Alzheimer's Disease: Social and Economic Impact, Risk Factors, and Management

1. Whitney Wharton, PhDCognitive NeuroscientistAssistant ProfessorDepartment of NeurologyEmory 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 2050.1 • 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 (www.alz.org/facts/downloads/facts_figures_2015.pdf). 2. Hurd MD et al. N Engl J Med. 2013;368:1326-1334.

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 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 • 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 Pathologic Load Cognitive Function Mild Cognitive Impairment Normal AD CSF biomarkers Neuroimaging Cognitive measures

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

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

16. AD Management • 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 • 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

17. Experimental Agents

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

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

20. Prevention Research Normal Cognition MCI • Worse Cognitive Abilities  better MildAD ModerateAD • 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

23. Normal Aging CognitiveFunctioning 20 30 40 50 60 70 72 74 76 78 80 Age Vascular Risk Factors:Cognitive Onset and Progression 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 • 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?? • 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! 404.712.7085 w.wharton@emory.edu