Evaluation and Management of Parkinson s Disease in the Older Patient David A. Hinkle, MD, PhD Comprehensive Movement Disorders Clinic Pittsburgh Institute for Neurodegenerative Diseases University of Pittsburgh School of Medicine
Overview Symptoms and signs of PD Geriatric PD vs. JO/YO PD Pharmacological management Surgical management
Parkinson s disease Average age at onset: ~62 years PD affects ~1% of the population > age 65 PD affects ~5 % of the population > age 85 M:F ~3:2 Mostly sporadic, ~10% familial
Clinical Features of PD Rigidity Bradykinesia Tremor Anteroflexed posture Postural instability Freezing/festinating gait Poor balance, falls Many non-motor features
Characteristics of PD tremors Unilateral at onset Predominate in resting position Pill-rolling quality Abate with postural / kinetic action Bradykinesia / rigidity co-exist Postural component is re-emergent Jaw / tongue involved (not head)
PD: Non-motor features Depression, anxiety, apathy, fatigue, low energy/initiative Sleep disturbance, REM behavior disorder, RLS/PLMS Bradyphrenia (slow thinking) and cognitive decline (to dementia) Autonomic nervous system abnormalities: gastrointestinal, orthostatic hypotension, genitourinary/sexual dysfunction Pain (shoulder/arm of affected limb)
Relative to geriatric PD, juvenileonset and young-onset PD are: Younger at onset: <20 JO, <40 YO More likely to have a genetic cause More likely to have anxiety/depression More likely to have dystonia and cramps More likely to have pain More likely to respond to (and tolerate!) amantadine, rimantadine, and trihexyphenidyl Less likely to respond to dopaminergic drugs More likely to experience dopaminergic side effects
Loss of dopaminergic SNpc neurons in PD: A major target for symptomatic medical therapy Lewy Body
β-cit SPECT: Estimation of number of dopamine transporters Worsening Parkinson s Disease * Diminished uptake in posterior > anterior putamen * Imaging progression correlates with worsened clinical severity Marek, in Olanow, Watts, and Koller, Neurology 56 Supplement 5:S1-S88, 2001
Dopamine
Dopamine
Treatment Stages of PD??? ~ 62 Birth Pre-clinical onset Clinical Onset Death Treat? Honeymoon Motor Fluctuations/Dyskinesias Failure Consider Medical Therapy
PD therapy: My initial approach Exclude other causes (i.e., drugs) Exercise / physical therapy Treat only when the patient is ready Tremor predominant / young Tremor + other / mild / young Tremor + other / moderate / older
Exercise and Physical Therapy Some evidence that exercise is neuroprotective in experimental PD models Range-of-motion, flexibility, strength, and balance training can be extremely helpful Gait assist devices, +/- projected lines onto floor Patients (and caregivers) need help adjusting to their new physical, mood, and cognitive limitations
PD therapy: My initial approach Exclude other causes (i.e., drugs) Treat only when the patient is ready Tremor predominant / young: Amantadine 100 mg PO QD 100 mg QID Rimantadine 100 mg PO QD 100 mg QID Trihexyphenidyl 1 mg PO QD 1+ mg BID/TID Dopamine agonist Tremor + other / mild / young Tremor + other / moderate / older
Dopamine Dopamine agonists
Starting dose Escalation Maximum dose Pramipexole 0.125-0.25 mg PO TID Weekly by 0.125-0.25 mg TID increments 1.5 mg PO TID Pramipexole ER 0.375 mg PO QAM First week by 0.375 mg QAM, then weekly by 0.75 mg QAM increments 4.5 mg PO QAM Ropinirole 0.25-0.5 mg PO TID Weekly by 0.25-0.5 mg TID increments 8 mg PO TID Ropinirole XL 2 mg PO QAM Weekly by 2 mg increments 24 mg PO QAM Rotigotine 2 mg/24 hr patch Weekly by 2 mg increments 6-8 mg/24 hr patch
Dopamine Agonist Drugs: The Downside Less clinically effective than levodopa ~Ineffective for gait imbalance, freezing, and postural instability (i.e., late motor problems) ~More likely than levodopa to produce sedating and neuropsychiatric side effects
Dopaminergic Side Effects Nausea Fatigue / sedation (sometimes sudden) Hypotension / orthostasis Confusion / poor concentration Hallucinations Compulsive behavior (gambling, shopping, sex) Peripheral edema
PD therapy: My initial approach Exclude other causes (i.e., drugs) Treat only when the patient is ready Tremor predominant / young Tremor + other / mild / young: Dopamine agonist Monoamine oxidase B inhibitor Tremor + other / moderate / older
Reduce dopamine breakdown (MAOB and COMT inhibitors) Dopamine Dopamine agonists
Martinez-Martin and O brien, Neurology 50 Supplement 6: S27-32, 1998
Starting dose Escalation Maximum dose Selegiline 5 mg PO QAM Increase to 5 mg BID after 2+ weeks 5 mg PO BID Zydis selegiline 1.25 mg SL QAM (mucosal absorption) Increase to 2.5 mg QAM after 6 weeks 2.5 mg PO QAM Rasagiline 0.5 mg PO QAM Increase to 1 mg after 2+ weeks 1 mg PO QAM *Dopaminergic side effects similar to other PD drugs
MAOBi and tyramine effect Potentially fatal: hypertension, agitation, anxiety, tremor, encephalopathy, hyperpyrexia, seizures Avoid use with cold remedies (dextromethorphan, pseudoephedrine, ephedrine), TCAs, SSRIs, COMTi, triptans, meperidine, stimulants, and ciprofloxacin within 14 days of MAOBi ~Avoid tyramine-rich foods: beer, beans, wine, aged meats and cheeses, sauerkraut, pickled herring B selectivity reduces risk, especially at doses currently used = generally safe but be careful!
PD therapy: My initial approach Exclude other causes (i.e., drugs) Treat only when the patient is ready Tremor predominant / young Tremor + other / mild / young Tremor + other / moderate / older: Levodopa Combinations with other PD agents
Reduce dopamine breakdown (MAOB and COMT inhibitors) Dopamine Levodopa Dopamine agonists
Levodopa ALONE Nutt, Neurology 55 Supplement 4:S33-37
Levodopa + Carbidopa = Sinemet Nutt, Neurology 55 Supplement 4:S33-37
Starting dose Escalation Maximum dose Carbi/Levo 25/100, ½ tablet PO QAM (I prefer over 10/100 or 25/250 at start) Increase by ½ tablet every 3-4 days, goal TID schedule Initial goal of 1-2 tablets PO TID, but can go higher and varies per patient Carbi/Levo CR 50/200, 1 tablet PO, usually QHS for AM symptoms Gradual, based on response Varies per patient Carbi/Levo ODT As for carbi/levo, same dosing combinations As for carbi/levo As for carbi/levo Carbi/Levo/ Entacapone 12.5/50/200 PO QAM (I prefer over 18.75/75/200 and 25/100/200 at start) Increase by 1 tablet every 3-4 days, TID, then use 25/100/200 As for carbi/levo Trials: Duodopa
Treatment Stages of PD??? ~ 62 Birth Pre-clinical onset Clinical Onset Death Treat? Honeymoon Motor Fluctuations/Dyskinesias Failure Consider Medical Therapy Consider Surgery
Best Candidates for Surgical Therapies Diagnosis is clearly ipd Levodopa responsive Motor fluctuations present No cognitive or mood impairment Normal MRI
Wearing-off phenomenon develops with disease progression Obeso et. al
Deep Brain Stimulation Globus pallidus interna, subthalamic nucleus Reversible and programmable Less prone to side effects than ablation Most commonly used surgical approach to PD
DBS lead placement
Reduce dopamine breakdown (MAOB and COMT inhibitors) Dopamine Dopamine agonists
Martinez-Martin and O brien, Neurology 50 Supplement 6: S27-32, 1998
Catechol O-methyltransferase inhibitors Starting dose Escalation Maximum dose Entacapone 200 mg PO with each dose of carbi/levo Same as start 8 doses/day Tolcapone 100 mg PO TID Same as start 200 mg PO TID *Dopaminergic side effects similar to other PD drugs