understanding personalized dementia risk david s. geldmacher, md, fana, facp patsy and charles...
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Understanding Personalized Dementia Risk
David S. Geldmacher, MD, FANA, FACPPatsy and Charles Collat Endowed Professor of Neuroscience
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Aging population = More dementia cases
Adapted from: Hebert et al. Alzheimer Dis Assoc Disord. 2001;15:169-173.
2000 2010 2020 20300
50
100
150
200
250
300
350Age 65-74 Age 75-84 Age 85+
Annu
al N
umbe
r of I
ncid
ent
Case
s (in
100
0s)
Year
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And how do people respond to these numbers?What disease you fear most?
Data from YouGov survey, August 2013; US respondents over 60Graphic from 2014 Alzheimer’s Disease Facts and Figures, Alzheimer’s Association, Chicago
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Memory and Aging
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Memory complaints are common with aging
• About 3 of 4 people over age 65 report that“memory is somewhat of a problem”
• For those with 12 or more years of education• Complaints are more frequent with more education• Complaints are less frequent over age 75
• Memory complaints relate to memory performance• More complaints = weaker memory performance• The relationship weakens with advancing age
Fritsch T et al. J Neurodegenerative Dis DOI: http://dx.doi.org/10.1155/2014/176843
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No matter how you slice it…Visual recall worsens in aging
Cross-sectional
Older people have more difficulty
Longitudinal
Individuals worsen as they age
From S. Resnick, NIH – Baltimore Longitudinal Study on Aging
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It’s not just memory that changes with age
Salthouse T. Psychological Bulletin 2011 doi: 10.1037/a0023262
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Over-learned skills such as vocabulary are preserved throughout the lifespan
From S. Resnick, NIH – Baltimore Longitudinal Study on Aging
You win some, you lose some…Age effects vary by mental function
WA
IS V
OC
AB
ULA
RY
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The challenge of early dementia diagnosisSubtly diverging paths
Healthy Age-Related Cognitive Decline
Alzheimer’s Disease
Mem
ory
abili
ty
Time
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So, what can we do to fight off the effects of aging?
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Optimizing the trajectory of cognitive aging
Lindenburger U. Science 2014;346:572-578
Intervention
Delayed loss of function
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Aging Brain: Aging MindFighting Back
• The brain is constantly changing• Unused connections get
pruned • Used connections get
strengthened• This process continues
throughout life
Can we harness these processes to promote better mental function in aging?
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Supply and Demand ModelResponse to injury or impairment
Lindenburger, U. Science 2014;346:572-578
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Lindenburger, U. Science 2014;346:572-578
Supply and Demand ModelBrain Training Model
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Exercise and Problem SolvingDurability of responses
Lindenburger, U. Science 2014;346:572-578
Benefits of navigation training with exercise persist after 4 months
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Exercise and Problem SolvingAnatomic Benefits
Lindenburger, U. Science 2014;346:572-578
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How might exercise protect the brain?
Muscles
Insulin-Like Growth Factor
FNDC5
Irisin
Exercise
BDNFBrain Derived Neurotrophic
Factor
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Multiple pathways for exercise to benefit
Image: http://yogadopa.com/wp-content/uploads/2013/11/memory-is-enhanced-by-exercise.png
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Adding to exerciseThe role of “wellness”
Image: http://yogadopa.com/wp-content/uploads/2013/11/memory-is-enhanced-by-exercise.png
Wellness
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WellnessWhat is it? Why should we care?
• Definitions• "...a state of complete physical, mental, and social well-
being, and not merely the absence of disease or infirmity." -World Health Organization.
• "a conscious, self-directed and evolving process of achieving full potential."
-National Wellness Institute
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What wellness attributes influence dementia risk?
• Interpersonal Connections
• Marriage
• Social networks
• Motivational ability
• Mind
• Formal education
• Intellectual activities
• Midlife occupation complexity
Strout & Howard. J Holistic Nursing 2012;30:195-204
• Body
• Physical activity
• Healthy nutrition
• Spirit
• Purpose in life
• Spirituality
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Wellness and cognition
• Wellness in one dimension may:• Protect cognition in aging • Enhance wellness in other dimensions• Compensate for wellness lacking in another dimension.
• Wellness in more dimensions may be more protective than wellness in one dimension
Strout & Howard. J Holistic Nursing 2012;30:195-204
“Promoting wellness may be an effective strategy to prevent cognitive impairment
and protect cognition in aging”
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Prevention of Dementia
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Delay AD onset Prevent AD cases
Brookmeyer et al, 1998
50% Reduction
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Elias Zerhouni, M.D.Director, National Institutes of Health Congressional Testimony April 2, 2003
Lesson Learned: Prevention Research Pays Off
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It is already happening!
• In the Framingham Heart study a person age 60 today has a 44% lower chance of developing dementia than a similar-aged person 30 years ago
• Dementia rates also are down in Germany
Langa KM. Alz Res Therapy 2015, 7:34 doi:10.1186/s13195-015-0118-1
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Risk Factors for Alzheimer’s Disease
Known risk factors
Aging Family History Gene markers Down’s syndrome
Possible risk factors
Head trauma Depression Diabetes mellitus Hypertension Stroke Hormone therapy*
Possible protective factors Higher level of education Physical activity Anti-oxidants
curcumin Estrogen* Anti-inflammatory drug use Alcohol Cholesterol lowering drugs Mediterranean diet
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How do common illnesses contribute to dementia?
High Cholesterol
Obesity
Dementia
Oxidative cell damage
Insulin resistance
Blood vessel dysfunction
Inflammation Stroke-like damage
Middleton & Jaffe, Arch Neurol 2009;66:1210-5
High Blood Pressure
Fat cell activity
Diabetes Mellitus
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Lifestyle Approaches
Target Observational Studies Controlled Trials
Diet* Risk with high antioxidant and healthy fat intake
Improved cognition and lower AD risk
Cognitive activity
Dementia risk with high education and more cognitive engagement
Improved cognition and less decline
Physical* activity
AD risk with high activity in mid & late life
Improved cognition with exercise
*Middleton & Jaffe, Arch Neurol 2009;66:1210-5
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• Physical exercise• Moderate intensity, e.g. walking, 150 minutes per week• Light weight lifting, too
• Healthy diet• Brightly colored fruits and vegetables (5 servings/day)• Fish (ocean, swimming) every week• Mediterranean diet, DASH diet
• Mental exercise• Creative/productive activities
• Puzzles, games, art, crafts, etc.
• Computerized Brain Games• www.aarp.org• www.lumosity.com• www.brainHQ.com
General Risk reduction recommendations
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Individualizing Risk Assessment
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Personalizing Dementia Risk Assessment
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Characteristic Points
Age 75-79 1
80-100 2
↓ Global Cognitive Score 2
↓ Digit Symbol Substitution 2
Body Mass Index <18.5 2
APOE ε-4 positive 1
MRI: Stroke-type damage 1
MRI: Enlarged ventricles 1
Carotid thickness >2.2mm 1
History of Coronary Bypass 1
Slowed time to dress 1
Lack of clcohol consumption 1
Dementia Risk Index (age >65)
Barnes DE, et al. Neurology 2009;73:173–179;
Possible Range 0-16
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Six-year Risk Prediction (Age 65 and older)
Barnes DE, et al. Neurology 2009;73:173–179
N=3375, n age =76
• Dementia risk at 6 years• All participants = 14%• Score ≤3 = 4%• Score 4-7 = 23%• Score ≥8 = 56%
N=3375, mean age =76
Possible Range 0-16
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Model 1 score Model 2 score
Age
47-53 3 3
>53 4 5
Education (years)
7-9 2 3
0-6 3 4
Male Sex 1 1
Systolic BP >140 2 2
Body Mass Index >30 2 2
Low physical activity 1 1
APOE ε-4 positive n/a 2
Mid-Life Dementia Risk Score (age 45-65)
Kivipelto, M et al Lancet Neurol 2006; 5: 735–41
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Model 1 (no gene tests) Model 2 (with gene test)Score Risk Score Risk
0-5 1.0% 0-5 0.3%6-7 1.9% 6-8 1.7%8-9 4.2% 9-10 4.6%
10-11 7.4% 11-12 4.4%12-15 16.4% 13-18 16.3%
Late-life dementia riskPredictions from mid-life risk scores
Kivipelto, M et al Lancet Neurol 2006; 5: 735–41
Study sample N=1409, mean age = 50
Overall 20-year dementia incidence = 4%
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20 year risk predictionGene testing did not infuence predictions!
Kivipelto, M et al Lancet Neurol 2006; 5: 735–41
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• 52 year old woman who complains: “Doctor, I can’t remember anything anymore. Am I getting
Alzheimer’s disease like my mom?”
• Medical History: • High Cholesterol (good control on statin treatment)• Past depression with good response to treatment
• Family history: Mother with Alzheimer’s disease• Diagnosed at age 55
• Exam: Obese, but otherwise normal • Blood Pressure 150/77• Height 5’1” Weight 173.4 lbs.: Body Mass Index 32.8
Risk Reduction: Case Study
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Lifestyle Targets: BP <140; Weight 159 (15# loss!); Physical activity: exercise 2x/week
• If either BP or weight are optimized, dementia risk lowers to < 2%• If all three are optimized, predicted risk lowers to 1%
Case StudyRisk score example
Patient Risk Score
Age 54 4
Education >10 0
Gender: Female 0
SBP: 150 2
BMI: 32.8 2
Cholesterol: <250 0
Activity: low 1
TOTAL 9
Kivipelto, M et al Lancet Neurol 2006; 5: 735–41
Personalized 20 year risk: 4.2%
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Conclusions
• Memory and thinking change with aging• This does not predict Alzheimer’s disease or dementia• Tasks take longer, but can still be done
• Many risk factors for AD can be modified• The glass is not “half empty”
• Simple steps like exercise, diet, brain games, and focusing on wellness can protect the brain• This is not magic• Many of the exact mechanisms are known
• Healthy lifestyle choices may already be working
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The first Alzheimer’s prevention studyhttp://A4study.org
UAB is a Participating Center
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Memory Disorders at UAB
• Clinical Care:• Alzheimer Risk Assessment and Intervention Clinic (205-975-7575)
• Memory Disorders Clinics (appointments: 205-801-8986)
• Research• Studies of memory and related function over time (information: 205-934-6223)
• Treatment studies• Mild and Moderate Alzheimer’s dementia
• Mild cognitive impairment
• Pre-clinical Alzheimer’s disease
205-996-3679 (99-MEMRY) [email protected] www.uab.edu/memorydisorders www.facebook.com/uab.memorydisordersclinic