Healthy Ageing and the Brain

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Healthy Ageing and the Brain

• Professor G A (Tony) Broe
• Prince of Wales Medical Research Institute

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Population Ageing in Australia
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Population Ageing in England 1541-1981
25
20
15

over 60
10
5
0
1541
1751
1921
1981
1798
Era
Laslett.P. 1986
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The Disease Transition Theory Omran 1971

• Three Disease Transitions
• The stage of pestilence and famine to mid
  18th C.
• The stage of receding epidemics 1750 to
  1900
• The stage of degenerative diseases 20th C.
  onward heart and lung disease, stroke,
  diabetes, cancer

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Population Ageing in England 1541-1981
25
The stage of pandemic infections
20
(... - c.1750)
The stage of receding
epidemics
15
(c.1750 - c.1900)
over 60
The stage of
10
degenerative
diseases
5
(c.1900 - ...)
0
1541
1751
1921
1981
Era
over 60
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Population Ageing - 1900 onWhy did the world
age?

• Less and less babies - ZPG
• Why?
• More wealth - food - salubrity
• Less infections Lower infant mortality
• Women chose better education and
  opportunities for their kids
• Hence small families

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Population Ageing 1970s on Phase 2 - The
Ageing of the Aged

• In the 1970s Australian demographers were
  predicting that average life expectancy would
  reach 70 years - then stop
• By the 1980s it became clear that older people
  were living longer and we had entered Phase 2 of
  ageing - rapidly growing numbers of very old
  people

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Healthy Ageing 1970s on Why ageing of the aged?

• Later onset of the fatal systemic diseases -
  heart lung disease, stroke cancer with a
  longer healthier life
• Later disability due to delayed chronic effects
  of the systemic diseases ischaemic heart
  disease, emphysema stroke healthy ageing

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A New Transition - Olshansky (1986) predicted
average survival would stop at 85 Yrs

• Fourth Disease Transition
• The stage of pestilence and famine
• The stage of receding epidemics
• The stage of systemic degenerative diseases
• Delayed degenerative diseases

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Age-standardised deaths - Australia
Respiratory system
(per 100,000 persons)
Cumpston Sarjeant Pty Ltd
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Age-standardised deaths - Australia
Circulatory incl. Stroke
(per 100,000 persons)
Cumpston Sarjeant Pty Ltd
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Neoplasms - Cancer
Age-standardised deaths - Australia
(per 100,000 persons)
Cumpston Sarjeant Pty Ltd
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Risk factors
Tobacco consumption
(kgs per head)
Cumpston Sarjeant Pty Ltd
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Risk factors
Alcohol consumption
(litres per head)
Cumpston Sarjeant Pty Ltd
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What has delayed the Systemic Diseases? SYSTEMIC
DISEASES KNOWN PROTECTIVE OF AGEING
FACTORS Heart diseases The ice chest and
refrigerator - Lower salt intake
Vascular diseases Lower smoking rates Stroke
Better nutrition Chronic lung disease
- Protein/Lipid/CHO balance Cancer
- More fresh fruit and veges Osteoporosis
Safer alcohol use Osteoarthritis
Better physical activity Medical
advances, new drugs
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Age related changes in mean physiologic
functionThe ski slopes of Ageing
Brocklehurst et al. 1998
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Maintaining Physical function
Mid Life
Older Life
Early Life
Age
Functional Capacity


Disability Threshold
Adapted from WHO, 2002
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What maintains physical function?

• The big 3 health promotion factors are
• Cigarettes out
• Regular exercise in
• Good nutrition

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Serious AgeingPhase 3 of ageing

• In the 21st century we are seeing a new
  phenomenon - rapidly increasing numbers of
  seriously old people, in their 80s 90s 100s
• Serious Ageing in developed countries
  - with average survival over 80 years -
  is the result of an epidemic of healthy
  ageing

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Serious Ageing - Declining death rates in the
over 80s
Vaupel et al. Science 1998
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Serious ageingAustralia in the 21st C.

• Malthus (1798) was wrong In developed countries
  we age get richer, rather than multiply get
  poorer
• The demographers were wrong Borrie Omran - 70y
  in 1970s, Fries Olshansky - 85y in the 1980s
• The UN Vaupel are probably closer 93 yrs
  average survival by 2050 - 100 yrs average
  (women) by 2060
• Our ABS predicts 1.3 million people aged 85 in
  Australia by 2051. gt 400 increase - as the
  total population grows by only 30 - to 26
  Million.

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Serious AgeingAustralia in the 21st Century

• Serious Ageing brings with it a New Disease
  Transition - to the late-life brain diseases -
  The major diseases are Alzheimers Disease and
  other cognitive disorders and Parkinsons disease
  and other movement disorders
• Brain Ageing and Brain Diseases should therefore
  be Australias research focus After all the
  body exists to carry the brain around

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A New Disease TransitionBrain disorders of
ageing - Broe Creasey 1995
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What is the evidence for a New Transition? Sydney
Older Persons Study 1992 - 2002 (Random Sample
of Community Dwellers Aged 75)
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Systemic disorders of ageing Prevalence
(N522. Age trends p lt 0.05 plt 0.01)
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Brain disorders of ageing Prevalence
(N522. Age trends p lt 0.05 plt 0.01)
Prevalence rate
The prevalence of depressive symptoms was 6 -
without any age-related rise
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What can delay the Systemic Diseases? SYSTEMIC
DISEASES KNOWN PROTECTIVE SYSTEMIC
AGEING FACTORS Heart diseases Less
salt Vascular diseases Less tobacco
Stroke Better nutrition Chronic lung
disease Physical activity Cancer
Medical advances
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What can delay Brain Diseases Brain
Ageing? PRIMARY BRAIN KNOWN PROTECTIVE
DISEASES OF AGEING FACTORS Alzheimers
disease other dementias
Parkinsons disease NIL other
movement disorders BRAIN AGEING Mild
cognitive impairment NIL Gait
slowing
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Alzheimers disease (AD) Parkinson disease (PD)
The Big Two Brain Disorders of Ageing

• AD and PD accumulate slowly over time
• Early Alzheimer changes (plaques tangles)
  accumulate in the hippocampus of the brain for 30
  - 40 years before AD onset
• Early Parkinson changes (Lewy bodies) accumulate
  in the brain stem for decades before the signs of
  Parkinsons disease

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What is Brain Ageing?

• Ageing itself has been described by many
  observers, including the ancients, as
  a clinical picture of brain decline with a slow
  walk, loss of balance and slowed thinking
• Brain Ageing results from reduced reserve in
  specific brain systems - particularly those
  systems which show progressive Alzheimer changes
  and Parkinson pathology in life

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Ancient Egypt Hieroglyph for old age
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China The modern ideogram for old is derived
from an ancient figure showing a flexed, unsteady
old man, leaning on a stick.
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The Israelites - old ageEcclesiastes Ch 12
Verses 3-5

• The keepers of the house shall tremble Action
  Tremor
• The strong men shall bow themselves Flexed
  posture
• Those that look out the window are dimmed
  Vision
• The daughters of music shall be brought low
  Hearing
• They shall be afraid of that which is high Gait
  instability
• The grass hopper drags itself along Gait
  slowing
• And desire shall fail Blessed relief

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Sydney Older Persons Study 1992 2002 Brain
Ageing predicts dementia at 3 year follow-up
40
30
20
Dementia Incidence at 3 yrs
10
0
Normal Ageing (171)
Cognitive Impairment (94)
Gait Slowing (62)
383 Non-demented older people at Wave 1
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Maintaining brain function into late-lifeWhat
is our aim?
Mid Life
Older Life
Early Life
Age
Functional Capacity


Disability Threshold

Adapted from WHO, 2002
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Can we maintain brain function into
late-life?Four lines of evidence suggest that we
can

• Our brain cells appear to be genetically
  programmed to outlast our bodies (the soma)
• Brain plasticity new brain cells synapses
  - means neuronal loss is not inevitable in ageing
• Better brain development and better education can
  improve cognition delay dementia onset
• Medical research can delay the onset and
  progression of age-related brain disorders

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1. Our brain cells appear to be genetically
programmed to outlast our bodies (the soma)
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2. Loss of neurones is not inevitable with
healthy brain ageing i.e no Alzheimer,
Parkinson or Vascular changes
cortex
male
female
White matter loss ( 2ml/year) accounts for all
brain volume reduction
of cerebral volume
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50
55
60
65
70
75
80
85
90
95
age at death (yr)
Double et al 1996
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3. Education and Brain Development in early life
improve cognitive outcomes in old age

• Brain size (determined in early life) predicts
  cognition dementia in old age (Sydney Study
  etc.)
• Mental ability in early life predicts cognition
  and dementia in old age (Scottish Nun Studies)

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Sydney Older Veterans Study (1997)
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Scottish Primary School Cohort (2001) 11 years of
age in 1936
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The Kentucky Nun Study (1996) Novices essays
around 20 years of age
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3. Education and mental activity throughout life
can improve cognitive outcomes in old age

• In Adult Life
• In London Taxi Drivers the size of the
  posterior hippocampus (a structure important in
  memory navigation) increases with time on the
  job
• In Later Life?
• Brain plasticity is retained in late-life - it
  is biologically likely that mental activity,
  while the brain is healthy, will maintain brain
  function - as per physical activity

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• How could Education work?
• Hippocampus and Pre-frontal lobe are important
  brain areas
• for development maturation in early life
• for premature neurodegeneration in late life

Pre-frontal lobe
Hippocampus

• Hippocampus shrinks with normal ageing (SOPS)

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How could Education work?to protect us from
Alzheimers - 2 Theories

• Brain Reserve Theory Building up the Brain
  The more brain we grow the longer it will
  function as neurons die off - But the brain is
  more than a muscle!
• A more appealing theory is that early education
  and lifelong mental activity act on specific
  brain networks - that are the seat of wisdom
  in adult life - that degenerate
  early in the dementias
• The hippocampus processing memory
• The frontal lobe network planning judgment

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4. Can medical research delay the onset and
progression of the age-related brain
disorders? Alzheimers disease Current Research
at POWMRI Possible Gene products and
mechanisms? Nerve Growth factors?
Protective Aspirin? Anti-inflammator
y drugs? Factors Folate and Vitamin B12?
Lipids and cell membranes?
Anti-oxidants? and Red Wine?
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4. Can medical research delay the onset and
progression of the age-related brain
disorders? Programs Projects Current Research
at POWMRI Alzheimers Disease Sydney Older
Persons Study and other dementias Australian
Familial Dementia Study Genes genetic
risk factors Parkinsons disease Gait, Balance
Falls Studies and other
movement Early Parkinsons disease Study
disorders Spinal Muscle and Nerve
research Brain Imaging Studies MRI, fMRI,
Doppler TMS Studies Basic Neuroscience Anatomy,
physiology cell biology
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Healthy Ageing the Brain Conclusions

• Population Ageing is a good thing 100
  yrs of wealth, health and salubrity have created
  a majority of healthy older people -
  who dont throw bombs
  - who wont have a premature death due to
  heart attacks, strokes, emphysema or cancer
• However their brains are in danger Australia
  needs more Brain Ageing Research - as this is the
  key to a better quality of life in any society
  faced with Serious Ageing

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Use it or Lose it

• The brain is a unique organ the more active it
  is, the more adequate it functions and the longer
  it lives.
• (Michael Hofman Neurobiology of Ageing, 1991)