Professor David Ames BA, MD, FRCPsych, FRANZCP

University of Melbourne Professor of Ageing and HealthDirector 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

PERTHMELBOURNE

Sites.

MajorSponsor

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?

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

ProgressAIBL 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-monthsAIBL-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

AIBL: Longitudinal cohort

Baseline(1,112)

18M(968)

36M(824)

318 NMC318 NMC318 NMC318 NMC 374 SMC374 SMC374 SMC374 SMC 81 MCI81 MCI81 MCI81 MCI 196 AD196 AD196 AD196 AD

301 NMC301 NMC301 NMC301 NMC 310 SMC310 SMC310 SMC310 SMC 58 MCI58 MCI58 MCI58 MCI 154 AD154 AD154 AD154 AD

(33) (29) (51)(30)

(97) (114) (7) (14)(4) (1) (3) (32)

(39) (40) (61)(23)

PsychometricsBloods

MRI/PETLifestyle

Genotype

PsychometricsBloods

MRI/PET

PsychometricsBloods

MRI/PET

(1)(79) (64) (5) (4) (14) (1) (16)

(1) (2) (5) (11)

396 SMC396 SMC396 SMC396 SMC 133 MCI133 MCI133 MCI133 MCI 211 AD211 AD211 AD211 AD372 NMC372 NMC372 NMC372 NMC

(220) (253) (159)

(211) (240)

(63)

(37) (133)

Non-Return:115

Deceased:NMC 2SMC 4MCI 5AD 17

Non-Return:115

Deceased:NMC 2SMC 4MCI 5AD 17

4 Non-AD4 Non-ADDementiaDementia4 Non-AD4 Non-ADDementiaDementia

(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 3SMC 3MCI 4AD 33

Non-Return:120

Deceased:NMC 3SMC 3MCI 4AD 33

Returned at 36 months

19

Returned at 36 months

19

1 Non-AD1 Non-ADDementiaDementia1 Non-AD1 Non-ADDementiaDementia

(1)PDD

(1 PDD)

• Imaging results

Villemagne / Rowe

1111C-PIB for AC-PIB for A imaging imaging

SUVR3.0

1.5

0.0

ADHC

BASELINE A burden correlates with memory decline over 3 years in HC

0.9 0.6 0.3 0.0 -0.3 -0.6 -0.9

1.0

1.5

2.0

2.5

3.0 r = 0.38 (p= 0.0005)

Neo

corti

cal S

UVR

Episodic memory decline

AIBL+Prediction of Progression: HC to MCI/AD

36 monthsn=195

PiB-ve Subjects: 129Converters to MCI/AD 7%

PiB+ve Subjects: 66Converters to MCI/AD 19%

AIBL+Prediction of Progression: MCI to Dementia

36 Monthsn=92

PiB -ve : 34Converters to AD 10%Other dementia 17%No dementia 73%

PiB +ve : 58Converters to AD 56%No dementia 44%

• Cognitive stream results

Anticholinergics

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

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)

• 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

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

• 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

* AIBL management committeeProf. David Ames Prof Ashley BushProf. Richard Head

Dr. Kathryn Ellis Prof. Ralph Martins Prof. Colin Masters Dr. Andrew Milner Prof. Christopher Rowe Dr. Cassandra Szoeke Dr. Lance MacauleyDr. Tim O’Meara

* The AIBL study team comprises 80+ scientists (see www.aibl.csiro.au) and 1112 Australian research volunteers

The AIBL management team

The AIBL Study Team The AIBL Study Team www.aibl.csiro.auwww.aibl.csiro.au

Osca AcostaDavid AmesJennifer AmesManoj AgarwalDavid BaxendaleKiara Bechta-MettiCarlita BevageLindsay BevegePierrick BourgeatBelinda BrownRachel BuckleyAshley BushTiffany CowieKathleen CrowleyAndrew CurrieDavid DarbyDaniela De FazioHarriet DowningDenise El- SheikhKathryn Ellis Kerryn Dickinson  Noel FauxJurgen FrippChristopher FowlerVeer Gupta Karra HarringtonGareth Jones

Adrian KamerJane Khoo Asawari Killedar Neil KilleenTae Wan Kim Eleftheria KotsopoulosGobhathai KunarakRebecca LachovitskiNat LenzoQiao-Xin Li Xiao Liang Kathleen LucasJames LuiGeorgia MartinsRalph Martins Paul MaruffColin MastersSabine MatthaesAndrew MilnerClaire MontagueLynette MooreAudrey MuirChristopher O’HalloranGraeme O'Keefe Anita PanayiotouAthena PatonJacqui PatonJeremiah Peiffer

Svetlana PejoskaKelly PertileKerryn Pike Lorien PorterRoger PriceStephanie Rainey-SmithParnesh RanigaAlan Rembach Miroslava RimajovaJo RobertsonMark RodriguesElizabeth RonsisvalleRebecca Rumble Christopher RoweOlivier SalvadoJack SachGreg SavageCassandra SzoekeKevin TaddeiTania TaddeiBrett TrounsonMarinos Tsikkos Victor Villemagne Stacey Walker Vanessa WardMichael WoodwardOlga Yastrubetskaya