1. Parkinson’s Disease Dementia (PDD) A Clinical Perspective
Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
Parkinson’s Disease Dementia (PDD) A Clinical Perspective
Howard Feldman, MDCM, FRCP (C)
Professor and Head Division of Neurology
Director-Clinic for Alzheimer Disease and Related Dementias University of British Columbia Vancouver, British Columbia, Canada

2. Overview of Parkinson’s Disease Dementia
Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
Overview of Parkinson’s Disease Dementia
Clinical presentation and definition of PDD
Disease burden and need for treatment
Diagnostic differentiation from other dementia syndromes and diagnostic criteria
Identification and diagnosis in routine clinical practice

3. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
Case Presentation
63-yr old male, retired bus driver
10-yr history of PD (fulfilling UK Brain Bank Criteria)
Initial presentation: R sided resting tremor, rigidity and bradykinesia
Motor symptoms initially improved with l-dopa 300 mg/day
Wearing-off dyskinesia and motor fluctuations after a number of years of L- dopa treatment
Dopamine agonist (bromocriptine) and entacapone initiated
8 yr into illness gradual cognitive decline and recurrent visual hallucinations (animals and children in the house)

4. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
Case Presentation
Behaviorally less motivated, excessive daytime sleepiness, inattentive and forgetful especially for recent events and conversations
Thought process slower, trouble navigating in his own home
Less involved in activities at home, increased assistance needed in ADL
Dopaminergic medication decreased, hallucinations became less frequent, but motor symptoms worsened
Additional hx of sleep disorder elicited
Suggestive REM sleep behavioral disorder 10 yr prior to motor symptom onset

5. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
Examination Findings
PE: Stooped posture
Cooperative; intermittently drowsy
MMSE 21/30: time (-3), poor recall (-3), poor visual construction (-1) and difficulties with serial 7’s (-2 ).
Bradymimia; hypophonic speech
Marked bradykinesia bilaterally, increased axial rigidity, cogwheel rigidity in all extremities
Gait: Small steps, festinating, severe start hesitation, postural instability and retropulsion
Total UPDRS score 55, motor part III score 27
Hoehn and Yahr stage 3
Diagnosis: Parkinson’s disease dementia

6. Parkinson’s Disease Dementia
Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
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4/19/2017 1:54 AM
Parkinson’s Disease Dementia
PDD is a cognitive, and neuropsychiatric disorder that occurs in patients with Parkinson’s disease
Core of diagnosis is Idiopathic Parkinson’s disease
PDD follows a PD diagnosis
Cognitive decline at least 1 yr after PD

7. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)27 DV
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Idiopathic PD Based on UK Parkinson’s Disease Society Brain Bank Criteria
Step 1—Diagnosis of Parkinsonian syndrome
Bradykinesia and ≥ 1 of the following:
Muscular rigidity
4 to 6 Hz rest tremor
Postural instability not caused by primary visual, vestibular, cerebellar, or proprioceptive dysfunction
Protocol_PDD2311EXPRESS Sec 9.5 Appendix 2
Hughes AJ, et al. J Neurol Neurosurg Psychiatry. 1992;55:

8. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)27 DV
4/19/2017 1:54 AM
Idiopathic PD Based on UK Parkinson’s Disease Society Brain Bank Criteria
Step 2 – Exclusion criteria
History of repeated strokes with stepwise progression of parkinsonian features
History of repeated head injury
History of definite encephalitis
Oculogyric crises
Neuroleptic treatment at onset of symptoms
Sustained remission
Strictly unilateral features after 3 yr
Supranuclear gaze palsy
Cerebellar signs
Early severe autonomic involvement
Early severe dementia with disturbances of memory, language, and praxis
Babinski sign
Presence of cerebral tumor or NPH on imaging study
Negative response to large doses of levodopa
MPTP exposure
Protocol_PDD2311EXPRESS Sec 9.5 Appendix 2
Hughes AJ, et al. J Neurol Neurosurg Psychiatry. 1992;55:

9. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)27 DV
4/19/2017 1:54 AM
Idiopathic PD Based on UK Parkinson’s Disease Society Brain Bank Criteria
Step 3 – Supportive prospective positive criteria PD
≥ 3 required for diagnosis of definite Parkinson’s disease
Unilateral onset
Rest tremor present
Progressive disorder
Persistent asymmetry affecting side of onset most
Excellent response (70% to 100%) to levodopa
Severe levodopa-induced chorea
Levodopa response for ≥ 5 yr
Clinical course of ≥ 10 yr
Protocol_PDD2311EXPRESS Sec 9.5 Appendix 2
Hughes AJ, et al. J Neurol Neurosurg Psychiatry. 1992;55:

10. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
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Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
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Prevalence of PDD
Prevalence of PD
500,000 Americans currently believed to have PD†
Approximately 50,000 additional cases diagnosed each year†
Prevalence of PDD
Cross-sectional prevalence of dementia ranges from 24%† to 40%‡ in patients with PD§
Risk of developing dementia is 4 to 6 times higher with PD compared with age-matched controls||,¶
† Parkinson’s Disease Backgrounder: NINDS.
‡ Cummings JL. Int J Geriatr Psychiatry. 1988;1:24-36; § Aarsland D, et al. Mov Disord. 2005;20:
|| Hughes TA, et al. Neurology. 2000;54: ; ¶ Aarsland D, et al. Neurology. 2001;56:

11. Impact and Burden of PDD
Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
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Impact and Burden of PDD
Dementia and associated behavioral symptoms (ie, hallucinations) predict and decrease time to nursing home placement†,‡,§
Cognitive and behavioral symptoms in PD patients are greatest contributors to caregiver distress||
Risk of mortality increased when PD patients develop dementia¶
† Aarsland D, et al. J Am Geriatr Soc. 2000;48: ; ‡ Goetz CG, et al. Neurology. 1993;43:
§ Parashos SA, et al. Mayo Clin Proc. 2002;77: ; || Aarsland D, et al. Int J Geriatr Psychiatry. 1999;14: ;
¶ Hughes, et al. Acta Neurol Scand

12. The Clinical Phenomenology of PDD and Contrast With AD
Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
The Clinical Phenomenology of PDD and Contrast With AD

13. Cognitive Profile in PDD
Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
Cognitive Profile in PDD
Impaired memory (retrieval > amnestic pattern)
Benefit from external cues
Preserved recognition
Executive dysfunction
Concepts, problem solving, set shifting
Internally cued behavior
Attentional impairment
Reaction times and vigilance
Fluctuations
Visuospatial deficit
Visuospatial analysis and orientation
Tasks that require planning and sequencing
Bradyphrenia
Emre M, Lancet Neurology. 2003;2:

14. Cognitive Profile in AD
Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
Cognitive Profile in AD
Language changes§
Anomia,
Information content in spontaneous speech,
Impaired comprehension
Memory deficit (retrieval and retention)‡
Apraxia
Both PDD and AD have progressive functional decline
‡ Helkala EL, et al. Ann Neurol. 1988;24:
§ Cummings JL, et al. Neurology. 1988;38:
¶ Stern Y, et al. Arch Neurol. 1993;50:

15. Behavioral Profiling in PD and PDD
Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
Behavioral Profiling in PD and PDD
Changes in personality frequent
Depressive symptoms common†
More frequent visual hallucinations in PDD‡
REM behavioral sleep disorder prior to PD (65%)§,||
† Aarsland D, et al. Int J Geriatr Psychiatry. 2001;16:
‡ Fenelon G, Mahieux F, Huon R, Ziegler M. Hallucinations in PD Brain. 2000;123:
§ Schenck C, Bundlie S, Mahowald. Sleep. 2003;26:A 316,
|| Boeve B, et al. Neurology. 61:40-45

16. Behavioral Symptoms Presents a Significant Therapeutic Challenge
Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
Behavioral Symptoms Presents a Significant Therapeutic Challenge
Dopaminergic therapy
Exacerbating/ triggering psychotic symptoms
Neuroleptics (atypical)
Hypersensitivity to neuroleptics†
Complications of antipsychotics in elderly (mortality rates)‡
Worsening cognitive function§
Worsening motor problems
† Aarsland D, et al. Nord J Psychiatry. 2003;57:94. SCNP Abstract: Poster 1.
‡ Accessed April 4, 2006 § Ballard C, et al. BMJ

17. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
Diagnosing PDD
The DSM criteria

18. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)1
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Diagnosis of Dementia Based on DSM-IV Criteria for Dementia Due to Other Medical Conditions
Memory impairment
One or more of the following cognitive disturbances
Aphasia
Apraxia
Agnosia
Executive dysfunction
Significant impairment in social or occupational functioning and decline from previous level of functioning
Deficits do not occur exclusively during the course of a delirium
There is evidence that the disturbance is the direct consequence of condition other than AD or CVD
Diagnostic & Statistical Manual of Mental Disorders – IV Text Revision. American Psychiatric Association. 1994

19. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)1
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Diagnosis of Dementia Based on DSM-IV Criteria for Dementia Due to PD 294.1
Presence of dementia judged to be direct pathophysiological consequence of PD
Occurs in patients with PD
Characterized by
Cognitive and motor slowing
Executive impairment
Impairment in memory (retrieval)
There are a number of syndromes that have dementia, parkinsonian movement disorders and other neurological features (ie, PSP, OPCA, VaD)
Diagnostic & Statistical Manual of Mental Disorders – IV Text Revision. American Psychiatric Association. 1994

20. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
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Parkinson’s Disease Dementia— Differentiation from Other Dementia Syndromes
Alzheimer’s disease (AD)†
“Probable AD” by NINCDS-ADRDA criteria state that PD must be excluded for diagnosis
Parkinsonism can develop with advancing AD, but is usually not prominent or full blown PD
Dementia with Lewy bodies (DLB)‡
Parkinsonism and dementia temporal relationship
Dementia occurs before, concurrently or within 1 year of the onset of parkinsonism
† McKhann G, et al. Neurology. 1984;34:
‡ McKeith IG, et al. Neurology. 2005;65:1-10.

21. PDD Can be Diagnosed in Routine Clinical Practice
Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
4/19/2017 1:54 AM
PDD Can be Diagnosed in Routine Clinical Practice
DSM criteria for dementia due to other medical conditions can be applied by physicians for diagnosis in routine clinical practice
These criteria do not require specific psychometric test scores
The temporal relationship between the onset of the dementia and the diagnosis of PD can be obtained from patient history (at least 1 year)
† McKeith I, et al. Neurology. 2005;65:

22. Parkinson’s Disease Dementia (PDD): A Clinical Perspective (CL)
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Conclusion
PDD is a clinical disease with a unique progression
Begins with Parkinson’s disease
Motor signs present for years before onset of dementia
Dementia syndrome characterized by memory, executive, attentional, and functional deficits
Prominent neuropsychiatric symptoms with psychotic features
PDD can be identified and diagnosed in usual settings of care
Need for effective treatments
There are no currently approved treatment options