Transcript Document

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
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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
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What Causes Dementia?
• Dementia itself is not a disease, but a
group of symptoms (called a syndrome)
caused by certain diseases or
conditions
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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)
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Dementia is Common
Prevalence of severe (Mini-Mental State Examination score, <=9), moderate (MiniMental 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 middleseries 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
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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).
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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
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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.
2.
3.
4.
Amnesia (Memory)
Aphasia (Language)
Apraxia (Doing things)
Agnosia (Recognizing the world)
• Plus loss of executive function (Getting
things done)
Rabins, Lyketsos, Steele. Practical Dementia Care 2nd Edition , OUP, 2006
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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
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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 mortality1
1. Rabins PV, Lyketsos CG, Steele CD. Practical Dementia Care. Oxford University Press, New
York, 2006
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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
Rabins, Lyketsos, Steele. Practical Dementia Care 2nd Edition, OUP, 2006
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Treat the Disease
• No true disease modifying agents for
Alzheimer’s Disease currently
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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 30point Mini-Mental State Examination [MMSE])
– Generally well tolerated but some potential serious
side effects: slowed heart rate, passing out, falls,
hip fracture
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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
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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)
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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
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Support the Caregiver (2)
• BUT there are positives
– Many (probably majority) do not report
significant emotional distress
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Support the Caregiver (3)
• Caregiver Distress Symptoms
– Grief
– Anger
– Demoralization
– Guilt
– Fatigue
• Distress ≠ “Clinical Depression”
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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.
2.
3.
4.
Discovery of potential treatments
Ability to test if the therapies work
Research teams to test the therapies
Patients willing to help find the cure by
being in studies
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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
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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
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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 6month trial at Johns Hopkins Bayview
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Comments or
Questions
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Thank You
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