mci talk-park web final

8/13/2019 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


-2

-1

0

1

2r = -.14

Fluid Reasoning

Mean Cortical A

1.2 1.4 1.6 1.8


-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


-2

-1

0

1

2r = -.63

Processing Speed

Mean Cortical A

1.2 1.4 1.6 1.8


-2

-1

0

1

2r = -.54

Processing Speed

Mean Cortical A

1.2 1.4 1.6 1.8


-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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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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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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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

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