Dementia An Increasing Challenge

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Dementia An Increasing Challenge

• Dr. Kieran OConnor
• Consultant Geriatrician
• Mercy University Hospital
• South Infirmary Victoria University Hospital
• University College Cork

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Anxiety

• LEAR "Pray, do not mock me
• I am a very foolish fond old man,
• Four score and upward, not an hour more nor less
• And, to deal plainly,
• I fear I am not in my perfect mind.
• Methinks I should know you, and know this man
• Yet I am doubtful for I am mainly ignorant
• What place this is and all the skill I have
• Remembers not these garments nor I know not
• Where I did lodge last night. Do not laugh at me
• For, as I am a man, I think this lady
• To be my child Cordelia."
• CORDELIA "And so I am, I am."
• Shakespeare, King Lear Act 4, Scene 760-70

Older Age
Orientation
Memory
Recognition
Affects family
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• Last scene of all,
• That ends this strange eventful history,
• Is second childishness, and mere oblivion,
• Sans teeth, sans eyes, sans taste, sans
  everything
• Shakespeare, As You Like It

Terminal Illness
Co-morbidities
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Brumback, RA, Leech RW, J. Ohio State Med Assoc.
1994 87, 103-111
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Dementia An Increasing Challenge

• The Human Brain
• What is dementia?
• Different types of dementia
• Differential Diagnosis
• Alzheimers Disease
• Risk Factors for Dementia
• Prevention
• Treatment

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Inside the Human Brain
To understand Dementia, its important to know a
bit about the brain

• The Brains Vital Statistics
• Adult weight about 3 pounds
• Adult size a medium
  cauliflower
• Number of neurons 100,000,000,000 (100
  billion)
• Number of synapses (the gap between
  neurons) 100,000,000,000,000 (100
  trillion)

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The Brain in Action
Hearing Words Speaking Words Seeing
Words Thinking about Words
Different mental activities take place in
different parts of the brain. Positron emission
tomography (PET) scans can measure this activity.
Chemicals tagged with a tracer light up
activated regions shown in red and yellow.
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Inside the Human Brain
Neurons

• The brain has billions of neurons, each with an
  axon and many dendrites.
• To stay healthy, neurons must communicate with
  each other, carry out metabolism, and repair
  themselves.
• AD disrupts all three of these essential jobs.

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What is dementia?
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Dementia

• Dementia is a condition characterised by a
  progressive decline of mental abilities
  accompanied by changes in personality and
  behaviour.
• There is a loss of memory and skills that are
  needed to carry out everyday activities.

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Dementia is a complex syndrome
Cognitive
Amnesia
Apraxia
Agnosia
Aphasia
Behavioral
Psychological / psychiatric symptoms
Behavioral disturbances
Functional
Personal ADL
Instrumental ADL
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Dementia

• Clinical syndrome
• which is acquired
• Is a deterioration from previous function
• Due to a disease of the brain
• Multiple higher cortical function
• Including memory, thinking, orientation,
  comprehension, calculation, learning capacity,
  language and judgment

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Alois Alzheimer
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Dementia - Types
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Depression ?
Delirium ?
Dementia ?
Reversible causes ?
MCI ? CIND ?
Acute onset Stepwise Risk factors Gait Neurologica
l
Gradual onset Memory loss Normal examination
Hallucinations Fluctuations Visuospatial Parkinson
ism
Behavioural Language Family hx Young onset
Frontotemporal Dementia
Lewy Body Dementia
Alzheimers Disease
Vascular Dementia
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Differential Diagnosis(commonly used mnemonic
device AVDEMENTIA)

• 1. Alzheimer Disease (pure 40, mixed70)
• 2. Vascular Disease, MID (5-20)
• 3. Drugs, Depression, Delirium
• 4. Ethanol (5-15)
• 5. Mild Cognitive Impairment / Medical /
  Metabolic System
• 6. Endocrine (thyroid, diabetes), Ears, Eyes,
  Environ.
• Neurologic (other primary degenerations,
  fronto-temporal
• - Consider diffuse Lewy body dementia, Parkinson
  component)
• 8. Tumour, Toxin, Trauma
• 9. Infection, Immunologic
• 10. Amnesia, Autoimmune

Adapted from Yesavage, 1979
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Mild Cognitive Impairment

• Patients who are memory impaired but are
  otherwise functioning well and do not meet
  clinical criteria for dementia are classified as
  having MCI
• Symptoms include
• Memory complaint, preferably with corroboration
• Objective memory impairment
• Normal general cognitive function
• Intact activities of daily living
• Not demented
• Patients with MCI should be recognized and
  monitored for cognitive and functional decline
  due to their increased risk for subsequent
  dementia

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What is Alzheimers Disease
Alzheimers disease is an irreversible,
progressive brain disease that slowly destroys
memory and thinking skills.

• The risk of developing AD increases with age
• Most people with AD, symptoms first appear after
  age 60
• AD is not a part of normal aging.
• It is caused by a fatal disease that affects the
  brain.

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Alzheimers Disease and the Brain
Plaques and Tangles The Hallmarks of AD The
brains of people with AD have an abundance of two
abnormal structures

• beta-amyloid plaques, which are dense deposits of
  protein and cellular material that accumulate
  outside and around nerve cells
• neurofibrillary tangles, which are twisted fibers
  that build up inside the nerve cell

An actual AD plaque
An actual AD tangle
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Neurofibrillary Tangles
Neurons have an internal support structure partly
made up of microtubules. A protein called tau
helps stabilize microtubules. In AD, tau changes,
causing microtubules to collapse, and tau
proteins clump together to form neurofibrillary
tangles.
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The Changing Brain inAlzheimers Disease
Normal Brain
Alzheimers Disease Brain
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Typical Clinical Features - AD
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Cognitive Function

• Perception
• Attention
• Spatial disorientation
• Ability to perform tasks in sequence

• Memory Short term
• Abstract thinking
• Orientation
• Language
• Judgment

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Function
Instrumental Tasks ( IADL) Self Care Tasks (ADL)
Performance in Employment Handling
Finances Keeping Appointments Handling
correspondence Travelling alone Use of Household
appliances Maintaining Hobbies
Washing Dressing Grooming Bathing Feeding Choosing
proper attire
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Behavioural Psychological Symptoms

• Aggression Psychomotor agitation

Walking aimlessly Pacing Trailing Restlessness Re
petitive actions Dressing/undressing Sleep
disturbance
Aggressive resistance Physical aggression Verbal
aggression
Apathy
Withdrawn Lack of interest Amotivation
Sad Tearful Hopeless Low self esteem Anxiety Guilt
Hallucinations Delusions Misidentifications
Psychosis
Depression
Adapted from McShane R. Int Psychogeriatr 2000
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Disease Progression
FUNCTION
COGNITION
BEHAVIOUR
Deterioration
MOOD
TIME
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Progression
MMSE
symptoms
diagnosis
Loss of independence
Behavioural problems
Nursing home placement
Death
Years
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Risk Factors for Dementia
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Age Gender
Source MRC-CFAS 1998
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Family History
Green, RC, Cupples, LA, Go, R, et al. JAMA 2002
287329
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Genetic Factors

• The genetic risk factors are best studied in AD
• Autosomal dominant forms of AD
• mutations of the amyloid precursor protein (APP)
  gene on chromosome 21
• genes encoding presenilin 1 (PS1) on chromosome
  14
• presenilin 2 (PS2) on chromosome 1.
• Also, AD pathology occurs in the brains of adults
  who have trisomy 21 (Down's syndrome).
• In late life nonfamilial AD most evidence that
  exists is for the Apolipoprotein E (ApoE) epsilon
  4 gene
• ApoE e4 is a susceptibility gene, not a
  determinative gene.
• Patients homozygous for this allele are much more
  likely but not absolutely destined to develop
  dementia.
• Almost 40 percent of patients with AD do not
  carry ApoE e4

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Modifiable Risk Factors

• Atherosclerosis Risk Factors
• Hypercholesterolaemia
• Diabetes Mellitus
• Hypertension
• Smoking
• Lifestyle Activity
• Education
• Head injury

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Life Course Epidemiology
Early Life
Genes
Lifestyle Environment
Brain Development reserve
Early - Mid Life
Socio-economic factors
Education
Atherosclerotic Risk Factors
Middle Life
Neurodegeneration
Lifestyle Activity
Age at symptom onset
Contributing Conditions
Late Life
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Prevention of Dementia
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Vitamins

• Antioxidant - Vitamin E
• Initial observation studies suggested possible
  benefit 1,2
• Not reproduced in randomised clinical trials
  3,4,5
• Vitamins B6, B12, and folate
• Trials of vitamin supplementation have not
  specifically addressed the prevention of dementia
• Mainly short observational studies
• In the FACIT trial a group with elevated
  homocysteine concentrations were randomised to
  treatment with folate or placebo for 3 years.
  Those in the folate group showed better results
  for speed of information processing and memory
  6.

1. Engelhart et al. JAMA 2002. 2. Morriset al.
JAMA 2002 3. Yaffe, K et al. Neurology 2004. 4.
Petersen, RC et al. N Engl J Med 2005. 5. Kang et
al. Arch Intern Med 2006. 6. Durga J et al.
Lancet 2007
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Ginkgo Biloba

• Studies do not show benefit in improving
  age-related memory loss in cognitively intact
  adults
• A review of 33 trials of ginkgo for cognitive
  impairment and dementia concluded that ginkgo is
  safe and shows promise 1.
• Most of the studies had poor methods
• Large US and French trials are underway to
  determine if ginkgo prevents dementia or
  Alzheimer's disease
• Results are expected around 2010

Birks J et al. Cochrane Database Syst Rev 2002
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Diet

• High intake of fish and omega-3 fatty acids may
  decrease the risk of cognitive impairment 1
• High fruit and vegetable intake may also decrease
  the risk of cognitive decline 2
• Studies are observational
• Confounding from economic and educational factors

1. Kalmijn et al. Neurology 2004 2. Dai Q et al.
Am J Med. 2006
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Lifestyle Activity

• Maintain cognitive function during ageing
• Higher levels of physical activity
• Mental activity
• Social interaction
• Cognitive training intervention
• Joe Verghese et al.N Engl J Med 20033482508-16.

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Exercise Dementia Risk
Exercise associated with a delay in the onset of
dementia
Larson, E. B. et. al. Ann Intern Med
200614473-81
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Protective Effect of Exercise
Myers, J. et al. N Engl J Med 2002346793-801
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Treatment of Dementia
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Multi-dimensional

• Accurate diagnosis
• Safety issues
• Legal issues
• Depression
• Medical issues
• Vascular risk factors
• Care-giver Support
• Voluntary Organisations

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William Utermohlens Self-portrait from 1967
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