Thursday, July 12, 2018

Affective Disorders and PD


Parkinson’s disease (PD) is a disease that affects movement and motor capabilities.  PD also has a variety of non-motor symptoms, of which anxiety and depression are especially common.  These psychiatric disorders are referred to by healthcare professionals as affective, or mood, disorders.  It is estimated that 25-75% of patients with PD will experience significant symptoms of anxiety or depression at some point during their illness [1, 2]. 

Depression is a common mental health issue. The National Health and Nutrition Examination Survey, 2009–2012 reported that 7.6% of Americans aged 12 and over, experienced moderate or severe depressive symptoms, when polled about mood during the last two weeks [3].  

Depression can be more difficult to identify in patients with PD.  Lack of energy or inability to accomplish daily activities may be attributed erroneously to the motor symptoms of PD, rather than to a depressive episode.  Some of the common signs and symptoms of depression are:  

Persistent sad, anxious, or “empty” mood
Feelings of hopelessness or pessimism
Irritability
Feelings of purposelessness
Loss of interest or pleasure in hobbies and activities   
Decreased energy or fatigue   
Excessive slowness in daily activities
Difficulty in concentrating, remembering, or making decisions   
Difficulty in falling asleep, or early morning awakening
Appetite and/or weight changes [4]

Doctors used to think that depression in patients with PD patients was an emotional response to the diagnosis of their disease.  A newer theory is that the disease itself is the cause of these mood issues [5-7].  

Depression is a result of chemical imbalances in the brain [8].  There have been significant successes in mental health treatment using drugs such as fluoxetine (Prozac) or bupropion (Wellbutrin).  These drugs are classified as selective serotonin reuptake inhibitors (SSRIs), which means that they block the reabsorption of serotonin—a chemical in the brain that is linked to mood stability.  By allowing this neurochemical to remain in the brain for longer, the mood benefits of these drugs are sustained. 
Anxiety—like depression—is common in PD patients [5, 6, 9].  Along with SSRIs, which can produce anti-anxiety benefits, another class of drugs exists for treating generalized anxiety disorders and panic attacks: serotonin-norepinephrine reuptake inhibitors (SNRIs).  These drugs block the reabsorption of these two neurotransmitters and should be used in preference to benzodiazepines, which have more side effects and can be habit-forming.  SSRIs and SNRIs stabilize mood, and in many cases can provide satisfactory relief from depression and anxiety. Psychological counselling, in addition to a drug therapy regimen, is optimal [10].

It may take up to three months or so after initiation of an anti-depressant before there is a reduction of symptoms [10, 11].  Patients must allow time for the medication to work and for most patients, treatment should continue for at least a year after it begins to help.

In addition to medication, exercise is effective [12-14] in the treatment of depression.  Outdoor exercise is particularly helpful as sunlight helps stimulate the brain to produce serotonin.   Social interaction is also beneficial for mood and stimulates the brain [15].  

Patients may not recognize that they are depressed.  It is helpful for a spouse, partner, or close friend to accompany patients to follow-up appointments, as they can help answer questions on mood changes and level of social activity.

For patients taking carbidopa/levodopa (Sinemet), complications can arise after months or years of treatment.  There may be response fluctuations, either “wearing off” effect or “on/off” periods.  A “wearing off” effect is when a patient is aware of a loss of symptomatic benefit of Sinemet before the next scheduled dose.  “On/off” periods are response fluctuations marked by rapidly cycling response changes—shifting between normal, under-medicated, and over-medicated states without any relationship to the timing of doses.  Depression and anxiety may occur in patients with these complications, particularly when a patient is in an “off” stage. While treating the on/off motor phenomena can be difficult, the medical treatment of depression and anxiety should be the same as in any patient with a similar mood complaint.

Patients with PD should see a neurologist regularly so that their symptoms are managed optimally.  Symptoms of depression and anxiety —similar to motor symptoms— should also be discussed. 

References
1.      Sagna A, Gallo JJ, Pontone GM: Systematic review of factors associated with depression and anxiety disorders among older adults with Parkinson's disease.  Parkinsonism Relat Disord. 2014; 20: 708-715
2.      Leentjens AF, Dujardin K, Marsh L, Martinez-martin P, Richard IH, Starkstein SE: Symptomatology and markers of anxiety disorders in Parkinson's disease: a cross-sectional study. Mov Disord. 2011; 26: 484-492.
3.      Pratt LA, Brody DJ: Depression in the U.S. household population, 2009–2012. NCHS data brief, no 172. Hyattsville, MD: National Center for Health Statistics. 2014
4.      “Depression.  Signs and Symptoms.” Accessed from National Institute of Mental Health, https://www.nimh.nih.gov/health/topics/depression/index.shtml#part_145397, on February 23, 2017.
5.      Yamanishi T, Tachibana H, Oguru M, et al: Anxiety and depression in patients with Parkinson's disease. Intern Med. 2013; 52: 539-545.
6.      Shulman LM, Taback RL, Bean J, Weiner WJ: Comorbidity of the nonmotor symptoms of Parkinson's disease. Mov Disord. 2001; 16: 507-510.
7.      Grosch J, Winkler J, Kohl Z: Early degeneration of both dopaminergic and serotonergic axons – A common mechanism in Parkinson’s disease. Front Cell Neurosci . 2016; 10: 293
8.      Frisina PG, Haroutunian V, Libow LS: The neuropathological basis for depression in Parkinson's disease. Parkinsonism Relat Disord. 2009; 15: 144-148.
9.      Zhu K, Van hilten JJ, Marinus J: Onset and evolution of anxiety in Parkinson's disease. Eur J Neurol.  2017; 24: 404-411.
10.  Thase ME, Greenhouse JB, Frank E, et al: Treatment of major depression with psychotherapy or psychotherapy-pharmacotherapy combinations. Arch Gen Psychiatry. 1997; 54: 1009–1015
11.  American Psychiatric Association: Practice Guideline for the Treatment of Major Depressive Disorder (Revision).  Am J Psychiatry 2000; 157(Suppl):1-45.
12.  Motl RW: Effect of exercise on depressive symptoms in adults with neurologic disorders: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2015; 96: 1329-1338.
13.  Tuon T, Valvassori SS, Dal pont GC, et al: Physical training prevents depressive symptoms and a decrease in brain-derived neurotrophic factor in Parkinson's disease. Brain Res Bull. 2014; 108: 106-112
14.  Adamson BC, Ensari I, Motl RW: Effect of exercise on depressive symptoms in adults with neurologic disorders: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2015; 96: 1329-1338.
15.  Crooks VC, Lubben J, Petitti DB, Little D, Chiu V: Social network, cognitive function, and dementia incidence among elderly women. Am J Public Health. 2008; 98: 1221-1227.




Tuesday, June 12, 2018

New blog from the Parkinson's Foundation, available at www.parkinson.org

What Are the New Therapies in Trial for Parkinson’s Disease?

We always advise patients to ask their doctor what’s new in Parkinson’s disease (PD). Recently, three leading experts at the Parkinson’s Foundation Center Leadership Conference reviewed the field and updated all attendees on several of the exciting therapies currently being tested by Albert Hung, MD, PhD, Massachusetts General Hospital (MGH); Irene Richard, MD, University of Rochester Medical Center; and Hubert Fernandez, MD, Cleveland Clinic. In this month’s What’s Hot in PD blog we review their latest therapies.
There are several drugs that have been repurposed and are in clinical trials. The advantage of a repurposed drug is that it is already approved by the U.S. Federal Drug Administration (FDA). The hope for the four drugs listed below is that they will meaningfully slow disease progression.
  • Isradipine (pill) is a calcium channel blocker that was previously approved for the treatment of high blood pressure. The idea behind the use of this drug is to block the entry of calcium into brain cells. Research has revealed tantalizing clues that blocking calcium may prevent brain cell death and lead to positive effects and perhaps even change disease progression.
  • Exenatide (injection) is an FDA-approved diabetes drug that promotes insulin release and inhibits glucagon secretion. It is glucagon-like peptide (GLP-1) agonist. There are pre-clinical studies which show potential neuroprotective effects in toxin-based PD models.
  • Nilotinib (pill) is a cancer drug used most frequently to treat leukemia. It works as a c-Abl tyrosine kinase inhibitor (blocks an enzyme). It is thought to treat the alpha-synuclein deposition that occurs in the brains of people with Parkinson.
  • Inosine (pill) was a previously used drug to improve athletic performance. It is not FDA approved, but there has been great interest in using this drug to address stroke, multiple sclerosis and Parkinson’s. The idea for its use in Parkinson’s disease is that higher blood levels of uric acid may possibly decrease disease progression and this drug is effective at raising levels. The safety of the drug will be monitored especially for things like gout and kidney stones.
There is great interest in gene targeted and enzyme targeted therapies:
  • GBA-associated Parkinson’s disease from the glucocerebrosidase (GBA) gene is of interest to many investigators. The pharmaceutical company Sanofi has a Phase II trial of a glucosylceramide synthase inhibitor to treat people with Parkinson’s who have the GBA gene (GZ/SAR402671).
  • The gene that makes amino acid decarboxylase (AADC) and promotes conversion of brain chemicals (dopamine, serotonin) has been a target for clinical trials. There are positive interim results from an ongoing phase Ib trial and a current open-label trial.
  • Ambroxol is an older drug that has been used to treat respiratory disease (decreases mucus). It also increases brain GCase activity. There are trials exploring disease modification and dementia. Allergan has a similar drug LTI-291 that may go into clinical trials soon.
  • Denali has a LRRK2 inhibitor for people with the genetic mutation (LLRK2) that causes Parkinson’s. It is called DNL201. There is also a second drug DNL151 that is being tested in the Netherlands.
Finally, there is great interest in vaccine and immunotherapy trials:
  • There is a vaccine trial called AFFiRiS that passed its safety testing. It is moving into the next phase to see how it will affect symptoms and disease progression.
  • There are two antibody Infusion trials using intravenous injections. The current trials are Biogen (phase 2a) and Roche (phase 2b). The safety data from these trials has been promising, but there are not results of efficacy or disease modification.
We encourage all people with Parkinson’s to stay abreast of new and emerging therapies.  It is important to regularly learn about the latest Parkinson’s treatments and medications, and to check clinicaltrials.gov for the current status of ongoing research. Even if you decide a clinical trial is not for you, you may still find it useful and hopeful to monitor the latest developments in the field.
Learn more about clinical trials at Parkinson.org/ClinicalTrials.
You can find out more about our National Medical Director Dr. Michael S. Okun by visiting the Center of Excellence University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life.
Link to the original article from the Parkinson's Foundation: http://www.parkinson.org/blog/whats-hot/2018-New-Therapies-in-Trial-for-Parkinsons-Disease 
If you want to know more about Parkinson's disease, please call the Parkinson's Foundation at 1-800-473-4636 or reach out to our center at 1-415-502-1672.

Friday, June 1, 2018

Moving Day- San Jose- June 2, 2018






Moving Day®, is more than just a walk. It highlights “movement” and exercise as a symbols of hope and progress because of their essential role in treating Parkinson’s disease.  Set in the beautiful San Jose hills with a walk through campus and along neighborhood walk paths, Moving Day® San Jose features our signature Movement Pavilion with stations such as yoga, Pilates, Tai Chi, dance and much more.  Whether you take part on a team or join as an individual, you’ll get a chance to move with thousands of supporters who share a common goal - to help beat Parkinson’s.

https://movingdaywalk.org/event/moving-day-san-jose/
Event Date
Saturday, June 2, 2018
Event Location
Evergreen Valley College
3095 Yerba Buena Rd
San Jose, CA 95135
United States

Contact:

Gena Lennon
Ph: 415-963-0304
glennon@parkinson.org

Thursday, May 24, 2018

Press Release from UCSF -- Football Scuffles, Auto Injuries May Raise Risk for Parkinson's



Football Scuffles, Auto Injuries May Raise Risk for Parkinson’s

Concussion Linked to 56 Percent Increase in Neurological Disease, UCSF Study Shows

Wednesday, May 2, 2018

New from the Parkinson's Foundation -- Stopping the Spiral Toward Demoralization in Parkinson's Disease

Stopping the Spiral Toward Demoralization in Parkinson’s Disease


People with chronic diseases such as Parkinson’s disease (PD) are at risk of spiraling into a demoralized state. Common symptoms include feeling helpless, hopeless, a sense of failure and incapacitated to respond to stressful situations. Doctors frequently fail to identify or address this issue. There is sparse research and a rare interest in screening for demoralization. In this month’s Whats Hot in PD? column we will address demoralization in Parkinson’s disease and suggest strategies to identify and address this problem.
Brian Koo, MD, and colleagues in the April edition of Neurology set out to determine the prevalence and associated features of demoralization. The researchers studied 96 people with Parkinson’s disease and compared them to 86 people without Parkinson’s.
Demoralization was measured by the Diagnostic Criteria for Psychosomatic Research, the Demoralization Questionnaire or the Kissane Demoralization Scale score. Study participants were counted as demoralized if any of the three scores were positive. Eighteen percent of people with Parkinson’s were demoralized as compared to eight percent of those without PD.
Depression was associated with demoralization, although interestingly there were participants who were demoralized but not depressed and those who were depressed but not demoralized. Younger unmarried participants with worse motor scores on the Unified Parkinson’s Disease Rating Scale (UPDRS)examination were at particular risk for demoralization (Koo, 2018).
The bottom line for people living with PD and care-partners is that demoralization is present in about one in five people with Parkinson’s. This symptom should not be confused with depression although it may co-occur with depression.
These tips that may be helpful for those suspicious of demoralization:
  1. Younger unmarried people with PD with a high burden of parkinsonian motor features have a higher risk of demoralization.
  2. Getting a referral for a licensed clinical social worker or counseling psychologist can be helpful.
  3. Cognitive behavioral therapy may be useful, but more research is needed on this technique.
  4. Do not assume that depression is the cause of demoralization.
  5. Treatment of depression and/or apathy (if present) can help.
  6. Getting a referral to a psychiatrist may be useful in select cases.
  7. Doctors and members of the healthcare team who are positive can help.
Selected References
Koo BB, Chow CA, Shah DR, Khan FH, Steinberg B, Derlein D, Nalamada K, Para KS, Kakade VM, Patel AS, de Figueiredo JM, Louis ED. Demoralization in Parkinson disease. Neurology. 2018 Apr 4. pii: 10.1212/WNL.0000000000005425. doi:10.1212/WNL.0000000000005425. [Epub ahead of print] PubMed PMID: 29618626.
For more from the Parkinson's Foundation, visit www.parkinson.org. 
If you have any questions or concerns regarding Parkinson's Disease, please call the Parkinson's Foundation at 1-800-473-4636 or reach out to our center at 1-415-502-1672.

Friday, March 9, 2018

Press Release from UCSF - Latest Publication from Dr. Christine

Low Levels of Vitamin B12 May Worsen Walking, Cognition in Parkinson’s Patients

Supplement May Boost Balance, Memory, But Impact on Disease Trajectory Unknown

A study of patients with early Parkinson’s disease found that groups with lower levels of vitamin B12 faced on average a more rapid acceleration of both motor and cognitive symptoms, which slowed in some cases after taking a daily multivitamin.


In the two-year study, blood levels of vitamin B12 were tested in 680 patients who had recently been diagnosed with Parkinson’s. Researchers led by first author Chadwick Christine, MD, a UCSF neurologist, also assessed patients’ gait and mobility, ability to perform activities of daily living, cognition and symptoms of depression.


“Our findings demonstrate that low B12 levels are associated with greater walking and balance problems, possibly due to the known effect of B12 deficiency on the central and peripheral nervous systems,” said Christine. “Alternatively, low B12 may have a direct effect on the progression of Parkinson’s disease, or it may be a marker of an unknown associated factor, perhaps correlating with another aspect of the disease or nutritional status.”


The study was published March 6, 2018, in the “early view” version of the journal Movement Disorders.


Parkinson’s affects more than 1 million people in North America, most typically after age 60, according to the National Institutes of Health. It is a progressive disorder of the nervous system that primarily impacts balance and movement. At five years following diagnosis, approximately 50 percent of patients also experience cognitive decline.


Deficiencies of B12, which are more common in people with Parkinson’s than the age-matched general population, are associated with weakness, tiredness, numbness, tingling and walking difficulties – symptoms that are found in Parkinson’s disease.


Higher B12 Translates to Less Disability



Using patient data and archived blood samples from a prior study, known as DATATOP, the researchers divided three groups of 200-plus patients according to their levels of vitamin B12 at the beginning of the study. They found that over time, symptoms in those from the lower-level group developed more rapidly than in those in the higher bracket. Average annualized changes from preliminary testing for walking capacity were ranked at 1.53 for the group with lowest B12 levels, 0.83 for the middle group and 0.77 for the higher cohort, demonstrating twice the rate of progression between the groups with the lowest and highest B12 levels.


Additionally, researchers tested patients’ blood levels of homocysteine, an amino acid that may be elevated in people with lower B12, and compared the levels to patients’ results from the Mini Mental State Examination, a test that measures cognitive skills. The group with higher homocysteine levels, and thus lower B12, was found to decline by an annualized average of 1.96 points, versus a modest improvement (0.06 points) in those with lower homocysteine.


Supplement Intake, Parkinson’s Meds Ruled Out Eligibility



Patients were eligible for the study if they had not started treatment for Parkinson’s and if they had not been taking a vitamin supplement of greater strength than a standard daily multivitamin (containing up to 6 mcg of B12), in the month before the start of the study. The study endpoint was disease progression to a degree indicating readiness for levodopa, standard Parkinson’s therapy that over time becomes less effective.


After preliminary testing, patients were offered the option of taking a daily multivitamin. Close to 50 percent of participants were found to have higher B12 on subsequent testing, suggesting that many took the supplement or improved their diets. For those patients who remained in a lower B12 level – suggesting they may not have started supplements – their annualized average increase of disability was 14.4 on the Unified Parkinson’s Disease Rating Scale (UPDRS), a test that assesses activities of daily life, motor skills, behavior and mood. In contrast, for the group whose B12 levels began low but improved during the study, their average increase in the UPDRS score was 10, showing less disability.


“Our results suggest that the measurement of B12 levels early in Parkinson’s may be beneficial,” said Christine. “If levels are at the low end of normal, supplementation to get the level into the middle or upper end of the normal range may slow development of symptoms. But because we don’t know the impact of B12 on Parkinson’s disease, future studies are needed to determine if supplementing will change the disease trajectory.”


The study was supported by funding from the Michael J. Fox Foundation and from gifts from the Ko and Tsu family, and William and Mary Ann S. Margaretten.


The senior author is Ralph Green, MD, PhD, of UC Davis, an international expert in vitamin B12, whose laboratory conducted the B12 and other biochemical measurements. Co-researchers are Peggy Auinger of the University of Rochester, N.Y., Amelia Joslin, Yuora Yelpaala, also of UC Davis, and the Parkinson’s Study Group – DATATOP investigators.


UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, transitional and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises three top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children's Hospitals in San Francisco and Oakland, and other partner and affiliated hospitals and healthcare providers throughout the Bay Area.