Neuropsychiatric symptoms in Parkinson's Disease

Parkinson's Disease is a neurodegenerative disorder that has historically been seen as a motor disorder. However, there are significant non-motor symptoms in almost all of the patients with PD. Including frequent Psychiatric Co-morbidities both in early and late PD

Introduction

  • PD is a neurodegenerative disorder that has historically been seen as a motor disorder
  • However, there are significant non-motor symptoms in almost all of the patients with PD
  • Including frequent Psychiatric Co-morbidities both in early and late PD

Epidemiology

  • More than 10 million people worldwide live with Parkinson’s disease (PD)
  • Non-motor neuropsychiatric symptoms in PD are common but under-recognized, often
  • Debilitating, with profound impact on
    • Social functioning
    • Ability to work
  • These neuropsychiatric symptoms may include:
    • Depression
    • Anxiety
    • Hallucinations
    • Memory problems
    • Cognitive impairment/Dementia
  • Symptoms are due to both:
    • Physical changes to the brain pathology
    • Psychological impact of the diagnosis of PD itself
  • Depression and anxiety are the most common symptoms;
    • Nearly half of people diagnosed with PD suffer one of these mental health issues

Depression

Overview and Diagnosis

  • Depression is recognized as a common non-motor symptom of PD
  • Patients often underreport their depressive symptoms
  • As recommended by International Parkinson and Movement Disorder Society, there are various screening tools used for diagnosing someone who has PD with depression such as
    • The Geriatric Depression Scale (GDS)
    • Beck Depression Inventory (BDI), Hospital Anxiety and
    • Depression Scale (HADS)

Etiology

  • Depressive symptoms are more common in PD patients with severe motor symptoms
  • Being diagnosed and living with a neurodegenerative condition such as PD can contribute to depressive symptoms
  • There is however also a biochemical basis for depression in PD with alteration of serotonin, as well as changes in noradrenaline and acetylcholine neurotransmitters

Treatment

  • The specific recommendation of pharmacological therapy depends on severity of symptoms and impact on quality of life
  • Like with depression in any chronic state, depression in patients with PD are prescribed
    • Selective serotonin reuptake inhibitors (SSRIs)
    • Serotonin–noradrenaline reuptake inhibitors (SNRIs)
    • Tricyclic antidepressants (TCAs) and
    • Monoamine oxidase type B (MAO-B) inhibitors
  • The best-studied drug for Depression in PD is Paroxetine (SSRI)
  • Other commonly used medications by experts are Duloxetine, Citalopram and Escitalopram as well as venlafaxine or mirtazapine especially with concomitant anxiety

Anxiety

Overview and Diagnosis

  • Approximately one-third of PD patients experience symptoms of anxiety such as:
    • Generalized anxiety disorder (GAD)
    • Obsessive-compulsive disorder
    • Agoraphobia, panic disorder and
    • Social phobia
  • Specific symptoms of anxiety in patients with PD include
    • Panic attacks
    • Excessive worry and
    • Increased subjective motor symptoms
  • To make diagnosis researchers rely on established criteria such as DSM-IV
  • Diagnosis remains challenges include:
    • Differentiate symptoms of anxiety from depression (they can occur simultaneously and identification of one should raise suspicion for the other)
    • Under-reporting of symptoms by patients
    • Under-recognition by clinicians
    • Some anxiety symptoms don’t meet the diagnostic criteria threshold

Etiology

  • The pathophysiology of anxiety is could be related to neurobiological changes including
    • serotonergic and noradrenergic systems which are widely involved in emotion
    • those with PD who also score high on anxiety questionnaires were found to have shorter serotonin transporter alleles
    • A potential contribution of neuropsychiatric genetics in patients with PD
    • psychosocial causes as a result of being burdened with a condition like PD.
      • Social anxiety is especially common in
        • PD are afraid of being negatively perceived in public which leads to fear of being in public and social withdrawal
      • Other patients may fear for their future and the progression of their condition, disability and death
      • A fear of falling may also develop among patients with PD (patients with PD are prone to fall accidents)
  • Social anxiety can lead to social isolation
    • Which consequently further exacerbates that anxiety
    • Isolation and loneliness can lead to feelings of depression, especially in older patients

Treatment

  • Treatment for patients with anxiety has a focus on
    • Lifestyle modification
      • Exercise
      • Sleep hygiene
      • Nutrition
      • Socializing
  • Cognitive behavioral therapy (CBT) is also beneficial in the form of mindfulness and meditation
  • Pharmacological include:
    • Prescription of SSRIs and SNRIs
    • Use of benzodiazepines is discouraged due to their adverse side effects

Apathy

Overview and Diagnosis

  • Apathy is one of the most frequent symptoms in patients with PD and one of the hardest to treat
  • Apathy can be defined as a state of reduced motivation as a result of a reduction in goal-directed behaviour.
  • Patients with apathy experience
    • Low levels of activity, interests and socialization
  • Apathy is sometimes confused as a ‘by-product’ of depression due to overlap in similarities
    • Particular thoughts and symptoms that are specific to apathy in the presence and absence of depression that helps differentiate between the two conditions
      • Loss of interest and activity in the world
      • Lack of concern for others and
      • Emotional indifference and reactivity

Etiology

  • Apathetic symptoms may precede the worsening of the motor symptoms of PD
  • The pathophysiology may be associated with a neuronal disruption in areas of the brain associated with and responsible for goal-directed behavior
    • i.e. dopaminergic projections between the frontal cortex and the ventral tegmentum

Treatment

  • Engaging in self-care activities (e.g. exercise) will
    • Help boost energy levels
    • Provide an opportunity for structure and socialization in the patient’s daily routine
    • Help with/overcoming apathy symptoms
  • Joining a support group for people with PD can also help
  • Dopaminergic medications are sometimes effective for apathy
    • Dopamine agonist are generally the most effective for apathy among all
  • SSRI may also be considered in difficult situations.

Psychosis

Overview and Diagnosis

  • About 20 to 40 percent of PD patients experience psychosis during the earlier stages and by the late stages, it may go up to 70 percent
  • There is common co-morbidity of cognitive impairment or dementia.
  • Positive symptoms of psychosis include:
    • Hallucinations
    • Illusions
    • Delusions
  • Hallucinations
    • can affect any of the senses
      • Visual, auditory, olfactory, tactical, and/or gustatory hallucinations
  • By far most common hallucinations are visual (70-90%) with auditory being second most common (up to 10%) and tactile being rare (<1%)
  • Delusions
    • Beliefs that aren’t grounded in reality
    • Not as frequent as hallucinations in PD patients:
      • usually 8-10 %
    • The most common form is persecutory delusion i.e. the fear that people are out to get you or that your significant other is being unfaithful etc.
    • Such beliefs can lead to aggressive behavior where the patient is both a danger to themselves and others
    • Delusions are less common than hallucinations, but harder to treat.
    • Delusions of grandiosity are unusual for PD.
  • Diagnosis of PD Psychosis requires:
    • Duration of the psychosis symptoms
      • Patients must experience symptoms of hallucinations and delusions for at least a month
    • Other preexisting psychiatric conditions
      • Not have another condition that could be causing these symptoms (e.g. dementia, delirium, major depression (MDD), or schizophrenia)

Etiology

  • The duration and severity of illness, as well as cognitive impairment, make the development of psychosis in PD patients more likely
  • Additional risk factors include:
    • Depression
    • Sleep disorder (insomnia or sleep apnea)
    • Visual or hearing problems
    • PD medications
      • Other medications such as anticholinergic medications.
  • There are two possible contributors for developing PD psychosis
    • The biochemical changes of neurotransmitters such as serotonin and dopamine
    • Imbalance of dopaminergic tone with low serotonergic tone with medications
  • Patients with PD have lower than normal levels of dopamine
  • Medication to improve mobility increases dopamine levels,
  • Psychosis can occur as a side effect of this treatment

Treatment

  • Since PD drugs can cause psychosis
    • One option will be to reduce the medications if possible
    • This is limited by worsening of motor symptoms
  • Goals:
    • improves movement without causing symptoms of psychosis and
    • remove hallucinations and delusions without making the motor symptoms much worse for the patient
  • Medications for PD Psychosis:
    • pimavanserin (Nuplazid) Only FDA approved options
    • Rivastigmine (good benefit on visual hallucination in a large trial)
    • Clozapine (highly effective but difficulty to use due to risk of aplastic anemia)
    • Seroquel (often use for agitation and insomnia, no benefit on hallucinations based on 7 trials)

Cognitive Impairment and Dementia

Overview and Diagnosis

  • Mild cognitive impairment (MCI)
    • impairment not enough to affect daily activities.
  • Parkinson Disease Dementia (PDD)
    • impaired daily activities
  • Concomitant Alzheimer's Dementia and other impairment can also occur in PD and should be considered.
  • Within the first 3 to 5 years, about 20% and 57% of patients are affected by MCI
  • Occurs on a continuum of severity:
    • the prevalence increasing with the duration of the disease
  • Common pattern of cognitive deficits in PD is considered sub-cortical dysfunction and includes:
    • Executive dysfunction
    • Poor Attention
    • Reduced processing speed
    • Impaired Verbal Fluency

Etiology

  • Dementia in PD patients was estimated to account for 3.6 of cases of dementia in general
  • Incidence rates of over 80% have been found in patients monitored for more than 20 years following the onset of PD
  • Patients who have been newly diagnosed with PD are two times more likely to develop MCI as compared to healthy elderly patients

Treatment

  • The only medication that has been FDA approved for PDD:
    • Rivastigmine, an acetylcholinesterase inhibitor,
  • As for MCI:
    • there is currently no successful pharmacological treatment.
  • important to consider non-biomedical approaches
    • exercise and programs that promote cognitive training and simulation

Further Reading

  1. Dujardin, K., & Sgambato, V. (2020). Neuropsychiatric Disorders in Parkinson’s Disease: What
    1. Do We Know About the Role of Dopaminergic and Non-dopaminergic Systems?. Frontiers In Neuroscience, 14. doi: 10.3389/fnins.2020.00025
  1. Molina Ruiz, R., Evans, A., Velakoulis, D., & Looi, J. (2016). Neuropsychiatric manifestations
    1. of Parkinson’s disease. Australasian Psychiatry, 24(6), 529-533. doi: 10.1177/1039856216654393

Bibliography

  1. Apathy. (2021). Retrieved 5 November 2021, from https://www.parkinson.org/Understanding-Parkinsons/Symptoms/Non-Movement-Symptoms-Apathy
  1. Jones, S., Torsney, K., Scourfield, L., Berryman, K., & Henderson, E. (2020). Neuropsychiatric symptoms in Parkinson's disease: Aetiology, diagnosis and treatment. BJPsych Advances
    1. 26(6), 333-342. doi:10.1192/bja.2019.79
  1. Kehagia, A., Barker, R., & Robbins, T. (2010). Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson's disease. The Lancet Neurology, 9(12), 1200-1213. doi: 10.1016/s1474-4422(10)70212-x
  1. Parkinson's and mental health. Parkinson's UK. (n.d.). Retrieved November 3, 2021, from https://www.parkinsons.org.uk/information-and-support/parkinsons-and-mental-health.
  1. Parkinson's Psychosis: Understanding Symptoms and Treatment. (2021). Retrieved 5 November 2021, from https://www.healthline.com/health/parkinsons/parkinsons-psychosis#hallucinations