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 Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons 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 patients 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 messengers, or neurotransmitters 1,2 One of the neurotransmitters that helps control movement is dopamine 1,2 In PD, neurons lose the ability to make and transmit dopamine 1,2 Loss of dopamine leads to difficulty controlling movement 1,2 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. neuron dopamine

Pathology continued When the neurons start to malfunction, they start to produce an waste products that they cant get rid of Lewy bodies are the abnormal aggregates of protein that develop inside neurons in Parkinsons 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 Parkinsons diseaserelated pathology. Cell Tissue Res. 2004; 318:121-134. A current hypothesis, called the Braak hypothesis, suggests PD begins long before movement symptoms appear 1 PD begins in the lower brainstem and progresses to other parts of the brain 1 Some nonmotor symptoms appear before diagnosis 1. 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):S1- S136.

Nonmovement (nonmotor) symptoms of PD Depression and anxiety Sleep problems Pain Slowed thinking Memory difficulty Constipation Urinary problems Fatigue Reduced sense of smell Loss of appetite 1. Symptoms. Parkinsons 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. 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 You MedicationNutritionBody MindSpirit Exercise Alternative therapies

The PD treatment team You Neurologist or Neurology provider Nurse Occupational therapist Primary care physician Physical therapist Psychiatric providers Speech therapist Sleep clinic providers

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 patients with Parkinsons 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, 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 Parkinsons 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 Parkinsons diseaserelated 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 Parkinsons 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 Parkinsons 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, cross- words, 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

Treatment for dystonia, essential tremor, Parkinsons disease, chronic pain and Obsessive Compulsive disorder. Research ongoing for use with chronic pain, Tourettes syndrome and mood disorders.

Deep brain stimulation http://professional.medtronic.com/video- player/index.htm?contentid=WCM_PROD089307&ch apnum=# 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=# http://professional.medtronic.com/video- player/index.htm?contentid=WCM_PROD089306&ch apnum=#

Questions??

Elise Juliette and Emme

Documents

What is this all about and how do these things go together?