Parkinsons Disease

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Parkinsons Disease

• Jane McCagh

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Aims of this session

• To introduce Parkinsons disease (PD) -
  neuroanatomy, symptoms and treatment.
• To outline some of the cognitive deficits
  associated with PD, particularly focusing on
  attention deficits.
• To highlight similarities in the presenting
  deficits in PD and frontal lobe pathology.
• To highlight some of the difficulties in using
  neuropsychological testing in patients with PD.

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Parkinsons Disease

• Movement disorder - effects the CNS
• Derives its name from the English physician,
• James Parkinson who first reported the
  condition
• which he referred to as shaking palsy in
  (1817) .
• Also referred to as paralysis agitans
• (Latin translation).

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Parkinsons Disease is .
caused by a deficient neurotransmitter system,
most prominent in the dopaminergic nigrostriatal
pathways of the basal ganglia - which lead to
certain
pathological motor symptoms that that
progressively debilitate freedom of movement.
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Neuroanatomy

• There is a reduction of neurons that make
  dopamine (DA) within the substantia nigra. The
  axons of these neurons normally release DA where
  they synapse in parts of the basal ganglia called
  the caudate nucleus and putamen or collectively
  the corpus striatam.
• The corpus striatum is responsible for producing
  smooth purposeful movement.
• DA usually works as an inhibitory NT in the
  corpus striatum where it acts on cholinergic
  neurons.
• Recently - the subthalamic nucleus has been
  implicated in PD.

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Different Types

• Ideopathic Parkinsons disease - cause is not
  known and the condition takes a long time to
  develop- degenerative.
• Parkinsonism - develop similar symptoms to PD -
  can develop immediately - non degenerative e.g
• - Drug induced e.g MPTP - synthetic heroin
• - Toxin induced - brought on by high
  concentrations or
• some medications/toxic substances e.g.
  tranquillisers,
• carbonmonoxide, manganese.
• - Postencephalitic- caused by viral
  infections ( Oliver
• Sacks (1973)-Awakenings).
• - Post-traumatic - after severe head injury
  or frequent head
• trauma e.g boxing.

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Facts

• IPD affects 1 of the population over 65.
• Incidence of PD increases with age, though some
  people get early onset PD.
• Usually clinical deficits become apparent when
  between 60-80 of nigrostriatal neurons die.

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Main Signs Symptoms

• Physical
• tremor
• rigidity
• akinesia
• posture balance are disturbed - stooped gait
• mask like facial appearance

• Psychological
• confusion
• (caused by medication)
• depression, anxiety dementia (very common)
• cognitive impairment

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Parkinsons Disease Parkinsonism

• Positive symptoms
• Muscular rigidity - resistance to passive
  movement, muscles in constant contraction
• Tremor - occurs when hand or foot at rest,
  regular and rhythmic. Pronounced during
  inactivity and suppressed during voluntary
  movement and sleep.

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Negative symptoms

• Akinesia - principle motor symptom. A collective
• noun for the following symptoms
• 1. Bradykinesia - slowness of movement
• 2. Hypokinesia - poverty of movement (voluntary
  automatic).
• 3. Inability/delay in initiating and continuing
  movement.

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Motor functions

• Motor functions - 2 groups
• Axial motor functions- related to the axis of the
  body. Important for posture, postural adaption
  and locomotion. Involve processes to maintain
  certain positions and to axially related
  movements required to shift from one position to
  another- global postural change, e.g. walking,
  rising from a chair, turning in bed.
• Distal motor functions - motor behaviour
  performed with the limbs (e.g. perceptuo-motor
  skills) .
• Axial motor functions form a basis for distal
  motor functions.

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Movement impairment in PD, taken from Riddoch
Humphries (1994).
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Treatment - Drug Therapy

• Levodopa is the most effective treatment to date.
  L-Dopa is
• the chemical from which dopamine is synthesised
  and it
• passes through the blood brain barrier.
• L-Dopa is effective in
• reducing tremor and rigidity.
• reducing the effects of akinesia in distal
  movement (e.g. movement of the limbs).
• BUT - difficulties in the in executing global
  postural changes remain, Lakke et al (1980).
  These are essential to everyday life.

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Difficulties

• Not everyone will improve with L-Dopa
• Produces side effects dyskinesias -
  uncontrolled involuntary movements as a
  consequence of supersensitivity of striatal DA
  receptors.
• Can stop working suddenly or produce an on-off
  syndrome - fluctuations in response.

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Neurotransmitters

• Other NT have been implicated such as
• acetylcholine (loss of DA production effects
  balance of this acetylcholine and DA in the
  brain)
• glutamate
• serotonin

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Surgery - 3 types

• 1.Ablative or Destructive Surgery
• 2. Stimulation Surgery or Deep Brain Stimulation
  (DBS)
• 3.Transplantation or Restorative Surgery -
  foetal transplantation.

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1. Ablative or Destructive Surgery

• Refers to locating, targeting then ablating or
  destroying a specific, clearly defined brain
  area or region.
• This is an area thats been altered or changed by
  PD which produces an abnormal chemical or
  electrical discharge. The discharge in turn
  produces an abnormal signal or "static." which
  interrupts the normal, harmonious operation of
  the brain.

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• Destruction of the abnormal discharging brain
  region lessens or negates the static.
• This allows restoration of more normal or
  closer to normal function. e.g. Stereotactic
  pallidotomy - targets the globus pallidus or
  thalamus (notes).

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2. DBS 3. Transplantation

• 2. Deep brain stimulation - electrode is placed
• within the brain to block or inhibit abnormal or
  
• discharging brain region.
• 3. Transplantation or Restorative Surgery -
• implants of foetal tissue containing aminergic
• cells may grow on implantation into the brain to
• innovate the basal ganglia - problems -
  overgrowth
• and ethical issues.

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Cognitive deficits (notes)

• 20-30 of PD have significant cognitive
  impairments,
• these include
• Visuo-spatial impairments
• Verbal fluency
• Memory
• Planning sequencing
• Temporal ordering
• Recency discrimination
• Attention (e.g set shifting)

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Attention PD
Naville (1922) first described a slowness
in thought of PD pts which was termed
bradyphrenia, it is characterized by decreased
voluntary attention, spontaneous interest,
initiative and reduced capacity for work, with
fatigability and a slight decrease in memory
function. Brown Marsden (1990) present two
related models to explain the attention deficits
seen in PD.
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Brown Marsdens (1990) models
1. Psychological model - depleted processing
resources is suggested to be a possible
mechanism. This uses information that we already
know from attention models to explain the
deficits in PD. 2. Neurobiological model -
integrates information to provide a model for the
neuroanatomical and neurochemical substrate that
may be underlying the behavioural deficits.
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Psychological Model

• Performance can suffer when we try to do many
  things at once- reflecting excessive demand on
  some limited psychological resource/capacity.
• Yet sometimes we can effectively do more than one
  thing at a time.

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Schnieder Schriffin (1977)

• Capacity model.
• Controlled processing - dealing with new
  information. Need lots of attention resources
  when acquiring or learning a new skill or
  something unfamiliar.
• e.g learning to drive
• available to conscious control.
• serial processing, i.e. one thing at a time.

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• Automatic processing little demand on attention/
  resources when using learned and practised
  skills, that are familiar.
• e.g. driving to an experienced driver.
• not accessible to conscious control.
• parallel processing - more than one thing at a
  time.
• Two pathways activated at same time and
  competing for attention resources.

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Norman Shallice (1986)

• In a similar model Norman Shallice describe a
• model to account for control of action with three
• levels of functioning
• fully automatic processing (controlled by
  schemas-organised plans).
• partially automatic - involves contention
  scheduling - without deliberate direction or
  conscious control.
• deliberate control - by a supervisory attention
  system.

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Contention Scheduling.

• Simple rules as to relative importance are built
  into the system to prioritise on going activities
  which may come into conflict.
• This determines which schema should be in
  operation at a particular time given a particular
  trigger. CS is used to resolve conflicts amongst
  schemas.
• e.g. driving and talking when a cyclist wobbles
  in front - usually stop talking) - partial
  conscious awareness. (notes)

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Supervisory Attention System

• The SAS enables appropriate responses in 5 types
  of
• situation
• planning decision-making.
• error correction or trouble shooting.
• in novel or poorly learned tasks
• dangerous or difficult situations.
• or where some habitual response has to be
  overcome (as may occur in switching sets)
• The SAS may well be located in the frontal lobes.

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Empirical Tests.

• Planning Tower of London, Six Elements Test and
  Multiple Errands Task.
• Error correction WCST.
• Novelty tests of conditional or associative
  learning.
• Danger no lab based tests but see Jim Reasons
  slips of action stuff.
• Over-coming habit Stroop, Hayling Sentence
  Completion task.

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Brown Marsden

• Reviewed the cognitive impairments in PD and
  found a pattern
• PD pts were poor at tasks that required
• cognitive effort (controlled tasks) and
• internal control - self directed task that
  require specific planning.
• e.g. in WCST (notes)

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Similar to Frontal Lobe pathology?

• Many similarities in the cognitive deficits in PD
  and pts with FL lesions.
• Norman Shallice have suggested that in FL pts
  the SAS may be impaired. Due to the many
  similarities in PD pts SAS damage has also been
  implicated.
• Brown Marsden argue that this FL definition of
  the deficits observed in PD is too broad. They
  narrow this down to an impairment in
  set-shifting.

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• Brown Marsden argue that PD pts are only
  impaired in switching set where they had to rely
  on internal cues and strategies for performing a
  task but that performance would be normal where
  external cues were provided.
• Tested this in an experiment using a version of
  the Stroop Test.

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Findings

• Found that PD were only impaired in a condition
  without external cues.
• The impairment was greatest in the first trial
  when they had to switch from processing one
  attribute of the stimulus to the other.
• The switching deficit was only present when
  internal cues or strategies were required.
  Suggesting that PD pts have impaired controlled
  processes.

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Attention - theory (visual)
Posner (1980) argues that is possible to
separate the overt motor shifts in visual
attention from the non motor covert shifts in
visual attention. A shift in spatial attention
involves three stages 1. Disengagement - from
the original location 2. Movement of covert
orientation from the original spatial
co-ordinates to the new focus. 3. Engagement with
the new target
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Wright, Burns, Geffen Geffen (1990) found
that PD patients tend to disengage too
readily, which could lead to poor maintenance of
attention. Posner et al (1984) found that
parietal patients too have difficulty in the
disengage function. Is parietal DA depletion
instrumental in spatial attention impairments in
PD patients??
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Frontal Caudate Loop Theory

• Based on pathological neurochemical changes
  found in the brains of PD pts.
• This theory suggest that while DA depletion in
  the putamen is primarily implicated in the motor
  symptoms (especially akinesia).
• Caudate depletion of DA is implicated in the
  cognitive impairments of PD.

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Testing - problems

• PD have impaired performance on cognitive tests
• for many reasons other than specific cognitive
• impairment.
• Natural age related decline
• Impaired motor speed and manual dexterity
• Mental and physical fatigability
• Psychiatric disturbance, particularly depression
• Distraction by pain and dyskinesia
• Sedation, confusion, hallucinations and other
  drug side effects.

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Depression

• Depression is very common in PD - possibly due to
  involvement of neurotransmitters. Neurochemical
  imbalances (amines).
• Need to look at tasks to control for depression-
  these can confound the results as pts will be
  slower if depressed.

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Dementia

• 15-20 of PD pts will have dementia as opposed
• to 5-10 in the normal population of the same
  age.
• DSMIII (US Psychiatric Assoc) to be diagnosed
• loss of intellectual abilities of sufficient
  severity
• to interfere social or occupational functioning
• Yet though the criteria is essential this is
  difficult to
• assess in PD as the progressive incapacitating
  motor
• impairment itself interferes with these aspects
  of life.

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Treatment considerations

• Consideration of current and prior treatment is
  of considerable importance in evaluating studies
  of cognitive function in PD.
• Medication
• L-Dopa some pts hallucinate, can cause
  confusion, delusions and depression Parks
  (1981)
• Anticholinergics lead to memory impairment.

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Surgery

• Recovery of function issues in ablative surgery.
  
• e.g impairment of language function being more
  common following left thalamic lesions and visuo-
  spatial deficits after right sided lesions.

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Motor impairment

• Need to try and tap into the cognitive
  impairments that do not require motor function
  e.g. having to speak still involves motor
  function. (IQ - notes)
• e.g Administer two identical task with similar
  motor involvement but differing in the level of
  cognitive processing required - in order to
  illustrate that overall response slowing is
  greater than expected from motor slowing alone -
  thus slowing with increased cognitive complexity
  above and beyond that shown by a control group.

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Recommended Reading

• Read any journals that specifically address
  deficits in attention in PD, particularly
• contemporary articles. Here are a few key
  articles that will give you some foundation
• for your literature review

Brown, R.G. Marsden, C.D. (1988) Internal
versus external cues and the control of attention
in Parkinsons disease. Brain, 111
323-345. Brown, R.G. Marsden, C.D. (1990)
Cognitive function in Parkinsons disease from
description to theory. TINS 13 1,
21-29. Lees, A.J. Smith, E. (1983) Cognitive
deficits in the early stages of Parkinsons
disease. Brain, 106 257-70. Owen, A.M.,
Roberts, A.C., Hodges, J.R., Robbins, T.W. (1993)
Contrasting mechanisms of impaired
attentional set-shifting in patients with frontal
lobe damage or Parkinsons disease. Brain,
116 1159-1175. Todd, S., Bub, D.N., Hunter,
M.A. (2002) Task switching deficits associated
with Parkinsons disease reflect depleted
attentional resources. Neuropsychologica, 40
1948-1955.