, emotions and
behaviors. Medications may help you with some of the
symptoms associated with dopamine imbalances, and
behavioral therapy may help with some of the
problems caused by low dopamine levels
Mood changes and PD
 Dopamine provides feelings of well-being such as
pleasure, attachment, and love. It also allows you to
integrate thoughts and feelings For example,
dopamine gives you the ability to focus or concentrate
on cognitive tasks, such as rationalizing. It helps you to
diffuse unpleasant thoughts or feelings appropriately.
Mood changes and PD
 Dopamine supplies those areas of the brain that are
particularly important for concentration, reasoning,
reflecting and planning. These are known as the
“executive cognitive functions” because they help to
control all the other more basic thinking processes of
the brain. It is important to note that these thinking
functions are NOT lost but slow down with this disease
process. Even small slowing in early stages can have
big effects on functioning if left untreated. As the
disease progresses, these mood changes can cause
lasting memory effects and executive dysfunction
given depletion of dopamine and serotonin over time
Mood changes and PD
 Dopamenergic medications are used in
the long term treatment of PD. Without
the use of properly balanced serotonin
precursors, chronic treatment with
dopamine may cause serotonin depletion
by competitive inhibition of 5-HTP
synthesis. Meaning that it is a checks and
balances system, you need EQUAL
amounts of the 2 neurotransmitters to
keep both movements and mood even.
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Marty L. Hinz, MD President Clinical Research NeuroResearch Clinics, Inc. Cape Coral, Florida USA
Research Office
•When serotonin depletion from levodopa use is
great enough, the levodopa may not work and
symptoms of the disease may return. With extreme
depletion of serotonin, the levodopa may not work
as intended at any dosing level, making symptom
control very difficult.
•As symptoms of movement worsen, we increase
the levodopa and many times the serotonin supply
is not replenished, causing more troubles with
control of motor symptoms and mood.
Putting PD treatment together –
a holistic approach
Medication
Alternative
therapies
Exercise
Nutrition
You
Body
Spirit
Mind
The PD treatment team
Sleep
clinic
providers
Speech
therapist
Neurologist
or
Neurology
provider
You
Psychiatric
providers
Physical
therapist
Nurse
Occupational
therapist
Primary
care
physician
Working with the team
 Symptoms change over time, and so will your
treatment
 Discuss changes in symptom severity
 Tell your provider about these often potentially
overlooked symptoms: Such as the nonmotor
symptoms we have discussed…
 Keep a diary of symptoms to make it easy to remember
Mood medications
 “tremor neutral” options – medications that we have found in
practice to have less side effects effecting movement
 Celexa (citalopram) – anxiety/depression
 Lexapro (escitalopram) – anxiety/depression
 Remeron (mirtazepine) - anxiety/depression/apathy
 Effexor (venlafaxine) – anxiety/depression, stimulating,
potential benefit for daytime sleepiness
 Side effects and benefits of these medications vary. The
medications listed above are typically very well tolerated in
patient’s with Parkinson’s disease but each patient is different
Mood disorders and talk therapy
 The role of psychotherapy in treating mood disorders
is to help the person develop good coping strategies for
dealing with everyday stressors. In addition, it can
encourage you to use your medications properly.
Depression and Bipolar Support Alliance: “Psychotherapy: How it works and how it can help.”
American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depression, 2000.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR, American
Psychiatric Pub, 2000.
Mood disorders and talk therapy
 Many studies support the idea that therapy can be a
powerful treatment for mood disorders. Some,
although not all, have also found that combining
depression medicine with therapy can be particularly
effective. A review published in the Archives of
General Psychiatry in 2011, for example, concluded
that therapy combined with antidepressants worked
better than mood medication alone. It also supported
the idea that therapy can help people stay compliant
with their drug treatment in the long term.
Mood disorders and talk therapy
 There are a number of benefits to be gained from using
psychotherapy in treating clinical mood disorders:
 It can help reduce stress in your life.
 It can give you a new perspective on problems with family,
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friends, or co-workers.
It can make it easier to stick to your treatment.
You can use it to learn how to cope with side effects from your
disease and mood medication.
You learn ways to talk to other people about your condition.
It helps catch early signs that your mood is getting worse.
Depression and Bipolar Support Alliance: “Psychotherapy: How it works and how it can help.”
American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depression, 2000.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR, American Psychiatric Pub, 2000.
Take home points
 Mood changes are a very common part of PD.
 Research has supported that the mood changes associated
with PD are likely related to neurochemistry changes and
not just changes in lifestyle and functioning, although
these do contribute
 Regulation of both dopamine and serotonin levels is very
important for adequate control of both motor and mood
symptoms.
 Medication can be used to help regulate both the
dopamine and serotonin levels
 Talk therapy can help support you during the life changes
associated with the PD and help you to live a more fulfilling
life
Cognitive impairment
and
Dementia
 Fairly common in Parkinson’s disease – may start in
stages 3 and 4 with onset of motor symptoms, but
most noticed in stages 5 and 6
 This has to do with WHERE in the brain the Lewy
body proteins develop and deposit.
 Medications can be used to slow progression but
memory changes will still occur over time as part of the
disease process. This has to do with the level of
dopamine/serotonin depletion in the brain
An evolving picture of PD
Adapted with permission from author (Braak H), taken from Braak H, Ghebremedhin E, Rub N, et al. Stages in the development of Parkinson’s
disease–related pathology. Cell Tissue Res. 2004; 318:121-134.
Cognitive impairment
and
Dementia
 Often have troubles with delayed verbal response and
word finding given the lack of dopamine to aide in
fluid transmission of thought and speech
 Often take more than the “normal amount” of time to
interpret and respond to information presented
although ability to comprehend and respond remains
intact most often into later stages.
 Delusional thinking, hallucinations and paranoia may
occur with these changes, depending on the parts of
the brain affected by the Lewy body deposits.
So if the changes are inevitable,
why talk about them?
 Research has shown that much like the physical effects
of PD, cognitive effects can be slowed and
compensated for - the theory of neuroplasticity –
overcoming “road blocks” by making or finding
“detours”.
Neuroplasticity
 The brain's ability to reorganize itself by forming new
neural connections throughout life. Neuroplasticity allows
the neurons (nerve cells) in the brain to compensate for
injury and disease and to adjust their activities in response
to new situations or to changes in their environment.
 Brain reorganization takes place by mechanisms such as
"axonal sprouting" in which undamaged axons grow new
nerve endings to reconnect neurons whose links were
injured or severed. Undamaged axons can also sprout nerve
endings and connect with other undamaged nerve cells,
forming new neural pathways to accomplish a needed
function.
Synaptic pruning &
neuroplasticity
 The idea that individual connections within the brain
are constantly being removed or recreated, largely
dependent upon how they are used.
 Neurons that fire together, wire together/neurons that
fire apart, wire apart.
 Those with neurological disorders such as Parkinson’s
disease, autism or those who have had a stroke that
resulted in lost function, are capable of retrieving
much of their lost function by practicing and
“rewiring” the brain in order to incorporate these lost
functions and behaviors.
What does this boil down to
regarding Parkinson’s disease?
 The research on neuroplasticity has shown that the
patients that are more active and aggressive with
physical and cognitive activity do better, longer.
 The more active you stay, the better off you are, as you
train your brain to “detour” and neurons to re-wire
 There has also been some research that has shown that
the changes in the brain induced by physical and
cognitive activity may postpone, slow or stop the
formation of the Lewy body proteins that cause
disease progression an resulting physical and cognitive
symptoms.
Take home points
 Stay active physically – LSVT BIG, walking, stationary
biking, water based exercise, balance training, yoga, Tai-chi
 Stay active cognitively – LSVT LOUD, conversation (best
with people less familiar), brain teasers, Suduko, crosswords, etc
 The more you use physical and cognitive functions, the
better you will be able to use them, potentially the less
function you will lose and the better you will be able to
adapt and learn ways to change behavior and activities.
 Keeping the brain and body active improve their ability to
rewire and compensate as well as potentially delay changes
brought on progression of the disease.
Deep brain stimulation
Deep brain stimulation
 Treatment for dystonia, essential tremor, Parkinson’s
disease, chronic pain and Obsessive Compulsive
disorder.
 Research ongoing for use with chronic pain, Tourette’s
syndrome and mood disorders.
Deep brain stimulation
 http://professional.medtronic.com/video-
player/index.htm?contentid=WCM_PROD089307&ch
apnum=#
 Lead delivers electrical stimulation to the brain, to
disrupt and modulate abnormal motor circuits
affecting movement. The exact mechanism of action is
unknown
Deep brain stimulation
 A “pacemaker” for the brain
 Medtronic - 500,000 devices implanted, 80,000 0f
which are DBS implants for treatment of movement
disorders.
 After initially considering surgery, takes patients on
average about a year to proceed
 Typically best window for consideration is 7-10 years
after onset of motor symptoms – long enough for the
symptoms to potentially cause dysfunction and the
patient to show response to dopamine but potentially
before onset of memory or mood problems
Deep brain stimulation
 Requirements for consideration for DBS:
 Responsive to dopaminergic medications
 Motor fluctuations that are causing interference in
activities of daily living, occupational function or leisure
pursuits
 Must pass pre-DBS evaluation of mood, memory and
presurgical requirements, including MRI of the brain
and general physical
 To complete evaluation may take months of preparation
Deep brain stimulation
 Currently sending patients to Minneapolis/St. Paul to
Dr. McIver at Regions or Dr. Abosh at the U of M.
 Expecting a new neurosurgeon at Sanford Fargo that is
planning to start implanting DBS for various
treatment reasons
Deep brain stimulation
 Patient consideration for surgery
 Should not be taken lightly – this is brain surgery
 Risks of the surgery of those potential with any brain
surgery –infection, seizure, bleed, coma or death
 May negatively impact speech, memory, mood or
balance based on lead placement and brain anatomy, as
well as response to placement and programming.
 If preexisting mood difficulties or memory troubles,
may be precluded from proceeding with the surgery
Deep brain stimulation –
stimulator with leads
Deep brain stimulation –
programmer
Regardless of
where the device is
implanted, initial
programming and
any adjustments
needed can be
done locally
Deep brain stimulation
 http://professional.medtronic.com/video-
player/index.htm?contentid=WCM_PROD089306&ch
apnum=#
Questions??
Elise Juliette and Emme