Understanding Personalized
Dementia Risk
David S. Geldmacher, MD, FANA, FACP
Patsy and Charles Collat Endowed Professor of Neuroscience
Annual Number of Incident
Cases (in 1000s)
Aging population = More dementia cases
350
Age 65-74
Age 75-84
Age 85+
300
250
200
150
100
50
0
2000
2010
2020
2030
Year
Adapted from: Hebert et al. Alzheimer Dis Assoc Disord. 2001;15:169-173.
And how do people respond to these numbers?
What disease you fear most?
Data from YouGov survey, August 2013; US respondents over 60
Graphic from 2014 Alzheimer’s Disease Facts and Figures, Alzheimer’s Association, Chicago
Memory and Aging
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
No matter how you slice it…
Visual recall worsens in aging
Cross-sectional
Longitudinal
Older people have more difficulty
Individuals worsen as they age
From S. Resnick, NIH – Baltimore Longitudinal Study on Aging
It’s not just memory that changes with age
Salthouse T. Psychological Bulletin 2011 doi: 10.1037/a0023262
You win some, you lose some…
WAIS VOCABULARY
Age effects vary by mental function
Over-learned skills such as vocabulary are
preserved throughout the lifespan
From S. Resnick, NIH – Baltimore Longitudinal Study on Aging
The challenge of early dementia diagnosis
Subtly diverging paths
Memory ability
Healthy Age-Related
Cognitive Decline
Alzheimer’s
Disease
Time
So, what can we do to fight off the effects
of aging?
Optimizing the trajectory of cognitive aging
Intervention
Delayed loss of function
Lindenburger U. Science 2014;346:572-578
Aging Brain: Aging Mind
Fighting 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?
Supply and Demand Model
Response to injury or impairment
Lindenburger, U. Science 2014;346:572-578
Supply and Demand Model
Brain Training Model
Lindenburger, U. Science 2014;346:572-578
Exercise and Problem Solving
Durability of responses
Benefits of navigation training with exercise persist after 4 months
Lindenburger, U. Science 2014;346:572-578
Exercise and Problem Solving
Anatomic Benefits
Lindenburger, U. Science 2014;346:572-578
How might exercise protect the brain?
Insulin-Like
Growth Factor
Muscles
Exercise
Irisin
FNDC5
BDNF
Brain Derived
Neurotrophic
Factor
Multiple pathways for exercise to benefit
Image: http://yogadopa.com/wp-content/uploads/2013/11/memory-is-enhanced-by-exercise.png
Adding to exercise
The role of “wellness”
Wellness
Image: http://yogadopa.com/wp-content/uploads/2013/11/memory-is-enhanced-by-exercise.png
Wellness
What is it? Why should we care?
• Definitions
• "...a state of complete physical, mental, and social wellbeing, 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
What wellness attributes influence dementia risk?
• Interpersonal Connections
• Body
• Marriage
• Physical activity
• Social networks
• Healthy nutrition
• Motivational ability
• Spirit
• Mind
• Purpose in life
• Formal education
• Spirituality
• Intellectual activities
• Midlife occupation complexity
Strout & Howard. J Holistic Nursing 2012;30:195-204
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
“Promoting wellness may be an effective
strategy to prevent cognitive impairment
and protect cognition in aging”
Strout & Howard. J Holistic Nursing 2012;30:195-204
Prevention of Dementia
Delay AD onset
Prevent AD cases
50%
Reduction
Brookmeyer et al, 1998
Lesson Learned:
Prevention Research Pays Off
Elias Zerhouni, M.D.Director, National Institutes of Health Congressional Testimony April 2, 2003
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
Risk Factors for Alzheimer’s Disease
Known risk factors
Possible protective factors
 Aging

Higher level of education
 Family History

Physical activity
 Gene markers

Anti-oxidants
 Down’s syndrome

curcumin

Estrogen*

Anti-inflammatory drug use

Alcohol
 Depression

Cholesterol lowering drugs
 Diabetes mellitus

Mediterranean diet
Possible risk factors
 Head trauma
 Hypertension
 Stroke
 Hormone therapy*
How do common illnesses contribute to dementia?
Oxidative
cell damage
Insulin
resistance
Fat cell
activity
Diabetes
Mellitus
High
Cholesterol
High Blood
Pressure
Dementia
Obesity
Blood vessel
dysfunction
Inflammation
Stroke-like
damage
Middleton & Jaffe, Arch Neurol 2009;66:1210-5
Lifestyle Approaches
Target
Observational Studies
Controlled Trials
 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
Diet*
*Middleton & Jaffe, Arch Neurol 2009;66:1210-5
General Risk reduction recommendations
• 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
Individualizing Risk Assessment
Personalizing Dementia Risk Assessment
Dementia Risk Index (age >65)
Characteristic
Age
Points
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
Possible Range
0-16
Barnes DE, et al. Neurology 2009;73:173–179;
Six-year Risk Prediction (Age 65 and older)
• Dementia risk at 6 years
•
•
•
•
All participants = 14%
N=3375,
Scoren age
≤3 ==76 4%
Score 4-7 = 23%
Score ≥8 = 56%
Possible Range
0-16
N=3375, mean age =76
Barnes DE, et al. Neurology 2009;73:173–179
Mid-Life Dementia Risk Score (age 45-65)
Model 1 score
Model 2 score
Age
47-53
3
3
>53
4
5
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
n/a
2
Education (years)
APOE ε-4 positive
Kivipelto, M et al Lancet Neurol 2006; 5: 735–41
Late-life dementia risk
Predictions from mid-life risk scores
Model 1 (no gene tests)
Score Risk
0-5
6-7
8-9
1.0%
1.9%
4.2%
10-11 7.4%
12-15 16.4%
Model 2 (with gene test)
Score Risk
0-5
6-8
9-10
0.3%
1.7%
4.6%
11-12 4.4%
13-18 16.3%
Study sample N=1409, mean age = 50
Overall 20-year dementia incidence = 4%
Kivipelto, M et al Lancet Neurol 2006; 5: 735–41
20 year risk prediction
Gene testing did not infuence predictions!
Kivipelto, M et al Lancet Neurol 2006; 5: 735–41
Risk Reduction: Case Study
• 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
Case Study
Patient
Risk Score
Risk score example
Age 54
4
Education >10
0
Gender: Female
0
SBP: 150
2
BMI: 32.8
2
Cholesterol: <250
0
Activity: low
1
TOTAL
9
Personalized 20 year risk: 4.2%
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%
Kivipelto, M et al Lancet Neurol 2006; 5: 735–41
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
The first Alzheimer’s prevention study
http://A4study.org
UAB is a Participating Center
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)
memory@uab.edu
www.uab.edu/memorydisorders
www.facebook.com/uab.memorydisordersclinic