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, Australia

dames@unimelb.edu.au

The underlying cause of most

dementia

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, 3 Wagner societies and former

unpaid medical advisor to Alzheimer’s Australia and

ADI

What is dementia? An acquired decline in higher mental function occurring in an alert patient, due to organic brain disease, producing decline in multiple

higher mental functions (memory, intellect, personality) which results in significant impairment in social or occupational functioning. Most

dementia is irreversible and progressive.

Prevalence doubles every 5 years from ages 60 to 90

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

Aetiology of Dementia

Neurodegenerative

• Alzheimer’s disease

• Dementia with Lewy

bodies

• Frontal dementias

• Huntington’s disease

Vascular

• Infarction

• Haemorrhage

• Vasculitis

• Other

Deficiency States

• B12

• Thiamine

• Nicotinic acid

Neurological

disorders/trauma

• “Normal pressure”

hydrocephalus

• Head injury

• Space occupation -

occupying lesions

• Multiple Sclerosis

Infection

• Syphilis

• Viral encephalitis

• HIV

Endocrine disorders

• Diabetes

• Thyroid disease

• Parathyroid disease

• Cushing’s disease

• Addison’s disease

Potentially reversible

• Drugs

• Depression

• Metabolic causes

• MPH

• SDH

• Neoplasm

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

epsilon 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

10

Amyloidogenesis

Emil Kraepelin

Alois Alzheimer (1864-1915)

Translating dementia research into practice

Beta-amyloid plaque shown with PiB PET

Beta amyloid plaques seen under a microscope in post mortem brain tissue from a patient with Alzheimer’s Disease

PiB PET scan showing brain areas containing beta-amyloid plaques (yellow and red areas) in a living person with early Alzheimer’s Disease

• Dementia is complex

• Like weather

• Requires complex system science

• Multidisciplinary teams to research

• Brain is becoming accessible to outstanding science

• CSIRO AIBL initiation established a cohort that attracts

global interest