From Diagnosis to Hope:

The Impact of Dementia & the Resolve to

Discover a Breakthrough
Marie A. Bernard, M.D.
Deputy Director
National Institute on Aging

April 28, 2019

 The Case of Mrs. J
• 82 y.o. retired school teacher
• Lost her husband 6 months ago
• Her children are very concerned
• Shows up inappropriately
dressed
• Gets lost in the neighborhood
• Leaves the gas stove on

2
Concerns of Mrs. J’s Family

• Is this dementia? If so, is it Alzheimer’s type?

• What is being done to prevent or treat Alzheimer’s
type dementia?
• What could Mrs. J have done to avoid it?
• What is the risk for her family?
• What can the family do for the future?

3
Concerns of Mrs. J’s Family

• Is this dementia? If so, is it Alzheimer’s type?

• What is being done to prevent or treat Alzheimer’s
type dementia?
• What could Mrs. J have done to avoid it?
• What is the risk for her family?
• What can the family do for the future?

4
 Thought Experiment #1

True or False
• Alzheimer’s type dementia (AD) is the most
common form
• AD hits its peak in those 70 – 80 years old
• People do not usually die of AD

5
Aging Population

6
 Risk of Alzheimer’s Disease
by Age in 2017
35

30

25
Percent

20

15

10

0
65-74 75-84 85+
Age
Adapted from Hebert, L. et al. (2013).
Neurology, 80:1778-1783.

7
Hallmarks of Alzheimer’s Disease
Pathology

Basics of Alzheimer’s disease and dementia video: https://bit.ly/2vOuoly

8
 Leading Causes of Death,
Adults 65+ Years, 2016
Rank Cause of Death
1 Heart Disease
2 Cancer
3 Chronic lower respiratory diseases Alzheimer’s
4 Stroke disease affects
5 Alzheimer’s disease more than 5
6 Diabetes million
7 Accidents (unintentional injuries) individuals in
8 Influenza and pneumonia the U.S. alone
9 Kidney disease
10 Septicemia
SOURCE: National Vital Statistics Reports, Vol. 67, No. 6, July 26, 2018. Available from: https://www.cdc.gov/nchs/data/nvsr/nvsr67/nvsr67_06.pdf.

9
 Thought Experiment #1

True or False
• Alzheimer’s type dementia (AD) is the most
common form
• AD hits its peak in those 70 – 80 years old
• People do not usually die of AD

10
Concerns of Mrs. J’s Family

• Is this dementia? If so, is it Alzheimer’s type?

• What is being done to prevent or treat Alzheimer’s
type dementia?
• What could Mrs. J have done to avoid it?
• What is the risk for her family?
• What can the family do for the future?

11
 Thought Experiment #2

True or False
• The nation’s investment in AD research has been
constant in the last few years
• There are four known genes associated with AD
• In order to make a definitive diagnosis of AD, there
must be an autopsy
• Most clinical studies focus on the amyloid
hypothesis of AD

12
 The National Alzheimer’s Project Act
• Signed into law in January
2011
• Calls for:
– An annually updated
national plan
– Annual evaluation of all
federally funded efforts
– Advisory Council on
Alzheimer’s Research,
Care, and Services
13
 AD/ADRD Targeted Increases

2011 2012 2013 2014 2015 2016 2017 2018 2019

National $50 M* $40 M* $100 M $25 M $350 M $400 M $414 M

Alzheimer’s redirected redirected additional additional additional additional additional
Project Act within NIH within NIH approp approp approp approp approp
(NAPA) budget budget

$425 M in
additional
*one-year money appropriations
Years displayed are Fiscal Years as of 09/28/18

14
 AD and Related Dementias (AD/ADRD) Research
How Much Are We Spending?
$2,000,000
$1,915M

$1,500,000
$1,423M
Dollars in Thousands

$1,000,000 $986M

$631M

$500,000
FY 2015 FY 2016 FY 2017 FY 2018 Estimated (Enacted)

NIH Funding to AD/ADRD Has Increased Three Fold!

FY19 Funding includes an Additional $425M for AD/ADRD
KEY
● Early-onset genes
● Lipid transport/metabolism

16
Aβ Deposition in Autosomal Dominant AD
Years before Expected Clinical Symptoms

Courtesy of Tammie Benzinger; Bateman, R et al. (2012). N Engl J Med, 367(9):795-804.

18
 Clinical, Cognitive, Structural, Metabolic, and
Biochemical Changes Years Before AD Symptom Onset

Adapted from Bateman, R et al. (2012). N Engl J Med; Aug 30; 367(9): 795-804.

19
 Clinical, Cognitive, Structural, Metabolic, and
Biochemical Changes Years Before AD Symptom Onset

Adapted from Bateman, R et al. (2012). N Engl J Med; Aug 30; 367(9): 795-804.

20
 Autosomal Dominant
Alzheimer’s Disease Trial

Fleisher, AS et al. (2012). Lancet Neurology 11(12):1057-65.

21
 Autosomal Dominant
Alzheimer’s Disease Trial

Beta-amyloid, late 20’s

Fleisher, AS et al. (2012). Lancet Neurology 11(12):1057-65.

22
 Autosomal Dominant
Alzheimer’s Disease Trial
Non-Carriers, late 30’s

Beta-amyloid, late 20’s

Fleisher, AS et al. (2012). Lancet Neurology 11(12):1057-65.

23
 Autosomal Dominant
Alzheimer’s Disease Trial
Non-Carriers, late 30’s

Beta-amyloid, late 20’s Gene Carriers, late 30’s

Dementia onset is in late 40’s

Fleisher, AS et al. (2012). Lancet Neurology 11(12):1057-65.

24
 Ongoing NIA AD/ADRD and Related
Intervention and Prevention Trials (~140)

29 Early- 7 Clinical
6 Late-stage
stage Clinical Therapy
Clinical Drug 3 Delirium/
Drug 53 Non- Development
Development 39 Care and Post-
Development Pharma- for the
(Phase II/III Caregiver Operative
(Phase I and cological Neuro-
and Phase III Interventions Cognitive
Phase II Interventions psychiatric
Clinical Decline Trials
Clinical Symptoms of
Trials)
Trials) AD/ADRD

Amyloid (8) Amyloid (5) Exercise (13) Pharmacological (5)

Receptors (4) Vasculature (1) Diet (5) Non-Pharmacological
Metabolism and Cognitive (2)
Bioenergetics (4) Training (14)
Vasculature (3) Combination
Growth Factors and Therapy (7)
Hormones (1) Other (14)
Multi-target (6)
Oxidative Stress (2)
Other (1) 25
14
NIA Pipeline of Discovery
12

10

0
Drug Discovery Drug Development Phase I/II Trials Phase III Trials

Amyloid Tau
Neurotransmitters Inflammation
Growth factors/hormones Neurogenesis
Metabolism/bioenergetics Synaptic plasticity/neuroprotection
Oxidative stress ApoE/lipids
Vascular targets Proteostasis/proteinopathies
Multitarget drugs Other
14
NIA Pipeline of Discovery
12

10 Amyloid targets = GRAY

Non-amyloid = RED
8

0
Drug Discovery Drug Development Phase I/II Trials Phase III Trials

Amyloid Tau
Neurotransmitters Inflammation
Growth factors/hormones Neurogenesis
Metabolism/bioenergetics Synaptic plasticity/neuroprotection
Oxidative stress ApoE/lipids
Vascular targets Proteostasis/proteinopathies
Multitarget drugs Other
 Thought Experiment #2

True or False
• The nation’s investment in AD research has been
constant in the last few years
• There are four known genes associated with AD
• In order to make a definitive diagnosis of AD, there
must be an autopsy
• Most clinical studies focus on the amyloid
hypothesis of AD

28
Concerns of Mrs. J’s Family

• Is this dementia? If so, is it Alzheimer’s type?

• What is being done to prevent or treat Alzheimer’s
type dementia?
• What could Mrs. J have done to avoid it?
• What is the risk for her family?
• What can the family do for the future?

29
 Thought Experiment #3

True or False
• It has been clearly demonstrated that you can
decrease your risk of developing AD
• Tight blood pressure control may reduce the risk of
mild cognitive impairment, often a precursor of AD

30
AHRQ-National Academies Study
• Two-part assessment of interventions to prevent
AD-type dementia, amnestic MCI, and age-related
cognitive decline
• 13 categories of interventions explored
• Final AHRQ evidence report published in 2017:
https://www.effectivehealthcare.ahrq.gov/search-for-guides-
reviews-and-reports/?pageaction=displayproduct&product
ID=2417

31
 AHRQ-National Academies Study,
cont’d
Key Messages from AHRQ:
• Most interventions showed no evidence of benefit
• Some forms of cognitive training improve the performance of
the specific target for adults with normal cognition
• Little evidence of transfer to other cognitive areas
• Little evidence of reduction of dementia incidence
• Benefit beyond 2 years less certain

32
 AHRQ-National Academies Study,
cont’d
Key Messages of NASEM synthesis:
• Insufficient evidence to justify a public
health campaign
• Encouraging but inconclusive evidence:
• Cognitive training
• Blood pressure management in
hypertensives
• Increased physical activity
www.nationalacademies.org/dementia
National Academies of Sciences, Engineering, and
Medicine (2017). Preventing cognitive decline and
dementia: A way forward. National Academies Press.

33
 SPRINT Study
(Systolic Blood Pressure Intervention Trial)

• 9,361 hypertensive older adults (50+) with increased

cardiovascular risk participated in the study

• Study participation included 30% African-Americans

and 10% Hispanics

The SPRINT Research Group (2015).

NEJM 373(22):2103-16.

34
SPRINT Study

The SPRINT Research Group (2015).

Years NEJM 373(22):2103-16.

35
 SPRINT-MIND Research Question
SPRINT Memory and Cognition in Decreased Hypertension

Does intensive blood pressure control compared with standard

control reduce the occurrence of dementia?

Randomized Controlled Trial Target Systolic Blood Pressure

Intensive Treatment Standard Treatment

Goal SBP < 120 mmHg Goal SBP < 140 mmHg
(n= 4,278) (n= 4,285)

The SPRINT MIND Investigators for the SPRINT

Research Group (2019). JAMA, 321(6):553–561.

36
 SPRINT-MIND:
Primary Cognitive Outcome

* Difference not
statistically
significant P= .1

The SPRINT MIND Investigators for the SPRINT

Research Group (2019). JAMA, 321(6):553–561.

37
 SPRINT-MIND:
Secondary Cognitive Outcomes
• 19% reduction in the rate of developing MCI

• 15% reduction in the rate of composite MCI

and probable dementia

The SPRINT MIND Investigators for the SPRINT

Research Group (2019). JAMA, 321(6):553–561.

38
 Thought Experiment #3

True or False
• It has been clearly demonstrated that you can
decrease your risk of developing AD
• Tight blood pressure control may reduce the risk of
mild cognitive impairment, often a precursor of AD

39
Concerns of Mrs. J’s Family

• Is this dementia? If so, is it Alzheimer’s type?

• What is being done to prevent or treat Alzheimer’s
type dementia?
• What could Mrs. J have done to avoid it?
• What is the risk for her family?
• What can the family do for the future?

40
 Thought Experiment #4

True or False
• The prevalence of dementia is decreasing
• The cost of AD is comparable to that of heart
disease and cancer
• Caregiver health can impact that of their loved one
for whom they are caring
• We know what interventions should be
disseminated to help with AD caregiving

41
 Cognitively healthy life span has
increased as much as life span
Male Life Expectancy at Age 65 Female Life Expectancy at Age 65
69%
20 65%
2.3
20
71% 2.6
66% 1.4 3.9
15 4.0
15 1.8

Time (years)
Time (years)

3.7
3.7

10 10

14.1
12.5 12.5
5 10.7 5

0 0
2000 2010 2000 2010
Year Year
Predicted Cognitively Intact Years (%)
Cognitively Intact Cognitive Impairment Dementia
without Dementia
Adapted from Crimmins, E. et al. (2016). SSM Popul Health 2: 793-797.

42
 The Economic Impact of
Dementia in the U.S.
$s in Billions
600

500

400
Direct Cost
300
Min Ttl Cost
Max Ttl Cost
200

100

0
2010 2040 - projections in 2010 dollars
Hurd, M.D. et al. (2013). NEJM 368(14): 1326–1334.

43
 Total Healthcare Spending in Last 5 Years
of Life, by Payer & Disease
$300,000 Total Costs
*
Total Government
$250,000
Medicare
$200,000 Informal Care
Out-of-Pocket
$150,000
*
$100,000
*
$50,000
*

$-
Dementia Cancer Heart Other
Disease Diseases
Adapted from Kelley, A. S., et al. (2015). Ann Intern Med 163(10):729-736.

44
Caregivers have Higher Odds of High
Strain when PWD at End of Life

Vick, J.B. et al. (2019). Pain &

Symptom Mgmt, 57(2): 199-208.

45
Poor Caregiver Mental Health Predicts Mortality
of Patients with Neurodegenerative Disease

Low Caregiver Mental Health

Cumulative Survival

High Caregiver Mental Health

Time to Death Lwi, S.J. et al. (2017). PNAS. 114(28): 7319-24.

46
 A New AHRQ-National Academies
Study on Dementia Care Interventions
• Two parts:
 National Academies of Sciences, Engineering, and Medicine:
Expert panel input on questions and study design
www.nationalacademies.org/dementiacare
 Agency for Healthcare Research & Quality: Evidence review
• Status:
 AHRQ Evidence-Based Practice Center Award – Made to the
Minnesota EPC – Drs. Mary Butler and Joseph Gaugler are leading
the study
 NASEM Committee list – posted to:
https://www8.nationalacademies.org/pa/projectview.aspx?key
=HMD-HSP-18-04

47
 Save the Date
Dementia Care/Services Summit (II)
March 24-25, 2020
Natcher Conference Center
Bethesda, MD

48
 iCare-AD/ADRD Challenge
Improving Care for People with AD/ADRD
Using Technology Challenge
• Technology applications to improve
dementia care coordination and/or care
navigation
• Up to $400,000 in cash prizes
• Submissions - October 1, 2018 through June 30, 2019
• See https://nia.nih.gov/challenge-prize for full prize details
and archived webinar for participants

49
 Thought Experiment #4

True or False
• The prevalence of dementia is decreasing
• The cost of AD is comparable to that of heart
disease and cancer
• Caregiver health can impact that of their loved one
for whom they are caring
• We know what interventions should be
disseminated to help with AD caregiving

50
Concerns of Mrs. J’s Family

• Is this dementia? If so, is it Alzheimer’s type?

• What is being done to prevent or treat Alzheimer’s
type dementia?
• What could Mrs. J have done to avoid it?
• What is the risk for her family?
• What can the family do for the future?

51
 Thought Experiment #5

True or False
• Alzheimer’s trials focus on recruiting individuals
with symptoms of AD

52
Enroll in a Clinical Trial

www.nia.nih.gov/alzheimers/clinicaltrials

53
 Take-Aways from Mrs. J

• Dementia is common in older adults, and

devastating to the person and family
• There are numerous lines of research ongoing to
address the problem
• We do not yet have a prevention or a cure
• What is good for the heart may be good for the
brain
• Clinical trial participation is crucial

54
 Ways to Stay Informed and Connected

Subscribe to our blog:

https://www.nia.nih.gov/research/blog

55
 Learn More About the NIA

Watch the “About NIA” Video:

https://www.youtube.com/watch?v=qMm5r
enQibo&feature=youtu.be

56
 NIA
The Leader in Aging Research