Neuropsychiatry of Parkinson's Disease Flashcards by Abdullah alnafea

What percentage of patients with PD exhibit psychiatric symptoms?

70%

(risk increase the longer you have had PD)

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What transmission is affected by neuronal degeneration in PD?

▪️ Catecholaminergic (dopamine and noradrenaline)
▪️ Cholinergic (acetylcholine)

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What are Lewy bodies?

Intracellular inclusion bodies of abnormal alpha-synuclein

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What pathological changes may precede movement disorder and dopamine dysfunction in prodromal PD?

▪️ Neurodegeneration in noradrenergic, serotonergic, and cholinergic nuclei
▪️ Causing extensive frontal and posterior cortical compromise

(up to 10 years before?)

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What is most commonly associated with psychosis in PD?

Medications such as dopamine agonists and levodopa)
▪️ Associated with starting DRT and improved with dose reduction

Rarely seen in absence of medications

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What is the most common manifestation of PD psychosis?

Visual hallucinations (8-40%)
▪️ Typically complex, and when alert/eyes open
▪️ More common at night
▪️ Predominance of human or animal forms, sometimes emotionally significant

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What delusions are most commonly seen in PD psychosis?

▪️ Spouse infidelity (Othello syndrome)
▪️ Persecution
▪️ Theft
▪️ Abandonment - linked to Othello?

(Can occur without hallucinations but rare)

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How much insight is usually seen in people with PD psychosis?

Usually do have insight and ‘know’ they are hallucinating (benign hallucinations)

~5% lack insight

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How should psychosis be viewed in PD?

As a spectrum instead of focusing on individual symptoms

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What might PD psychosis be a biomarker for?

▪️ PD stage
▪️ Disease distribution
▪️ Progression of disease

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What are some of the earlier symptoms of PD psychosis?

▪️ Passage and presence of hallucinations
▪️ Illusions
▪️ Formed hallucinations with preserved insight
▪️ Unidentified figures (executive dysfunction?)

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What are some of the later symptoms of PD psychosis?

▪️ Loss of insight
▪️ Delusions
▪️ Misidentification (associated with lower MMSE)
▪️ Auditory, tactile, and olfactory hallucinations

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How does prevalence of PD psychosis change during the duration of PD?

Often increases with longer duration of illness

(~60% by end of 10-12 year follow-ups)

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What are the main risk factors for psychosis in PD?

▪️ Thinning of retinal ganglion layer (in hallucinating PD)
▪️ Visual perception deficits
▪️ Executive dysfunction (inhibitions, verbal fluency)
▪️ Progressive deterioration in cognition
▪️ Presence of depression, RBD, and vivid dreams

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What is the association between cognition and risk of PD psychosis?

Bidirectional relationship:
▪️ Those with visual hallucinations at increased risk of dementia
▪️ Those with worse cognition at increased risk of psychosis

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How might changes in neuropathology explain the progression from minor visual hallucinations to fully formed multi-modality hallucinations in PD?

▪️ Braak progression of Lewy bodies from brainstem to the forebrain
▪️ Becomes multi-modal as spread through cortex (+ loss of insight and delusions)

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What role does antiparkinsons medications play in the development of PD psychosis?

Likely a modifier rather than a necessary feature as still see cases in unmedicated patients

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What are the main steps for managing PD psychosis?

Exclude causes of delirium
Withdraw antiparkinsonian medications
Keep L-dopa therapy at lowest dose possible to maintain motor function
Antipsychotics or cholinesterase inhibitors?
Other options (e.g., supportive treatment, ECT)
Pimavanserin

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Why should risperidone and olanzapine be avoided in PD psychosis?

Can cause significant motor deterioration

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What antipsychotic shows the most promise for the treatment of PD psychosis?

Clozapine - BUT use is limited to routine settings as must be monitored closely

What is use of antipsychotics for PD psychosis associated with?

Increased mortality

Why do clozapine and quetiapine show the best effectiveness for PD psychosis?

▪️ They are serotonin 2A and 2C receptor antagonists
▪️ Able to use them effectively at low doses with low occupancy of D2 receptors
▪️ Increased serotonin 2A receptor binding in ventral visual pathway associated with VH in PD

Why might pimavanserin be a promising medication for PD psychosis?

It is based on evidence for serotonergic activity so avoids dopaminergic activity that may worsen motor function

What have trials of pimavanserin in PD psychosis found?

▪️ ~74% improvement
▪️ Nearly 14% complete resolution
▪️ Reductions in positive symptoms for PD
▪️ Importantly, no worsening of motor symptoms

What is the evidence for the use of cholinesterase inhibitors for PD psychosis?

▪️ Limited - not yet specifically studied in PD ▪️ Rivastigmine may possibly be more useful for hallucinations than delusions but not much evidence

How might supportive treatment be used for PD psychosis?

▪️ In addition to pharmacological treatment ▪️ Develop coping mechanisms such as focusing on false object, looking away etc ▪️ Interacting with hallucinations can often help it to disappear

What percentage of PD patients experience anxiety and when is it most common?

▪️ Up to 40% ▪️ Especially in younger patients

What are the most common forms of anxiety in PD?

▪️ Panic disorder ▪️ GAD ▪️ Social phobia ▪️ Panic attacks with onset of "freezing"/"off" episodes

How does anxiety in PD interact with motor symptoms?

Often report worsening of tremor when anxious

How is anxiety thought to be related to dopamine dysfunction in PD?

▪️ Inverse relationship between anxiety in untreated PD and striatal DAT availability ▪️ Involvement of hypofunction of nigrostriatal dopaminergic system?

What percentage of people with PD present with depression and when?

▪️ Up to 50% ▪️ Can often precede movement disorder - predictor of future diagnosis?

How can medication for PD affect depression and mood?

▪️ Levodopa and dopamine agonists can cause mood changes ranging from euphoria to mania ▪️ Sometimes see hypomanic symptoms during times of peak dose ▪️ Can fluctuate alongside motor fluctuations

What approaches to psychotherapy may be considered for PD patients with anxiety and/or depression?

▪️ CBT - helpful in reducing both ▪️ Metacognitive therapy - helpful in reducing distress

What is the main problem with CBT for anxiety and depression in PD?

There is a limit on the ability to reality-test negative beliefs E.g., 'there is no cure for this disease'

What is the theoretical basis of metacognitive therapy?

Psychological distress results from perseverative cognitive processes (e.g., rumination) and attentional strategies (e.g., hypervigilance)

What is the theoretical model of off-period distress in PD?

▪️ Trigger = off period ▪️ Positive metabelief = "worrying & monitoring symptoms helps me better control them" ▪️ Cognitive attentional syndrome ▪️ Negative metabelief = "worry is uncontrollable and cannot focus on anything but symptoms"

What is the first line of pharmacological treatment for anxiety and depression in PD?

SSRIs ▪️ Fluoxetine/sertraline ('activating') ▪️ Paroxetine (sedating) ▪️ Citalopram (helpful for anxiety, less potential for drug interactions)

What medications could be considered if SSRIs are ineffective for anxiety/depression in PD?

Atypical antidepressants ▪️ Mirtazapine (depression + anxiety, insomnia) ▪️ Venlafaxine ▪️ Bupropion (apathy, fatigue and poor concentration) ▪️ Trazodone (helpful for neurodegeneration in mice?)

What medications may be considered as third line treatments for anxiety/depression in PD?

Tricyclic antidepressants ▪️ Amitriptyline/Imipramine (most sedation) ▪️ Nortriptyline (less sedation and hypotension)

Why are tricyclic antidepressants typically avoided in PD?

▪️ Anticholinergic effects can cause confusion/worsen cognition ▪️ Hypotension can increase risk of falls ▪️ Other common side effects such as sedation, weight gain, and sexual dysfunction

What symptoms might occur with the interaction of antidepressants with PD medications rasagiline and selegiline?

Serotonin syndrome: ▪️ Fever ▪️ Confusion/stupor ▪️ Agitation ▪️ Sweating ▪️ Diarrhoea ▪️ Delusions ▪️ Mania ▪️ Tremor ▪️ Rigidity

How might you treat apathy in PD?

DA agonists or cholinesterace inhibitors

What is the aetiology of ICDs in PD?

▪️ Dopamine depletion in motor dorsal striatum ▪️ Ventral striatum relatively preserved ▪️ Thus antiparkinsonian medications to compensate for dorsal dopamine depletion may 'overdose' the limbic ventral system

What could you consider for ICD treatment?

▪️ Reduce dopamine replacement therapies ▪️ CBT Possibly: ▪️ Antipsychotics ▪️ Amantadine ▪️ Naltrexone

What are the two schools of though for DBS use in ICDs?

1. ICDs can occur de novo post DBS - spread to limbic areas? 2. DBS allows reduction of DRT and offers more consistent stimulation, reducing likelihood of ICDs?

What can DBS help with in cases of ICD?

▪️ Allows for 74% DRT reduction when stimulate STN ▪️ Restores impaired learning ▪️ Reversible ventral striatum hypersensitivity and abnormal decision making?

What is the psychosocial theory for increased risk of suicide post-DBS?

▪️ Due to expectations not being realised despite clinical improvement ▪️ Changes in social situation, roles or coping strategies ▪️ 'burden of health'

What is dopamine agonist withdrawal syndrome?

▪️ Resembles other psychostimulant withdrawal ▪️ Anxiety, panic, depression, agitation, dysphoria, insomnia, cravings etc ▪️ Improvement with agonist replacement ▪️ Associated with tendency to develop ICDs

How might DBS be used for DLB?

▪️ Target nucleus basalis ▪️ Improves attention, concentration and alertness? ▪️ Possibly also for AD if increases cholinergic output?