1. Professor David Ames BA, MD, FRCPsych, FRANZCP University of Melbourne Professor of Ageing and Health Director National Ageing Research Institute Co-leader Australian Imaging Biomarkers and Lifestyle (AIBL) flagship study of ageing dames@unimelb.edu.au Three year follow up results from the Australian Imaging Biomarkers and Lifestyle (AIBL) study of Ageing

2. PERTH MELBOURNE Sites. Major Sponsor

3. Australian Imaging Biomarkers and Lifestyle study of ageing Launched in November 2006, largest study of its kind in Australia Initial cohort of 1112 participants (minimum age 60 years) –211 Patients with Alzheimer’s disease (AD), 133 with Mild Cognitive Impairment (MCI) and 768 healthy volunteers – cohort assessed in multiple modalities and undergoing follow-up every 18 months 2 site study – 40% Perth and 60% Melbourne What is the AIBL study?

4. Assessments BP, HR, weight, height, abdominal girth 80 ml blood 2 hours neuropsychological testing HADS and GDS Medication list Diet and lifestyle questionnaires PiB PET scan and MRI for ¼ Diagnostic panel evaluation DA file review Repeat every 18 months

5. Progress AIBL 1 – initial phase of the study 2006-2010 Recruit cohort of 1000+ people (1112 by August 2008) Conduct thorough assessment at baseline Repeat assessment at 18-months AIBL-2 refunded by SIEF 2011-2014 Repeat assessments at 36 months Repeat assessments at 54 months Recruit 200+ replenishment/expansion Image most of cohort LPs for 100+ ROCS study AIBL active study

6. AIBL: Longitudinal cohort Baseline (1,112) 18M (968) 36M (824) 318 NMC 374 SMC 81 MCI 196 AD 301 NMC 310 SMC 58 MCI 154 AD (33)(29)(51)(30) (97)(114)(7 ) (14)(4)(1)(3 ) (32) (39)(40)(61)(23) Psychometrics Bloods MRI/PET Lifestyle Genotype Psychometrics Bloods MRI/PET Psychometrics Bloods MRI/PET (1)(79)(64)(5)(4)(14)(1)(16) (1 ) (2 ) (5 ) (11) 396 SMC 133 MCI 211 AD 372 NMC (220)(253)(159) (211)(240) (63) (37)(133) Non-Return: 115 Deceased: NMC 2 SMC 4 MCI 5 AD 17 Non-Return: 115 Deceased: NMC 2 SMC 4 MCI 5 AD 17 4 Non-AD Dementia Dementia (2)VaD (1)VaD November 2011 (NMC) Non-Memory Complainer, (SMC) Subjective-Memory Complainer, (MCI) Mild Cognitive Impairment, (AD) Alzheimer’s disease, PDD (Parkinson’s Disease Dementia), VaD (Vascular Dementia). Non-Return: 120 Deceased: NMC 3 SMC 3 MCI 4 AD 33 Non-Return: 120 Deceased: NMC 3 SMC 3 MCI 4 AD 33 Returned at 36 months 19 Returned at 36 months 19 1 Non-AD Dementia Dementia (1)PDD (1 PDD)

7. Imaging results

8. Villemagne / Rowe 11 C-PIB for A  imaging SUVR 3.0 1.5 0.0 ADHC

9. BASELINE A  burden correlates with memory decline over 3 years in HC 0.90.60.30.0-0.3-0.6-0.9 1.0 1.5 2.0 2.5 3.0 r = 0.38 (p= 0.0005) Neocortical SUVR Episodic memory decline

10. AIBL+ Prediction of Progression: HC to MCI/AD 36 months n=195 PiB-ve Subjects: 129 Converters to MCI/AD7% PiB+ve Subjects: 66 Converters to MCI/AD 19%

11. AIBL+ Prediction of Progression: MCI to Dementia 36 Months n=92 PiB -ve : 34 Converters to AD 10% Other dementia 17% No dementia 73% PiB +ve : 58 Converters to AD 56% No dementia 44%

12. Cognitive stream results

13. Anticholinergics Anticholinergic drugs associated with modest cognitive difficulty – Sittirannorit et al. 2011

14. Predictors of rapid decline in AD Alessandro Sona, Ping Zhang et al. (Int Psychogeriatrics, 2012, 24: 197-204) 211 AD at baseline – 156 followed at 18 months 33% (51) rapid decliners (lost 6+ MMSE points in 18 months) Higher CDR and CDR box score plus baseline prescription of a CheI predicted faster decline (OR 3.4 univariate)

15. 672 HC and 64 MCI completed a subjective memory questionnaire at 18 month follow up. MMSE, CVLT, RCFT, BNT, GDS, HADS, group membership and APOE ε4 status were used to determine predictors of SMC scores. Group membership explained 20% of variance. Adding affective measures explained 27%. Only group membership and HADS were significant individual predictors. In HCs SMCs reflect mood rather than objectively measured cognitive performance. R. Buckley, M. Saling, K. Ellis, N. Lautenschlager, P Marruff, R. Martins, C Masters, C. Rowe, G. Savage, C. Szoeke, D. Ames and the AIBL group Predictors of subjective memory complaints in AIBL

16. Study is conducted between Perth (40%) and Melbourne (60%) CSIRO P-Health* University of Melbourne* Neurosciences Australia Ltd (NSA)* Edith Cowan University (ECU)* Mental Health Research Institute (MHRI)* National Ageing Research Institute (NARI) Austin Health University of WA (UWA) CogState Ltd. Charles Gairdner Hospital radiology and nuclear medicine Alzheimer’s Australia Macquarie University *denotes signatories to the AIBL study contract AIBL collaborators

17. CSIRO (AUS) National Health and Medical Research Council (NHMRC) (AUS) Alzheimer’s Association (USA) Alzheimer’s Drug Discovery Foundation (USA) An Anonymous Foundation (USA) Pfizer GE Healthcare Astra Zeneca Science and Industry Endowment Fund Financial Supporters

18. * AIBL management committee Prof. David Ames Prof Ashley Bush Prof. Richard Head Dr. Kathryn Ellis Prof. Ralph Martins Prof. Colin Masters Dr. Andrew Milner Prof. Christopher Rowe Dr. Cassandra Szoeke Dr. Lance Macauley Dr. Tim O’Meara * The AIBL study team comprises 80+ scientists (see www.aibl.csiro.au)www.aibl.csiro.au and 1112 Australian research volunteers The AIBL management team

19. The AIBL Study Team www.aibl.csiro.au The AIBL Study Team www.aibl.csiro.au Osca Acosta David Ames Jennifer Ames Manoj Agarwal David Baxendale Kiara Bechta-Metti Carlita Bevage Lindsay Bevege Pierrick Bourgeat Belinda Brown Rachel Buckley Ashley Bush Tiffany Cowie Kathleen Crowley Andrew Currie David Darby Daniela De Fazio Harriet Downing Denise El- Sheikh Kathryn Ellis Kerryn Dickinson Noel Faux Jurgen Fripp Christopher Fowler Veer Gupta Karra Harrington Gareth Jones Adrian Kamer Jane Khoo Asawari Killedar Neil Killeen Tae Wan Kim Eleftheria Kotsopoulos Gobhathai Kunarak Rebecca Lachovitski Nat Lenzo Qiao-Xin Li Xiao Liang Kathleen Lucas James Lui Georgia Martins Ralph Martins Paul Maruff Colin Masters Sabine Matthaes Andrew Milner Claire Montague Lynette Moore Audrey Muir Christopher O’Halloran Graeme O'Keefe Anita Panayiotou Athena Paton Jacqui Paton Jeremiah Peiffer Svetlana Pejoska Kelly Pertile Kerryn Pike Lorien Porter Roger Price Stephanie Rainey-Smith Parnesh Raniga Alan Rembach Miroslava Rimajova Jo Robertson Mark Rodrigues Elizabeth Ronsisvalle Rebecca Rumble Christopher Rowe Olivier Salvado Jack Sach Greg Savage Cassandra Szoeke Kevin Taddei Tania Taddei Brett Trounson Marinos Tsikkos Victor Villemagne Stacey Walker Vanessa Ward Michael Woodward Olga Yastrubetskaya