MCI Talk-Park Web Final
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Transcript of MCI Talk-Park Web Final
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Beta Amyloid Deposition inVery Healthy Adults: Risk
Factors and CognitiveConsequences
Denise C. ParkDistinguished University Professor
Regents Research Scholar
University of Texas at Dallas
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RESEARCH SUPPORTED BY
The National Institute on Aging
28 years of continuous support
The Alzheimers Association
Avid Radiopharmaceuticals
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Collaborators
Gerard Bischof Andy Hebrank
Dr. KristenKennedy
Dr. KarenRodrigue
Jenny Rieck
Dr Mike
Devous
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Approaching the Issue of MCI from a Healthy Aging Perspective
What is healthy or normal aging ?
Assumptions typically associated with researchon healthy participants
Individuals who are functioning at highlevels have healthy brains..
Individuals with neurological disease are
excluded from healthy aging studies
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The Aging Mind in Healthy Adults:2002
Park et al., 2002, Psychology & Aging
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Neuroimaging and a Revised View ofthe Aging Mind
It is a false dichotomy to conceptualize a mind as healthy orunhealthy with age .
Few people by the age of 60 are without some type of subtle orfrank neural pathology.
People can exhibit very high levels of .cognitive function in inthe context of pronounced neuropathology.
The brain can adapt and remodel in response to pathology
People differ in their cognitive reserve and how much they are
able to adapt.
The Scaffolding Theory of Aging and Cognition provides a viewof the aging mind that integrates brain structure and function topredict cognitive function.
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The Scaffolding Theory of Aging and Cognition
NeuralChallenges
Amyloid BurdenShrinkage
White Matter ChangesCortical Thinning
Dopamine Depletion
AgingLevel of
CognitiveFunction
CompensatoryNeural
Scaffolds
Frontal RecruitmentNeurogenesis
Distributed ProcessingBilaterality
ScaffoldingEnhancement
New Learning
EngagementExerciseCognitive Training
Education
Park & Reuter-Lorenz (2009), adapted from Annual Review of Psychology
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How early in the lifespan can wedetect Alzheimers disease and whydoes it matter?
Consider the progress we have made onheart disease and many types of cancer.
We are at the beginning of this era in the
brain
Tremendously excited and hopeful about developingdrugs and behavioral interventions to slow age-relateddecline.
Delaying aging process by five years would cut the rateof Alzheimers disease in half. Slowing the rate of aging of various aspects of the brain
is a tremendously important goal.
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Basic Research: The Dallas LifespanBrain Study
Conduct a very large study of the brainacross the entire lifespan. How do changes in the brain relate to cognitionas we age? Can the brain protect itself from some aspects
of neural deterioration associated with aging?How? Can we use this information to determine onwhom and what age we need to intervene? Use every available technique to fully
characterize the brain as it ages. Develop a neural footprint of healthy versusunhealthy aging.
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Screening
Cog Session 1
Cog Session 2
Psycho-Social
MRI Session
Genetics
PET Session
Study Protocol
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The Complete Sample
Decade N Mean YrsEducation MMSE Women/ Men
N N
20-29 50 16.3 (11 - 20) 29.00 32 18
30-39 49 17.5 (11 - 24) 28.49 31 18
40-49 50 16.1 (11 - 23) 28.47 32 18
50-59 51 17.4 (12 - 24) 28.65 34 17
60-69 50 16.9 (12 - 24) 28.10 32 18
70-79 51 15.9 (11 - 23) 27.78 32 19
80-89 49 15.2 (11 - 23) 27.28 32 17
Total By Sex
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The Hippocampus, a part of the braincritical to memory, shrinks with age
Age (years)
20 30 40 50 60 70 80 904
5
6
7
8
9
HippocampusA
dj (cm
3) r = -.38, p < .001
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Increases in White Matter Hyperintensities as a function of age
ICC 2 >.90
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Functional Imaging -Measures of Neurovascular Health
Lu et al., (2010)
Cerebral Cortex The investigation of Cerebral Blood Flow andVascular reactivity allows us to understand
how the BOLD response is modified byvascular health
Lu et al. 2011, Cerebral Cortex.
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Responding to NeuralChallenge: Imaging a
Word Judgment TaskIs this word a living or nonliving thing? Book Dog House Ghost Virus Sponge
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Age Differences in Brain PatternsWhen Judging a Word
21-29
30-49
50-58
60-69
70-88
p
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Amyloid and the DallasLifespan Brain Study
We examined the implications of amyloiddeposition on cognition in a largesubsample from the DLBS.
Interventions are ultimately likely tofocus on healthier and younger adultsthan have previously been studied withamyloid imaging.
Imaged 137 healthy adults age 30 to 90using PET and Florbetapir (AvidRadiopharmaceuticals)
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Healthy adults withdifferent levels of amyloidmeasured by florbetapir
Low amyloid in 75
year old male
High amyloid burdenin 62 year old male
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Questions We Addressed
What is the prevalence of amyloid depositionin DLBS adults aged 30 to 90?
Do high amyloid individuals show lowerperformance on cognitive tasks?
Do high amyloid individuals show differentpatterns of neural activity on functionalMRI tasks?
How much of cognitive decline attributed to aging in normal adults is due to thepresence of amyloid?
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What is the prevalence of amyloid deposition inhealthy adults?
Effect of Age on Mean Cortical Uptake
Age (years)
30 40 50 60 70 80 90
SUVR
1.0
1.2
1.4
1.6
1.8r =.37, p
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Effect of Age on Mean Cortical Uptake
Age (years)
30 40 50 60 70 80 90
SUVR
1.0
1.2
1.4
1.6
1.8r =.37, p
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Mean amyloid uptake in Age andGender-Matched High and LowAmyloid Subjects
Images are on same scale; red is highest uptake
High Amyloid (N=18)
Rodrigue , Kennedy, Devous et al. In press.Neurology
Low Amyloid: n = 18
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Working Memory
Mean Cortical A
1.2 1.4 1.6 1.8
StandardizedCompositeZ
-2
-1
0
1
2r = -.49
Recall Memory
Mean Cortical A
1.2 1.4 1.6 1.8
StandardizedCompositeZ
-2
-1
0
1
2r = -.14
Fluid Reasoning
Mean Cortical A
1.2 1.4 1.6 1.8
StandardizedCompositeZ
-2
-1
0
1
2r = -.63
Processing Speed
Mean Cortical A
1.2 1.4 1.6 1.8
Standardized Composite Z
-2
-1
0
1
2r = -.54
In the 18 high amyloid adults, cognitiveperformance decreased with more amyloid.
Fluid Reasoning
Mean Cortical A
1.2 1.4 1.6 1.8
StandardizedCompositeZ
-2
-1
0
1
2r = -.63
Processing Speed
Mean Cortical A
1.2 1.4 1.6 1.8
Standardized Composite Z
-2
-1
0
1
2r = -.54
Processing Speed
Mean Cortical A
1.2 1.4 1.6 1.8
Standardized Composite Z
-2
-1
0
1
2r = -.54
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Amyloid Burden by Risk GroupGenetic Risk
V a s c u
l a r R
i s k
N o r m o
t e n s
i v e
H y p e r t e n s i v e
APOE 4 - APOE 4 +
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Adults with a genetic risk factor for Alzheimers anduncontrolled hypertension had the most amyloid
APOE 4+
Genetic Risk
1.0
1.1
1.2
1.3
1.4
1.5
NormotensiveMedicated HypertensiveUncontrolled Hypertension
Mean Amyloid (SUVR)
APOE 4 - APOE 4+
*
*Hypertension Group APOE: F(1 , 113) = 9.52, p = .003 Age-adjusted means plotted
Rodrigue et al., in prep.
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Age effects are still largewhen amyloid is controlled
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What have we learned and what wewill learn from the DLBS?
The structure of your brain matters for cognition,particularly white matter lesions. How does this interact with amyloid to movepeople closer to Alzheimers?
Your brain works harder to perform cognitive
tasks as you age and this begins in the 30s andcontinues through the 70s. We think that this extra activity in middle agewill predict poor cognitive aging.
It looks like neural effort tops out by age 80 and
does not increase and probably even decreases. Almost nothing is known about the neural life of
oldest adults.
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What have we learned and what wewill learn from the DLBS?
About 20% of very healthy adults have highlevels of amyloid, but 80% have low levels\ How long can a person with a high amyloid load
remain functionally normal? Does high amyloid ALWAYS convert to
Alzheimers? What about middle-aged with above-average
loads for their age group? Uncontrolled hypertension and genetic risk
together are accompanied by a high level of
amyloid - But what is causal?? Doeshypertension cause amyloid or does amyloidcause hypertension?
Does a high level of education protect you? We are adding a sample of less-educated andless healthy individuals.
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TIME WILL TELL. The importance of longitudinal research.
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THE SYNAPSE PROJECT: ATRANSLATIONAL APPROACH
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The Intervention Groups
Participants spent at least15 hours per week inSynapse 5 hours were spent on
formal instruction 10 hours were spentcompleting assignments
Classes were held 2 times
per week Classes were made up of 6
participants in sameintervention.
COMBO
QUILT
PHOTO
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The Intervention Groups
A professional quiltinginstructor taught weeklyclasses
Training started with
learning basic machine skills Progressed to more difficult
skills, used in a final project Binding Machine quilting Hand quilting
COMBO
QUILT
PHOTO
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The Intervention Groups
A professional digitalphotography instructortaught weekly classes
Training started with
learning basic camera andcomputer operations Progressed to more difficult
skills, used in a final project Photo editing Photo journaling Using PhotoshopCOMBO
QUILT
PHOTO
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The Intervention Groups
Participants took part inboth digital photographyand quilting classes The first half was spent inone and the second half wasspent in the other The ordering wascounterbalanced acrossparticipants
COMBO
QUILT
PHOTO
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Verbal Memory Gains for Each Group
*Verbal Memory
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Lets look at memory improvement for eachsubject
51% Change 55% Change 39% Change
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Lets look at memory improvement for eachsubject
76% Change 56% Change 46% Change