Malaysian Healthy Ageing Society Professor David Ames BA MD - PowerPoint PPT Presentation

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Professor David Ames BA MD FRCPsych FRANZCP Director National Ageing Research Institute University of Melbourne Professor of Ageing and Health PO Box 2127, Royal Melbourne Hospital, 3050, Victoria, Australia dames@unimelb.edu.au Alzheimer’s disease – why it matters to all of us (and what we are doing about it)

Conflict of interest declaration • I have received honoraria for talks/consultancies, assistance with conference attendance, and/or financial support of research from Astra-Zeneca, Eisai, Eli Lilly, Forrest, GSK, Janssen-Cilag, Lundbeck, Novartis, Pfizer, Roche, Sandoz, Sanofi-Aventis, Servier, SmithKlineBeecham, Voyager, Wyeth. • Former Editor-in-Chief International Psychogeriatrics 2003-11 • Member International Psychogeriatric Association, Geelong Football Club, 2 Wagner societies and unpaid medical advisor to Alzheimer’s Australia and ADI

Australia • 22 million people • 13.1% aged over 65 (10.3% 1985), 315,000 85+ • 6 states and 2 territories • Mixture of national and state government health care responsibilities • Mixed private and public system with universal health insurance (medicare) • Rapid growth in dementia population • 100,000 late 1980s, 220,000 now (1% total population), 1,000,000 (3%) by 2050

Dementia Acquired decline in multiple higher mental functions (intellect, memory and personality) occurring in an alert patient which is usually progressive and irreversible and caused by an organic medical condition. To be diagnosed the cognitive impairment must affect daily function. Dementia is a syndrome with many causes Dementia is an age related disorder whose prevalence doubles every five years between age 60 and 90

Life Expectancy Ikeda N. et al. The Lancet. 2011; 378:1094-105

Demographic Ageing • Increasing life expectancy • Falling fertility rates (declining child mortality, increasing education, economic development) • Variable migration patterns • Rates of demographic ageing in China, India and Latin America are unprecedented in world history

Growth of numbers of people with dementia • The World Alzheimer Report (2009) estimated: – 35.6 million people living with dementia worldwide in 2010 – Increasing to 65.7 million by 2030 – 115.4 million by 2050

Worldwide cost of dementia • The societal cost of dementia is already enormous. • Dementia is already significantly affecting every health and social care system in the world. • The economic impact on families is insufficiently appreciated. • The total estimated worldwide costs of dementia are US$604 billion in 2010. • These costs are around 1% of the world’s GDP 0.24% in low income 1.24% in high income

Worldwide costs of dementia • The World Alzheimer Report (2010) estimated that: If dementia care were a country, it would be the world’s 18th largest economy

N o of working-age persons per person with dementia 2000-2050 74.84 80 70 60 Ratio of 50 working-age 26.05 40 to dementia 30 20 10 0 2000 2010 2020 2030 2040 2050 Year Jorm A et al. 2007 ANZ J Psychiatry

Dementia - the concept • Dementia is an umbrella term to describe a syndrome of – memory loss and – other cognitive impairments – interfering with daily function • Over 100 causes of dementia • Alzheimer’s disease is the most common

Alois Alzheimer (1864-1915)

The Amyloid Plaque From W Spielmeyer, Histopathologie des Nervensystems. 1922

Tangles – tau protein

Beta-amyloid plaque shown with PiB PET PiB PET scan showing brain areas Beta amyloid plaques seen under a containing beta-amyloid plaques microscope in post mortem brain (yellow and red areas) in a living tissue from a patient with Alzheimer’s person with early Alzheimer’s Disease Disease Translating dementia research into practice

Alzheimer’s disease • Causes 50-80% of all dementias • Characterised by insidious onset and slow steady progression of deficits • Initially new learning is affected, later praxis, language and some frontal functions will deteriorate • Pathological hallmarks are plaques (amyloid) between cells and tangles (tau) within neurons • Appears related to breakdown of amyloid precursor protein leading to amyloid production • Main risk factors are unmodifiable – age, family history, APOE ε 4, female sex, but potentially modifiable may include head injury and vascular risk factors • No perfect diagnostic test in living patient but clinical diagnosis correlates 80-90% with autopsy findings in experienced hands • Typical course 7-10 years from onset to death

Compelling evidence for the A beta theory of AD • A beta is the major macromolecule in the AD plaque • Mutations in APP and gamma-secretase (PS1, PS2) cause AD • Correlations of AD with PiB-PET and CSF A beta 42 (  ) • Pathologic lesions of AD occur in DS (APP triplication) • Zn / Cu interactions with A beta explain the selective topography of AD in the excitatory glutamatergic system • ApoE polymorphism – the only major risk factor - may act through A beta clearance pathway • Preliminary evidence of 1-2% loss of clearance capacity of A beta in sporadic AD (Bateman) • Preliminary evidence that therapeutic targeting of A beta is effective • Alternate theories not developed

What has Australia done to help? • 1985 Masters and Beyreuther – molecular structure of A β amyloid protein • 1987 Jorm, Korten and Henderson – meta-analysis of published studies showed that dementia prevalence doubled with every 5.1 years of age from 60-90 • 1989 Brodaty and Gresham – showed that support and education of 100 spouse caregivers decreased caregiver stress and delayed institutionalisation of people with dementia • From early 1990s Bush, Masters et al – role of metals in amyloid toxicity • From 2003, LoGiudice, Smith et al. - dementia detection in remote community tribal aborigines • From 2004 Rowe et al. - amyloid imaging • From 2006 AIBL study • 2008 Lautenschlager et al. – exercise appears protective for cognitive function (JAMA)

Partner logo here Research funding per $1 of 2023 direct care costs

The Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing – an example of Australian research on Alzheimer’s disease

Sites . Major Sponsor MELBOURNE PERTH

Partner logo here The Cohort  A$3+ million study launched Nov 14 th 2006 largest study of its kind in Australia  3-year prospective longitudinal study  Large scale cohort study: 1112 participants  Patients with AD, MCI and healthy volunteers  Multi-disciplinary approach, 4 research streams cognitive, imaging, biomarkers and lifestyle Baseline Follow-up (every 18 months) Clinical/cognitive data Clinical/cognitive data 80ml blood 80ml blood Lifestyle information PET & MRI scans PET & MRI scans (250 volunteers) Translating dementia research into practice

AIBL collaborators 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

Study aims 1. To improve the understanding of the pathogenesis and diagnosis of Alzheimer’s disease using neuropsychological, neuroimaging and biomarker techniques, with a focus on early diagnosis of AD 2. To examine lifestyle and diet factors that may be involved in the pathogenesis of AD, towards future lifestyle intervention

Why AIBL? Why would we want pre-symptomatic detection? – To enable research into causes – To identify at risk individuals for lifestyle research – To identify at risk individuals for putative drug therapies – Ultimately, to identify people who can have the onset of AD delayed by intervention – Essential arm of a twin track strategy (early detection and effective intervention)

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

Progress AIBL 1 – initial phase of the study • Recruit cohort of 1000+ people (1112 by August 2008) • Conduct thorough assessment at baseline • Repeat assessment at 18-months 18-month assessments completed in mid-2010 (90%) Commitment from the AIBL partners and CSIRO SIEF fund to continue the study for at least 2 more timepoints (36-months and 54-months) while replenishing cohort (AIBL expansion – at least 200) 3 year assessments completed end 2011 Sponsorship to enable additional imaging AIBL active intervention study