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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 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

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  1. Summary of Neuropathological and Clinical Features of PDD Clive Ballard, MD Professor of Age Related DiseasesInstitute of PsychiatryKing’s 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 PD—Kurz 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. 2005:58;773-776. ‡ Perry R, et al. Neurol. 2006. In press. § Ballard C, et al. Am J Psychiat. 2004:161;843-849.

  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 < 0.0001 p < 0.0001 Ballard C, et al. Neurology. 2002; 59:1714-1720.

  7. Clinical Symptoms of PDD vs AD Ballard C, et al. Am J Psych. 1999;156:1039-1045. Ballard C, et al. J Clin Psych. 2001;2001:46-49.

  8. Autonomic Function (Parasympathetic) in AD and PDD 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.

  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 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

  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 • > 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.

  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

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