Lecture 9: Parkinson's Disease Flashcards
What is Parkinson’s disease?
- a long-term degenerative disorder of the central nervous system
- Symptoms generally come on slowly, subtly, over time
- it is a progressive disease because it gets worse over time. Someone could have Parkinson’s for a decade or even two decades before they show symptoms
- Mainly affects the motor system; it affects other systems as well but the motor system one is the most noticeable
- Average life expectancy following diagnosis is between 7 and 14 years
- Currently no cure for PD
What is the epidemiology of PD?
- Typically, PD occurs in people over 60 years of age
- —> Prior to age of 50, considered young-onset PD
- Males are more often affected than females
What are the motor symptoms of PD?
Tremor (resting)
Rigidity
Akinesia (aka Bradykinesia)
Postural instability
What is the resting tremor symptom of PD?
- Slow velocity
- Asymmetrical; not same on both sides (one side is more affected)
- Tremors may affect chin, jaw, arms, legs
- “Pill-rolling”
- The most common presenting symptom; presenting means it makes the person present at the doctors office
- 30% of PD patients do not show tremor
What is the rigidity symptom of PD?
– Occurs in over 90% of patients
– Characterized by increased resistance (the “cogwheel” phenomenon)
– Increased muscle tone and contraction
– Present through the range of passive movements of a limb
E.g. flexion, extension, or rotation about a joint
– Can occur in neck, shoulders, hips, wrists, ankles
Proximally & distally
What is the akinesia (Bradykinesia) symptom of PD?
– The most characteristic clinical feature
Present in every single case of PD
– Slowness in performing activities of daily living
– Loss of spontaneous movements & gesturing
– Monotonic (speaking in one tone) and hypophonic (no pitches or changes in tone) dysarthria (speech)
– Loss of facial expressions (hypomimia) and decreased blinking
– Drooling
– Reduced arm swing while walking
What is the postural instability symptom of PD?
- Loss of postural reflexes
- Generally, manifestation of late stage PD
- Can lead to impaired balance and frequent falls
- Most common cause of falls
- —> Along with freezing of gait; stuck mid-step
- —> Contributes significantly to risk of hip fractures (hip fractures can be fatal)
What are the non-motor symptoms of PD?
1) Psychiatric Disturbances
Depression
Anxiety
Apathy
2) Autonomic Disturbances
Constipation
Sexual dysfunction
Orthostatic hypotension (drop in blood pressure when you stand)
3) Cognitive Impairment (late-stage of PD)
Executive function deficit
Dementia
Hallucinations
4) Sleep Disturbances
Insomnia/fractured sleep (constantly waking up)
Narcolepsy (stimulation overload leading to falling asleep out of nowhere)
REM behavior disorder (RBD) –acting out your dreams
What does the Basal Ganglia consist of?
-- Dorsal Striatum Caudate Putamen -- Globus Pallidus Externa, Gpe Interna, Gpi -- Substantia Nigra Pars compacta Pars reticula -- Subthalamic Nucleus
What does the Basal Ganglia do?
- Sets the overall “tone” or “motivation” for action; BG helps decide which one is the best option for movement. It receives information from all parts of the brain and then decides an action (ex. running away instead of hiding)
- BG communicates directly with the motor cortex (the output of the BG will either turn on or not turn on the motor cortex); it basically tells the motor cortex what to do
- BG is organized into loops; Speaks to different brain regions, integrates information
What are the different loops of the Basal Ganglia?
1) Cognitive Loop
- Turns on/off regions of frontal lobe
- Task switching
- Priority setting; frontal lobe needs to be engaged (decides what your priorities are; if an emergency happens this loop is responsible for switching your priorities/focus)
2) Visual/Oculomotor Loop
- Scanning environment
- Spatial recognition
3) Affective Loop
- Emotional component
- Desire, apathy, impulse
4) Motor Loop
- To move or not to move?
- Putamen, Globus Pallidus and Substantia Nigra
the first three loops helps the basal ganglia decide to activate the motor loop (to move or not to move)
What happens to the BG in PD patients?
Main pathological characteristics of PD are cell death in the BG, specifically in the Substantia Nigra
- Up to 70% of the dopamine (DA) secreting neurons in the SN are affected; this is at the point of presenting to the doctor/seeing symptoms
- Leads to DA depletion in the SN and the nigrostriatal (between substantia nigra and dorsal striatum) DA pathway
- Dysfunctional motor loop of the BG
What’s the role of dopamine in the BG?
- DA neurons in the SN form strong connections with the dorsal striatum, globus pallidus and the motor cortex
- —> These are excitatory connections
- —> Dorsal striatum (motor) has dense expression of (D1 and D2) dopamine receptors (D1 and D2 Medium Spiny Neurons)
- —> DA is main driver of motor cortex activation
What other NT are responsible for the non-motor symptoms of PD?
1) Noradrenergic Urinary frequency Erectile dysfunction 2) Serotonergic Sleep disturbances REM Behavioral disorder 3) Cholinergic Constipation
What are the progressive stages of PD?
Stage 1: Olfactory bulb, Dorsal motor nucleus
Stage 2: Locus coeruleus; autonomic function disturbances
Stage 3: Substantia nigra; motor symptoms, TRAP, clinical symptoms
Stage 4: Cortex; cognitive impairement behavioural/personality changes
