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Summary of Neuropathological and Clinical Features of PDD. Clive Ballard, MD Professor of Age Related Diseases Institute of Psychiatry King’s College London. Overview. PDD is a distinct dementia syndrome PDD can be diagnosed unambiguously in routine clinical practice

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Summary of neuropathological and clinical features of pdd

Summary of Neuropathological and Clinical Features of PDD

Clive Ballard, MD

Professor of Age Related DiseasesInstitute of PsychiatryKing’s College London


Overview
Overview

  • PDD is a distinct dementia syndrome

  • PDD can be diagnosed unambiguously in routine clinical practice

  • PDD is a rational target for treatment


Genetic associations of pdd in familial pd kurz et al 2006
Genetic Associations of PDD in Familial PD—Kurz et al, 2006†

SN = Sub-stantia nigra; NC = Neocortex.

† Kurz et al. Dementia and Geriatr Cog Disorders. In press.


Relationship between pathology and duration of pd before dementia
Relationship Between Pathology and Duration of PD Before Dementia

† Aarsland D, et al. Ann Neurol. 2005:58;773-776.

‡ Perry R, et al. Neurol. 2006. In press.

§ Ballard C, et al. Am J Psychiat. 2004:161;843-849.


Pdd predicts a characteristic neuropathologic and clinical profile
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


Attention and fluctuating attention in pdd and ad
Attention and Fluctuating Attention in ProfilePDD and AD

p < 0.0001

p < 0.0001

Ballard C, et al. Neurology. 2002; 59:1714-1720.


Clinical symptoms of pdd vs ad
Clinical Symptoms of PDD vs AD Profile

Ballard C, et al. Am J Psych. 1999;156:1039-1045.

Ballard C, et al. J Clin Psych. 2001;2001:46-49.


Autonomic function parasympathetic in ad and pdd
Autonomic Function (Parasympathetic) in AD and PDD Profile

PDD vs. AD: p-value <0.05 for all comparisons. PDD vs. Controls: p-value <0.001 for all comparisons.

Kenny RA, et al. Dementia with Lewy Bodies and Parkinson’s Disease Dementia. 2006. Taylor & Francis Pub.


Pdd can be diagnosed simply and unambiguously in routine clinical practice
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 Parkinson’s disease

    • Developing dementia at least 1 to 2 yrs after onset of PD

    • Exclusion of other causes of dementia, eg, VaD, MSA, PSP


Severe neuroleptic sensitivity reactions in pdd and ad
Severe Neuroleptic Sensitivity Reactions in PDD and AD Clinical Practice

  • Severe neuroleptic sensitivity reactions (NSR), characterized by severe parkinsonism, autonomic instability, increased confusion, rhabdomyolysis, and often death

  • Severe NSR occurs in

    • > 30% of DLB†‡§ and PDD†

    • 0% of AD†‡§

† Aarsland D, et al. J Clin Psych. 2005;66:633-637.

‡ McKeith I, et al. BMJ. 1992;305:673-678.

§ Ballard C, et al. Lancet. 1998;351:1032-1033.


Cholinergic deficits in pdd
Cholinergic Deficits in PDD Clinical Practice

  • 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.


Conclusions
Conclusions Clinical Practice

  • 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


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