Parkinsons's Disease Dementia (PDD)

Parkinsons's Disease Dementia (PDD)

Parkinsons's Disease Dementia (PDD)

Primer

Parkinson’s Disease Dementia (PDD) is a form of dementia that develops after the diagnosis of Parkinson's Disease. Patients with PD have an almost six-fold increased risk of developing dementia. By definition, Parkinson's disease dementia is cognitive decline that occurs after the onset of Parkinson's disease.

Incidence

The majority of patients with Parkinson’s will experience some degree of cognitive impairment over time. The time of progression to a Parkinson's Disease dementia depends on the length and stage of disease. Some longitudinal studies have shown that the progression to dementia is inevetiable.^[1] Parkinson's disease is more common in males than in females. Among individuals with Parkinson's disease, as many as 75% will develop a major neurocognitive disorder at sometime in the course of their disease.

DSM-5 Diagnostic Criteria

Criterion A

The criteria are met for major or mild neurocognitive disorder.

Criterion B

The disturbance occurs in the setting of established Parkinson’s disease.

Criterion C

There is insidious onset and gradual progression of impairment.

Criterion D

The neurocognitive disorder is not attributable to another medical condition and is not better explained by another mental disorder.

Major or mild neurocognitive disorder probably due to Parkinson’s disease should be diagnosed if 1 and 2 are both met. Major or miid neurocognitive disorder possibly due to Parkinson's disease should be diagnosed if 1 or 2 is met:

There is no evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease or another neurological, mental, or systemic disease or condition likely contributing to cognitive decline).
The Parkinson’s disease clearly precedes the onset of the neurocognitive disorder.

MDS Criteria

The diagnosis of Parkinson's disease dementia (PDD) is most often based on the Movement Disorder Society Task Force 2007 recommendations.^[2]

Diagnostic Criteria

Dubois, Bruno, et al. Movement disorders 22.16 (2007): 2314-2324.

Criterion	Description	Asessment
1	A diagnosis of PD	Queen's Square Brain Bank Criteria
2	PD developed prior to the onset of dementia	Patient/caregiver history or ancillary records
3	PD associated with a decreased global cognitive efficiency	MMSE < 26
4	Cognitive deficiency severe enough to impair daily life	Caregiver interview or pill questionnaire
5	Impairment of more than one cognitive domain	Impairment of at least 2 of the following domains: attention, executive function, visuo-constructive ability, memory

Presence of one of the following behavioural symptoms (apathy, personality changes, hallucinations, delusions or excessive daytime sleepiness) may support the diagnosis of probable PDD.

Differential Diagnosis

Major or mild neurocognitive disorder with Lewy bodies
- This distinction is based substantially on the timing and sequence of motor and cognitive symptoms. For NCD to be attributed to Parkinson's disease, the motor and other symptoms of Parkinson's disease must be present well before (by convention, at least 1 year prior) cognitive decline
Major or mild neurocognitive disorder due to Alzheimer's Disease (AD)
- The motor features are the key to distinguishing major or mild NCD due to Parkinson's disease from major or mild NCD due to Alzheimer's disease. However, the two disorders can co-occur.
Major or mild vascular neurocognitive disorder
Neurocognitive disorder due to another medical condition (e.g. - neurodegenerative disorders)
Neuroleptic-induced parkinsonism (i.e. - extrapyramidal symptoms)
- In these cases of potential confounding effects from medications such as antipsychotics, the clinician should try to elicit a clear history if the Parkinsonian symptoms developed before or after the initiation of antipsychotics.
Other medical conditions and delirium
- Delirium and neurocognitive impairments due to side effects of dopamine-blocking drugs and other medical conditions (e.g. - sedation or impaired cognition, severe hypothyroidism, B12 deficiency) must also be ruled out. Sometimes it may be clinically difficult to distinguish between Parkinsons's dementia and delirium, and patients must be followed longitudinally.

Treatment

Acetylcholinesterase Inhibitors

The currently available evidence supports the use of acetylcholinesterase inhibitors as a class in patients with Parkinson's disease dementia, with a positive impact on global assessment, cognitive function, behavioural disturbance and activities of daily living rating scales.^[3].
Donepezil and rivastigmine are typically recommended first, with galantamine having less evidence.

Parkinson's Psychosis

See also: Fernandez, H. H. et al. (2005). Rebound psychosis: effect of discontinuation of antipsychotics in Parkinson's disease. Movement disorders: official journal of the Movement Disorder Society, 20(1), 104-105.

Psychotic symptoms in Parkinson's disease (PD) are relatively common.
- PD psychosis has unique clinical features, in that patients are usually aware and have insight.
- Parkinson's psychosis is a poor prognostic factor, and there is a higher risk for weight loss, caregiver burden, placement, and death.^[4]
The use of Parkinson's medications (particularly dopamine receptor agonists) has been the most widely identified risk factor for psychosis. The psychosis most commonly involves visual hallucinations, which progresses over time. Other symptoms may include auditory hallucinations, delusions, and illusions.
Clozapine is the most effective treatment for Parkinson's-related psychosis,^[5] and should be used if patients can tolerate the required blood monitoring.
There is actually limited positive evidence for the use of quetiapine in Parkinson's-related psychosis.^[6] However, it is often clinically used due to the lack of need for regular bloodwork.
Anticholinesterase inhibitors are the first line of treatment of psychosis, with rivastigmine having the most evidence, followed by donepezil.^[7]
More recently, pimavanserin was approved for the treatment of PD psychosis in the USA.