NON-MOTOR SYMPTOMS OF PARKINSON’S DISEASECHRISTINA L. VAUGHAN, MD, MHS

ASSISTANT PROFESSOR OF NEUROLOGY, UNIVERSITY OF COLORADO, ANSCHUTZ MEDICAL CAMPUS

OCTOBER 6, 2018

GOALS

• To provide a comprehensive overview of key non-motor

features of PD

• To provide practical tips regarding management of some

non-motor symptoms

NON-MOTOR FEATURES OF PD

• Non-motor features of PD are often under-

recognized by clinicians

• Non-motor (and non-levodopa responsive) symptoms

predominate at 15 years

• Also occur often in people w/o PD: normal aging

Pfeiffer 2015; Fernandez 2012 & Shulman et al 2002

LOST SENSE OF SMELL

• most common pre-motor symptom

• ~85% early PD

• can precede onset of motor symptoms

by years

• multifactorial

• also common in Alzheimer’s and Lewy

Body Disease

• disease may start in GI tract and/or

olfactory bulb

LOST SENSE OF SMELL: PRACTICAL

• No treatments for lost sense of smell

• Reduced ability to smell might affect your appetite, since taste is linked to smell

1. Adequate provision of fire and/or smoke alarms

2. Specific food and nutritional advice if you also have a reduced taste sensation

3. Labels to ensure food safety as you may not be able to smell degraded food

SLEEP DISORDERS

• ~90%

• ↑ with advanced PD

• Most common sleep complaints:

• Difficulty falling and staying asleep

• Sleep fragmentation*

• Excessive daytime sleepiness

• Talking or yelling out while asleep

• Vivid dreaming

• Leg movements, jerking, cramping

• Difficulty turning over in bed

• Waking up to go to the bathroom

SLEEP DISORDERS: EXCESSIVE DAYTIME SLEEPINESS

• 30-50% of patients with PD

• Common causes:

• Poor night’s sleep

• Dopaminergic medications, especially dopamine agonists:

• Mirapex (pramipexole)

• Requip (ropinirole)

• Neupro patch (rotigotine)

• Apokyn (apomorphine)

SLEEP DISORDERS:EXCESSIVE DAYTIME SLEEPINESS: PRACTICAL

Do not drive while sleepy.

1. Good sleep hygiene, includes a set bedtime and wake-up time.

2. Exposure to adequate light during the day and darkness at night.

3. Avoid sedentary activities during the day.

4. Participate in activities outside the home, as they may be helpful in providing stimulation to prevent

daytime dozing.

5. Get physical exercise appropriate to your level of functioning, which may also promote daytime

wakefulness.

6. Strenuous exercise, however, should be avoided for 3 - 4 hrs before sleep.

7. If you are on a dopamine agonist and you experience daytime sleepiness or sleep attacks talk to your

doctor about possibly decreasing the dose.

http://www.parkinson.org

SLEEP DISORDERS: NIGHT

• Obstructive sleep apnea (OSA)

• Restless legs syndrome (RLS)

• REM sleep behavior disorder (RBD)

• Sleep fragmentation

• Patients may have a combination of a few sleep problems

http://www.parkinson.org

SLEEP DISORDERS:OBSTRUCTIVE SLEEP APNEA (OSA)

• ~40% PD patients

• Loud snoring

• Restless sleep

• Sleepiness during the daytime

• Pauses in breathing during night sleep

• Diagnose: sleep study

• Treat: Continuous positive airway

pressure (CPAP)

• Associated with many bad health

consequences:

• stroke

• high blood pressure

• heart arrhythmias

• heart attack

• insulin resistance

• depression

• worsening cognition

SLEEP DISORDERS:RESTLESS LEGS SYNDROME (RLS)

• Irresistible urge to move the legs, which interferes with rest

and sleep

• Usually at night, or sometimes daytime when sitting for long

periods

• Creeping, crawling, aching, pulling, searing, tingling, bubbling

• Sometimes also in upper leg, feet, or arms

• 5 -15% of adults; ~2x as likely in PD

SLEEP DISORDERS: RLS

• Treatment:

• Iron replacement (in those

who are deficient)

• Pramipexole (Mirapex)

• Ropinirole (Requip)

• Rotigotine (Neupro)

• Gabapentin (Neurontin)

• (Pain medication)

SLEEP DISORDERS:REM SLEEP BEHAVIOR DISORDER (RBD)

• ~ 50% PD patients

• = continued ability to move

during REM sleep

• “thrashing about” in sleep or “acting

out” of dreams

• often precedes the PD diagnosis

by 5-10 years

• people with RBD may have 80-

90% risk of later developing PD

• Treat:

• clonazepam (effective in 75-

90%)

• melatonin may help

SLEEP DISORDERS:FRAGMENTATION

• interrupted sleep

• significantly less time spent in slow-wave

and REM sleep (the deepest and most

restorative phases of sleep)

• may worsen daytime sleepiness and

predispose to later hallucinations

• Treatment:

• Clonazepam

• tends to help regulate sleep and allow

for a more normal nighttime sleeping

pattern

• adjust anti-PD drugs

• daytime stimulant (ex: Provigil, Ritalin)

• treat nighttime urinary frequency

MOOD DISORDERS

• maintaining emotional health is essential to your physical health

• stress can make PD symptoms worse

• depression and anxiety affect up to 50% of people living with PD

• mood changes can bring on worsening function, leading to a decreased

quality of life

MOOD DISORDERS: DEPRESSION

• can pre-date other signs

• highly treatable

• Risk factors

• Older age

• Female

• Personal history of depression

• Family history of depression

• Other medical disease(s)

• Severity of PD symptoms

Joseph Hirsch, Lunch Hour (1942)

MOOD DISORDERS: DEPRESSION

• Often present:

• Prominent anxiety

• Dysphoria (low mood)

• Pessimism

• Somatic/physical symptoms

• Less often present:

• Guilt

• Self-blame

• Suicide (low rate despite high

frequency of ideation)

• Delusions/hallucinations

• Especially in advanced PD, it can be

difficult to distinguish between

physical symptoms of depression and

those of PD:

– such as slowness of movement

and thinking, loss of appetite and

weight, or sleep problems

MOOD DISORDERS: DEPRESSION: PRACTICAL

• Treatment is personalized, multidimensional

• Determine whether the symptoms occur only during OFF periods

• Adjust anti-PD medication accordingly

• Assess severity:

• If mild, consider counseling, patient education, or cognitive-behavioral therapy (CBT)

• If moderate-severe, consider:

• Psychotropic medication

• Dopaminergic medication

• Electroconvulsive therapy (ECT)

Dopamine agonists

Pramipexole (Mirapex)

Tricyclic antidepressants

Nortriptyline

Desipramine

Amitriptyline (Elavil)

SSRIs (selective serotonin reuptake inhibitors)

Citalopram (Celexa)

Sertraline (Zoloft)

Paroxetine (Paxil)

Fluoxetine (Prozac)

SNRIs (serotonin/norepinephrine reuptake inhibitors)

Venlafaxine (Effexor)

Duloxetine (Cymbalta)

COMMON MEDICATIONS FOR DEPRESSION IN PD

MOOD DISORDERS: ANXIETY

• Panic attacks (often during OFF-periods), generalized anxiety disorder, simple and social

phobias, obsessive-compulsive disorder (OCD)

• Associated with subjective motor symptoms, freezing, more severe gait problems, and

dyskinesiasRelated to anxiety, there is

some evidence of a PD

personality:

lower novelty seeking and

higher harm avoidance; less risky

behavior

MOOD DISORDERS: ANXIETY

• Risk factors:

• Female sex

• Previous history of anxiety disorders

• +/- younger age

• Severity (not duration) of PD

• No tremor > tremor-predominant

• Common fears with anxiety in PD:

• fear of being unable to function,

particularly during a sudden OFF period

• sometimes leads to a need to be with

someone at all times and a fear of being

left alone

• being embarrassed—often related to

having people notice symptoms of PD in

public

MOOD DISORDERS: ANXIETY: PRACTICAL

1. Exercise

2. All basic forms of physical activity can help:

walking, stretching, yoga, tai-chi, dance, etc.

3. Relaxation techniques

4. Massage therapy

5. Acupuncture

6. Aromatherapy

7. Meditation

8. Music therapy

• Newer antidepressants such as SSRIs typically

tried first

• Benzodiazepines (with caution!)

• diazepam (Valium)

• lorazepam (Ativan)

• clonazepam (Klonopin)

• alprazolam (Xanax)

• can cause: memory difficulties, confusion,

increase in balance problems and tiredness

Dopamine agonists

Pramipexole (Mirapex)

Tricyclic antidepressants

Nortriptyline

Desipramine

Amitriptyline (Elavil)

SSRIs (selective serotonin reuptake inhibitors)

Citalopram (Celexa)

Sertraline (Zoloft)

Paroxetine (Paxil)

Fluoxetine (Prozac)

SNRIs (serotonin/norepinephrine reuptake inhibitors)

Venlafaxine (Effexor)

Duloxetine (Cymbalta)

COMMON MEDICATIONS FOR ANXIETY IN PD

MOOD DISORDERS: APATHY/AMOTIVATION

• general lack of motivation and interest,

dampening of emotional expression

• prevalence up to ~40%

• can be misinterpreted as laziness, poor

initiative or depression

• not explained by cognitive impairment,

emotional distress, or decreased

consciousness

• higher risk: older age, severe motor

impairment

• Can cause:

• less physical activity (which can

worsen already impaired mobility)

• fewer social interactions (which

could lead to depressive

symptoms)

• poorer adherence to medication

regimens

MOOD DISORDERS: APATHY/AMOTIVATION: PRACTICAL

1. Maintain a regular sleep and wake

schedule

2. Create a schedule that incorporates

physical, social and cognitive (memory

and thinking) activities. List what you

will do each day and at what time

3. Set personal goals

4. Exercise

• Possible treatments:

• dopamine agonists

• rivastigmine (Exelon)

• memantine (Namenda)

• mood medication

• stimulants

• Cognitive behavioral therapy

FATIGUE

• a feeling of deep tiredness that does not

improve with rest

• may predate onset of motor symptoms

• single most disabling symptom for up to

1/3 PD patients

• associated frequently with depression,

cognitive deficits, and daytime sleepiness

FATIGUE: PRACTICAL

1. Eat well.

2. Stay hydrated.

3. Exercise. Fatigue may make it hard to start exercising, but it may make you feel more energetic

afterward. If you find it difficult to get going, consider exercising with another person or a group.

4. Keep a regular sleep schedule.

5. Take a short nap (10-30 minutes) after lunch. Avoid frequent naps or napping after 3:00 p.m.

6. Stay socially connected.

7. Pace yourself: plan your day so that you are active at times when you feel most energetic and have a

chance to rest when you need to.

8. Do something fun: visit with an upbeat friend or pursue a hobby.

9. At work, take regular short breaks.http://www.parkinson.org

FATIGUE: PRACTICAL

• Adjusting PD medications

• Possible treatments: stimulant (low dose), levodopa, dopamine agonists

• Investigate for other causes (ex: anemia, hypothyroidism, nutritional deficiencies)

CONSTIPATION

• Fewer than 3 bowel movements/week

• Can predate motor symptoms – by years

• Up to 60% in PD patients compared to 6-33% in controls

• Contributes to symptoms: nausea, bloating, feeling full, and weight loss

• Contributes to irregular absorption of medications motor fluctuations

• PD medications can contribute to constipation

CONSTIPATION: PRACTICAL

1. Eat a well-balanced diet with plenty of fiber. Good sources of fiber include fruits, vegetables, legumes,

bran, and whole grain bread.

2. Drink 48 to 64 ounces of water each day.

3. Exercise daily.

4. Drink warm liquids, especially in the morning. Consider warming your prune juice instead of drinking

it cold.

5. Add fruits and vegetables to your diet.

6. Eat prunes and/or bran cereal.

7. If needed, use a very mild laxative or stool softener.

CONSTIPATION: PRACTICAL

• Senna/Senokot

• Stool softener(s)

• Polyethylene glycol electrolyte solution

(Miralax)

• Enemas

• Note: bulking agents like Metamucil may

make it worse (“cement block”)

• Recipe 1:

• Equal parts bran cereal, applesauce, and

prune juice (example: 1 cup of each)

• Mix into a container with a lid; store in

the refrigerator

• Eat two tablespoons a day (preferable

the same time each day)

• Recipe II:

• Yakima Fruit paste, 1 Tb/day

OVERVIEW OF NON-MOTOR SYMPTOMS

EARLIER SYMPTOMS

• ↓Taste/sense of smell

• Sleep disorders

• Mood disorders

• Fatigue

• Constipation

The importance

of EXERCISE!

WHAT DO MOST HAVE IN COMMON?

COGNITIVE CHANGES

• Mild cognitive impairment ~25% in early

PD

• Dementia ~80% for those with >20 yrs of

PD

• while approximately 50 percent of people with

PD will experience some form of cognitive

impairment, not all lead to dementia

• Note: if dementia precedes parkinsonism,

consider Lewy Body Disease

COGNITIVE CHANGES

• Executive dysfunction: problem solving, making plans, formulating goals, anticipating

consequences

• Attention difficulties

• Slowed thinking

• Word-finding trouble

• Difficulty learning and remembering information

• Visuospatial trouble: where things are in space

COGNITIVE CHANGES: DEMENTIA

• Not a specific disease

• An overall term: wide range of symptoms

associated with ↓memory or other

thinking skills severe enough to reduce a

person's ability to perform everyday

activities

• Progressive

• Multiple types: Alzheimer’s (60-80%),

Parkinson’s-type, vascular,

frontotemporal,…

• At least 2 are impaired with

dementia:

1. Memory

2. Communication and language

3. Ability to focus and pay attention

4. Reasoning and judgment

5. Visual perception

http://www.alz.org/what-is-dementia.asp

COGNITIVE CHANGES

• Risk factors for PD Dementia

• Age

• Motor severity

• Older age at PD onset

• Longer PD duration

• No tremor > tremor

• Hallucinations

• Depression +/-

• Genetic forms of PD +/-

COGNITIVE CHANGES

• Treatment

• Exclude other medical causes of

cognitive problems, especially if sudden

onset

• Address safety and care-giver issues

• Driving evaluations

• Cognitive remediation therapy

• alternative ways to compensate for

memory or thinking problems

• Cholinesterase inhibitors:

1. donepezil (Aricept)

2. galantamine (Razadyne)

3. rivastigmine (Exelon)*

• NMDA antagonists:

1. memantine (Namenda)

COGNITIVE CHANGES: PRACTICAL

• Offer help only when asked.

• Prompt the person — for example, instead of asking, “Did anyone call?” ask, “Did Linda call?”

• Say the name of the person and make eye contact when speaking to gain and hold attention.

• Put reminder notes and lists in a prominent place.

• Keep things in routine places.

• To ensure medications are taken on time, provide a dispenser, perhaps with a built-in alarm.

• Use photos on cell phone contact entries to prompt face-name association.

• If the person is searching for a word, provide a cue, such as, “the word you are looking for probably begins with ‘d’.”

• Do not finish the sentences of a person who needs more time to put them together.

• When presenting the person with a list of actions, first verbalize them, then write them down.

• Ask questions to moderate the conversation pace and allow catch up and reinforcement.

http://www.parkinson.org

COGNITIVE CHANGES: PRACTICAL

• Get adequate rest

• Eat a healthy diet

• A Mediterranean diet, for example, has been associated with improved cognitive function

• Do not multitask

• Focus on your abilities

• Introduce novelty - learn something new

• Exercise

• SOCIALIZE!

• Stay busy and fill your schedule

http://www.pdf.org/pdf/slides_pdexpertbriefing_cognition15_111015.pdf

COGNITIVE CHANGES: PRACTICAL

• An active and socially integrated lifestyle in late life might protect against dementia

• Incidence and progression of dementia increases with isolation

ORTHOSTATIC HYPOTENSION (OH)

If symptomatic:

• lightheadedness

• fatigue

• unsteadiness

• generalized

weakness

• visual blurring

• headache

• coat-hanger ache

• neck tightness

• cognitive slowing

• leg buckling

• gradual or

sudden loss of

consciousness

• Definition:

• ↓(systolic blood pressure) > 20

and/or

• ↓(diastolic blood pressure) > 10

after a 3 minute delay

when changing from sitting to

standing

• Prevalence in PD: 20% - 60%

ORTHOSTATIC HYPOTENSION

• Associated with:

• Disease duration

• Disease severity

• Use of higher daily levodopa doses

• Older age

• Increased risk of falls

• Hydration

• Arising slowly

• Elevated head of bed

• Compression stockings

• Medication adjustments

Figueroa et al 2010

Orthostatic hypotension:

PRACTICAL

ORTHOSTATIC HYPOTENSIONTREATMENT

1. Fludrocortisone (Florinef): ↑increases

salt retention ↑blood volume, ↑blood

pressure

2. Midodrine (ProAmatine): causes blood

vessels to constrict ↑blood pressure

3. Droxidopa (Northera® ):

norepinephrine ↑blood pressure

URINARY DYSFUNCTION

• Prevalence 38-71% (57%)

• Nocturia** (overnight)

• Frequency *

• Urgency*

• Urge incontinence

• Hesitancy and bladder retention

• Proper referral to a urologist is

important for guidance in assessment

and treatment

URINARY DYSFUNCTION

• Urge incontinence or “overactive

bladder” = most common in PD

URINARY DYSFUNCTION

• Medications that work to block or reduce bladder over-activity:

OLDER MEDICINES

• oxybutynin (Ditropan)

• tolterodine (Detrol)

NEWER MEDICINES

• solifenacin (Vesicare)

• darifenacin (Enablex)

• trospium (Sanctura)

• mirabegron (Myrbetriq)

• “Botox” injections

URINARY DYSFUNCTION : PRACTICAL

• Examine the medications

• Look for infection (UTI)

• Weight loss

• Dietary changes – cut back on alcohol, caffeine

and carbonated beverages

• Cut back on excessive fluid intake but avoid

dehydration!

• Cut back on night time fluid intake if nocturia

• Smoking cessation

• Pelvic floor (Kegel) exercises

• Bladder training

• voiding diary

• void at regular timed intervals

• urgency episodes are dealt with by distraction

and Kegel movements

• voiding intervals are gradually increased

SWALLOWING DIFFICULTY

• Can happen at any stage

• 4 out of 5 patients affected BUT 1/3

report it

• difficulty swallowing certain foods or

liquids

• coughing or throat clearing during or after

eating/drinking

• feeling as if food is getting stuck

• Risk: aspiration pneumonia

• Assessment:

• videofluoroscopy (modified barium

swallow study)

• endoscopy (visualizing the throat with a

scope)

SWALLOWING DIFFICULTY: PRACTICAL

• Strategies to help food or liquid go down

safely

• swallowing hard

• holding breath while swallowing

• tucking the chin while swallowing

• Exercises

• Diet changes

• thickening liquids

• making foods softer

• Ask your doctor to refer you to a

speech/language pathologist for a

swallowing evaluation

CHANGES IN SPEECH

• The voice may get softer, breathy, or hoarse, causing others difficulty hearing

what is said

• Speech may be slurred

• Speech may be mumbled or expressed rapidly

• The tone of the voice may become monotone, lacking the normal ups/downs

• The person may have difficulty finding the right words, causing speech to be

slower

• The person may have difficulty participating in fast-paced conversations

CHANGES IN SPEECH: PRACTICAL

• Assessment and treatment with speech therapist/pathologist

• Lee Silverman Voice Treatment (LSVT) - improvements may last up to 2 years: “LOUD”

• Assistive communication device

• portable voice amplifier

• electronic device for stuttering (Speech Easy)

• Collagen is injected into the vocal folds (only when vocal cords don’t close completely)

PAIN

• 60% prevalence

• Dystonia/dyskinesia: pulsing or aching

• Musculoskeletal pain: aching or burning

• Nerve/nerve root pain: sharp, numbness

or “pins and needles”

• Primary/central pain: sudden, sharp

burning pain that occurs for no known

reason

• Akathisia: restlessness

• Musculoskeletal pain

• Frozen shoulder

• Flexed fingers or toes

• Stooped posture (camptocormia)

• Leaning sideways (Pisa syndrome)

• Scoliosis

• Dropped head (anterocollis)

• Bone fractures

PAIN: PRACTICAL

• Dopamine agonists, carbidopa/levodopa

• Medication for nerve pain

(gabapentin/Neurontin, pregabalin/Lyrica)

• Topical (Lidoderm, capsaicin)

• Medical cannabis? (CBD>THC)

• Physical therapy

• Acupuncture

• Tai chi and yoga

• Exercise

THANK YOU