What causes Parkinson’s disease?

John Deck, Parkinson awareness Association of Central Indiana

January 27, 2018

This is one of the most frequently asked questions, when an individual has been diagnosed with Parkinson’s disease. The answer is, we do not know of just one cause. We do, however, know there are higher incidences in those who are exposed to certain environmental risk factors, while some individuals have a genetic component, and then others we just don’t know.

Within the brain there are structures. The midbrain portion of the brain has connections with nerve networks called the basal ganglia. The basal ganglia are the areas that Parkinson’s disease affects, primarily the area of the substantia nigra where dopamine is produced. The substantia nigra are a fraction of 1% of all nerve cells. Each nerve cell in the substantia nigra connects with tens of thousands of other nerve cells. The substantia nigra releases dopamine that is the chemical that make these nerve cells work properly and gives us the smoothness of movement.

Lewey bodies are microscopic abnormalities that can occur in the brain and if there is an excessive amount of a protein called alpha-syneuclein, it kills nerve cells including those in the substantia nigra. Currently, we have no means of getting rid of this excess protein. Nerve cells at the base of the brain connect to the basal ganglia and then nerve cells from there connect to the cortex of the brain. In this loop is a pathway that facilitates desired movement and suppresses undesired movement. When this balance is off because of an inadequate supply of dopamine, movements are compromised. If levels of dopamine are not just right the nerve cells are constantly trying to adapt, frequently becoming unstable, thus creating movement problems.  

Exercise increases dopamine in the brain. A tailored exercise program can help those affected by Parkinson’s disease manage their symptoms better.  

In future articles we will be sharing more information about treatment and management of Parkinson’s disease. For more information contact: Indiana Parkinson’s Foundation and the Climb: (317) 550-5648, or Parkinson’s Awareness Association of Central Indiana, Inc.: (317) 255-1993

The Times is partnering with the Indiana Parkinsons Foundation to promote education and awareness of Parkinson’s Disease. For more information visit http://www.indianaparkinson.org

https://thetimes24-7.com/Content/Columnists/Columnists/Article/What-causes-Parkinson-s-disease-/13/163/57538

Lacing up the gloves to fight Parkinson's disease

January 27, 2018

Nearly a dozen people in Glace Bay take a boxing class regularly to help with the disease's symptoms

Participants at Ring 73 boxing club in Glace Bay work out with heavy bags. The class helps people with Parkinson's disease manage their symptoms. (CBC)

It's gloves on for boxers in Glace Bay, N.S., who are using the sport to deal with the symptoms of Parkinson's disease.

From jumping jacks to sparring, boxing training gets people moving.

Mora MacCormick has lived with the neurodegenerative disease for almost three years. She's one of nearly a dozen people who were practising their jabs Friday at the Ring 73 boxing club. 

• Townshippers fight Parkinson's disease a punch at a time

MacCormick says she can already feel a difference since the classes began. 

"I found out I'm much more limber and my mobility has definitely increased. Boxing is it, I would say, definitely. I'm so glad they came up with this."

Mora MacCormick works out at Ring 73 regularly to help keep her limber and maintain her mobility as she copes with Parkinson's disease. (CBC)

Shaking, rigidity, slowness of movement and difficulty with walking are the most common early symptoms of Parkinson's disease. Thinking and behavioural problems as well as dementia often occur as the disease progresses.

Kyle Cameron, who coaches the class, has boxed his whole life. He underwent specialized training in Indiana to teach the sport to people with Parkinson's. 

• Neil Diamond says he has Parkinson's disease, retires from touring

"They really look forward to coming to classes. I started it once a week, now they want it three times a week," he said. "My hope is to help them lead a better quality of life. That's what this is about."

Staying active helps symptoms

From general exercises to squats with weights to sparring with the gloves, the athletes give it their all.

Jim Kelly was diagnosed with Parkinson's several years ago. 

• Parkinson's disease diagnosis could be aided with blood test

He said initially he was doubtful about how effective boxing would be to help with the disease. 

"Now that I've had a couple of sessions here with Kyle and other people who are afflicted with Parkinson's, I'm convinced that this is what the researchers were talking about it counteracting Parkinson's, the importance of staying active," he said.

Cameron says there are still spots open for people who want to join the group. 

http://health.einnews.com/article/429134776/xSEZaDZihhVmJOba?lcf=Hzf-KE6h-Xmcpvzwcdl3CuzbRmZ8XaTUdg3y3lN96pg%3D

Indianola graduate publishes first book

Paige Godden  -  January 26, 2018

An Indianola native managed to find enough time in her busy college schedule to write a book. 

The three-year time commitment for the recent graduate of Coe College's history program paid off because her book has been published by Adelaide books.

Nina Wilson's coming-of-age story about a Vietnam veteran-turned professor who's suffering from Parkinson's disease and the student he mentors was inspired by an idea pulled out of a hat during a creative writing class at Coe.

"The idea was something along the lines of a history professor who hates everyone," Wilson, a 2013 Indianola graduate, said. "So, I wrote a monologue and I kept writing and writing. It got to about 178 pages within the next two months."

Wilson's professor told her to keep writing and in another month she had all 200 pages finished.

Meanwhile, Wilson had submitted a short story to Adelaide Magazine about a woman with Alzheimer's who could only think through '80s rock ballad lyrics. The magazine liked her submission so much the editor called Wilson and asked if she had any other content because they had a book imprint. 

Wilson sent them her book, "Surrender Language" and they published it.

The literary book, Wilson said, will probably appeal more to older audiences, but added "I think it's important for anyone to read a story about human suffering and mortality and understand what other people feel in order to understand empathy."

Her book outlines what it's like for the main character to be forced to retire from his job while dealing with the side effects of Parkinson's disease. During his last year of teaching, the professor befriends one of his students and helps him come of age while learning about his own mortality in the process.

The book is being sold on Amazon.com and on Adelaide books' website.

While "Surrender Language" is the first book Wilson wrote, it isn't her last. Her second book, called "Malady" will be published in May.

Wilson said she wasn't planning on writing to be her full-time job, but said it's probably going to end up that way because it takes a lot of time to submit work to literary magazines, agents and publishers.

Wilson said she's currently working on a fantasy series and a historical fiction piece. 

Wilson's mother, Sharon Wilson, is supportive of her daughter's published works.

"The weirdest thing is that I can Google my kid," Sharon said. "You usually Google somebody who sings a song or who's a serial killer or something. But my kid is on there because she's been doing right since she was little."

https://www.desmoinesregister.com/story/news/local/indianola/2018/01/26/indianola

-graduate-publishes-first-book/1058481001/

Arizona State University to Grow Human Neurons in Search of New Therapies for Neurodegenerative Diseases

JANUARY 26, 2018     BY PATRICIA INACIO

Arizona State University will soon launch a new biomanufacturing platform to grow human neurons in vitro to develop and test new therapies for neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer’s disease, and Parkinson’s disease.

The effort includes the development of several types of neurons on a large scale to test the effectiveness of small therapeutic molecules.

The $5 million project is financed by the U.S. Department of Defense’s Advanced Regenerative Manufacturing Institute and is a collaboration between the laboratory of David Brafman, assistant professor of engineering at Arizona State University (ASU), Biogen, one of the world’s largest pharmaceutical companies, and Trailhead Biosystems, an Ohio-based biotechnology company. ASU will receive $1.4 million.

“There is much excitement about the potential of human pluripotent stem cells to treat numerous devastating diseases. While the public is more familiar with the tissue and organ replacement aspects of pluripotent stem cell research, these cells also have tremendous utility in developing pharmacological interventions to combat these diseases,” Brafman said in a press release.

“As such, the focus of this project will be to develop the biomanufacturing processes needed to engineer the various neural cell types needed for drug screening,” he added.

“ASU’s growing leadership in this field, combined with the strengths of our partners Biogen, Inc., and Trailhead Biosystems, will bring innovative solutions to the fore impacting the future of treatments for neurodegenerative diseases,” said Sethuraman Panchanathan, executive vice president of Knowledge Enterprise Development and chief research and innovative officer at ASU.

One of the strategies researchers may use to develop the different neuronal lines for future research is generating human induced pluripotent stem cell lines from peripheral blood mononuclear cells.

As part of his research in Alzheimer’s disease, Brafman already has used blood cells from Alzheimer’s patients and reprogrammed them back into an embryonic-like pluripotent state. These cells can then be transformed into virtually every cell in the body and constitute an unlimited source of any type of human cell needed for therapeutic purposes.

https://alsnewstoday.com/2018/01/26/arizona-state-university-grows-human-neurons-test-treatments-neurodegenerative-diseases-including-als/

WPC: PARKINSON'S DISEASE, PRECISION MEDICINE, AND LRRK2

BASIC SCIENCE   JANUARY 22, 2018

Molecular model of LRRK2’s kinase. The position of the G2019S mutation is shown as a yellow ball, at one ‘hinge’ of the activation segment. The effect of the mutation, of having a serine (S) at this position, is to keep the ‘activation segment’ (shown in red) always ajar. Normally this may close and open to regulate access to the pocket beneath, to allow LRRK2 substrates access to be phosphorylated (P). An ATP molecule that donates the phosphate (P) is shown in light blue. Other domains of the LRRK2 kinase are shown in pink and dark blue for contrast.

Ten years ago, in 2008, I participated in a meeting in New York with the management of eight of the world’s largest pharmaceutical companies. The Michael J. Fox Foundation had asked us to discuss investment in leucine-rich repeat kinase (LRRK2 – pronounced ‘Lark 2’) inhibitors for Parkinson’s disease (PD), and whether such a development might halt or even prevent it. Typically, it takes a billion dollars to take a novel drug to market. 

At that time ‘precision medicine’ for PD was a relatively new concept, as was neuroprotection for the US Food and Drug Administration i.e. to halt or prevent disease and by lifelong administration of a therapeutic targeted to a genetic cause. While I was elated to be part of this development it was sobering to hear the arguments that ensued. Nevertheless, genetic discoveries are revolutionary, and they continue to provide novel approaches to predict and prevent PD.

LRRK2 was identified using a classical genetic linkage approach. In 2002 a region of chromosome 12p12 was reported to segregate ‘identical-by-descent’ with clinical parkinsonism in the Japanese Sagamihara family¹,. We found similar results for chromosome 12 in two Caucasian kindreds, Family A (German-Canadian) and Family D (Western Nebraska)², and soon after in Norwegian pedigrees³. In these families Parkinson’s disease (PD) is inherited in a dominant fashion i.e. approximately half of every generation eventually becomes affected. Although fourteen percent of patients have an affected first-degree relative (a parent, sibling or child) with PD⁴, it is uncommon to find more than two affected subjects in a family. Genetic research requires informed consent to ask questions about family history, to perform clinical exams, take blood for DNA extraction, and potentially ask permission for studies of brain pathology post-mortem. For the advances made we are indebted to those who have participated.

In 2004, we described the precise LRRK2 mutations that resulted in PD, namely LRRK2 R1441C (Families D and 469), Y1699C (Family A) and I2020T (Family 32)⁵. The work was done with Dr. Zbigniew Wszolek at Mayo Clinic, and as part of an international team. Concomitantly, a group at the US National Institutes of Health reported LRRK2 R1396G in four Basque Spanish families and Y1654C in an English kindred⁶. Although incorrectly labelled, LRRK2 R1396G is actually R1441G, and Y1654C is Y1699C, these families provided more evidence for pathogenicity. LRRK2 I2020T was also found to cause disease in the Sagamihara kindred⁷.

Notably, six affected subjects of Family A and D, and six members of the Japanese Sagamihara family donated their brains to research^8,9. All were found to have mid-brain neurodegeneration with profound neuronal loss in the substantia nigra, typical of sporadic PD. However, only about a quarter of these patients had mid-brain Lewy body disease (‘alpha-synuclein immunopositive’ aggregates). Many patients had neurofibrillary tangles (‘tau immunopositive’ aggregates) or alternatively ‘ubiquitin immunopositive’ aggregates. It was amazing the brain pathology was so different (termed ‘pleomorphic’) among individuals, despite clinically similar presentations, and even within each family with the same disease-causing LRRK2 mutation⁸. 

Until recently, a diagnostic requirement for ‘definite’ PD had required the presence of mid-brain Lewy body disease so this observation was really contentious. Nevertheless, as many as ~20% of autopsy-confirmed cases with “probable” PD may not have mid-brain Lewy body pathology, (although clinically these patient may have been quite typical)¹⁰. To this date, and with >37 brains examined, only half of all patients with LRRK2 mutations and clinical PD develop mid-brain Lewy body pathology¹¹.

With Dr. Jan Aasly’s help, then Head of the Department of Neurology at St. Olav’s, Trondheim, we discovered LRRK2 G2019S in Norwegian families³. The mutation also segregated with PD in a dominant fashion¹², and through many generations of affected subjects dating as far back as the 15th century¹⁸. While we also reported affected families in Poland, Ireland, Spain and the US³, LRRK2 G2019S proved to be most frequent in ‘seemingly sporadic’ PD south and east of the Mediterranean. The frequency was highest in Ashkenazi Jews in Israel (and New York) and Arab-Berber populations in North Africa (Algeria and Tunisia), where it is found in 13% and 30% of their PD, respectively^13,14. I write ‘seemingly sporadic’ as in all these families and populations – whether from Trondheim in Norway, Tel Aviv in Israel or Tunis in Tunisia – LRRK2 G2019S originates from the same ancestral founder, in effect, these patients are all distant cousins^3,15. 

Arguably, the LRRK2 G2019S mutation has been dated to ~1,000 BC, a time when Mediterranean sea trade was most active between Phoenician ports in North Africa (Tunisia, Algeria and Morocco), Europe (Spain and Italy) and the Levant (Lebanon, Syria, Israel)¹⁶. In the present day populations of Israel and Tunisia, 1.9% of Ashkenazi and Arab-Berber subjects have LRRK2 G2019S due to a combination of genetic selection and drift. Ancient Norse trade, that included long-term settlements in Carthage ~1000 AD, may explain LRRK2 G2019S families in Norway. In contrast, the absence of LRRK2 G2019S in Central Europe, in Austrian and German patients, may reflect migration during World War II and the holocaust.

Although its origin is lost in history the LRRK2 G2019S diaspora is arguably the greatest single genetic cause of PD. Why most individuals appear to have “sporadic” rather than familial disease remains unclear. From meta-analysis the lifetime probability of LRRK2 G2019S heterozygotes becoming affected (termed penetrance) is ~30% (28% at 59, 51% at 69 and 74% at 78 years)¹⁷. However, there are families in which LRRK2 G2019S PD is clearly inherited, as that is how it was originally identified^12,18,19. 

In 2005, I started working with Dr. Faycel Hentati, the Director of the National Institute of Neurology in Tunis, North Africa. There is a pandemic of PD in Arab-Berbers, the predominant population in North Africa, and to visit the Clinic and families in their homes has been a humbling experience, given their plight. Their generosity to help describe the clinical syndrome and its penetrance, and to help find genetic modifiers that influence when subjects with LRRK2 G2019S will become affected, has been remarkable^19–21. Many other LRRK2 genetic variants contribute to risk, albeit more modestly. For example, LRRK2 G2385R, specific to Asian populations from Korea to Taiwan, is found in 6-8% of patients and doubles the risk of PD^22,23. There are also LRRK2 genetic variants that are ‘protective’ i.e. inversely associated with PD²⁴.

LRRK2 G2019S directly affects the ‘activation segment’ of LRRK2’s kinase (Figure). In effect this mutation ‘always keeps the door ajar’, allowing LRRK2 to phosphorylate other proteins (substrates), even when it should be inactive³. This notion has been supported with each substrate identified - first auto-phosphorylation of LRRK2 itself, and most recently in phosphorylation of many members of the Ras GTPase superfamily²⁵. Thus a competitive but specific inhibitor of LRRK2 kinase activation, even with modest efficacy, might prevent disease in those susceptible.

To develop a safe and affordable drug, and without off-target side-effects for a lifetime of use, is our challenge. 

Several classes of LRRK2 inhibitors have now been identified, but which will meet this criteria is unclear²⁶. Recent studies have shown LRRK2 kinase inhibition more often destabilizes the protein, lowering its expression, and may result in undesirable side-effects in lung and kidney. More research funding is needed in three areas: i) to identify and measure “PD-relevant” outcomes of LRRK2 kinase inhibition; ii) to develop preclinical models in which such effects can be easily and reliably assessed, and; iii) to prospectively identify and follow the natural evolution of disease in those patients and families with LRRK2 genetic variability, most likely to benefit from such a therapeutic approach.

“PD-relevant” outcomes of LRRK2 dysfunction may be contested but in neurons many agree mutant effects are subtle, chronic and initially synaptic²⁷. Animal models that faithfully recapitulate the etiology and physiology of germline LRRK2 mutations in humans have been successfully developed, with measureable differences^28,29. While drug screening requires more simple, innovative and informative assays of LRRK2 function, several avenues hold promise and not least in human “inducible-pluripotent stem cell’ derived dopaminergic neurons³⁰. LRRK2 G2019S is also appreciated to cause PD in >50,000 Arab-Berber patients, and Tunisia, among other North African nations, definitely has the infrastructure, expertise and desire to develop neuroprotection, anticipating such drugs might be made affordable.

Now we know genetic causes of PD, the associated biologic mechanisms, and the patients most likely to benefit, “neuroprotection” to halt or prevent symptoms can be realized. LRRK2-directed therapeutics are likely to have broad efficacy as neuroprotective agents and beyond patients with specific mutations²⁴. A similar approach has been taken for patients with PD and glucocerebrosidase (GBA) mutations by Sanofi-Genzyme who recently launched as Phase II clinical trial of their ceramide substrate inhibitor (GZ/SAR402671)³¹.

Several clinical trials have also been initiated to clear or prevent Lewy body formation by lowering alpha-synuclein expression³². While neuropathologic examination of LRRK2 patients suggests Lewy bodies may be neither cause nor consequence of the disease process, clearing those protein aggregates is likely to be of benefit to many patients who develop that pathology.

1.     Funayama, M. et al. A new locus for Parkinson’s Disease (PARK8) maps to chromosome 12p11.2-q13.1. Ann. Neurol. 51, 296–301 (2002).

2.     Zimprich, A. et al. The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval. Am. J. Hum. Genet. 74, 11–19 (2004).

3.     Kachergus, J. et al. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. Am. J. Hum. Genet. 76, 672–80 (2005).

4.     Rocca, W. A. et al. Familial aggregation of Parkinson’s disease: The Mayo Clinic family study. Ann. Neurol. 56, 495–502 (2004).

5.     Zimprich, A. et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44, 601–7 (2004).

6.     Paisán-ruíz, C. et al. Dardarin Mutations in PARK8 PD Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson’s Disease Dardarin Mutations in PARK8 PD. Neuron 44, 595–600 (2004).

7.     Funayama, M. et al. An LRRK2 mutation as a cause for the Parkinsonism in the original PARK8 family. Ann. Neurol. 57, 918–921 (2005).

8.     Wszolek, Z. K. et al. Autosomal dominant parkinsonism associated with variable synuclein and tau pathology. Neurology 62, 1619–22 (2004).

9.     Hasegawa, K. et al. Familial parkinsonism: Study of original Sagamihara PARK8 (I2020T) kindred with variable clinicopathologic outcomes. Park. Relat. Disord. 15, 300–306 (2009).

10.  Hughes, A. J., Daniel, S. E., Kilford, L. & Lees, A. J. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: A clinico-pathological study of 100 cases. J. Neurol. Neurosurg. Psychiatry 55, 181–184 (1992).

11.  Kalia LV, Lang AE, Hazrati LN et al. Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease. JAMA Neurol. 72, 100-5 (2015).

12.  Aasly, J. O. et al. Clinical features of LRRK2-associated Parkinson’s disease in Central Norway. Ann. Neurol. 57, 762–765 (2005).

13.  Lesage, S. et al. LRRK2 G2019S as a Cause of Parkinson’s Disease in North African Arabs. N. Engl. J. Med. 354, 422–423 (2006).

14.  Ozelius, L. J. et al. LRRK2 G2019S as a Cause of Parkinson’s Disease in Ashkenazi Jews. N. Engl. J. Med. 354, 424–425 (2006).

15.  Lesage, S. et al. Parkinson’s disease-related LRRK2 G2019S mutation results from independent mutational events in humans. Hum. Mol. Genet. 19, 1998–2004 (2010).

16.  Farrer, M. J., Gibson, R. & Hentati, F. The ancestry of LRRK2 Gly2019Ser parkinsonism - Authors’ reply. The Lancet Neurology 7, 770–771 (2008).

17.  Marder, K. et al. Age-specific penetrance of LRRK2 G2019S in the Michael J. Fox Ashkenazi Jewish LRRK2 Consortium. Neurology 85, 89–95 (2015).

18.  Johansen, K. K., Hasselberg, K., White, L. R., Farrer, M. J. & Aasly, J. O. Genealogical studies in LRRK2-associated Parkinson’s disease in central Norway. Parkinsonism Relat. Disord. 16, 527–530 (2010).

19.  Trinh, J. et al. DNM3 and genetic modifiers of age of onset in LRRK2 Gly2019Ser parkinsonism: a genome-wide linkage and association study. Lancet Neurol. 15, 1248–1256 (2016).

20.  Hulihan, M. M. et al. LRRK2 Gly2019Ser penetrance in Arab–Berber patients from Tunisia: a case-control genetic study. Lancet Neurol. 7, 591–594 (2008).

21.  Trinh, J. et al. A comparative study of Parkinson’s disease and leucine-rich repeat kinase 2 p.G2019S parkinsonism. Neurobiol. Aging 35, 1125–1131 (2014).

22.  Farrer, M. J. et al. Lrrk2 G2385R is an ancestral risk factor for Parkinson’s disease in Asia. Park. Relat. Disord. 13, 89–92 (2007).

23.  Xie, C. L. et al. The association between the LRRK2 G2385R variant and the risk of Parkinson’s disease: A meta-analysis based on 23 case-control studies. Neurological Sciences 35, 1495–1504 (2014).

24.  Ross, O. A. et al. Association of LRRK2 exonic variants with susceptibility to Parkinson’s disease: a case–control study. Lancet Neurol. 10, 898–908 (2011).

25.  Steger, M. et al. Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. Elife 5, (2016).

26.  West, A. B. Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease.  Experimental Neurology 298, 236–245 (2017).

27.  Volta, M., Milnerwood, A. J. & Farrer, M. J. Insights from late-onset familial parkinsonism on the pathogenesis of idiopathic Parkinson’s disease. Lancet Neurol. 14, 1054–1064 (2015).

28.  Yue, M. et al. Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice. Neurobiol. Dis. 78, 172–95 (2015).

29.  Volta, M. et al. Initial elevations in glutamate and dopamine neurotransmission decline with age, as does exploratory behavior, in LRRK2 G2019S knock-in mice. Elife 6, (2017).

30.  Beevers, J. E., Caffrey, T. M. & Wade-Martins, R. Induced pluripotent stem cell (iPSC)-derived dopaminergic models of Parkinson’s disease. Biochem Soc Trans 41, 1503–1508 (2013).

31.  Sanofi Initiates Phase 2 Clinical Trial to Evaluate Therapy for Genetic Form of Parkinson’s Disease | Sanofi Genzyme News. Available at: http://news.genzyme.com/press-release/sanofi-initiates-phase-2-clinical-trial-evaluate-therapy-genetic-form-parkinsons-disea. (Accessed: 8th January 2018)

32.  Olanow, C. W. & Kordower, J. H. Targeting α-Synuclein as a therapy for Parkinson’s disease: The battle begins. Mov. Disord. 32, 203–207 (2017)

_______________________________________________________________________________________________

Matthew Farrer, PhD presented at the 1st World Parkinson Congress in Washington DC; the 2nd World Parkinson Congress in Glasgow, Scotland; and the 3rd World Parkinson Congress in Montreal, Canada. He is a Professor in the Department of Medical Genetics at the University of British Columbia, the Canada Excellence Research Chair, and the Don Rix BC Leadership Chair in Genetic Medicine.

https://www.worldpdcongress.org/home/2018/1/18/parkinsons-disease-precision-medicine-and-lrrk2?platform=hootsuite

Healthy Women: Understanding Parkinson's Disease Psychosis

Medically reviewed by Karen Elta Anderson, MD, Neuropsychiatrist, MedStar Georgetown University Hospital, Washington, DC

Imagine learning to care for a loved one with Parkinson's disease (PD), which is a neurodegenerative brain disorder that affects nearly one million people in the United States. He may move slowly or is rigid, lose his balance easily or shake uncontrollably while resting, which are common symptoms of PD.

But then other symptoms begin to occur. He starts asking why the kids are in the car, but your kids have grown up and moved away. Or he thinks someone is watching him. And, of course, no one is there.

Hallucinations and delusions like these are symptoms of Parkinson's disease psychosis, which occurs in about 50 percent of people with PD at some point during their illness.

Sometimes described as "tricks" played by the brain, hallucinations can cause a person to see, hear, feel, smell or even taste something that isn't real. A person with hallucinations may say they see people or animals that aren't there. As their hallucinations become more frequent, they may not be able to tell what's real and what's imagined and may react to things that aren't real.

Delusions occur less frequently than hallucinations and are generally more difficult to treat. Delusions are fixed, false beliefs not supported by evidence and often have paranoid themes. A common delusion that occurs in people with Parkinson's is that their partner is having an affair, even if they have been married for decades and their spouse is with them nearly all of the time.

When a loved one is experiencing hallucinations and delusions, it can add more frustration to the already challenging physical limitations of Parkinson's. Research has found that hallucinations and delusions can lead to increased distress, greater responsibility for caregivers, and even nursing home placement.

Yet, as difficult and distressing as these hallucinations and delusions may be, only about 10 percent to 20 percent of patients who have hallucinations or delusions associated with PD proactively report the symptoms to their health care providers.

That may be because they don't understand that these symptoms are associated with PD or are embarrassed to report that they are experiencing visions and false beliefs. Sometimes these "invisible" symptoms can cause more problems than the motor issues—especially if people with Parkinson's don't seek help.

Hallucinations and delusions usually appear later in the disease's progression and often catch caregivers by surprise if they and the doctor are focused on motor symptoms, which are easier to identify.

Causes of Parkinson disease psychosis 

The cause of hallucinations and delusions associated with Parkinson's is not clearly understood. The drugs commonly used to treat PD, which raise dopamine levels to improve motor control, can cause physical and chemical changes in the brain that may lead to hallucinations and delusions. In addition, the natural progression of Parkinson's disease may cause brain changes that trigger symptoms.

Treatment for Parkinson's disease psychosis

A health care provider can help to identify hallucinations and delusions associated with Parkinson's, monitor signs that symptoms may be progressing, and offer ways to help manage any related challenges.

The first step is for the physician to confirm that the hallucinations and delusions are caused by Parkinson's disease by eliminating other possible causes. Once the diagnosis is made, the health care provider will decide how to treat the symptoms. Treatment may involve adjusting or switching PD medications. Antipsychotic medications also may be used, including an FDA-approved treatment option specifically for hallucinations and delusions associated with Parkinson's disease that may be appropriate for some people.

For more information about Parkinson's disease and its non-motor symptoms, such as hallucinations and delusions, visit www.parkinson.org.

http://www.healthywomen.org/content/article/understanding-parkinsons-disease-psychosis