Alzheimer’s Disease: What’s New on the Horizon

March 25, 2015 Christopher Marano, M.D.

Assistant Professor Division of Geriatric Psychiatry and Neuropsychiatry Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Johns Hopkins Bayview Medical Center 1

Objectives

• Briefly review symptoms and causes of dementia • Briefly review current treatments for Alzheimer’s dementia • Future directions for Alzheimer’s treatment – Seeing amyloid in the living brain – Potential disease-modifying treatments – Can we prevent Alzheimer’s?

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What is Dementia?

• Loss of thinking, memory and reasoning skills to a degree that seriously affects the ability to carry out daily activities http://www.nia.nih.gov/HealthInformation/Publications/forgetfulness.htm Accessed 5/13/2009 3

What Causes Dementia?

• Dementia itself is not a disease, but a group of symptoms (called a syndrome) caused by certain diseases or conditions 4

What Causes Dementia?

• The 2 most common causes of dementia are: 1.

Alzheimer’s Disease – 60-70% 2. Vascular Dementia – 10-20% • Alzheimer’s and Vascular Dementia often exist together (Mixed dementia) 5

Dementia is Common

Prevalence of severe (Mini-Mental State Examination score, <=9), moderate (Mini Mental State Examination score, 10–17), and mild (Mini-Mental State Examination score, >=18) Alzheimer disease, in each of 3 age groups, in the community population providing data for these estimates.

Hebert: Arch Neurol, Volume 60(8).August 2003.1119–1122 6

Dementia is Common

Projected number of persons in US population with Alzheimer disease by age groups, 65 to 74 years old, 75 to 84 years old, and 85 years and older, using the 2000 US Census Bureau middle series estimate of population growth.

Hebert: Arch Neurol, Volume 60(8).August 2003.1119–1122 7

Dementia is Costly

• Alzheimer's and dementia triple healthcare costs for Americans age 65 and older • The direct and indirect costs of Alzheimer's and other dementias to Medicare, Medicaid and businesses is more than $148 billion each year • Alzheimer’s is the seventh-leading cause of death.

Alzheimer’s Association, 2009 Alzheimer’s Disease Facts and Figures 8

What is Alzheimer’s Disease?

• Named after Dr. Alois Alzheimer.

• 1906: discovered changes in the brain of a woman who died from an unusual mental illness • Symptoms included memory loss, language problems, and unpredictable behavior • After her death, he examined her brain and found many abnormal clumps (amyloid plaques) and tangled bundles of fibers (neurofibrillary tangles). 9

What is Alzheimer’s Disease?

• Plaques and tangles in the brain are two of the main features of AD • Progressive loss of brain cells • Damage to the brain begins up to 10 to 20 years before symptoms develop 10

Plaques and Tangles

http://www.memorydisorder.org/research/amyloid/images/klnk/plaques.jpg

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Symptoms of Dementia

• Four “A”s of Dementia 1. Amnesia (

Memory

) 2. Aphasia (

Language

) 3. Apraxia (

Doing things

) 4. Agnosia (

Recognizing the world

) • Plus loss of executive function (

Getting things done

) Rabins, Lyketsos, Steele.

Practical Dementia Care

2nd Edition , OUP, 2006 12

Behavioral (or Neuropsychiatric) Symptoms of Dementia

• Delusions • Hallucinations • Agitation or aggression • Depression or dysphoria • Anxiety • Elation or euphoria Cummings et al., Neurology, 1994 • Apathy or indifference • Disinhibition • Irritability or lability • Motor disturbance • Nighttime behaviors • Appetite and eating 13

Symptoms of Alzheimer’s Disease

• Cognitive and functional symptoms are disease hallmarks • However: – Neuropsychiatric symptoms are nearly universal – Associated with multiple adverse consequences including worse quality of life, greater disability, accelerated cognitive or functional decline, greater caregiver burden, earlier institutionalization, and accelerated mortality 1 1. Rabins PV, Lyketsos CG, Steele CD. Practical Dementia Care. Oxford University Press, New York, 2006 14

Current State of Care: Four Pillars of Dementia Care

1. Treat the Disease 2. Treat the Symptoms – Cognitive Symptoms – Neuropsychiatric Symptoms 3. Support the Patient 4. Support the Caregiver R abins, Lyketsos, Steele.

Practical Dementia Care

2nd Edition, OUP, 2006 15

Treat the Disease

• No true disease modifying agents for Alzheimer’s Disease currently 16

Treat the Symptoms: Cognitive (1)

• Cholinesterase inhibitors: – donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne) – Increase the amount of acetylcholine in the brain – Modest benefit (1-2 points on average in the 30 point Mini-Mental State Examination [MMSE]) – Generally well tolerated but some potential serious side effects: slowed heart rate, passing out, falls, hip fracture 17

Treat the Symptoms: Cognitive (2)

• Memantine (Namenda) – Different mechanism than the cholinesterase inhibitors – FDA approved for moderate to severe disease – Same modest benefit as cholinesterase inhibitors – Usually well-tolerated 18

Treat the Symptoms: Behavioral (1)

• Prevention through good care • Medications – Antidepressants: Used for mood and agitation – Antipsychotics: • Can be effective for agitation • High potential for side effects • Slightly increased risk of death (FDA Black Box Warning) 19

Support the Patient

• Comfort and emotional support • Safety: driving, living alone, medications, falls • Structure – Proper approach and communication – Safe predictable place to live with help with daily activities as needed • Activity and stimulation • Planning/assistance with decision making • Management of medical problems

Support the Caregiver (1)

• 2/3 patients with dementia live at home and majority cared for by family • Caregiver distress is common – Studies show symptoms of depression or distress are 2-3x higher compared to general population 21

Support the Caregiver (2)

• BUT there are positives – Many (probably majority) do not report significant emotional distress 22

Support the Caregiver (3)

• Caregiver Distress Symptoms – Grief – Anger – Demoralization – Guilt – Fatigue • Distress ≠ “Clinical Depression” 23

Support the Caregiver (4)

• Emotional support and comfort (including support groups) • Education • Instruction in the skills of caregiving • Problem solving and crisis intervention • Respite and time away • Attention to personal needs and wants • Be on the lookout for depression

Future Directions: The Promise of Research

• Four building blocks toward a cure: 1. Discovery of potential treatments 2. Ability to test if the therapies work 3. Research teams to test the therapies 4. Patients willing to help find the cure by being in studies 25

Visualizing Amyloid in the Living Brain

• Florbetapir (Amyvid) PET Scan • FDA-approved in 2012 • Limitations: – What does a positive scan mean? (especially without a disease modifying treatment) – Not reimbursed by insurance as of yet 26

Typical Negative and Positive Florbetapir Scans Yang L et al. N Engl J Med 2012;367:885-887.

Altering Amyloid in the Brain

• Potential future treatments currently being tested that remove, decrease the production or change the composition of amyloid in the brain • Vaccines, antibodies, enzyme inhibitors 28

A Preliminary Study of Carvedilol for the Treatment of Alzheimer’s Disease

• Carvedilol is a beta-blocker long used to treat heart disease • May reduce the aggregation of amyloid • Currently enrolling participants for a 6 month trial at Johns Hopkins Bayview 29

SNIFF: Study of Nasal Insulin to Fight Forgetfulness

• Growing evidence that insulin has multiple functions in brain and that poor insulin regulation may contribute to development of Alzheimer’s • Examine effects of intranasally-administered insulin in amnestic mild cognitive impairment or mild Alzheimer's disease • Currently enrolling participants for a 18-month study at Johns Hopkins Bayview 30

DIADS-3: Venlafaxine for Depression in Alzheimer’s Disease

• Large studies of various depressants in patients with both AD and depression fail to show a benefit compared to placebo • Venlafaxine (Effexor) is a commonly used antidepressant that acts on 2 different brain chemicals (serotonin and norepinephrine) • Currently enrolling participants for a 12-week study at Johns Hopkins Bayview 31

Challenges in Developing Better Treatments for Alzheimer’s

• May need to start much earlier – Amyloid deposition starts years before symptoms • We may not be able to remove enough amyloid safely (adverse events) • Amyloid may not cause the symptoms of dementia 32

Can We Prevent Alzheimer’s Disease? (1)

• Potentially modifiable dementia risk factors are vascular risk factors – Smoking – Hypertension in midlife – High body mass index (overweight) in midlife – High cholesterol in midlife – Diabetes 33

Can We Prevent Alzheimer’s Disease? (2)

• How to lower vascular risk factors: Control hypertension, cholesterol, stop smoking, weight loss • Mediterranean diet : unsaturated fats and anti-oxidants • Education and exercise are cognitive protective factors so: – Participate in mental and physical exercise 34

Key Components of the Mediterranean Diet

• Eating a generous amount of fruits and vegetables • Consuming healthy fats such as olive oil and canola oil • Eating small portions of nuts • Drinking red wine, in moderation (flavinoids = anti-oxidants) • Consuming very little red meat • Eating fish on a regular basis 35

Mental Health Resources for Seniors and Families

• Primary Care Physician • Specialist care with a neurologist, psychiatrist or geriatrician if needed • Local Department of Aging • Local Health Department 36

Mental Health Resources for Seniors and Families

• Alzheimer’s Association

www.alz.org

– Greater Maryland Chapter 1850 York Road, Suite D, Timonium, MD 21093 410-561-9099 37

Mental Health Resources for Seniors and Families

•

National Library of Medicine MedlinePlus

•

www.medlineplus.gov

Alzheimer’s Disease Education and Referral (ADEAR) Center

800-438-4380 (toll-free)

www.nia.nih.gov/Alzheimers

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Mental Health Resources for Seniors and Families

•

Eldercare Locator

800-677-1116 (toll-free)

www.eldercare.gov

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Johns Hopkins Memory and Alzheimer’s Treatment Center

• Located at Johns Hopkins Bayview Medical Center Campus • Interdisciplinary program involving neuropsychiatrists, neurologists, and geriatric medicine specialist physicians • Evaluation and ongoing treatment working closely with primary care physicians • Assess “cognitively concerned” individuals with or without progressive memory disorders • On-campus state of the art 3 Tesla MRI scanning and brain PET to assist in differential diagnosis

Johns Hopkins Memory and Alzheimer’s Treatment Center

• Comprehensive caregiver & family support & education • Supportive interventions provided by dementia-care specialist nurses, • Access to clinical trials of research therapies for Alzheimer’s disease and related conditions For more information: 410-550-6337 www.hopkinsmedicine.org/memory

Contact information for clinical trials at Johns Hopkins

Wendy Golden at (410) 550-9022 42

Comments or Questions

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Thank You

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