Parkinson's Disease: Moving ForwardPage 9 of 17

7. Nonmotor Aspects of Parkinson’s Disease

Nonmotor symptoms of Parkinson’s disease are common, but unfortunately are often under-recognized in clinical practice. This may be because of the lack of spontaneous complaints by the patients or the absence of systematic questioning by healthcare professionals (Bonnet et al., 2012).

At the time of diagnosis, pain, urinary symptoms, depression, and anxiety are present in about 20% of patients. After about seven years, the occurrence of these nonmotor symptoms increases to 88%. Additionally, symptoms such as sleep disturbances, bowel disruptions, gastroesophageal reflux, and olfactory changes occur in a large percentage of patients with PD.

In a recent international study, nonmotor symptoms such as constipation, bladder dysfunction, and feeling of sadness were reported by more than half of the patients, significantly more prevalent among PD patients than controls, and correlated with the duration of the disease (Bonnet et al., 2012).

*Source: Bonnet et al., 2012.

Major Nonmotor Symptoms in Parkinson’s Disease*

Neuropsychiatric symptoms

  • Depression, anxiety, apathy
  • Hallucinations, delusions, illusions
  • Delirium (may be drug induced)
  • Cognitive impairment (dementia, MCI)
  • Dopaminergic dysregulation syndrome (usually related to levodopa treatment)
  • Impulse control disorders (related to dopaminergic drugs)

Sleep disorders

  • REM sleep behavior disorder
  • Excessive daytime somnolence, narcolepsy type “sleep attack”
  • Restless legs syndrome, periodic leg movements
  • Insomnia
  • Sleep disordered breathing
  • Non-REM parasomnias (confusional wandering)


  • Central fatigue
  • Peripheral fatigue

Sensory symptoms

  • Pain
  • Olfactory disturbance
  • Hyposmia (reduced ability to smell and detect odors)
  • Functional anosmia
  • Visual disturbance (blurred vision, diplopia; impaired contrast-sensitivity)

Autonomic dysfunction

  • Bladder dysfunction (urgency, frequency, nocturia)
  • Sexual dysfunction (may be drug-induced)
  • Hyperhydrosis (sweating abnormalities)
  • Orthostatic hypotension

Gastrointestinal symptoms

  • Dribbling of saliva
  • Dysphagia
  • Agueusia (loss of taste)
  • Constipation
  • Nausea, vomiting

Dopaminergic drug-induced nonmotor symptoms

  • Hallucinations, psychosis, delusions
  • Dopamine dysregulation syndrome
  • Impulse control disorders
  • Ankle swelling
  • Dyspnea
  • Skin reactions, subcutaneous nodules
  • Erythematous

Nonmotor fluctuations

  • Dysautonomia
  • Cognitive/psychiatric
  • Sensory/pain
  • Visual blurring

Other symptoms

  • Weight loss, weight gain

Sleep Disturbances

It has been long observed that PD patients experience a variety of sleep disturbances, which can precede the clinical motor symptoms associated with PD by several years. Rapid eye movement sleep-behavior disorder (RBD), in particular, is strongly correlated with the development of synucleinopathies in which alpha-synuclein proteins form into fibrils that accumulate in dopamine cells, leading to the degradation and death of the cell (Haas et al., 2012). Sleep disturbances are estimated to occur in 60% to 98% of patients with PD (Swick, 2012).

REM Sleep Behavior Disorder (RBD)

Rapid eye movement sleep-behavior disorder (RBD) has long been associated with PD. This nonmotor symptom can start years, if not decades, before the development of the classical clinical motor symptoms. RBD is characterized by loss of skeletal muscle atonia during REM sleep with prominent motor and behavioral activity and dreaming (Swick, 2012). When loss of atonia occurs, a person is unable to suppress motor responses during REM sleep and may react to a dream by screaming, kicking, punching, or jumping out of bed. They may remember the dream but have no recollection of having engaged in any movement.

Excessive Daytime Sleepiness

Excessive daytime sleepiness (EDS)—inappropriate and undesirable sleepiness during waking hours—is one of the most commonly reported sleep complaints in patients with PD, affecting between 15% and 50% of patients (Swick, 2012). The degree of EDS has been shown to be a key determinant of a patient’s quality of life.

EDS is a multifactorial issue—it can be caused by fragmented sleep resulting from a primary sleep disorder such as obstructive sleep apnea, periodic limb movement disorder, narcolepsy, idiopathic hypersomnia, or behaviorally induced insufficient nocturnal sleep. Medications, pain syndromes, and numerous medical and psychiatric disorders also have been associated with EDS (Swick, 2012).

Patients may start napping more often even before the diagnosis of PD. As the disease progresses this may increase, although tiredness may also be a side effect of the medications prescribed for PD.

Restless Legs Syndrome

There have been numerous cross-sectional studies examining the frequency of restless legs syndrome (RLS) symptoms in patients with PD. The generally accepted frequency is 10% to 20% association of RLS symptoms in patients with Parkinson’s (Swick, 2012).

In a 2011 study, Gjerstad and colleagues looked at 200 patients with early untreated PD and compared them to appropriate community-based controls. They were unable to find a statistically significant association between RLS in patients with PD versus the controls. They found that the patients with PD complained of leg motor restlessness but did not have the “urge to move” that characterizes the sensory phenomenon in patients with RLS (Swick, 2012).

Alan: Living with Parkinson’s

After going on the new meds I found I could walk again without using a cane. I began typing again, putting the voice recognition software back in the box. My voice, which had become weak, was getting stronger.

Both doctors recommended I reduce the amount of stress in my life and get more rest. That was a difficult challenge for a newspaper publisher. I love what I do. Volunteerism had been my way of giving back to the community that has been so good to me. In 2007 I spoke to the local Parkinson support group and told them my quality of life had improved over the previous two years.

In 2008, however, I started having trouble sleeping. I was never one to sleep very long. Even as a young boy I generally slept only five to six hours a night, Sleep was something I had to put up with. My attitude growing up was I would rather read an encyclopedia under the covers by flashlight than sleep. And I couldn’t wait to hear the morning newspaper plop on the driveway. As an adult with my own business, I was often at the office by 6:15 to get my regular work done so I could work on volunteer activities in the afternoon.

Now I would go to bed, fall instantly asleep, but wake up two hours later. This went on for months. After falling asleep while driving on the freeway, I went to my GP to tell him about my sleep problems.

He sent me to the Mayo Clinic (fortunately the Arizona campus is only a few miles away), where I was tested for sleep apnea. The test was conducted during an overnight stay. I was wired up at points all over my body. It was very strange. But at least the test confirmed it was mainly stress keeping me awake.

My regular doctor let me try some sleep aids. Ambien made my head do weird things. We went through a number of over-the-counter drugs. But then he tried me on Lunesta and that was the magic pill for me. I’ve been sleeping much better since then and of course I feel much better after a full night’s sleep.

To maintain my new sleep status, I wear a mask over my eyes and try to avoid bright lights during the night. Television is taboo after I go to bed. I changed my eating habits. No caffeine. No chocolate or other sweets in the evening.

Sometimes I try counting backward from 100, mentally drawing each number as I go. I precede each number by inhaling deeply through my nose, holding the air in my lungs for varying amounts of time, and exhaling through my mouth.

I also began practicing some relaxation techniques I read about in a flight magazine. I imagine a cabin in the woods with snow falling. Everything is seen in a light blue tint. I don’t like snow or cold weather, but for some reason that scene is very peaceful to me.

I also envision a favorite beach in Cabo San Lucas. That is what I call relaxation. Warm, sunny, with a Corona in hand! Sadly, there are no vendors in my dreamland version.

Sleep Disordered Breathing

The reported frequency of sleep-disordered breathing (SDB) in patients with PD varies from 20% to 60%. This is an unexpected association because the usual patient with PD is not obese, a major factor in the development for SDB. Possible etiologic explanations include decrease in upper airway muscle tone because of degeneration of the brainstem, serotoninergic neurons that ennervate the muscles of the upper airway, deficient respiratory muscle coordination, or autonomic dysregulation (Swick, 2012).

In a cross-sectional survey, researchers assessed the risk of SDB in patients with PD versus controls in a university-based movement disorders clinic. They identified a high risk of SDB in 49% of the patients with PD compared to 35% of controls. After adjustment for age, gender, and body mass index, patients with PD showed a higher risk for SDB than controls did. The survey also found that quality of life was significantly decreased in patients with PD at high risk for SDB (Swick, 2012).

REM Sleep and Hallucinations

Treatment with dopaminergic agents has been associated with hallucinations in up to 40% of PD patients. Three factors have been shown to be independently predictive of visual hallucinations: severe cognitive impairment, duration of PD, and daytime sleepiness. The presence of RBD has been found to increase the risk of hallucinations by a factor of 3. The brainstem degeneration that is responsible for RBD may also be responsible for the intrusions of dream mentation into wakefulness that are then manifested as hallucinations. Parkinson’s disease hallucinations are best treated by the discontinuation of centrally acting anticholinergic agents, anxiolytics, antidepressants, and opiate pain medications. The use of the newer “atypical” antipsychotics has been shown to reduce the hallucinations without substantially worsening the motor symptoms of PD (Swick, 2012).

Bowel Disruptions

Disruptions in bowel function is another known co-morbidity of PD. Constipation affects most PD patients and can arise many years prior to the motor symptoms of PD. The frequency of bowel movements has been correlated inversely with PD risk, and constipation may be one of the first symptoms of PD. These findings were supported by an epidemiologic study involving women in Olmsted County, Minnesota, where an association between earlier life constipation and PD risk was well documented. Constipation may emerge as much as 20 years prior to a diagnosis of PD (Haas et al., 2012).

Gastroesophageal Reflex Disease (GERD)

Gastrointestinal dysfunction is one of the most common nonmotor features of Parkinson’s disease, and was included in the original description by James Parkinson. Gastroesophageal reflux symptoms characterized by heartburn and regurgitation are generally recognized as clinical symptoms of GERD. Gastroesophageal reflux disease can also show dyspeptic manifestations other than reflux symptoms. In clinical practice, disappearance of these symptoms following treatment with proton pump inhibitors (PPIs) allows general physicians to reasonably conclude that the patient had acid-related dyspepsia (Maeda et al., 2013).

Variable abnormalities from the mouth through the rectum may contribute to the onset of GERD in those with PD. Dysphagia is relatively common, being observed in 29% to 80% of PD patients, and can be related to dyscoordination of various organs such as the mouth, pharynx, and esophagus. In addition to abnormalities of esophageal peristalsis, dysfunction in the lower esophageal sphincter can also produce clinical symptoms of gastroesophageal reflux (Maeda et al., 2013).

Olfactory Disruptions

Difficulties in detecting, discriminating, and identifying odors are observed in up to 90% of PD patients. As with other nonmotor symptoms, olfactory deficits can begin several years before motor impairments lead to a clinical diagnosis. In PD patients with mild symptoms, severity of olfactory deficits has been found to correlate with dopaminergic dysfunction (Haas et al., 2012).

To determine whether these early olfactory symptoms might prove useful as a premotor biomarker for PD, a number of studies have examined olfaction in early or asymptomatic patients. A recent prospective study showed that patients with poor olfaction were more likely to develop PD in the four-year followup period than those with normal olfaction (Haas et al., 2012).

Another study found that, when assessing asymptomatic first-degree relatives of PD patients, performance levels of odor discrimination robustly correlated with future PD risk. In addition, olfactory identification dysfunction on the University of Pennsylvania Smell Identification Test was able to distinguish PD from other movement disorders and is a strong candidate for a clinical premotor PD biomarker (Haas et al., 2012).

Olfaction in Differential Diagnosis of PD

Inexpensive olfactory probes may improve the diagnostic process in patients with PD. In contrast to imaging procedures, olfactory testing is quick and easy to perform. Validated tests can be used as reliable diagnostic tools even in non-specialized centers (Haehner et al., 2011). The American Academy of Neurology now recommends olfactory testing as an aid in diagnosing Parkinson’s disease (Fornazieri et al., 2013).

In a study comparing a smell test with a dopamine transporter scan (DaTSCAN), researchers found that a basic smell test is just as sensitive. According to this study, the sensitivities of the University of Pennsylvania Smell Identification Test and DaTSCAN are high at 86% and 92%, respectively. Although DaTSCAN is superior for localization, a smell test is considerably cheaper. Structured and validated tests of olfactory function should be a mandatory part of the early and differential diagnosis of PD (Haehner et al., 2011).

UPSIT Smell Identification Test

Originally published only in English, the University of Pennsylvania Smell Identification Test (UPSIT) has been translated into more than a dozen languages. This widely used test is considered by many to be the gold standard to which other tests of olfactory function have been compared. It is sensitive to the influences of a wide range of variables, including age, gender, environmental pollution, and numerous diseases (Fornazieri et al., 2013).

The UPSIT consists of four booklets, each with ten pages. Microencapsulated “scratch and sniff” odorant strips are positioned on brown strips that are located at the bottom of each page, resulting in a total of 40 odorants. The subject releases the odor by scratching the strip with a pencil tip in a standardized manner. He or she then indicates the smell that is perceived by choosing a name from a set of four odor descriptors located just above the odorized strip. The number of correctly identified odors serves as the test score (Fornazieri et al., 2013).

A response is required for each odor even if no smell is perceived (i.e., it is a forced-choice test). This procedure enables the detection of malingering based on improbable responses and increases the likelihood that a subject will pay close attention to the released odorant. The UPSIT is strongly correlated with odor threshold tests, and the magnitude of these correlations is limited by the reliability of the threshold test that is being evaluated (Fornazieri et al., 2013).

Speech and Language Impairments

Nearly 90% of individuals with Parkinson’s disease develop voice and speech disorders. Difficulties getting speech started and a quiet or weak voice are commonly noted changes. Patients report they are often asked to repeat their words because listeners have difficulty understanding, although patients themselves may self-estimate their speech as loud and sufficiently articulated (Skodda, 2012).

Changes in communication brought about by neurologic disorders are most often defined and described in terms of the individual’s impairments of speech and voice (dysarthria) or language (aphasia). Different aspects of speech and language can be measured and quantified using clinical tests and instrumental analyses. The individual’s perception of degree of impairment and its impact can also be assessed, using qualitative interviews or self-report questionnaires. However, communication is an interaction, a joint effort, which makes the conversational partner a key player. This is true in all types of everyday conversations, but especially so when one of the interacting persons has a communicative impairment (Hartelius et al., 2011).

The necessary prerequisites in communicative interaction are:

  • Intact sensory-motor processes (auditory and visual perception, voice and speech function, ability to gesture, change posture, and so on)
  • Linguistic ability (knowledge of the sound system, semantics, syntax, and discourse)
  • Cognitive abilities (attention, memory, inference, executive function, affect, and the ability to infer mental states in others, ie, theory of mind)

These capacities interact to form a person’s pragmatic ability. The occurrence of any type of neurologic damage can have a negative impact on the ability to communicate in several different ways. Of interest, some studies have indicated that those whose speech is affected by neurologic damage may be unaware of the extent of their communication problems (Hartelius et al., 2011).

There is a growing recognition that language impairments and pragmatic deficits occur in Parkinson’s disease. There is increased interest in the role of basal ganglia and frontostriatal systems in the processing of complex language. Affected abilities include:

  • Interpretation of the intentions underlying verbal irony and lies
  • Theory of mind
  • Comprehension of metaphors
  • Ability to use vocal cues effectively to infer a speaker’s emotions and attitudes (Hartelius et al., 2011)


Dysarthria is a motor-speech disorder in which the muscles of the mouth, face, and respiratory system become weak. Dysarthria is fairly common in PD and can emerge at any stage of the disease. It generally worsens in the later stages, leading to a progressive loss of communication and social isolation.

Parkinsonian dysarthria has traditionally been considered a manifestation of rigor (stiffness) and hypokinesia of the speech effector organs. This leads to a multidimensional motor-speech impairment that alters speech respiration, phonation, articulation, and prosody.* Hypokinetic dysarthria is characterized by a breathy and harsh voice, monotony of pitch and loudness, reduced stress, variable speech rate with short rushes of speech, and imprecise articulation resulting in a reduction of overall speech intelligibility (Skodda, 2012).

*Prosody is the rhythm, stress, and intonation of speech.

From the therapeutic point of view, the effect of dopaminergic medication on various speech parameters and overall speech intelligibility in particular remains somewhat inconclusive. There are some reports of positive levodopa effects on tongue strength and endurance and of an improvement of speech intelligibility. However, the majority of studies have found no relevant effect of dopamine therapy on speech rate, prosody, and phonatory parameters, or on overall intelligibility (Skodda, 2012).

The results of medical, surgical, and deep-brain stimulation treatments of dysarthria in patients with PD have been variable and generally disappointing. Several studies have suggested that the pathophysiology of speech disorder may be different from the limb movement disorders of Parkinson’s, including studies employing functional imaging, demonstrating a negative correlation between disease severity and impaired speech, and showing nonresponsiveness towards levodopa in people with PD-induced oral festination (Kwan & Whitehill, 2011).

Perception of Loudness

For some time, there have been anecdotal reports of a distorted perception of one’s own loudness in individuals with PD. Speakers with PD tend to overestimate the loudness of their own voice and when asked to speak with “normal” loudness perceive that they are shouting or producing abnormally loud speech. Another common observation is the ability of individuals with PD to improve their loudness (and other aspects of speech production) when prompted to do so in a clinical or laboratory setting, but with a return to reduced loudness and poorer speech production upon leaving the clinical setting (Kwan & Whitehill, 2011).