Parkinson’s Flashcards
Parkinson’s disease
- Prevalence
- Primary motor symptoms (4)
- Non-motor symptoms (4)
- Degeneration of dopamine neurons in substantia nigra causing motor symptoms
- Second most prevalent after Alzheimer’s, affects 1% of pop over age 55
- Resting tremor, rigidity, akinesia/bradykinesia, postural instability (2 must be present in PD)
- Dysautonomia (disorder of autonomic nervous system), psychiatric disorders, sleep disturbances, cognitive impairments
Cause of parkinson’s? (2)
- Caused by genetic (PARK chromosomal regions) and environmental factors, but many cases happen spontaneously
- Braak’s hypothesis (dual-hit hypothesis): Unknown pathogen enters body via nose or gut and comes into contact w/ olfactory and entery neurons, triggering aggregation of alpha-Synuclein (forming Lewy bodies and neutrites). Misfolding spreads via cell-to-cell contact to brain via olfactory tract and vagus nerve, leading to brain neuron degeneration
Basal ganglia:
- Nuclei (6)
- Dorsal striatum, ventral striatum
- Role
- Caudate, lentiform nucleus (putamen, ext globus pallidus, int globus pallidus), substantia nigra, subthalamic nucleus, nucleus accumbens, olfactory tubercle, ventral pallidum
- Dorsal striatum: Caudate and putamen, Ventral striatum: Nucleus accumbens and olfactory tubercle
- Regulates motor cortex to facilitate smooth voluntary movement; NA, OT, VP are important for reward learning
Nigrostriatal pathway
- Origin + termination, what happens w/ neurons in parkinson’s
- Direct vs Indirect pathway
- What happens in each path w/ parkinson’s
- Originates in substantia nigra (pars compacta) in midbrain, terminates in dorsal striatum; Dopamine neurons degenerate
- Direct: Motor cortex (glutamate) + pars compacta/SNc (excitatory dopamine), striatum, globus palladus interna (GPi), thalamus, motor cortex, motor activity increased
- Indirect: Motor cortex + SNc (inhibitory glutamate), striatum, globus palladus externa (GPe), subthalamic nucleus (STN), GPi + pars reticulata (SNr), thalamus, motor cortex, inhibit motor activity
- Degen of DA neurons sends less input to striatum, preventing inhibition of GPi -> inhibits thalamus; indirect pathway becomes dominant
Parkinson’s treatments:
- Levdopa/Carbidopa
- Agonists
- MOA-B And COMT inhibitors
- Deep brain stimulation (DBS)
- Levdopa is DA precursor that can cross blood-brain barrier and increase DA production in surviving neurons
- Carbidopa taken at same time to be taken up by DOPA decarboxylase (enzyme) instead
- Alleviates rigidity and akinesia but can cause on-off fluctuations of symptoms
- Can cause dyskinesia (excessive uncontrolled movements) and hallucination/delusion side effect
—— - Mimic DA by binding to dopamine receptors
- Can cause impulse control problem and hallucination/delusion side effect
—— - Block breakdown of dopamine
- Can be used w/ levdopa/carbidopa to reduce on-off effect
—— - For patients w/ dyskinesia and motor symptoms not working w/ medication; lessens symtoms of stiffening, slowness, tremor
- Electrodes implanted into subthalamic nucleus (STN) and globus pallidus interna (GPi) to make indirect path less dominant
- Worsens cognition like verbal fluency, esp w/ STN DBS + can cause intracranial bleeding w/ surgery
Mild cognitive impairment (MCI) in parkinson’s disease
Cognitive decline that’s greater than would be expected w/ normal aging, but does not significantly interfere w/ an individual’s ability to perform daily activities
Cognitive domains typically impaired in parkinson’s disease:
- Attention
- Executive functions
- Visuospatial skills
Attention: Ability to focus awareness in relevant stim and shift awareness when needed
- Cortical thinning in superior frontal gyrus, frontal eye field, superior parietal lobule (Last 2 interact w/ dorsal attention network involved in orienting attention to relevant stim)
- More cortical thinning w/ progression, leading to greater decline
Executive functions: Set of higher-order abilities necessary for goal-directed behav
- Caudate and fronti-parietal network (FPN) (dorsolateral prefrontal cortex and inferior parietal cortex) impacted bcuz of degeneration of nigrostriatal pathway
Visuospatial skills: Processes that enable us to understand where objects are in space and the spatial relations between objects
- Impaired mental rotation, difficulty judging distances, colour vision changes, impaired facial + emotional recognition
- Hallucinations can occur after 20 years of disease
- Cortical thinning of occipital, parietal and temporal regiobs
Dual-syndrome hypothesis
(Parkinson’s disease)
Two patterns of cognitive impairment:
- Fronto-striatal dysexecutive syndrome (impairment in executive functions due to dopaminergic path disruption) not progressing to dementia
- Dementia syndrome characterized by cholinergically-mediated memory and visuospatial deficits assoc w/ dysfunction in temporal lobe and posterior cortical regions
How to tell difference between dementia and Parkinson’s disease dementia
Both start w/ same Lewy body process so use the 1 year rule!
- Dementia develops at same time or 1 year before parkinson’s motor symptoms = Dementia w/ Lewy bodies
- Dementia develops 1+ years after onset of motor symptoms = Parkinson’s disease dementia
Cognitive states influencing dopamine-driven aberrant learning in Parkinson’s (Cavanagh et al., 2017)
- Goal (Cost of conflict vs Value of volition)
- Recently diagnosed OFF patients
- Difficult instructed choices
- Goal: Test influence of high level cog states (cost of conflict vs value of volition); OFF dopaminergic medication patients would have enhanced cost of conflict and decreased value of volition
— - Effect found in OFF patients who were recently diagnosed
- Recently diagnosed patients esp had trouble w/ value of volition task where they did difficult instructed choices when on medication (Showed that this relies more on indirect pathway)
Cholinergic basal forebrain atrophy predicts cognitive decline in Parkinson’s (Ray et al., 2018)
- Results in patients w/ smaller nucleus basalis of Meynert
- Patients w/ smaller than expected nucleus basalis of Meynert (NMB) in the cholinergc basal forebran (cBF) volumes had:
1) Greater change in global cognitive but not motor scores after 2 years
2) Greater risk of being mildly cognitively impaired
3) Showed more severe and rapid cognitive decline in memory and semantic fluency but not executive function
