Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the most common motor related disorder worldwide. 1-3 PD belongs to a group of motor-related conditions known as Parkinsonism4 and is characterized by a loss of dopamine producing nerve cells called dopaminergenic neurons and the development of inclusions known as “Lewy bodies” in the brain.2,4 PD manifests as both a chronic and progressive condition having four primary symptoms. These symptoms are tremors of the hands, arms, legs, jaw, or face; rigidity and stiffness in the limbs and torso; bradykinesia, or slowness of movement; and postural instability, or impaired balance.4,5 In addition to the four primary symptoms there are numerous secondary symptoms which induce motor, non-motor, and psychological complications. Among these secondary complications, sexual dysfunction (SD) is common and underrecognized in patients with Parkinson disease; it plays a major role in the deterioration of quality of life of patients and their partners.6 Both primary and secondary symptoms of PD may progress over a period greater than 20 years and will more significantly impair quality of life in the late stages of the disorder.7
Parkinson’s disease was first described as a neurodegenerative disorder called “the shaky palsy” in 1817 and its incidence has risen to affect nearly one percent of the population over 60 years of age and four percent of the population over 80 in the last two centuries.1,2,4 PD affects over one million people in the United States alone, and physicians diagnose 60,000 new cases each year.7 This rate of diagnosis is expected to rise as life expectancy of the world’s population increases at a unprecedented rate.2 Currently, the average age of onset is 60 years, however 10% of cases are diagnosed as “early onset” with patients between the ages of 20 and 50.1,2 Men are more likely to suffer from Parkinson’s disease than women.1,7 Studies report that the prevalence ratio for men to women ranges from 1.1:1 to 3:1, which may indicate protective properties of estrogen.1
Parkinson's disease and related neurological complications such as multiple systems atrophy (MSA) are commonly associated with sexual dysfunction. Quality of life studies conducted by The American Parkinson’s Disease Association have documented sexual dysfunction in 60% to 80% of men and women with PD. Higher incidence is far more common in the elderly than young people. The incidence of sexual dysfunction in younger patients is approximately 30% compared to 3-15% in healthy populations.7
Causes and Risk Factors of PD
The traditional understanding of Parkinson’s disease as a movement disorder is concentrated on two principle neurological findings: the loss of dopaminergenic neurons and the presence of Lewy bodies in the brain.8,9 Dopaminergenic neurons, which reside in the midbrain region called the substantia nigra pars compacta (SNPC) are the primary source of the neurotransmitter, dopamine for the central nervous system.8
Although dopaminergenic neurons account for less than one percent of the total number of neurons in the brain10, they play an important role in the control of multiple brain functions including voluntary movement and a broad array of behavior processes like mood, reward, addiction, and stress.8 Dopamine is a chemical that transmits signals between different regions of the brain and dictates the ability to coordinate smooth muscle movement; thus it is critical to sexual function on two fronts. Low concentrations of dopamine result in decreased sex drive and additionally induce the four physically detrimental motor disorders of PD. The combination of these factors drastically limits one’s ability to have sex. Although the exact cause of domaminergenic cell death is unknown, the selective degeneration of these neurons in the SNPC definitively leads to Parkinsonism and thus sexual difficultyvThe presence of Lewy bodies is the second hallmark of Parkinson’s pathology. Lewy bodies are composed of protein filaments that are suggested to regulate neurotransmission, or the exchange of information between neurons.2,11,12 Although researchers have not definitively concluded why proteins aggregate into Lewy bodies, or how they cause the symptoms of PD, the presence of Lewy bodies inside neuron cells is linked to the atrophy of multiple cerebral regions.8
Sexual functioning is a complex processes that requires the functioning of the body’s autonomic, sensory, and motor systems in coordination with the neurological, vascular, and endocrine systems to regulate hormones and provide sufficient blood flow for vasocongestion. Sexual dysfunctions such as the lack of desire (in both sexes), erectile dysfunction, disturbances of ejaculation, deficient lubrication, dysparenunia, and difficulties orgasming are not uncommon in the general population. They are a consequence of many different factors. Increased risk of SD is dependant on age and history of chronic disease. Because old age is principally correlated with increased risk of Parkinson’s disease, sexual dysfunction and PD prevalence are highly intertwined. Additionally, because neural control is a prerequisite of sexual response, sexual dysfunction in a patient with PD is multifactorial and a result of the combinatory effects of primary and secondary PD symptoms.6 Although the onset of sexual dysfunction due to multiple system atrophy is age related, most cases of PD that are caused by dopaminergenic neuron death and Lewy body aggregation are hypothesized to be a consequence of a combination of environmental and genetic factors.7
Hereditary factors correlated with Parkinson’s disease have only been identified in roughly 10% of total patients, who exhibit distinct clinical and pathological symptoms.1,9 As gene decoding technology advances, hereditary factors may prove greater relevance to PD onset; researchers estimate they could account for up to 40% of those at risk.1 When genetic factors contributing to early Parkinson’s onset were compared in identical twins with 99.99% gene similarity and fraternal twins with 50% gene similarity, it was determined that the incidence of early onset PD was low and nearly indistinguishable for both groups. By contrast, the incidence of PD onset after 50 years of age occurred concordantly in all sets of identical twins, but only half as often in fraternal twins.8 The findings indicate that common genetic factors are significantly more influential for late onset PD. Clearly, the prevalence of hereditary Parkinson’s is defined by increasing age. The genetic causes for late onset PD have been identified in families of varying ethnicities with similar rates of incidence for many of the commonly identified gene mutations. The mechanisms of how these genetic anomalies cause Parkinson’s and resulting system atrophy related to sexual dysfunction are still unknown.12
The development of Parkinson’s disease is commonly associated with environmental risk factors in addition to genetic predisposition. Rural living conditions, consumption of ground water, exposure to heavy metals and pesticides, and proximity to industrial facilities have been correlated with dopaminergenic neuron degeneration and increased risk of PD.3,13 A cumulative analysis of 89 case studies recently indicated that exposure to any type of pesticide, herbicide, insecticide, or toxic solvent increased the risk of PD 33% to 80%. Similarly, increased risk was associated with exposure to organic pollutants produced as byproducts of farming. The magnitude risk associated with environmental factors was observed to increase in proportion to the duration of exposure and proximity.13
There are several environmental factors that have an inverse correlation to the onset of Parkinsonism. Research conducted by the National Institutes of Health has indicated that drinking coffee and smoking cigarettes effectively reduces the risk of sporadic PD onset, yet may independently increase the risk of sexual dysfunction. These findings hypothesize the importance of dopaminergenic neurons, as patients with PD were found to be less prone to the addictive effects of caffeine and nicotine consumption as consequence of their genetics or dopamine shortage.3,9 Recent studies on similar dietary factors, including fat and antioxidant intake have not yet been correlated with PD prevalence but do affect sexual functions such as the ability to maintain an erection.3
Parkinson’s disease and sexual dysfunction does not affect everyone identically. Symptoms and rate of progression may vary significantly.14 The onset of non-motor-related symptoms often precedes physical manifestations and may occur several years before a clinical diagnosis.15 Loss of smell, constipation, REM behavior sleep disorder, mood fluctuations, and orthostatic hypotension (low blood pressure upon standing) are the most recognizable precursors to the onset of muscle-related complications.4,15 The initial motor-related symptoms of PD may be subtle and occur gradually. These symptoms typically originate from one side of the body and spread until the entire muscular system becomes affected.4,14 Motor-related symptoms typically remain more severe on the side of origin.
Primary Symptoms of PD
There are four primary symptoms of Parkinson’s disease. These symptoms are tremors, rigidity, bradykinesia, and postural instability. The tremors associated with PD have a distinctive appearance which manifests as rhythmic oscillating motions of four to six beats per second.4 Tremors most commonly occur in the hands and may involve repetitive movements of the thumb and forefinger, known as “pill rolling” tremors. Tremors are most apparent when a hand is at rest or during psychological stress.4,14 Most people who suffer from PD also experience rigidity and inflexibility of the limbs, neck, and trunk due to continuous muscle contractions. Muscle stiffness generally limits range of motion and results in persistent aching. PD associated rigidity can occur in any area of the body.4,14 Bradykinesia is another defining symptom of Parkinson’s which describes the general reduction of spontaneous and automatic movements, the appearance of abnormal stiffness, and decreased facial expressions.4,14 Postural instability often accompanies the other primary symptoms of PD.4 A person with postural instability will demonstrate impaired muscle control which affects their ability to maintain upright posture. Some patients may develop a dangerous tendency called retropulsion, where an individual sways when rising to stand, resulting in a backwards fall.14
Secondary Symptoms of PD
In addition to the four defining motor symptoms of Parkinson’s disease, there are many secondary symptoms. The freezing of gait is an important indication of PD onset that is not explained by rigidity or bradykinesia.14,15 Those who experience freezing will hesitate before stepping forward when starting to walk, crossing through a doorway, or pivoting. Freezing can occur in tandem with unwanted accelerations, where movements become uncontrollably rapid. These accelerations manifest as festination, or the uncontrollable acceleration of gait, and tachyphemia, which is defined as excessively accelerated speech or stammering.15 Other common secondary symptoms include micrographia, which describes the progressive shrinkage of handwriting attributed to Parkinsonism.15 Micrographia occurs as a result of bradykinesia and contributes to an individual’s impaired ability to perform repetitive tasks.
There are numerous other secondary symptoms that are not as prevalent. These symptoms include stooped posture, dystonia (involuntary muscle contractions), impaired fine motor dexterity, impaired gross motor coordination, akathisa (feelings of inner restlessness), slurred speech, softness of voice, difficulty swallowing, cramping, drooling, constipation, and seborrheic dermatitis (increased oil production by the skin). In addition to impaired motor functionality, non-motor symptoms associated with advanced Parkinsonism commonly manifest as psychiatric and cognitive disorders.16 Non-motor-related secondary symptoms are frequently neglected in clinical practice due to insufficient consultation time, and the perception that psychological symptoms are unrelated to PD.16,17
The Effect of Primary and Secondary Symptoms on Sexual Function
Sexual dysfunction is common in patients with PD. In clinical practice, physicians often find that sexual function is most interfered with by the primary symptoms of Parkinson’s.6 Muscle rigidity, bradykinisia, and clumsiness in fine motor control make sexual activities difficult. The severity of tremors and dyskinesias are commonly enhanced during sexual arousal and further inhibit the patient’s physical ability to have sex. Secondary complication such as hypersalivation and excess sweating may disturb intercourse, while hypomimia (reduced facial expressions due to muscle rigidity) may objectively reduce appeal for a sexual partner, and negatively influence the self-image of the patient. Additionally, sleep dysfunction often results in partners having to sleep separately. When coupled with the inability to focus as a result of cognitive deterioration, partners often report a significant loss in bed intimacy. 6
In addition to impaired sexual coordination, the broad spectrum of PD’s symptoms frequently causes depression and relationship dissatisfaction. Sexual dysfunction is reported to be common in young groups of Parkinson’s by an average age of 50 years old. Couples in which a male suffers from PD have the most severe sexual difficulties. Erectile dysfunction (ED) and premature ejaculation are the most prevalent issues. Patients (both men and women) display decreased sexual desire and half of the males are unable to maintain an erection. Studies report that 54-79% of men with PD experience erectile dysfunction is. This range contrasts the age-matched control of healthy men, who reported a prevalence of 37.5%. Males who are able to maintain an erection and overcome ED are often still unable to ejaculate and achieve orgasm.6
Like males, females also suffer from their gender specific symptoms of sexual dysfunction. Although less is known about the affects of Parkinson’s in females, women with PD report vaginal tightness, lack of lubrication, anxiety, and increased inhibition compared to matched controls of healthy women. Incontinence and urinary urgency during sexual activity are often of particular concern to females with PD and typically cause anxiety. Increased anxiety commonly results in a decline in sexual desire and a reduced ability to experience orgasm during sex.18 Overall, females with PD were found to be the demographic to more dissatisfied with the quality of their sexual experiences than men. Females who had experienced menopause were the most dissatisfied.18
Diagnosis of PD
Parkinson’s disease is a clinical diagnosis; there are no reliable or easily applicable diagnostic tests availible.3,7 MRI, CT, and PET scanners provide unremarkable results and have limited accessibility when attempting to diagnose PD. Thus, diagnosis relies exclusively on the presence of clinical symptoms.7 In order to be diagnosed with Parkinson’s disease a patient must exhibit at least two of the four primary symptoms, independent of secondary disorders.3 Asymmetric symptom onset and significant improvement of motor-related symptoms in response to the medication levodopa (L-DOPA) were found to be the most important factors when differentiating Parkinson’s from other diagnoses. Although it is difficult to diagnose Parkinson’s disease in the early stages of symptom progression, pathological studies have indicated that in 80-90% of cases, a clinical diagnoses of Parkinson’s was confirmed after autopsy.3
The diagnosis of sexual dysfunction most commonly relies on an individual recognizing the issues that interfere with their enjoyment or stimulation during sexual activity.19 To evaluate a patient’s sexual difficulties, a clinician will compile a complete medical history of symptoms and conduct a physical examination. Like the diagnosis of PD, lab results play a very limited role in the diagnosis of sexual dysfunction. Diagnostic tests are typically only employed to rule out medical conditions, which may cause sexual dysfunction through secondary side effects. Diabetes, heart and vascular disease, neurological disorders, hormonal imbalances, chronic diseases such as kidney or liver failure, and alcoholism are commonly associated with an array of sexual side effects.10 Because many sexual dysfunctions (like lack of desire or inability to achieve orgasm) are largely psychosomatic, one’s attitudes about sex and other contributing factors (fear, anxiety, past sexual trauma/abuse, relationship concerns, medications, alcohol or dug abuse, ect.) are evaluated to help a physician or therapist determine the underlying cause of the sexual difficulties.19
The Five Stages of Parkinson’s Disease
Following a clinical diagnosis of PD, the long-term symptomatic progression of the disease is characterized using the Hoehn and Yahn scale. This scale organizes the severity of Parkinsonism into five stages.14 The first stage represents the mildest form of Parkinson’s, where motor symptoms manifest unilaterally with minimal or no functional impairment.21 During stage I, a patient may experience slight stiffness, slowness and paucity of movement, and mild tremors. Occasionally, one side of the face may be affected, producing a slight asymmetry or lack of expression.21,22 This stage of PD is often entirely overlooked during clinical examinations. Stage II is defined by bilateral or midline impairment, after symptoms appear on opposite sides of the body. During the second stage of PD, balance is not noticeably affected and physical impairments may include bilateral loss of facial expression, decreased blinking, speech abnormalities, rigidity of truncal muscles, and postural abnormalities.21 Stage III is characterized by the first signs of impaired righting reflexes (when patients are no longer able to make rapid, automatic movements to protect against falling).21 In general, while increased muscle stiffness may prolong task completion and make engaging in physical sexual activity more difficult, the most important identifying feature of stage III Parkinson’s is that a patient remains capable of independent living; one has the potential to work and remain sexually active depending on the level of physicality required.21,22 Once motor-related symptoms have fully developed, PD severity has progressed to stage IV. By stage IV, patients become severely disabled and despite being able to stand or walk without assistance, there exists is a significant degree of incapacitation. Independent living is no longer possible because patients are unable to complete the activities necessary for daily living such as dressing, maintaining personal hygiene, and eating.20 By stage IV sexual activity is no longer possible. The most severe manifestations of PD symptoms are characterized by stage V, where patients are confined to a bed or wheelchair unless otherwise aided and have the tendency to fall when standing or turning. The severity of symptoms in stage V PD will dramatically impair one’s quality of life.21 While the progression of physical handicaps represents a major challenge to patients with mid to advanced Parkinson’s disease, the condition becomes most distressful when non-motor complications become severe. Stage V is associated with frequent psychosis, hallucinations, dementia, depression, anxiety, and sleep disorders.16,23 Community-based studies have determined the prevalence of dementia to be 75% for those in advanced stages of PD. Additionally, 30% of stage V patients maintained behavioral disorders and hallucinations, while another 40-60% suffered from depression.1
Despite continuous research, there is currently no cure for Parkinson’s disease has not been found.4,5,19 At present there are numerous treatments that provide dramatic improvement for motor and non-motor symptoms. Treatments for Parkinson’s disease typically fall into four categories: drugs which increase levels of dopamine in the brain, drugs that affect other neurotransmitters to reduce symptoms, drugs that ease non-motor symptoms, and surgical alternatives.4,20 While many of these treatments provide an effective way to reduce the severity of Parkinson’s symptoms, they also have profound negative effects on sexual ability and can induce additional dysfunction.
Symptomatic drug therapies (which facilitate the accumulation of dopamine in the SNPC) are generally very effective in managing motor symptoms for the first four to six years after onset.498,14 Levodopa/carbidopa drug therapies are considered the gold standard for symptomatic Parkinson’s tratment.10 Levodopa (L-DOPA) is a natural chemical utilized by nerve cells to stimulate the synthesis of dopamine. When combined with carbidopa, the chemical conversion of levodopa to dopamine becomes limited to the brain, reducing peripheral PD side effects.4,14 Although L-DOPA treatments are typically very effective in combating bradykinesia and rigidity in the early stages of PD progression, issues related to postural instability may not respond and higher doses of levodopa/carbidopa are associated with involuntary movements, known as dyskinesia.4,16Dopamine agonists including apomorphine, paramipexole, ropinirole, and rotigotine are similar to L-DOPA treatments, in that they increase the “effective” dopamine concentrations by mimicking the dopamine functionality.4 Agonist monotherapy is frequently employed during the early stages, while adjunctive therapy with L-DOPA is effective in moderate to advanced stages. Although dopamine agonists are somewhat less effective than L-dopa, they are capable of treating motor symptoms for a longer duration.14 Similar classes of symptomatic drug treatments known as MAO-B and COMT inhibitors also increase dopamine concentrations by inhibiting enzymes from metabolizing dopamine in the SNPC. Both types of inhibiters can delay or reduce the need for levodopa in early stages of Parkinson’s disease.4,9,14Unlike L-DOPA, agonist, and inhibitor treatments that increase dopamine concentrations in the brain, anticholinergic medications are drugs which interfere with the production and uptake of the neurotransmitter aceylcholine.4 Anticholinergic treatments are generally used to supplement other medications to reduce the frequency and severity of tremors. The antiviral drug, amantadine is commonly prescribed with anticholinergics to reduce the motor symptoms of PD and L-DOPA induced dyskinesia.4,8
Recent studies have reported mixed findings on dopaminergenic drug treatments in relation to sexual ability. A 2004 study linked erectile dysfunction and low sexual desire in PD patients to dopaminergenic treatments, while clinical reports indicates that the drug therapy may result in an apparent increase or normalization of sexual desire. Similarly, levodopa treatments were found to increase libido through an adverse biochemical reaction; compulsive hypersexual behavior was noted in 3.5% of PD patients using dopamine agonists such as apomorphine.6
Because of the high prevalence of sexual dysfunction in patients with parkinsonism, physicians and other health care providers should discuss and treat the sexual health issues as an integral part of treating PD.6 Patients who are in the early states of the disease should discuss the possible influences of dopaminergenic treatments on sexual desire prior to drug therapy. Because age has such a profound correlation with Parkinson’s disease, normalized libido resulting from dopaminergenic treatments may be unwelcome as older people often become accustom to their current levels of sexual activity and wish to not be bothered.6 Although these medications may improve motor related abilities and thus increase sexual activity, patients may want to consider overcoming dysfunction through counseling, alternative methods, and the appropriate timing of drug treatment.6 Females suffering from poor lubrication should consider using lube during sex, and those who experience incontinence are encourage to urinate prior to intercourse. Similarly, males patients who ejaculate prematurely may want to consider counseling on the use of sexual techniques, while patients who have difficulties with orgasm can try stimulation apart from vaginal intercourse through the use of sex toys. Openly communicating with one’s partnercan significantly reduce the stresses of PD and drug induced sexual side effects. 6
In order to compliment the treatment associated with primary motor symptoms, there are a plethora of medications, which alleviate the wide array of secondary physical and psychological complications associated with PD. Sedating antidepressants are often administered to patients with advanced PD to combat depression and anxiety.16 Unfortunately, in many circumstances the administration of antidepressants to patients receiving other drugs is discouraged because of the potential for detrimental side effects from drug-drug interactions.16 Depression and the use of antidepressants with PD patients is common, but are associated with sexual difficulties. Patients who suffer from depression who are treated with dopamine agonist therapy may experience hypersexual behavior; the prevalence of hypersexuality (HS) was reported to be 2%, while 8% of patients reported a significant increase in sex drive. HS was most frequently associated with early onset Parkinson. Hypersexual patients showed greater general cognitive impairment, including lower performance on learning tests and poorer inhibitory control in comparison with PD patients with pathological addictions (gambling or eating) alone. Hypersexual behaviors in patients with PD are often very troublesome and contribute to a considerable familial tension when dealing with treatment. Discontinuation of dopamine agonists proves to be the most effective way in treating hypersexual behavior, but results in the increased intensity of PD motor symptoms.6
There are several other commonly utilized medications that are used to treat secondary symptoms. Erectile dysfunction is among the prevalent sexually related symptoms of PD. To date, ED is the only sexual symptom that has been evaluated using drug treatment in relation to parkinsonism. Although sildenadil (generic Viagra) is prescribed for erectile dysfunction in men with severe neurological disorders, adverse side effects are frequent and include headache, flushing, and color disturbances in vision. The efficacy of sildenadil in patients with ED and depression is cited to be approximately 85%. The medication may be taken as an orally or via intra-penile injection. Patients with ED who respond poorly to the medication often consider vacuum devices to aid their ability to get an erection. Unfortunately this method requires dexterity and is not adopted by patients who are in the late stages of PD progression. 6
Studies over the last few decades have lead to great improvements in surgical techniques for the treatment of Parkinson’s disease.4 Because of the risks associated with surgery, surgical procedures are only considered for patients in advanced stages of PD, whose symptoms cannot be adequately controlled by medications alone. Deep brain stimulation (DBS) is presently the most effective surgical procedure for reducing tremors, rigidity, stiffness, bradykinisia, involuntary movements, and stabilizing medication fluctuations.4 In a deep brain stimulation procedure surgeons implant electrodes into predetermined regions of the brain. The implanted electrodes are connected to a battery pack called a neurostimulator that is inserted under the skin near the collarbone. Electrical impulses are sent through an extension to stimulate the targeted cerebral regions that control abnormal nerve impulses. These impulses effectively reduce tremors and motor-related symptoms.
Studies report that DBS may increase the quality of life for advanced PD patients by 18-30% over drug and behavioral therapies alone, and provide an additional 4.6 hours of symptom-free time per day.24-26 Moreover, DBS was found to affect sexual functioning in a small but positive way.27 Male patients with PD, especially those under the age of 60, are more satisfied with their sexual well being over a short term follow up period. Unfortunately, recent studies have indicated that the procedure does not have any influence over sexual dysfunction in females.27 While DBS may provide years of relief for many symptoms, the technique is unable to prevent Parkinson’s disease from progressing and more than 40% of patients experienced serious side effects following the procedure.26
There is currently no cure for Parkinson’s disease. The chronic and progressive symptoms of PD continue to devastate nearly 10 million patients worldwide who suffer from ongoing physical and cognitive deterioration.28 Although Parkinson’s disease itself is not fatal, related complications may contribute to reduced life expectancy. Recent studies have indicated that the increased odds of aspiration, deep vein thrombosis (deep clots that can block blood vessels), pulmonary embolism (arterial blockage in the lungs), or having a serious fall directly affect the longevity of patients.26, 28,29 Moreover, of the 75% patients in advanced stages of PD with dementia, 25% had a higher death rate than those without. A six-year study identifying demographics, geographic, and clinical factors indicated that American women with Parkinson’s had a 26% lower risk of death than men, while African-Americans had the highest crude death rate (66.4%), followed by Caucasians (64.6 %), Hispanics (55.4 %), and Asians (50.8 %).30 After adjusting for age, race, and sex, the same study determined that those suffering from Parkinson’s had nearly four times greater risk of death than those with no disease, and nearly double the risk of death within the six year period than others living with other common diseases such as colorectal cancer, stroke, or ischemic heart disease.30
Currently the goal of the medical management of Parkinson’s disease is to control and treat motor symptoms as well as sexual dysfunction, while minimizing the number of adverse side effects. Though it is well established that there is high frequency of sexual dysfunction among patients with PD, the data on sexual difficulties in relation to this disease is incomplete and contradictory. It is important to note that the intricacies and diversity of needs in the sex lives of PD patients are extremely personal and require communication and realistic expectations. Over the last two decades continued success in identifying the genetic and environmental contributors of PD has provided the scientific community with an abundance of incite into the molecular foundations of this complex neurodegenerative disorder.12 While there are still many unanswered questions, future advances in diagnostic techniques and treatments may one day reduce the prevalence of Parkinson’s disease and provide a comprehensive cure for motor, psychological and sexual symptoms.
1. Dexter D, Jenner P. 2013. Parkinson disease: from pathology to molecular disease mechanisms. Free Radical Biology and Medicine [Internet]. [cited 2015 May 15] 62: 132-144. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16713924
2. Chauhan C, Jeans A. 2015. Is Parkinson’s Disease Truly a Prion-Like Disorder? An Appraisal of Current Evidence. Neurology Research International [Internet]. [cited 2015 May 15]. Available from: http://www.hindawi.com/journals/nri/2015/345285/
3. de Lau L, Breteler M. 2006. Epidemiology of Parkinson's disease. The Lancet Neurology [Internet]. [cited 2015 May 15]; 5(6): 525-535. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16713924
4. NINDS Parkinson’s Disease Information Page [Internet]. Bethesda (MD): National Institute of Neurological Disorders and Stroke [homepage on the Internet]; [cited 2015 May 15]. Available from: http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease....
5. Parkinson's Disease: Hope Through Research [Internet]. Bethesda (MD): National Institute of Neurological Disorders and Stroke [homepage on the Internet]; [cited 2015 May 15]. Available from: http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease.htm.
6. Bronner G, Vodusek D. 2011. Management of sexual dysfunction in Parkinson’s disease. Ther Adv Neurol Disord [Internet]. [cited 2015 May 21] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229252/
7. Parkinson's Disease [Internet].:Florida Hospital; [cited 2015 May 15]. Available from: https://www.floridahospital.com/parkinsons-disease-pd
8. Chinta, S . 2004. Dopaminergenic neurons. The International Journal of Biochemisty & Cell Biology [Internet]. [cited 2015 May 15]; 37(5): 942-946. Available from: http://www.sciencedirect.com/science/article/pii/S1357272504003711
9. Hauser R, Benbadis S. Parkinson Disease [Internet]. Medscape[cited 2015 May 15]. Available from: http://emedicine.medscape.com/article/1831191-overview#showall
10. Dopaminergenic neurons [Internet]. NeuronBank; [cited 2015 May 15]. Available from: http://neuronbank.org/wiki/index.php/Dopaminergic_neurons
11. Lewy Body Dementia: Information for Patients, Families, and Professionals [Internet]. 2013. [cited 2015 May 15]. Available from: http://www.nia.nih.gov/alzheimers/publication/lewy-body-dementia/basics-...
12. Understanding Drug Abuse and Addiction: What Science Says [Internet]. Bethesda (MA): National Institute on Drug Abuse; [2007 Jan, cited 2015 May 15]. Available from: http://www.drugabuse.gov/publications/teaching-packets/understanding-dru...
13. Recessive and Dominant Inheritance [Internet]. Access Excellence Resource Center. [cited 2015 May 15] Available from: http://www.accessexcellence.org/RC/VL/GG/recessive.php
14. Parkinson's disease [Internet]. Rochester (MN): Mayo Clinic; [cited 2015 May 15]. Available from: http://www.mayoclinic.org/diseases-conditions/parkinsons-disease/
15. What is Parkinson's Disease [Internet]. Parkinson's Disease Foundation [homepage on the Internet]; [cited 2015 May 15]. Available from: http://www.pdf.org/symptoms_primary
16. Varanese S, Birnbaum Z, Rossi R. 2010. Treatment of Advanced Parkinson's Disease. Parkinson's Disease [Internet]. [cited 2015 May 15]; 2010: 1-9. Available from: http://dx.doi.org/10.4061/2010/480260
17. Nonmotor Symptoms [Internet]. New York (NY): Parkinson's Disease Foundation [homepage on the Internet]; [cited 2015 May 15]. Available from: http://www.pdf.org/symptoms_nonmotor_early
18. Sexual Health and Parkinson's [Internet]. [cited 2015 May 15] . Available from: https://www.michaeljfox.org/understanding-parkinsons/living-with-pd/topi...
19. An Overview of Sexual Dysfunction [Internet]. [2015 Jan 1, cited 2015 May 21] . Available from:http://my.clevelandclinic.org/health/diseases_conditions/hic_An_Overview....
20. Nonmotor Symptoms [Internet]. New York (NY): Parkinson's Disease Foundation [homepage on the Internet]; [2015, cited 2015 Mar 9]. Available from: http://www.pdf.org/symptoms_nonmotor_early
21. Hoehn M. The FIVE Stages of Parkinson’s Disease [Internet]. Palm Desert (CA): Parkinson's Resource Organization; [cited 2015 May 15]. Available from: http://parkinsonsresource.org/wp-content/uploads/2012/01/The-FIVE-Stages...
22. Cherney K. 5 Stages of Parkinson's [Internet]. Healthline. [cited 2015 May 15]. Available from: http://www.healthline.com/health/parkinsons/stages#Overview1
23. Hu Y, Yu SY, Cao LJ. 2015. Parkinson disease with REM sleep behavior disorder: Features, α-synuclein, and inflammation. Nerology [Internet]; [cited 2015 May 15] Available from: http://www.neurology.org/content/early/2015/02/06/WNL.0000000000001308.f...
24. Browner N. Deep Brain Stimulation [Internet]. Miami (FL): National Parkinson Foundation; [cited 2015 May 15]. Available from: http://www.parkinson.org/parkinson-s-disease/treatment/surgical-treatmen...
25. Tomaszewski KJ, Holloway RG. 2001. Deep brain stimulation in the treatment of Parkinson's disease: a cost-effectiveness analysis. Neurology [Internet]. [cited 2015 May 15]; 57(4):663-71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11524476
26. Statistics on Parkinson's [Internet]. New York (NY): Parkinson's Disease Foundation [homepage on the Internet]; [cited 2015 May 15]. Available from: http://www.pdf.org/en/parkinson_statistics
27. Castelli L, Perozzo P, Genesia ML. 2004. Sexual well being in parkinsonian patients after deep brain stimulation of the subthalamic nucleus.. J Neurol Neurosurg Psychiatry [Internet]. [cited 2015 May 15]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15314111/
28. Mehta A. 2009 Mar 27. Deep Brain Stimulation More Effective for Parkinson’s, Study Confirms [Internet]. New York (NY): The DANA Foundation; [cited 2015 May 15]. Available from: http://www.dana.org/News/Details.aspx?id=4293027.
29. Cherney K, Krucik GT. 2013 Sept 9. What's the Life Expectancy for Parkinson's Disease [Internet]. Healthline; [cited 2015 May 15]. Available from: http://www.healthline.com/health/parkinsons/life-expectancy#Causes2
30. Predicting Survival in People with Parkinson’s [Internet]. 2012 Jan 4. Parkinson's Disease Foundation; [cited 2015 May 15]. Available from: http://www.pdf.org/en/science_news/release/pr_1325692019