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Welcome Real Health: Dementia and Ageing
Welcome Real Health: Dementia and Ageing
Professor Lyn GriffithsIHBI Executive Director
Join the conversation Follow us @qut_ihbi
#QUTDementia
#WeAreIHBI
Professor Elizabeth BeattieDementia Collaborative Research Centre
IMPROVING DEMENTIA CARE WITH RESEARCH:
CHALLENGES AND PROGRESS
Elizabeth Beattie, PhD, RN, FAANProfessor, Aged and Dementia Care, School of Nursing.
Director, Dementia Centre for Research Collaboration and Dementia Training Australia.
Dementia
Describes a collection of symptoms caused by a large group of diseases that affect the brain.
Refers to the loss of cognitive functioning (thinking, remembering, learning, reasoning) and behavioral abilities to such an extent that it interferes with daily life and activities.
Not a normal or inevitable part of aging.
NO CURE
Affecting approx. 50M people worldwide in
2017
The Australian Situation 2018-2056
2018
191,367 (45%) men 234,049 (55%) women $15 Billion
2025 536,164 18.7 Billion
2056 1,100,890 36.8 Billion
[1] Australian Bureau of Statistics (2017) Causes of Death, Australia, 2016 (cat. no. 3303.0)[2] The National Centre for Social and Economic Modelling NATSEM (2016) Economic Cost of Dementia in Australia 2016-2056
425,416
Focus on Quality of Life
Quality of life for older adults with dementia: a sense of well-being, satisfaction with life, and self-esteem, accomplished through the care received, the reaching of desired goals, and the ability to exercise a satisfactory
degree of control over one’s life.
“No two people with dementia, and no two families, are alike in their needs for care and support. Maintaining and enhancing quality of life is the ultimate objective”.
2013 World Alzheimer’s Report
Focus on research co-design with consumers
Development of the national dementia research priorities relating to care and living with dementia.
Involvement of people with dementia and carers at every stage of the research process from first idea through translation into everyday practice.
Engagement with providers of care and support to people with dementia across all sectors of health care – community, RACF, respite care, acute care.
Community education about research involvement and becoming a research volunteer.
Close involvement with advocacy organizations focused on supporting people with dementia, carers and families.
Getting Lost in Dementia
Occurs frequently, demonstrated by numerous studies of wandering and getting lost over the last 3 decades.
Can occur quite early in the disease course and persist until the person is no longer able to move by walking, driving, riding a bike etc.
Occurs both inside the person’s home and in the community Is often viewed as benign, even if it happens repeatedly, because the person is
quickly found, recognised by known people, for example. No current way of predicting the first event of getting lost. Can be highly distressing for the person with dementia, the carer, members of
the public and those involved in search and rescue or retrieval. Can compromise the dignity and autonomy of the person with dementia. The first getting lost event may be the last event because it is a fatal event.
Why do people with dementia get lost?
Fu, H., Rodriguez, G. A., Herman, M., Emrani, S., Nahmani, E., Barrett, G., … Duff, K. E. (2017). Tau Pathology Induces Excitatory Neuron Loss, Grid Cell Dysfunction and Spatial Memory Deficits Reminiscent of Early Alzheimer’s Disease. Neuron, 93(3), 533–541.e5. http://doi.org/10.1016/j.neuron.2016.12.023
A grid cell is a type of neuron in the brains of many species that allows them to understand their position in space.
Excitatory grid cells fire in response to movement through space, creating a grid-like internal map of a person’s environment.
The spatial dissociation in Alzheimer’s disease that causes people to wander and get lost may be a result of tau accumulation in the entorhinal cortex’s grid cells.
Current Research and Activities re Safe Walking with Dementia
Carer’s experiences of keeping a person with dementia who gets lost safe. Beattie et al 2016
People with dementia getting lost in Australia: Dementia‐related missing person reports in the media. MacAndrew et al, 2018
Safe Walking Assessment and Planning (SWAP) tool. MacAndrew
et al in review
Walking safely with dementia toolbox for carers and people living with dementia
Collaboration with Dementia Australia, carers + people with dementia, SAR, police develop an effective alert system and standardised protocol for dementia-related getting lost events
Completed In Progress
+
The experience of carers
30 carers of people with dementia who wander and live at home were interviewed.
Asked to describe experience – 24/7 caring role to ensure safety– Fear person with dementia would become lost– Accepted that person would dementia would require permanent care
as their needs would become too great. Some very innovative strategies used to maintain safety
– String and tin can line around property– Series of barriers and sensor lights to help person with dementia to
navigate at home. Some had exhausted all options and resorted to extreme measures that
caused them grief and guilt and reduced QoL of the person with dementia and carer– Chemical and physical restraint– Locked in house and/or car.
The carer’s voices
“…..at night time we secure the
place and there’s no way out, normally.”
“You don’t know what’s gonna happen to her and who is she gonnaend up with.”
“He never sits down .. I mean not for longer than a minute or so
and he’s on the go again …outside with him I can’t keep
up.”
The Moral Imperative for Action
Couple with Dementia found in scrub in New Norfolk
News reports of lost older adults
Gender Found Well Found Injured or
Unwell
Found Dead Total
Male 65% (43) 12% (8) 23% (15) 66
Female 64% (12) 38% (10) 15% (4) 26
Table 1: Gender by outcome of people who were found ( N= 92)
Review of newspaper articles reporting a missing person with dementia (N=130 people) 2011-2016
L. Schnitker, N. Shepherd, M. MacAndrew, E.R. Beattie; LOST WITH DEMENTIA: REPORTS IN THE AUSTRALIAN PRINT MEDIA, Innovation in Aging, Volume 1, Issue suppl_1, 1 July 2017, Pages 992, https://doi.org/10.1093/geroni/igx004.3589
The SWAP Tool Draft Safe Walking Assessment and Planning
(SWAP) tool has been developed:– 3 parts: Part 1 – Assess risk associated with walking
behaviour; Part 2- evidence based care planning strategies for each risk factor; Part 3 – Information about the person with dementia - used if person becomes lost
– Items developed using review of literature and a delphi process involving an expert panel
– Tool now in preliminary testingPsychometric testing to follow
Recommendations made
1. Need for accurate assessment in all care settings across disease trajectory.
2. Need evidenced based resources for carers that aim to promote independence and reduce risk.
3. Need a standardised search strategy that involves immediate search of area person last seen including under dense bushland and out houses.
4. The introduction of an early alert system such as the Silver Alert or Purple app.
Dementia and Getting Lost Workshop September 4, 2018 Victoria Park Golf Club
Presentations from a range of industry representatives including the Police Search and Rescue Unit, Dementia Australia and carers who have experienced searching for the person they care for or are concerned about them getting lost.
Target Audience:Police, search and rescue personnel, SES volunteers, community carers (professional and family), community nurses
Workshop Overview:
1. Have an understanding of what dementia is and why people with dementia are more at risk of becoming lost.
2. Understand why current search strategies have been developed based on past experiences.3. Understand the applications and limitations of current strategies for reducing the risk of a person
with dementia becoming lost.
HOLD THE DATE!
Other Areas of Recent Research
What Is a Good Day Out?: Working Towards Optimal Day Centre Respite for People Living with DementiaFielding et al 2017
A guide for carers of people with dementia to prepare them for natural Disasters: the CarerReady Guide.Schnitker et al 2017 The Delirium Action Response
Intervention (DARE-ED): Improving the care of people with dementia in the Emergency DepartmentSchnitker et al 2017
Preferred Music for RACF residents with dementiaMacAndrew et al, 2017
Ensuring a Smooth Journey: Improving the accessability of airports for travellers with Dementia.O’Reilly et al, 2017
Quality of Life of residents with dementia in Australian RACFBeattie & Aus-QoL, 2016
Planned walking outdoors for people with dementiaMacAndrew et al, 2017
Health Outcomes for people with dementia in acute careMacAndrew, Fox et al
Useful Dementia-focused Web Siteshttps://www.alz.co.uk/info/faqInternational Alzheimer’s Association
https://www.nnidr.gov.au/National Institute of Dementia Research
http://www.dementia.unsw.edu.au/NHMRC Dementia Centre for Research Collaboration
https://www.dementiatrainingaustralia.com.au/Dementia Training Australia
https://www.dementia.org.au/Dementia Australia
https://www.alzheimersonline.org/Alzheimer’s Queensland
http://sydney.edu.au/medicine/cdpc/documents/resources/Dementia-Guideline-Recommendations-WEB-version.pdfAustralian Clinical Dementia Guidelines (2016)
Thanks to:
Dr Margaret MacAndrew, my QUT colleague in our work on getting lost.
The team members of the DCRC and DTA at QUT.
The many people living with dementia, carers and health care staff who have generously participated in our work.
The members of the broader dementia research and care community whose everyday efforts give us all hope for improving prevention strategies, bringing cures closer, making more treatments available, and providing better care and support so that people can live well with dementia.
Professor Graham Kerr Neuroscientist: dementia and Parkinson’s disease
THINKING ON YOUR FEET: TRANSLATIONAL LESSONS FROM NEUROSCIENCE
FOR FALLS PREVENTION
• Movement Neuroscience, Institute of Health & Biomedical Innovation• School of Exercise & Nutrition Sciences
Prof. Graham Kerr
CLINICAL BACKGROUND
Australia’s Ageing Population is Increasing
Market Size
Prevalence of Parkinson ‘s Disease
• 70,000 people with Parkinson’s in Australia.• Prevalence of 294 per 100,000.• People diagnosed as young as 30 yrs.• $10 billion total economic cost in 2014.
Vision SomatosensoryVestibular
Auditory
NeurologicalPe
rcept
ion
Cognition
Proprioception
Strength
Motor
Balance MobilityCardiorespiratory
Cardiovascular
Polypharmacy
Nut
rition
Falls are a major health problem• 61% injuries in
people >75yrs• Falls lifetime
costs $20.2 billion p.a. (USA)
• 33% community dwellers >65 yrs fall ≥ once a year
• Leading cause of injury deaths
Postural
Instability
Gait impairment
including freezing
Rapid disease
progression
Nursing home
admission
Reduced
quality of lifeDepression
High mortality
risk
Cognitive
decline
Weakness Constipation Reduced fitness Social isolation
Insomnia
Fractures Other injuries Fear of falling
Osteoporosis
Environment
Immobilisation
Frequent falls
Parkinson’s Disease: Clinical Impact of Falls
Bloem et al. Mov Disord 2004; 8:871-884
http://www.aquatictherapist.com/
Motor Symptoms Non-Motor Symptoms
Cognition / Executive Function
• Volition
• Self awareness
• Planning
• Response inhibition
• Response monitoring
•Attention
Psychological Function
• Cognitive Impairment
• Dementia
• Depression
• Anxiety
NEUROSCIENCE & AGEING
↓ Dopaminergic (D2) activity with ageing in a young (25yrs) & old (70yrs) healthy woman.(Kassinen & Rinne 2002).
PD MCI: Frontal , hippocampal & temporal atrophy (Weintraub et al. 2011, 2012)
↓ DLPFC & thalamus in Executive Function (Ko et al. 2012)
Neuroanatomical Changes in PD
Cerebral Blood Flow Changes
(Hsu et al, 2007)
• Changes in vasculature that affect
blood supply to and within the
brain.
• These changes can lead to cerebral
hypoperfusion & cognitive
impairment
• In people with Parkinson’s there is
generally marked hypoperfusion
throughout the cerebral cortex.
• Some brain areas do have
hyperperfusion – cerebellum,
brainstem, lateral frontal lobes.
Dual Tasking
EXERCISE
WHAT TYPE OF EXERCISE?
Aerobic
: activity which increases the demand for oxygen which increases respiration and heart rate.
Resistance
: the activity of lifting heavy objects for exercise, especially to improve the strength of the muscles.
• chest press
• lateral pull down
• reverse flys
• double leg press
• biceps curl
• shoulder press
• triceps extension
• back extension
• knee extension
• hip extension
• rotary calf.
Resistance Exercises
Exercise Motivation
have difficulty walking in dim light
have an urgency to go to the toilet at night
sometimes feel dizzy, light headed or drowsy
are taking more than three medications, particularly sleeping tablets, tranquillisers or anti-
depressants
If you answered “yes” to one or more of these questions you are at risk of having a fall. You need to
speak to your doctor or physiotherapist about elderly falls prevention.
It’s never too late to start an exercise
program for elderly falls prevention
Positive studies have been carried out on seniors 60 plus and even on a group of women 80 years
of age and more. They showed that doing a tailored balance and exercise program at home greatly
reduces your risk of a fall and injury.
One study also showed that alongside the exercise program, management of hazards and reduced
vision was also effect ive.
A mobile physiotherapist can assist with falls prevention aged care. They will visit you in your own
environment to assess your risk of a fall.
Exercise Adherence
Further Considerations
QUT PROGRAMS
0
10
20
30
40
50
60
Chest Press AbdominalCurl
BackExtension
Pull Down Push Up LegExtension
Leg Curl Leg Press
Str
ength
change (
%)
DANCE FOR PARKINSON’S
Multivariate Model
• UPDRS total
• Freezing of gait
• Postural orthostasis
• Tinetti balance & gait
• AP postural sway
Sensitivity 78%; Specificity 84%
Frederick GrahamClinical Nurse Consultant: dementia and delirium,Princess Alexandra Hospital
Professor Lyn GriffithsIHBI Executive Director
Alzheimer’s
Disease
clinical trials
at the
Genomics
Clinical Trial site
Dementia vs. Alzheimer’s
Disease
Dementia is a catch-all term which
embraces many causes of reduced mental function.
Alzheimer’s Disease is a specific type of dementia, with its own characteristics.
Alzheimer’s Disease is the most common
form of dementia, making up 50-60% of all
dementia affected people.
AD is characterised by a progressive and
gradual decline in cognitive function
Alzheimer’s Disease vs. Ageing
Alzheimer’s Disease History
Even in the very first case, Dr Alzheimer
noticed the presence of unusual proteins in the brain.
These proteins are still the main contenders for the cause of Alzheimer’s Disease
There are two types, Amyloid Beta and Tau protein.
Amyloid Beta is the target of many clinical trials.
Amyloid Beta
Amyloid Beta is part of a normal
protein, called Amyloid Precursor Protein (APP).
APP is involved in helping brain cells grow and survive.
On detection of damage in the brain, APP undergoes enzymatic cleavage.
Cleavage of APP by beta secretase
produces amyloid beta.
AD characterized by the accumulation
of amyloid beta plaques between
nerve cells in the brain
Tau Protein
Tau is a protein that helps to maintain
microtubules, which are important for cell structure and stability
Once thought to stabilise microtubules, new
evidence suggests Tau has a role in maintaining the ability to dynamically reform them at need.
Tau becomes hyperphosphorylated in AD and forms tangles in neurons in the brain
The ApoE Gene There are three forms of ApoE that are
important for Alzheimer’s Disease.
ApoE2, ApoE3 and ApoE4
Each of these variants alters propensity for the VLDL particle to deposit in arteries.
The ApoE Gene Age of onsent of Alzheimer’s disease
differs depending on genotype.
AD Clinical Trials
Tests of memory and thinking ability.
General health check and medical history.
Test for ApoE4
Scans of the brain to detect Alzheimer’s
Disease changes and Amyloid Beta and/or Tau (PET)
Participants also need a partner, who can help
the study team determine how well the participant is doing.
Participants will receive either study drug, or a placebo.
Trial 1: TOMMORROW
The TOMMORROW study is sponsored by the company Takeda.
The TOMMORROW study was for
prevention of the development of
Alzheimer’s Disease, testing the drug pioglitazone.
Pioglitazone is a drug approved for
diabetes treatment, selected for this trial
because it had been observed that those
taking it had lower rates of AD development.
TOMM40 In addition, the TOMMORROW trial aimed to
determine whether genotyping of the
TOMM40 gene alongside APOE could
improve prediction of Alzheimer’s Disease
development.
TOMM40 is a membrane transport channel for
mitochondria.
It is located very close to APOE.
A poly-T repeat is associated with earlier age
of onset.
Trial Outcomes
The TOMMORROW study is wrapping up
presently.
Database freeze is scheduled for
September.
Once database is frozen, analysis will be
completed on measures of drug efficacy
and the predictive power of the genetic
test.
Trial 2: Engage
The Engage study is sponsored by the
company Biogen.
The Engage study was for people with a
diagnosis of Alzheimer’s Disease, but are
in an early stage.
The study wants to find out if the
experimental medication Aducanumab
prevents the progression of Alzheimer’s
Disease.
Aducanumab
Aducanumab is a monoclonal antibody.
Aducanumab has been designed to bind to
Amyloid Beta, either in deposits or floating
around loose.
The immune system then clears the antibody
and the attached Amyloid Beta out of the
brain and destroy it.
Aducanumab is delivered by a regular
infusion of the antibody, with a dose starting
low and increasing over time.
Results of Previous Trial
Results of Previous Trial
Trial Outcomes
Engage trial is ongoing.
Results so far are encouraging and initial
analyses support continuation of the trial.
Some mild side effects but are within
acceptable limits and are a known
consequence of mechanism of action.
Trial 3: Early
The Early trial is sponsored by the
company Janssen.
The Early Trial was for people who do not
yet have Alzheimer’s Disease, but are at
risk for developing it due to beta amyloid
accumulation.
The Early trial aims to determine if an
experimental drug JNJ-54861911 can
prevent the development of Alzheimer’s
Disease.
JNJ-54861911
JNJ-54861911 is a drug designed to prevent Amyloid Beta from being formed.
It blocks the action of beta secretase that
cuts the Amyloid Precursor Protein to produce beta amyloid.
This means either a larger fragment is
produced, or only alpha secretase processing occurs.
Trial Outcomes
The Early Trial is wrapping up.
Unfortunately, side effects were
experienced at too high a rate for
acceptable safety.
Some data collection still ongoing.
Drug will need to be redesigned, or
source of adverse events identified.
Trial 4: GN39763
The GN39763 trial is sponsored by the
company Genentech.
The GN39763 Trial is for people who have
early Alzheimer’s Disease, or mild
cognitive impairment.
Ages 50-80 years.
The Early trial aims to determine if an
experimental drug MTAU9937A can
prevent the progression of Alzheimer’s
Disease.
MTAU9937A
MTAU9937A is a monoclonal antibody
against Tau.
It is intended to capture excess
extracellular Tau, which is believed to play
a role in AD pathology and encourage
the formation of tangles within nerve cells.
The trial is looking to determine efficacy as
well as the most effective dose.
Trial Conduct
The GN39763 Trial is just beginning.
Ethics approvals obtained and final
sponsor approvals moving ahead.
Expected to be a relatively low number of
participants.
Participants will be dosed for 68 weeks,
with an additional 96 week open label
extension phase.
Dose will be via injection.
Trial 5: Graduate
The Graduate trial is sponsored by the
company Roche.
The Graduate Trial is for people who have
early Alzheimer’s Disease, or mild
cognitive impairment.
Ages 50-90 years.
The Graduate trial aims to determine if an
experimental drug Gantenerumab can
prevent the progression of Alzheimer’s
Disease.
Gantenerumab
Gantenerumab is a monoclonal antibody
against aggregated amyloid beta.
It is intended to cause the immune system
to destroy extracellular amyloid beta
plaques.
The trial is looking to determine efficacy as
well as the most effective dosing strategy.
Previous trials have shown promise in
terms of cognitive decline at high doses.
Trial Conduct
The Graduate Trial is just beginning.
Ethics approvals obtained and finalsponsor approvals moving ahead.
Participants will be treated for 103 weeks,
with an additional 41 week follow upphase.
Dose will be via infusion of the antibody.
Participation
The trials take place at our QUT Clinical Trials site at
299 Rio Vista Boulevard, Mermaid Waters, Gold
Coast.
For current trials, a diagnosis of early Alzheimer’s
Disease helps, because trial entry conditions are
quite specific.
Can call (07) 5688 7170 for more information
Or email: [email protected].
Q&A panelProfessor Lyn Griffiths: Alzheimer’sProfessor Elizabeth Beattie: DementiaProfessor Graham Kerr: Parkinson’s and fallsFrederick Graham: Dementia and hospital careDr Daniel Schweitzer: NeurologyJohn Quinn and Glenys Petrie: Advocacy
