NON-MOTOR SYMPTOMS OF PARKINSON S DISEASE CHRISTINA 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 underrecognized 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 disease may start in GI tract and/or olfactory bulb can precede onset of motor symptoms by years multifactorial also common in Alzheimer s and Lewy Body Disease
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)
COMMON MEDICATIONS FOR DEPRESSION IN PD 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)
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 dyskinesias Related 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
COMMON MEDICATIONS FOR ANXIETY IN PD 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)
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 Possible treatments: dopamine agonists rivastigmine (Exelon) memantine (Namenda) mood medication stimulants Cognitive behavioral therapy 4. Exercise
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 WHAT DO MOST HAVE IN COMMON? The importance of EXERCISE! Fatigue Constipation
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) 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% 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
ORTHOSTATIC HYPOTENSION Associated with: Disease duration Disease severity Use of higher daily levodopa doses Older age Increased risk of falls
Orthostatic hypotension: PRACTICAL Hydration Arising slowly Elevated head of bed Compression stockings Medication adjustments Figueroa et al 2010
ORTHOSTATIC HYPOTENSION TREATMENT 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) Proper referral to a urologist is important for guidance in assessment and treatment Frequency * Urgency* Urge incontinence Hesitancy and bladder retention
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! 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 Cut back on night time fluid intake if nocturia Smoking cessation
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 Assessment: videofluoroscopy (modified barium swallow study) endoscopy (visualizing the throat with a scope) Risk: aspiration pneumonia
SWALLOWING DIFFICULTY: PRACTICAL Strategies to help food or liquid go down safely swallowing hard holding breath while swallowing Diet changes thickening liquids making foods softer tucking the chin while swallowing Exercises 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
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