1. Whitney Wharton, PhD Cognitive Neuroscientist Assistant Professor Department of Neurology Emory University

2. Learning Objectives Alzheimer’s Defined Social and Economic Impact
Risk Factors
Neuropathology and Disease Trajectory
AD Diagnosis, Treatment and Management
Healthy Brain Tips

3. Social and Economic Costs of AD
AD is the 6th leading cause of death among CCs and the 4th among AAs, in the US.1
Annual cost in US is $226 billion in healthcare costs + the equivalent of $217 billion in unpaid caregiving.1
Annual costs for health care, long-term care, and hospice care for patients with AD and other dementias are expected to increase to more than $1 trillion in
Total annual per-person healthcare and long-term care payments in the US in 2014 were $47,752 for patients with AD, which is more than three times the costs for someone without AD.1
AD is the most costly illness in the United States, more so than cancer and stroke and heart disease combined.2
Alzheimer’s Association, 2015 ( 2. Hurd MD et al. N Engl J Med. 2013;368:

4. Dementia
Dementia: A group of symptoms affecting thinking and social abilities severely enough to interfere with daily functioning.
The difference depends the cause and location of the brain damage.
Alzheimer's Disease (AD): a specific neurodegenerative disease and is the most common cause of dementia in older individuals.

5. What is ‘Probable AD’? An acquired condition Persistent symptoms
Decline from normal baseline
Persistent symptoms
Not temporary confusion
Severe
Interfere with normal social or occupational function
Affects ≥2 areas of higher brain functions
Memory
Language
Learned motor skills
Visuospatial abilities
“Executive” functions
Judgment and problem solving abilities
Personality and behavioral changes

6. What is Mild Cognitive Impairment (MCI)?
An acquired condition
Decline from normal baseline
Persistent symptoms
Not temporary confusion
Symptoms are mild
Does not interfere with normal activities
May affect only one area of higher brain function, most often:
Memory
Language
“Executive” functions
Earliest detectable stage of illness
High risk of progression to dementia

7. AD Symptoms Executive Dysfunction Memory Loss
Repetition of words, stories, phrases
Personality Changes- belligerent, apathy, withdrawal
Psychoses- paranoia
Gait instability- falls
Inability to independently dress, groom, or manage finances or meals
Loss of bowel and bladder function

8. Alternative Causes Other neurodegenerative disease Medications
Stroke (Vad)
Medications
Chemotherapy
Depression
Fever / Infection / HIV
Nutritional deficit
TBI
Alcoholism

9. Why the Need to Correctly Diagnose?
Different projected path
Different Medications
Family Planning / Caregiving

10. AD Risk Factors Age Gender Race Genetics (AopE 4) Parental History
Stress / inflammation
Midlife Hypertension
Midlife Hypercholesterolemia
Obesity
Diabetes
Sleep disturbances
Healthcare neglect (nutrition, exercise, Dr.)

11. AD Neuropathology
Normal AD

12. Atrophy of the hippocampus in normal aging, MCI, and AD
Normal Brain
MCI
Moderate AD

13. AD Disease Progression
Cognitive Function
Pathologic Load
Mild Cognitive Impairment
Normal AD
CSF biomarkers
Neuroimaging
Cognitive measures

14. Clinical Evaluation MCI or Dementia Cognitive Impairment
History from informant
exam, mental status
MCI or
Dementia
Delirium
Depression
Vascular dementia
Hydrocephalus
Tumor
Subdural MS
B12 or folate
Thyroid
Organ failure
Neurosyphilis
HIV
Blood tests
Imaging
Degenerative Dementias
Alzheimer’s disease
Dementia with Lewy Bodies
Frontotemporal dementias
PD, PSP, CBGD, HD, CJD
Clinical features
CSF, genetics

15. Treatment There is no known cure for AD
Medications prescribed are used to treat symptoms

16. AD Management Caregiver support Education and training Planning
Respite care
Support groups
Hope and encouragement
The promise of new and more effective treatments
Access to cutting edge clinical trials
Reduced risk for family members
Cholinesterase inhibitors
Aricept –donepezil
Razadyne (galantamine)
Exelon(rivastigmine)
NMDA Antagonists
Namenda- Memantine
Antidepressants to manage mood/sleep
Zoloft, Citalopram, Lexapro, Trazodone, Mirtazepine
Antipsychotics to manage psychosis

17. Experimental Agents Mechanism Agent Outcome β-secretase inhibitionLY
E2609
MK-8931
RG7129
HPP854
Phase 2 ongoing
Phase 1 complete
Phase 1 ongoing
-secretase inhibition
Semagacestat
Avagacestat
NIC5-15
X (decline)
X (nonsignificant)
-secretase modulation
Tarenflurbil
Fibrillogenesis inhibition
Tramiprosate
Chelation to prevent metal-based oligomers
Clioquinol, PBT2
Ongoing trials
5HT6 antagonism
RVT 101, Idalopirdine
Cerebral glucose metabolism
Caprylindene
Cerebral insulin resistance
Rosiglitazone, T3D959,
Pioglitazone
RAGE antagonism
Azeliragon
Ongoing trial
Melatonin receptor antagonism
Piromelatine
Protein kinase C activator
Bryostatin

18. Prevention Research Increasing Age Worse Cognitive Abilities  better
Normal Cognition
Worse Cognitive Abilities  better
MCI
Mild AD
Moderate AD
Severe AD
Increasing Age

19. Prevention Research Increasing Age Start Treatment HERE
Normal Cognition
Worse Cognitive Abilities  better
MCI
Mild AD
Start Treatment HERE
Moderate AD
Severe AD
Increasing Age

20. Prevention Research MCI Mild AD Moderate AD Severe AD Increasing Age
Normal Cognition
MCI
Worse Cognitive Abilities  better
Mild AD
Moderate AD
Start Treatment HERE
Severe AD
95 Years
Increasing Age

21. How do we clinically shift the curve???
What factors do we know that….
Are linked to cognitive decline and AD symptomatology
Are linked to the pathological hallmarks of AD (plaques and tangles)
Occur during Midlife
TREATABLE / REVERSIBLE

22. Vascular Risk Factors and Alzheimer’s disease
AD has been associated with:
Increased cholesterol levels in midlife
Elevated blood pressure in midlife
Increased levels of inflammation
Obesity
Diabetes
Physical inactivity
What are the environmental risk factors?

23. Vascular Risk Factors: Cognitive Onset and Progression
Cognitive Functioning 20 30 40 50 60 70 72 74 76 78 80
Age
Normal Aging
Hypertension
Plus Diabetes
Vascular Risks
Plus Hyperlipidemia

24. The Brain-Body Connection
The brain needs a healthy blood supply
25 % of the blood from every heartbeat goes to the brain
The brain depends on oxygen from this blood flow to work well

25. Maintain Blood Flow

26. Blood Pressure Meds and AD
Certain meds = reduced risk (55%), progression and conversion from MCI to AD.
ACE-Is and ARBs
Not commonly prescribed to African Americans

27. Strategy Be Aware. Pubmed, Medscape, Google Scholar Start EARLY
Ensure good control is achieved
Only 36% of adults taking antihypertensive medication had good BP control (less than 140/90 mm Hg)

29. Strategy Reduce risks Reduce Stress (depression, caregiver resources)
Exercise!! Physical activity increases the number of connections between brains cells as well as maintains the old connections.
30 minutes moderate aerobic activity 5 days/week 20 minutes vigorous activity 3 days/week
Reduce Stress (depression, caregiver resources)
Ask for help

30. Diet Moderate alcohol intake DASH diet
Columbia University examined the relationship between diet and development of Alzheimer’s disease.
Analyses from 2,000 dementia-free adults ages 65 and older
Persons who consumed a Mediterranean-type diet regularly were 38% less likely to develop Alzheimer’s disease over a four year follow-up

31. Mediterranean Diet Fruits Vegetables Beans Moderate amounts of fish
Low to moderate dairy
Very limited red meat
Olive oil instead of butter or margarine
Tree Nuts such as walnuts or pecans
Red Wine in Moderation

32. What else?? Stay cognitively active Get involved in RESEARCH!!
See your Dr. (Take notes, go with questions
Correct meds
Diagnose and prevent sleep disturbances.
Nighttime BP patterns
Supplements (fish oil, glucosamine, daily vitamin, ensure)
But buyer beware
Stay cognitively active
Get involved in RESEARCH!!

33. Summary AD is not a normal part of aging
Medications, in use, treat symptoms only
Vascular risk factors are linked to AD risk
Slowing disease progression will significantly improve quality of life for patients and caregivers
Prevention studies, in conjunction with treatment studies, are needed to help better define the disease process and find effective treatments

34. Thank You!