Summary of Neuropathological and Clinical Features of PDD

1
Summary of Neuropathological and Clinical
Features of PDD

• Clive Ballard, MD
• Professor of Age Related DiseasesInstitute of
  PsychiatryKings College London

2
Overview

• PDD is a distinct dementia syndrome
• PDD can be diagnosed unambiguously in routine
  clinical practice
• PDD is a rational target for treatment

3
Genetic Associations of PDD in Familial PDKurz
et al, 2006
SN Sub-stantia nigra NC Neocortex. Kurz
et al. Dementia and Geriatr Cog Disorders. In
press.
4
Relationship Between Pathology and Duration of PD
Before Dementia
Aarsland D, et al. Ann Neurol.
200558773-776. Perry R, et al. Neurol. 2006.
In press. Ballard C, et al. Am J Psychiat.
2004161843-849.
5
PDD Predicts a Characteristic Neuropathologic and
Clinical Profile

• Lewy body pathology (LBP) is the predominant
  substrate of cognitive decline in PDD
• Overlapping AD plaque pathology is not the main
  correlate of dementia in PDD patients
• 93 to 94 of patients with PDD lack sufficient
  pathologic changes to meet diagnostic criteria
  for AD
• Dementia in PDD has a characteristic profile of
  neuropsychiatric, cognitive, neurologic, and
  autonomic features

6
Attention and Fluctuating Attention in PDD and AD
p lt 0.0001
p lt 0.0001
Ballard C, et al. Neurology. 2002 591714-1720.
7
Clinical Symptoms of PDD vs AD
Ballard C, et al. Am J Psych. 19991561039-1045.
Ballard C, et al. J Clin Psych. 2001200146-49.
8
Autonomic Function (Parasympathetic) in AD and PDD
PDD vs. AD p-value lt0.05 for all comparisons.
PDD vs. Controls p-value lt0.001 for all
comparisons. Kenny RA, et al. Dementia with Lewy
Bodies and Parkinsons Disease Dementia. 2006.
Taylor Francis Pub.
9
PDD Can be Diagnosed Simply and Unambiguously in
Routine Clinical Practice

• Diagnosis of PDD is straightforward in routine
  clinical practice using 3 simple principles
• Established diagnosis of Parkinsons disease
• Developing dementia at least 1 to 2 yrs after
  onset of PD
• Exclusion of other causes of dementia, eg, VaD,
  MSA, PSP

10
Severe Neuroleptic Sensitivity Reactions in PDD
and AD

• Severe neuroleptic sensitivity reactions (NSR),
  characterized by severe parkinsonism, autonomic
  instability, increased confusion, rhabdomyolysis,
  and often death
• Severe NSR occurs in
• gt 30 of DLB and PDD
• 0 of AD

Aarsland D, et al. J Clin Psych.
200566633-637. McKeith I, et al. BMJ.
1992305673-678. Ballard C, et al. Lancet.
19983511032-1033.
11
Cholinergic Deficits in PDD

• There is established cholinergic deficit in PDD
• The cholinergic deficits are associated with many
  of the key neuropsychiatric symptoms and
  cognitive deficits

AChE total/AChE 10S form. Included PD/PDD
together.
12
Conclusions

• Lewy body-related alpha-synucleinopathy is the
  pathology predominantly associated with cognitive
  impairment in PDD
• PDD can most effectively be diagnosed using
  simple clinical criteria based on the presence of
  PD and the time course of development of dementia
• The shared cholinergic deficit in PDD and AD
  presents a common treatment target