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Metis Cognition Ltd     Cognitive dysfunction in Parkinson’s andAlzheimer’s disease: Can we use the same tests for       e...
Financial disclosures• In the past 12 months I have received consultancy  payments and/or honoraria from the following  or...
Issues for consideration• Issues relating to cognition test selection in early AD• Issues relating to cognition test selec...
Issues and examplesTRADITIONAL MEASURES AND PATTERNS OFCOGNITIVE DECLINE IN ALZHEIMER’SDISEASE                            ...
Patterns of impairment in AD                                                                                     Worst pos...
New options in early AD                                                                                              EVP-6...
Issues and examplesPATTERNS OF COGNITIVE DECLINEIN PARKINSON’S DISEASE                        7   metis
Early PD - Patterns of Impairment  • Early PD – evidence of cognitive dysfunction in 33-    50%1 of patients, largely in: ...
EMA Guidance Notes• ‘PDD and Dementia with Lewy Bodies (DLB) are subsumed  under the umbrella Lewy Body Dementia’ (p.8)• ‘...
Traditional ApproachTRADITIONAL PARKINSON’SDISEASE TEST SELECTION                          10   metis
AAV2-GAD gene therapy study• Cognition tests selected to investigate safety• Cognition assessment composed of:   –   Matti...
Suggested ApproachONE SIZE FITS ALL?                     12   metis
Recommended Tests• Psychomotor speed (Simple Reaction Time )• Attention (Choice Reaction Time)• Episodic visual memory (e....
Conclusions and recommendations• Patterns of cognitive impairment in early PD & AD can be  quite different• However, our c...
Questions?        Email: john@metiscog.com    Email: john.harrison@imperial.ac.ukhttp://www.linkedin.com/in/drjohnharrison...
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JH Alzheimer's and Parkinson's disease meeting presentation Florence March 2013

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This presentation was made at the AD/PD meeting in Florence on 8th March 2013. In the presentation I discuss early patterns of cognitive dysfunction in patients with Parkinson's disease and Alzheimer's disease. I describe the tests traditionally used to measure cognitive impairment and propose the use of an assessment with the potential to be used successfully in both indications. I propose also that the same collection of measures can profitably be used in other CNS indications. I stress that selection is best made on the basis not of specific tests, but instead on the use of good tests that meet current best practice guidance for measuring cognitive change.

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JH Alzheimer's and Parkinson's disease meeting presentation Florence March 2013

  1. 1. Metis Cognition Ltd Cognitive dysfunction in Parkinson’s andAlzheimer’s disease: Can we use the same tests for exploratory and confirmatory trials? John Harrison BSc (Hons), PhD, CSci, CPsychol Honorary Senior Lecturer, Imperial College, London, UK. Consultant Psychologist, Metis Cognition Ltd., Kilmington, UK. 1 metis
  2. 2. Financial disclosures• In the past 12 months I have received consultancy payments and/or honoraria from the following organisations: – Astra-Zeneca, Boehringer Ingelheim, Bracket (Clinical) – CRF Health, EnVivo Pharma, ePharmaSolutions – Eisai, Eli Lilly, Janssen AI, Lundbeck, MedAvante – Merck, MyCog, Novartis, Nutricia, Orion Pharma – Pharmanet/i3, Pfizer, Prana Biotech, Reviva – Servier, Shire, TCG, TransTech Pharma and Velacor. metis
  3. 3. Issues for consideration• Issues relating to cognition test selection in early AD• Issues relating to cognition test selection in early PD• Options for test selection – Traditional test selection – Proposed test selection• Conclusions and recommendations 3 metis
  4. 4. Issues and examplesTRADITIONAL MEASURES AND PATTERNS OFCOGNITIVE DECLINE IN ALZHEIMER’SDISEASE 4 metis
  5. 5. Patterns of impairment in AD Worst possible score = 10 Worst possible score = 12 • Most patients score at ceiling • No difference between controls and MCIGrundman MPH et al. (2004). Mild cognitive impairment can be distinguished fromAlzheimer’s disease and normal aging for clinical trials. Archives of Neurology;61: 59-66. metis
  6. 6. New options in early AD EVP-6124 0.3 mg Cognition Composite Score: EVP-6124 1 mg ADAS-cog Word Recall, Word Recognition, and Orientation, and EVP-6124 2 mg COWAT and CFT Placebo (Increase Indicates Improvement) 0.2 0.15 LSMEAN Change From 0.1 Baseline (± S.E.M.) 0.05 0 EVP-2 mg vs. Placebo -0.05 Week 23: P-value = 0.0037 Effect Size = 0.42 -0.1 -0.15 0 4 8 12 16 20 24 Study Visit (Week)Presented at AAIC, July 2012. For a fuller account visit: http://www.alzforum.org/new/detail.asp?id=3214. metis
  7. 7. Issues and examplesPATTERNS OF COGNITIVE DECLINEIN PARKINSON’S DISEASE 7 metis
  8. 8. Early PD - Patterns of Impairment • Early PD – evidence of cognitive dysfunction in 33- 50%1 of patients, largely in: – Tests of executive function2 – Tests of attention3 – Timed motor tasks3 • Above tasks have been shown to be drug sensitive3,41) Emre M. (2003) Dementia associated with Parkinson’s disease. Lancet Neurology, 2:229-37; Robottom BJ & Weiner WJ (2009)Parkinson’s disease dementia. Current Psychiatry Reviews, 5: 218-225.2) Henry J & Crawford J (2004) Verbal fluency deficits in Parkinsons disease: A meta-analysis, Journal of the InternationalNeuropsychological Society, 10: 608-622.3) Harrison J et al. (1995) Abnormal refractoriness in patients with Parkinsons disease after brief withdrawal of levodopa treatment.Journal of Neurology, Neurosurgery, and Psychiatry;59:499-506; Harrison J, Edgar, C, Wesnes, K. (2005) Reaction time tasks: Sensitivemeasures of drug efficacy in Parkinson’s disease clinical drug trials. 7th AD/PD meeting. Sorrento, Italy.4) Emre M et al. (2004). Rivastigmine for the dementia associated with Parkinson’s disease. New England Jnl of Medicine 351:29-38. 8 metis
  9. 9. EMA Guidance Notes• ‘PDD and Dementia with Lewy Bodies (DLB) are subsumed under the umbrella Lewy Body Dementia’ (p.8)• ‘PDD cognitive deficits are characterised by impairment in executive function, attention and working memory’(p.8)• ‘7.1 Pharmacodynamics: ‘As pharmacological effects on cognition and/or memory and/or psychological function and/or reaction time are expected, these should be studied.’ (p.11) CHMP (2008) Guideline on clinical investigation of medicinal products in the treatment of Parkinson’s disease. Doc.Ref.CPMP/EWP/563/95 Rev. 1. London, EMEA. 9 metis
  10. 10. Traditional ApproachTRADITIONAL PARKINSON’SDISEASE TEST SELECTION 10 metis
  11. 11. AAV2-GAD gene therapy study• Cognition tests selected to investigate safety• Cognition assessment composed of: – Mattis dementia rating scale – Symbol digit modality test – Stroop color and word test – Hopkins verbal learning test – Controlled oral word association test• Also employed: – Neuropsychiatric Inventory – Beck Depression Inventory LeWitt PA et al. (2011) AAV2-GAD gene therapy for advanced Parkinson’s disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurology:10:309-19. 11 metis
  12. 12. Suggested ApproachONE SIZE FITS ALL? 12 metis
  13. 13. Recommended Tests• Psychomotor speed (Simple Reaction Time )• Attention (Choice Reaction Time)• Episodic visual memory (e.g. PAL tasks, One Card Learning)• Working memory (e.g. N-back tasks, Digit Span)• Episodic verbal memory task (e.g. ADAS-cog Word Recall, Hopkins Verbal Learning Test, Rey Auditory Verbal Learning Test)• Planning and strategy (e.g. COWAT & CNT)• Executive function (e.g. DSST, COWAT & CNT) 13 metis
  14. 14. Conclusions and recommendations• Patterns of cognitive impairment in early PD & AD can be quite different• However, our concerns in exploratory development extend to considerations of both safety and efficacy• Consequently a broad assessment of cognition is recommended• Employ brief, reliable and stable cognitive measures• Maximise reliability through continuity metis
  15. 15. Questions? Email: john@metiscog.com Email: john.harrison@imperial.ac.ukhttp://www.linkedin.com/in/drjohnharrison 15 metis

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