# Presentation: 686297

## 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**

## 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**

## 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)**

## 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**

## 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**

## 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**

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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

- 27
**DV**

**Hughes AJ, et al. *****J Neurol Neurosurg Psychiatry*****. 1992;55:181-184.**

## 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

**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

- 27
**DV**

**Hughes AJ, et al. *****J Neurol Neurosurg Psychiatry*****. 1992;55:181-184.**

**Step 2 – Exclusion criteria**

**Idiopathic PD Based on ****UK ****Parkinson’s Disease Society ****Brain Bank ****Criteria**

## Idiopathic PD Based on UK Parkinson’s Disease Society Brain Bank Criteria 

**≥**** ****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

- 27
**DV**

**Hughes AJ, et al. *****J Neurol Neurosurg Psychiatry*****. 1992;55:181-184.**

**Step 3 – Supportive prospective positive criteria PD**

## 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. http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease_backgrounder.htm**** **
**‡ ****Cummings JL. *****Int J Geriatr Psychiatry*****. 1988;1:24-36; ****§ Aarsland D, et al. *****Mov Disord*****. 2005;20:1255-1263.**
**|| Hughes TA, et al. *****Neurology*****. 2000;54:1596-1602; ¶ Aarsland D, et al. *****Neurology*****. 2001;56:730-796.**

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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****¶**

- 15-10

**† ****Aarsland D, et al. *****J Am Geriatr Soc*****. 2000;48:938-942; ‡ Goetz CG, et al. *****Neurology*****. 1993;43:2227-2229.**
**§ Parashos SA, et al. *****Mayo Clin Proc*****. 2002;77:918-925; || Aarsland D, et al. *****Int J Geriatr Psychiatry*****. 1999;14:866-874; **
**¶ Hughes, et al. *****Acta Neurol Scand*****. 2004.**

## The Clinical Phenomenology of PDDand Contrast With AD

##  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;2:229-237**

## 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;24:214-217.**
**§ Cummings JL, et al. *****Neurology. *****1988*****;*****38:680-684.**
**¶ Stern Y, et al. *****Arch Neurol*****. 1993;50:1040-1045.**

##  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;16:184-191.**
**‡ ****Fenelon G, Mahieux F, Huon R, Ziegler M. Hallucinations in PD Brain. 2000;123:733-734.**
**§ Schenck C, Bundlie S, Mahowald. *****Sleep*****. 2003;26:A 316, **
**|| Boeve B, et al. *****Neurology*****. 61:40-45 **

## 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.**
**‡ ****http://www.fda.gov/cder/drug/advisory/antipsychotics.htm. Accessed April 4, 2006****§ Ballard C, et al. *****BMJ.***** 2005.**

## Diagnosing PDD

**The DSM criteria**

## 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**

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**Diagnostic & Statistical Manual of Mental Disorders – IV Text Revision. *****American Psychiatric Association*****.***** *****1994**

## 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)**

- 1

**Diagnostic & Statistical Manual of Mental Disorders – IV Text Revision. *****American Psychiatric Association*****.***** *****1994**

## 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 **

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**† ****McKhann G, et al. *****Neurology.***** 1984;34:939-944.**
**‡ ****McKeith IG, et al. *****Neurology*****. 2005;65:1-10.**

## 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;65:1863-1872.**

## 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**