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UNDERSTANDING ALZHEIMER’S DISEASE:

Malaika K. Singleton, Ph.D. Presentation to the Alzheimer’s Disease and Related Disorders Advisory Committee California Health & Human Services Agency September 18, 2013

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OUTLINE Origin of Report Part 1: Alzheimer’s Disease: Diagnosis, Prevention, and Treatment Part 2: Alzheimer’s Disease in California: The State’s Changing Demographics, the State Plan, and Other Resources to Address Alzheimer’s Disease Part 3: The Federal Response to Alzheimer’s Disease: A National Plan to Prevent and Effectively Treat Alzheimer’s Disease by 2025

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ORIGIN OF REPORT enate Office of Research • Nonpartisan office established in 1969 to serve the research needs of the Senate • Respond to research requests from member offices and committees • Responses include e-mail, memorandums, briefing papers, and published reports • Prepare background info for the Senate Rules Committee to review for the confirmation of Governor appointees to state agencies, boards, and commissions • I volunteered to write this report while a Science and Technology Policy Fellow in 2010 • Legislative interest and sponsorship for investigating the use of antipsychotic drugs in nursing homes

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PART 1: ALZHEIMER’S DISEASE: DIAGNOSIS, PREVENTION, AND TREATMENT efinitions and Background • Dementia • Alzheimer’s Disease (AD) • Risk Factors & Prevention

ew Criteria for Diagnosis: Three Stages of AD • Preclinical • Mild Cognitive Impairment • Dementia Due to Alzheimer’s Disease

ow Is AD Treated? • FDA-approved drugs • Non-pharmacological approaches • Antipsychotics

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DEMENTIA ascular dementia • Multi-infarct, post-stroke dementia • Impaired judgment and ability to plan

ementia with Lewy Bodies (DLB) • Alpha-synuclein aggregates • Sleep disturbances, hallucinations, motor problems

rontotemporal lobar degeneration (FTLD) • Front and side regions of the brain • Changes in behavior, personality, difficulty with language

ixed dementia

arkinsons’s disease • Problems with movement; similar dementia to DLB or AD • Alpha-synuclein aggregates

reutzfeldt-Jakob disease • Infectious, misfolded protein (prion) causing malfunction • Impaired memory, coordination, and behavioral changes

“Alzheimer’s Disease Facts and Figures in California”, 2009

ormal pressure hydrocephalus • Build-up of fluid in the brain; difficulty walking, memory loss, and urinary incontinence

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ALZHEIMER’S DISEASE AD Hallmarks/Biomarkers M

ost common type of dementia (60 – 80%

of cases) A progressive and ultimately fatal brain

disorder characterized by memory loss

(recent events), behavioral changes, and loss

of other functions, including language,

decision-making, walking, and swallowing.

Coloradodementia.org 5

th

leading cause of death in CA as of 2010,

after heart disease, cancer, cerebrovascular

Biomarkers = naturally occurring, measurable substances that can reliably predict the presence, absence, and severity of disease.

disease, and respiratory disease

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RISK FACTORS FOR AD  Age • Prevalence doubles every 5 years beyond age 65 • Prevalence reaches 50 percent for those 85 and over • However, AD is not normal aging, and evidence suggests that a healthy lifestyle, higher levels of education, cognitive activity, and other factors could prevent some cases of AD.  Inherited Genetic Factors • Mutations in genes involved in amyloid beta processing (seen in familial early onset cases) • Variation in a gene (apolipoprotein) that produces a protein essential for clearing cholesterol and other molecules out of the bloodstream — seen in the general population (sporadic AD cases)

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NEW CRITERIA FOR AD DIAGNOSIS  In 2011, the criteria were updated for the first time in 27 years since the criteria was initially established in 1984.  Guidelines establish 3 stages of the disease with a spectrum between and within each stage.  Guidelines emphasize new research methodologies and provide a framework for studying and characterizing the disease in earlier stages; critical for prevention and treatment.

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THREE STAGES OF AD  Preclinical AD • Can last up to a decade or more before any symptoms of memory loss and cognitive dysfunction are apparent • Undetected AD hallmarks revealed during autopsy • Now used as biomarkers to diagnose living individuals

Sperling et al., 2011

From a 7/18/2013 Sacramento Bee article titled, “Some Sense Signs of Disease” •Some people complain of memory problems but perform well on neuropsychological and memory tests •Research suggest they are more likely to have AD pathology and develop MCI (56% more likely to be diagnosed in one study) and dementia later •New category considered, “Subjective Cognitive Decline”

 Mild Cognitive Impairment • Concerns and evidence of cognitive impairment • Preservation of independence and social and occupational functioning • Symptoms mild enough to rule out dementia  Dementia Due to AD • Substantial declines in cognition and behavior that affect the ability to function independently

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TOOLS USED IN THE DIAGNOSIS OF MCI AND AD  Individual/Informant Reports

Positron Emission Tomography (PET)

 Cognitive, Episodic Memory, and Neuropsychological testing  Brain Imaging  Genetic Testing  Cerebrospinal fluid • Amyloid • Less in the CSF, more in the brain = evidence of AD • Tau • More in the CSF, less intact in the brain = evidence of AD

Grundman et al., 2013

Magnetic Resonance Imaging (MRI)

 Blood test for miRNA (novel; more research needed) • •

Regulates gene expression; 12 involved in proper development of neurons and nervous system Can differentiate between healthy, AD, and other diseases www.mayo.edu

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HOW IS AD TREATED?  California Workgroup on Guidelines for Alzheimer’s Disease Management recommends: • Pharmacology to treat cognitive decline and memory loss • Appropriate structured activities for recreation and exercise • Nonpharmacological approaches to address changes in mood and behavior, followed by pharmacological approaches, if necessary • Treatment for comorbid (coexisting) conditions • End-of-life care

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TREATING AD: FDA-APPROVED DRUGS  Five FDA-approved drugs to temporarily slow the worsening of memory loss and cognitive decline  Acetylcholinesterase Inhibitors • Donepezil (Aricept), galantamine (Razadyne), rivastigmine (Exelon), and tacrine (Cognex—discontinued in the U.S.) • Help maintain the brain’s level of acetylcholine, a chemical involved in memory  N-methyl-D-aspartate (NMDA) receptor antagonist • Memantine (Namenda) • Blocks glutamate activity (a chemical involved in learning and memory) to prevent excitotoxicity in the brain

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NON-PHARMACOLOGICAL APPROACHES  The recommended first step to treat behavioral and

psychiatric symptoms associated with Alzheimer’s • Sleep disturbances, verbal and physical outbursts, hallucinations, and delusions

 Environment modification, task simplification,

appropriate activities, and seeking from social services or organizations  Example: Modifying day/night time activities and

behaviors to address sleep disturbances

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ANTIPSYCHOTIC DRUGS  Suggested last resort to treat behavioral and psychiatric problems  Doctors have discretion to prescribe “off-label”  Serious side-effects (FDA black-box warning)— adverse cerebrovascular events and increased risk of death in the elderly  Some modest benefits based on some clinical trials, but more research is needed due to safety and efficacy concerns

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PART 2: ALZHEIMER’S DISEASE IN CALIFORNIA: THE STATE’S CHANGING DEMOGRAPHICS, THE STATE PLAN, AND OTHER RESOURCES TO ADDRESS AD  California’s Demographics  Challenges • • • •

Caregivers AD & Dementia: Medi-Cal Costs Health Care Costs Additional Challenges

 State Plan •

Goals and Recommendations for 2011–2021

 Resources • • •

Alzheimer’s Disease Centers California Institute for Regenerative Medicine Other Programs and Services

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CALIFORNIA’S DEMOGRAPHICS  Currently an estimated

480,000 cases or 11.2% of those age 65 and over  Estimated 37.5% increase

in AD cases between 2010 and 2025, in comparison to a 9% increase between 2000 and 2010

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CHANGES IN CA DEMOGRAPHICS  4.2 million seniors (age 65 and over) and one-tenth of the nation’s AD patients—more than any other state  The first wave of baby boomers (born between 1946– 1964) turned 65 in 2011, the age when the likelihood for AD begins to double every five years  While Caucasians will see the largest absolute growth in AD cases, the proportional increase relative to the entire Caucasian population will not be as steep as that seen in other ethnic groups

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CA DEMOGRAPHICS AND DISPARITIES  AD cases are estimated to triple among Latinos and Asians and double among African Americans (age 55 and older) by 2030 • Large number of baby boomers and social, health, environmental, and genetic risk factors • Education levels • Chronic health conditions (diabetes and heart disease) • Access to health care and clinical trials (challenges include: immigration status, bias in screening and assessment, and level of comfort with clinician) • Cultural competency issues (i.e. language access)

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CHALLENGES: AD CAREGIVERS  Traditionally the wives or adult daughters of individuals with AD  75% of individuals with AD are cared for at home  Emotional, physical, and financial impacts • Mental health disturbances • Health difficulties • Decline in work productivity and attendance, which impact job security and benefits

 Broader societal and economic impacts as the value of unpaid care, cost for formal services, Medicare, and Medicaid continue to rise

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DEMENTIA DOG PROJECT

dementiadog.org

• ed by Alzheimer Scotland, the Glasgow School of Art, Dogs for the Disabled, and Guide Dogs • Fetch medicine in response to an alarm • Take items between the individual and caregiver • Relieve stress for both

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AD AND DEMENTIA: MEDI-CAL COSTS  According to one estimate (in 2007 dollars), Medi-Cal costs are 2.5 times greater for individuals with AD and other dementias compared to those without  Costs are driven primarily by nursing home expenditures, which are about 3 times “Alzheimer’s Disease Facts and Figures in California”, 2009

greater for AD and dementia

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CHALLENGES: HEALTH CARE COSTS  Changes, reductions, and elimination of programs due to the state’s recent fiscal crisis • In-Home ive Services • Adult Day Health Program to Community-Based Adult Services Program

 Opportunities for reform • Coordinated Care Initiative • The Excellence in Dementia Care Project in San Francisco • Includes full-time dementia nurse, 24-hour help line, consultation services, and training existing caregivers for crisis prevention and to reduce emergencies • ~40% reduction in emergency room services and potential for costsavings

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ADDITIONAL CHALLENGES  Long-term care services and • Ability to pay is an issue since Medicare and private insurance plans do not cover • Medicare covers limited skilled nursing facility and home health care services but not respite or custodial care, which is what many individuals with dementia (and their caregivers) need

• Supplemental policies are limited and expensive • Medi-Cal, which covers skilled nursing facility stays, including custodial care, has eligibility requirements (family income and age)

 Workforce • Shortage of formal caregivers and health care professionals with geriatric training

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CA ALZHEIMER’S DISEASE STATE PLAN  10-year action plan  6 categories of goals and recommendations  Published March 9, 2011  The first of 5, 2-year action plans was published in June 2011 and focused on 3 of the 6 goals  Alzheimer’s Disease and Related Disorders Advisory Committee and others within the task force are assessing the implementation of the “California’s State Plan to Address Alzheimer’s Disease”, 2011

plan

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RESOURCES: CA ALZHEIMER’S DISEASE CENTERS  Since 1985, the state has invested more than $90 million in 10 university-

based centers, which raised over $500 million in federal and private research funding.  Due to the state’s recent fiscal crisis, funding was reduced by 50% and

research and data collection were discontinued in 2009.  The centers evaluate a minimum of 100 new patients per year, but

comprehensive, multidisciplinary diagnostic and treatment evaluations were eliminated; follow-up for each newly evaluated patient, complete follow-up reevaluations for all existing patients, clinical follow-up services, and long-term follow-up services were discontinued.  Services offered by the centers include: professional training, specialty

referral clinics, education and community services, research funding, and specialized knowledge provided to committees and task forces.

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RESOURCES: CA INSTITUTE FOR REGENERATIVE MEDICINE  Established in 2004 following the age of Proposition

71, the California Stem Cell Research and Cures Initiative.  Prop. 71 provided $3 billion in bond funding for stem cell

research at CA universities and other research institutions and established a stem cell agency to provide grants and loans to fund research focused on discovering and developing cures, therapies, diagnostics, and technologies to alleviate suffering from disease.  The site currently lists 7 grants targeting Alzheimer’s

disease for a total of ~$26 million of funding.

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RESOURCES: PROGRAMS & SERVICES  See page 40 of the report for a list of programs and services offered from the: • • • •

Department of Aging Department of Health Care Services Department of Social Services California Health and Human Services Agency

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PART 3: THE FEDERAL RESPONSE TO ALZHEIMER’S DISEASE: A NATIONAL PLAN TO PREVENT AND EFFECTIVELY TREAT ALZHEIMER’S DISEASE BY 2025

ational AD Demographics

ementia Costs to the Nation

egislation and National Plan

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NATIONAL AD DEMOGRAPHICS  Estimated 5.2 million Americans living with AD; expected to rise to 7 million by 2025  AD is 6th leading cause of death across all ages; 5th leading cause of death for those over age 65  1 in 3 seniors dies with some type of dementia  Older individuals living with AD could reach an estimated 13.8 million to 16 million by 2050

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DEMENTIA COSTS TO THE NATION (RAND STUDY)

• • •

Formal and informal caregiving cost = $159 billion to $215 billion in 2010 Expected to reach $379 billion to $511 billion by 2040 75% to 84% due to nursing home and home-based LTC, rather than medical services

•

Direct Care Cost • Dementia = $109 billion (estimated cost in 2010) • Heart Disease = $102 billion (in 2010 dollars) • Cancer = $77 billion (in 2010 dollars)

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FEDERAL LEGISLATION & NATIONAL PLAN  National Alzheimer’s Project Act • Signed into law in 2011 • Requires the creation of a national plan to address AD and coordinates AD efforts throughout the federal government • Established the Advisory Council on Alzheimer’s Research, Care, and Services • Charged with holding quarterly public meetings and producing an annual report • First report with set of recommendations was released in April 2012 and was updated in January 2013  National Plan to Address Alzheimer’s Disease (released in May 2012 and updated June 2013) • Goal 1: Prevent and Effectively Treat AD by 2025 • Goal 2: Enhance Care Quality and Efficiency • Goal 3: Expand s for People with AD and Their Families • Goal 4: Enhance Public Awareness and Engagement • Goal 5: Improve Data to Track Progress  Immediate Actions Taken (in 2012): Increased NIH funding for AD research and clinical trials

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2013 UPDATE TO NATIONAL PLAN  Identified actions completed, updated, and new

actions to meet the plan’s goals • Example (Completed): Review evidence on care coordination models for people with Alzheimer’s disease (report is scheduled to be released in August 2013) • Example (Updated): Regularly convene an Alzheimer’s disease research summit to update priorities • First held in May 2012, second planned for 2015

• Example (New): Develop and disseminate a unified primary care Alzheimer’s disease curriculum • Will involve partnering with Alzheimer’s Disease Centers (ADCs)

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SUMMARY HIGHLIGHTS  AD diagnosis and treatment is evolving due to medical advancements and ongoing research  State, federal, and local resources available • Coordination is key and is a shared goal

 State and National Plan to Address AD (and San Francisco) • Both being continuously evaluated and updated

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REFERENCES Alzheime

r’s Disease Facts and Figures in California, 2009 •

http://www.alz.org/cadata/fullreport2009.pdf

2013

Alzheimer’s Disease Facts and Figures •

http://www.alz.org/s/facts_figures_2013.pdf

“Some

Sense Signs of Disease”, Sacramento Bee, July 18, 2013 •

http://www.sacbee.com/2013/07/18/5574935/some-sense-signs-of-disease.html?storylink=lingospot

http://de

mentiadog.org/ “Amazing

Dog Trained To Help People With Dementia ‘Has Given Them Their Life Back’ •

http://www.huffingtonpost.co.uk/2013/07/15/dementia-dog-training_n_3597470.html

“'Dement

ia Dogs' Begin Work, Already Making A Difference With Their Owners In Scotland” (PHOTO) •

http://www.huffingtonpost.com/2013/07/18/dementia-dogs-help-owners-in-scotland_n_3605444.html?utm_hp_ref=tw

“S.F.

Alzheimer's Pilot Results Released” •

http://www.californiahealthline.org/capitol-desk/2013/7/results-out-for-alzheimers-pilot-plan-in-sf

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REFERENCES CONTINUED  “California’s State Plan for Alzheimer’s Disease: An Action Plan for 2011–

2021” • http://caalz.org/PDF_files/CA%20State%20Plan.pdf  California Alzheimer’s Disease Centers • http://cadc.ucsf.edu/cadc/  California Institute for Regenerative Medicine, Alzheimer’s Disease Fact Sheet • http://www.cirm.ca.gov/about-stem-cells/alzheimers-disease-fact-sheet  “Monetary Costs of Dementia in the United States” • http://www.nejm.org/doi/pdf/10.1056/NEJMsa1204629  National Alzheimer’s Project Act • http://aspe.hhs.gov/dalt/napa/

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