Movement Disorders
in the Elderly
Herbert Sier MD, FACP, AGSF
Clinical Professor of Medicine
UCI School of Medicine
Movement Disorders
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Result of dysfunction of the basal ganglia or the extrapyramidal
motor system: includes the subsantia nigra, striatum ( caudate
and putamen), globus pallidus, subthalamic nucleus and thalamus
 not weakness or sensory deficits
Classified as:
 Hyperkinesias: (excessive movement)
 Tremor, Tic, Chorea, Dystonia, Myoclonus, Akathesias
 Hypokinesias ( paucity of movement): PD
A particular movement disorder may be characterized by several
types of involuntary movements
Parkinson’s Demographic Info
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1.5 Million people in USA
Affects 1/100 over age of 60 yrs
Mean age at diagnosis is 70.5 yrs
5 to 10% of all persons with PD are diagnosed
prior to age 40
Affects men and women in equal numbers
Some studies: African American and Asians are
less likely than Caucasians to develop PD
Causes of PD
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Loss of dopamine producing neurons in substantia
nigra results in difficulty with movement
Free radicals: contribute to an oxygenation process in
brain that damages neurons
Toxins: such as pesticides; Viral infections
Genetic factors: majority of cases do not have a clear
genetic link, while several genes are known to cause
specific forms of Parkinsons
Accelerated aging in some fashion: mitochondrial
dysfunction
Diagnosis: PD
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Chronic progressive neurodegenerative disorder
Cardinal signs for diagnosis:
Rest tremor: pill rolling
 Rigidity
 Bradykinesia
 Gait disturbance, Postural instability
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Essential Tremor
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Present when the limbs are in active use
Common in the arms, head and/or voice; may
also include the chin, tongue, and legs
Amplitude varies: tremor sometimes mild or
absent, other times severe
May interfere with activities of daily living
Family hx is common, tremor improved with
alcohol
Intention tremor: action tremor increases
toward end of action: cerebellum disorders, MS
Treatment of Essential Tremor
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Initial therapy includes BB or primodone
Second line drugs include gabapentin,
topiramate, mirtazipine, benzodiazepenes
Response is variable and tremor is rarely reduced
to asymptomatic levels
Severe, medically refractory tremor may be
treated with deep brain stimulation
Other Symptoms of PD
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Non motor
Musculoskeletal:
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Micrograhpia, dystonia, shuffling gait, freezing, festination
Motor
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Hypomimia: masked facies
Decreased blink rate
Speech impairment: dysarthria, hypohponia
Dysphagia
Sialorrhea
Vision: gaze problems
Differential Dx: PD
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Dementia with Lewy Bodies
Atypical Parkinsonism ( Parkinson Plus)
 Multisystem Atrophy: Shy Drager, Striatoniagral
degeneration, Olivopontocerebellar atrophy. MSA
characterized by rigidity, bradykinesia, balance issues,
autonomic dysfunction, pseudobulbar palsy, gait ataxia
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Progressive Supranuclear Palsy: difficulty moving eyes
especially looking up, marked trunk as opposed to limb
rigidity. Experience balance problems, difficulty swallowing,
confusion, or inappropriate behavior
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Corticobasal Degneration: bradykinesia, rigidity, postural
instability, language problems, myoclonus-dystonias, alien
limb
Differential Dx: PD
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Secondary:
 Drug Induced Parkinsons: antipsychotics,
metaclopramide, ssri’s, amiodarone
 Head trauma: boxing
 Toxins: MPTP, organic solvents
 Metabolic, Neoplastic: Wilson’s disease
 Infections: HIV/AIDS, neurosyphilis
 Small vessel: lacunar infarctions= small strokes in
basal ganglia
Normal Pressure Hydrocephalus
Essential tremor, Intention tremor
Diagnostic Testing
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Careful neurologic exam
Blood tests: CBC, Comprehensive Chem Panel
Brain imaging: CT or MRI brain
Clinical Diagnosis
Features suggestive of Parkinsonism other than PD
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Falls at presentation and early in disease
Poor response to Levodopa
Symmetry at onset
Rapid progression, Lack of tremor, Dysautonomia
Gait Dysfunction
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One of the most disabling signs of PD
Slow gait initiation
 Stooped posture
 Small shuffling steps
 Difficulty with turns
 All create a potential for falls
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Gait freezing=inability to initiate gait
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Most pronounced in small spaces like doorways,
elevators, crowded spaces, etc.
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Spectrum of PD Symptomatology
Dementia
Depression and
Anxiety
Psychosis
Motor Symptoms
Autonomic
Dysfunction
Pain,
Fatigue,
Olafactory
Sleep
Dysfunction
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Non-motor Manifestations of PD
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Wide distribution of dopamine deficiency
Neurodegneration and LB in SN, noradrenergic neurons in locus
coeruleus, cholinergic neurons in nucleus basalis of Meynert, and
diffusely through cerebral cortex
Involvement of non-dopaminergic pathways
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Serotonin/Cholinergic/Noradrenergic
Impact of dopaminergic therapy
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Nonpharmacological Tx
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Education
Patient and family support
Physical and occupational therapy
Speech therapy
Nutrition is a key
Community services/resources
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Cognitive Dysfunction and Dementia
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Prevalence of dementia is as high as 41%
Lewy Body vs PD Dementia: depends on age of onset
Sxs: psychomotor retardation, altered personality,
executive dysfunction, visual spatial problems early.
Deficits in exec dysfxn occur early on in contrast to
AD, where features of aphasia and apraxia occur early.
Memory problems early on less prominent than AD.
Hallucinations, delusions, paranoia, depression, anxiety
are also found in PDD
Lewy bodies are seen under microscope, but also
amyloid plaques and tangles seen.
Lewy Body Dementia
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Cardinal feature: progressive cog decline that interferes with
social and occupational function. Usually motor sxs occur
before or within 1 year of PD symptoms, as opposed to late
onset PD
Supportive features:
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Core features:
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Falls, fainting, temporary loss of consciousness, delusions, depression,
REM sleep disorders
Cognitive fluctuations: thinking ,level of alertness
Visual hallucinations
PD sxs: stiffness, bradykinesia, gait problems, tremor less likely
Treatment:
- Rivastigmine ( pill or patch )
- Quetiapine or Clozaril if necessary
Mood disorders
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Psychoses: 20-40% of drug treated pts and visual
hallucinations are most common psychotic
symptom. All antiparkinson meds can induce
psychoses, in addition to the disease itself.
Delusions: usually paranoid: spousal infidelity,
stealing money
Psychoses is single greatest risk factor for NH
placement
Management of PD Psychosis
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Rule out symptomatic causes (infection) and
correct underlying problems
Review medications list--Simplify
Step-wise reduction of PD meds
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anitcholinergics, amantadine, maobi and comt
inhibitors, dopamine agonists
Consider cholinesterase inhibitor if patient is
cognitively impaired
Use Atypical Neuroleptics
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Antidepressants
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Atypical Neuroleptics
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Clozapine- “gold standard” 6.25-50mg
 Very effective (Neurology 2004; 62:381)
 CBC monitoring due to agranulocytosis
 Can reduce tremor, and cause weight gain,
sedation, OH, seizures
®
Quetiapine (Seroquel ) 6.25->200mg
 sedating, weight gain (Fernandez 2003)
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Olanzapine (Zyprexa ), Risperidone (Risperal ),
Aripiprazole
 Can worsen PD symptoms (Neurology 2009; 72:
s 1-136)
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Mood Disorders
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Depression: most common psychiatric
disturbance in PD. Up to 50% have depressive
symptoms. Rates of clinically significant
depression is 10-20%
Anxiety: 29-38%; panic disorder and generalized
anxiety disorder seem to be most common
Treatment for PD Depression
1. Correct diagnosis
2. Psychotherapy/Counseling
3. Medical management
 Dopamine agonists (Pramipexole)
 Anti-depressants: SSRIs most
commonly used
 Mirtazapine or Trazodone
 Electroconvulsive therapy for severe
depression not helped by meds
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Treatment of Anxiety/Apathy
Anxiety
 Adjust PD meds to minimize off periods
 SSRIs
 Short acting benzodiazepines:
Alprazolam: 0.5 to 1 mg tid prn
 Lorazepam: 0.5 to 2 mg prn
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Apathy
- Stimulants: Methylphenidate or Modafinil
Sleep Disorders
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Prevalence: 74-98% have sleep disorders
Sleep disorders:
 Night dreams: reduce dop qhs, ? antipsychotic
 Insomnia: trouble falling-staying asleep, frequent awakenings:
rx behavioral means, possible melatonin, rx pain if interfering
with sleep, consider sleep study
 Restless leg syndrome: rx dop med
 Periodic limb movement of sleep: rx dop med
 REM sleep behavior disorder: rx clonazepam
 Excessive daytime somnolence: rx ? modafinil
Rx: Autonomic Dysfxn in PD
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Orthostatic hypotension
Behavioral: elevating head of bed, compression
stockings, increasing salt and fluid consumption
 Fludrocortisone
 Midodrine
 Droxidopa
 Domperidone
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Rx Autonomic Dysfunction
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Nocturia/urinary incontinence
 Rule out urinary infection and other causes
 Consider urologic evaluation
 Meds for Detrusor Hyperactivity
Constipation
 Bowel regimen, dietary changes, exercise
Hypersalivation
 Glycopyrrolate
 Botulinum toxin
Hyperhydrosis
 Very refractory to treatment
 Adjustment of dopaminergic meds ( on/off issues)
 Botulinum toxin for focal hyperhydrosis
Pharmacologic Treatment
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Neuroprotective: none definitively shown
MAOB inhibitors: Rasagline: can block free radical
formation
 Dopamine agonists: neuroprotective in lab because
they act as antioxidants and free radical scavengers
 Coenzyme Q10: stimulated by evidence that
mitochondrial dysfunction may paly a role in
pathogenesis of PD
 NMDA antagonists: antiexcitatory
 Gene therapy: prevent protein accum/aggregation
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Symptomatic Therapy
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Effect of disease on dominant hand
Degree to which disease interferes with functional
activities, work, ADLs, or social or leisure activities
Presence of significant bradykinesia or gait disturbance
Major drugs:
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Levodopa
MAOB inhibitors
Dopamine agonists
Comt inhibitors
Anticholinergic Agents
Amantadine
Levodopa
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In elderly: often first line agent
Usually combined with a peripheral decarboxylase
inhibitor carbidopa to block its conversion to dopamine
peripherally in order to prevent nausea, vomiting and
orthostasis.
Immediate vs Controlled release
Adverse: nausea, somnolence, dizziness, headache, OH
Associated with higher risk of dyskinesias than direct
dopamine agents
Complications Long-term Levodopa Tx
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Decreased response to Tx
Less “on” time
Unpredictable motor fluctuations
Drug induced dyskinesias, hallucinations
Motor complications: related to
nonphysiologic pulsatile stimulation of
dopamine receptors
Does not treat nondopaminergic sxs
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Dopamine Agonists
Ropinorole, Pramipexole,
Rotigotine patch, Apomorphine
Advantages
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Effective monotherapy early on
Levodopa-sparing effect as
adjuncts to levodopa later on
Reduced incidence of levodoparelated adverse events
Potential neuroprotective effect
Often initial agent in those less
than 65
Ineffective in those who show
no response to levodopa
Disadvantages
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Less potent
Long titration schedule
More prone to induce cognitive side
effects
More prone to cause somnolence
Do not eliminate need for
Levodopa eventually
Not Rx non dopaminergic sxs
N/V/OH/legedema/hallucinations
/confusion
Somnolence, ICD
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MAOB Inhibitors
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Modestly effective as sx treatment in early disease, may
be used as adjunct to levodopa (may increase on time
while reducing motor fluctations)
Value for neuroprotection is unclear
Adverse: nausea, headache; confusion, OH, dyskinesias,
insomnia; need to be careful with SSRI antidepressants.
Usually does not cause a hypertensive crisis when eating
tyramine rich foods
Agent: Rasagiline
COMT Inhibitors
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Mechanism: inhibit catechol-o-methyl transferase and
degredation of dopamine, and prolongs activity of
dopamine in the brain
Useful in treating motor fluctuations, wearing off.
Only effective when used with levodopa
Adverse: due to increased dopaminergic stimulation
and include dyskinesia, hallucinations, confusion,
nausea and OH
Agent: Etacapone
Anticholinergics
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Most helpful with tremor
Problems in elderly due to anticholinergic side
effects:
Constipation
 Confusion
 Hallucinations
 Urinary retention
 Dry mouth
 Tachycardia
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Amantadine
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Antiviral agent initially used for influenza
Mech of action: uncertain
Known to increase dopamine release, inhibit dopamine
reuptake, stimulate dopamine receptors, and may exert
anticholinergic effects
Relatively weak AntiPark drug, but may be useful in
early or mild PD and perhaps later if dyskinesia
becomes problematic
Adverse: livedo reticularis, ankle edema, confusion,
halluincations, nightmares
Motor Fluctuations
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50% of patients on levodopa for 5 years
experience MF and dyskinesias
As disease progresses, effect of levodopa tends
to wear off earlier after doses.
MF: are alterations between periods of being on,
which there is a good response to med, and
being off during which the patient has increased
PD symptoms
Wearing Off
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Management
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Increasing dose of levodopa: issue dyskinesias
Shortening interval between doses and decreasing dose at
each administration
Long acting Sinemet CR may be useful in early stages of
wearing off phenomenon, but then does not work, so not
great plan
Addition of dopaminergic agonist and decrease of levodopa
dose
Addition of COMT inhibitor, often need to reduce dose of
levodopa
MAOB inhibitor: Rasagiline may be added
Failure of On Response
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Management
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May be due to delayed gastric emptying, which results in
inadequate plasma concentration of drug due to narrow
therapeutic window
Avoid taking Levodopa with high protein meals
Take 30 minutes before eating
In future:
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Different preparation of levodopa, such as gel infusion via g tube
Dyskinesias
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Variety of involuntary movements, occur as a
direct effect of levodopa.
Occur in up to 30-40% after 5 yrs of Levodopa
and nearly 60% by 10 years
Usually choreiform: continuous, restless
appearing movements of extremities, head, face,
trunk, and respiratory muscles. But can also take
form of large amplitude ballistic movements that
interfere with function
Dyskinesias
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Peak dose dyskinesias most common
Management: for dyskinesias or dystonias
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Lowering dose of Levodopa
Reducing dose of adjunctive drugs with Levodopa such as
MAOB inhibitors, COMT inhibitors
In more advanced patients may need to greatly reduce dose
of Levodopa and go up on Dopamine agonists
Amantadine may be useful in advance PD with dyskinesias
For early morning dystonias: bedtime dose of sustained
release levodopa/carbidopa or long acting dopamine agonist.
Surgical Treatment for PD
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Used when MFs, tremors or dyskinesias are
severe and meds no longer working, or unable
to tolerate side effects of Anti PD meds
Generally done on younger patients
PDD is a contraindication to surgery
Rationale for surgery:
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Striato nigral degeneration and dopamine deficiency
leads to excessive Subthalamic Nucleus excitation of
the Globus Pallidus, and excessive GP inhibition of
the Thalamus. This causes symptoms of rigidity and
akinesia
Surgical Treatment: PD
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Pallidotomy: ablates GP and reverses the excess pallidal
inhibitory effect: non reversible surgery
Deep brain stimulation: preferred method now, it suppresses GP
inhibition: generally not done in frail elderly
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Decreases dyskinesias and MFs
Studies have shown effect good for at least 5 yrs after initiated
Surgical complications:
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Death: 0.6%
Permanent neurologic sequelae: 2.8%
Hemorrhage: 3.1%
Infection: 4%
Confusion: 3.1%, especially in postoperative period
Depression
CSF leak: 0.6%
Hardware malfunction: 2.5 – 5%
Tics
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Repetitive stereotyped purposeless brief actions, gestures,
sounds, and words that emerge suddenly from a background of
normal motor activity
Simple: blinking, facial grimacing, neck movements throat
clearing, grunting: generally quick and short lived
Complex: sequenced, stereotyped acts: tapping or touching,
obscene gesturing, Tourettes in young
Rx: - focal tics blinking: botulin toxin injections
Centrally acting alpha agonists such as clonidine first line drug;
clonazepam may be helpful
- meds that block dopamine transmission: tetrabenazine and
reserpine, neuroleptic drugs ( but significant side effects )
Dystonias
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Torsional , twisting movement that is slightly sustained
at peak of contraction and may cause twisted postures
Involves the basal ganglia
Path: idiopathic, infectious, ischemic, hypoxic, drug
induced, metabolic, genetic, or degenerative, PD,
Wilson’s Disease
Focal: spasmodic torticollis, craniofacial, eyelids or
hands: responds to botulin toxin
Anticholinergic and baclofen: improvement limited
Chorea
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Flowing, continuous, random movement that flits
from one part of the body to another; arises from
dysfunction of striatum
Cause: linked to basal ganglia: Huntington’s disease,
drugs, stroke, age ( senile chorea ), PD, post
infectious, autoimmune, hemiballism
Rx: dopamine depleter or dopamine D2 receptor
blockers
 Tetrabenazine: FDA approved for HD;
associated depression, parkinsonism, QT prolong
 Typical or atypical antipsychotics ( OL )
associated with tard dyskinesia, parkinsonism,
metabolic syndrome
Myoclonus
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Single, rapid, shocklike muscle jerk
Causes: postanoxic, neurologic diseases such as
Cretuzfeldt-Jakob, Alzheimers, paraneoplastic,
metabolic ( uremic or hepatic encephalopathy
Physiologic: sleep states nocturnal myoclonus, hiccups
Focal restricted to body part: from tumor or stroke
Generalized: disease involving cerebral cortex diffusely:
hypoxia or encephalitis
Rx: anticonvulsant agents with antimyocloinc activity:
valproic acid, clonazepam, levetiracetam
Akatheisa
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Inner restlessness coupled with repetitive
movements
Cause:
Parkinsonism
 Drug induced tardive dyskinesias
 Restless leg syndrome
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Drug Induced MD
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Antipsychotics can cause acute dystonia; treat severe
cases with IV diphenhydramine or lorazepam
Chronic reversible movement disorders can occur with:
 Lithium, theophylline, valproic acid, antiemetics,
antipsychotics, estrogen, antiepileptics, dopamine
replacement therapy in PD
Chronic non reversible: usually antipsychotic: tardive
dyskinesia, dystonia, myoclonus, tics, akathesia
Tardive Movement Phenomena
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Chronic and irreversible; older age and duration of
antipsychotic treatment are risk factors
May begin weeks or months after initiation of drug;
outcome improved if offending drug can be stopped
Rx: reduce or eliminate med causing the problem
Rx includes trihexyphenidyl, baclofen (ol),
tetrabenazine (ol) or clozapine (ol)
Botulin toxin (ol) injections are an option for severe
cases of dystonia (neck jerking or sustained eye
closure)