Transcript ppt: alzheimer`s disease

Lifespan Development
Alzheimer’s Disease
Agenda:
1.What is Dementia? What is Alzheimer’s
Disease?
2.Statistics for the U.S.
3.Stages of AD
4.The Brain and Alzheimer’s
5.Causes
6.Risk/Protective Factors
7.Other forms of dementia… How are they
different from Alzheimer’s?
Normal Aging
STRUCTURAL BRAIN CHANGES
Thinning of the Cortical Gray Matter
Age-Related changes in Neuronal Morphology
Oxidative Stress
DNA Damage
Less efficient Neural Circuits and Brain Plasticity
CHEMICAL BRAIN CHANGES
Dopamine
Serotonin
Glutamate
GENETIC CHANGES
Decline in Gene expression functions
Normal Aging vs. Progressive dementia
Mild
NCD
Major
NCD
http://www.alz.org/downloads/Facts_Figures_2014.pdf
Prevalence by Age
What’s Normal
What’s Not
Forgetting your ATM
number or where you
parked.
Forgetting what an ATM
card is or what kind of car
you own.
Forgetting what you were
about to say
Forgetting how to do an
everyday task, like writing
a check.
Forgetting which day of
the week you had a dental
appointment
Getting lost in your own
neighborhood.
Misplacing of losing your
keys or phone
Putting the ice tray in the
oven instead of the freezer
Forgetting the name of the Forgetting who your family
person who sits in front of members are
you in class
RISK FACTORS FOR ABNORMAL
COGNITIVE DECLINE
Increasing Age
Hypertension
Cardiac disease
Diabetes
Poor nutrition
Social isolation
Family history of dementia
Psychological factors: stress & depression
AGING VS DISEASE CONTINUUM
Normal Aging
Primarily
intact cognition,
subtle processing
speed slowing &
less efficient
attention &
executive
reasoning
Mild
Neurocognitive
Disorder
Decline from
lifelong abilities
in 1 or more
areas of
thinking +
inefficiency in
daily activities
Major
Neurocognitive
Disorder
Needs help
with daily
activities +
substantial
decline in 1 or
more
cognitive
abilities
Dementia vs. Alzheimer’s
What is the
difference between
dementia and
Alzheimer’s
disease?
Evidence for Neurologic Injury
Structural MRI
Normal Hippocampi
Mild Cognitive Impairment
Alzheimer’s Disease
http://www.youtube.com/watch?v=9Wv9jrk-gXc
Flowers
Pansies
Mums
Tulips
Daisies
Roses
Dementia
Frontotemporal
dementia
Vascular dementia
Parkinson’s
dementia
Lewy body dementia
Alzheimer’s dementia
Functional/Clinical Decline
COGNITIVE DOMAINS
DAILY FUNCTIONING
General Intelligence
BASIC transfers, ambulation,
bathing, hygiene, & feeding
Sensory Motor
Attention/Concentration
Processing Speed
Visual Spatial Functions
Language Functions
Memory – Auditory & Visual
Executive – higher thinking &
reasoning
MOOD & BEHAVIORS
INSTRUMENTAL ACTIVITIES
• Safe use of appliances
• Phone answering & dialing
• Laundry
• Housekeeping
• Meal Preparation
• Shopping
• Management of finances
• Management of meds
• Driving
DSM-V Criteria for Major Neurocognitive Disorder Due to
Alzheimer’s Disease
• insidious onset & gradual progression ≥ 2 cognitive domains
• Probable- either:
– genetic mutation (fmh or test)
– 1) decline in memory & ≥ 1 other cognitive
domain,
– AND 2) steady progression,
– AND 3) no evidence of mixed etiology
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, American
Psychiatric Association, 2013.
Symptoms
DSM-5 MILD NEUROCOGNITIVE DISORDER
Evidence of modest cognitive decline from premorbid fx in 1 or
more cognitive domains based on:
CONCERN of pt OR a knowledgeable informant, OR the
clinician that there has been a mild decline in cognitive fx
+
MODESTLY IMPAIRED cognitive performance on standardized
neuropsychological testing or, in its absence, another
quantified clinical assessment.
Cognitive deficits do NOT affect independence in IADLs, but may
require greater effort or compensatory strategies.
The cognitive deficits do not occur exclusively in the context of a
delirium & are NOT better explained by another mental disorder
(e.g., major depressive disorder, schizophrenia).
DSM-5 MAJOR NEUROCOGNITIVE DISORDER
A. Evidence of significant cognitive decline from previous
abilities in one or more cognitive domains based on:
1. Concern of pt OR a knowledgeable informant OR clinician
that there has been a significant decline in cognitive
function; AND
2. SUBSTANTIALLY IMPAIRED cognitive performance on
standardized neuropsychological testing or, in its absence ,
another quantified clinical assessment.
B. Cognitive deficits INTERFERE with independence in activities.
C. Cognitive deficits not due exclusively to a delirium.
D. Cognitive deficits not better explained by another mental
disorder (e.g., major depressive disorder, schizophrenia).
Major NCD
SPECIFY:
1. Without behavioral disturbances
2. With behavioral disturbances: if cognitive disturbance
plus a clinically significant behavioral disturbance
psychosis, mood disturbance, agitation, or apathy.
SPECIFY:
1. Mild: difficulties limited to IADLs
2. Moderate: difficulties with basic activities of daily living
3. Severe: fully dependent
NeuroCognitive
Disorder
due to
Alzheimer’s
disease
Vascular
Neurocognitive
Disorder
Fronto-Temporal
Neuro-Cognitive
Disorder
Neurocognitive
disorder
with
Lewy
Bodies
OTHERS:
Parkinson’s
Depression
Seizures
NPH
Trauma
Infection
Metabolic
Drugs/Toxins
Neoplasms
Anoxia
PROPORTIONAL RANGE OF DEMENTIA
SUBTYPES
http://cargocollective.com/ritamaldonadobranco/Visualising-dementia
“Alzheimer’s disease is bankrupting America”
AD – 6th-leading cause of death in US.
AD - only disease in top 10 causes of death in America without a
way to prevent it, cure it or significantly slow its progression.
Currently $172 billion is spent caring for people with AD & other
dementias.
By 2050, the costs may reach over $1 trillion without adjusting
for inflation.
Almost 1/2 of all AD costs are paid by Medicare & more than one
in every six Medicare dollars is spent on a pt with AD
Between 2010 & 2050, Medicare costs Medicare of caring for a
pt with AD will increase over 600 % & out of pocket costs to
families will grow more than 400 %.
Ten Key Warning Signs for AD
Alzheimer’s Assoc. AD10:
AD10 (continued):
1. Memory loss
6. Problems with abstract
thought
2. Difficulty performing
familiar tasks
3. Problems with language
4. Disorientation to time and
place
5. Poor or decreased
judgment
www.ALZ.org
7. Misplacing things
8. Changes in mood or
behavior
9. Changes in personality
10. Loss of initiative
Alzheimer’s disease facts and figures
5.3 million Americans have AD - 5.1 million are aged 65 and over
(1 in 8).
By 2050, 13.5 to 16 million in US will have AD
Nearly 1 in 2 aged 85 and over has the disease.
Every 70 seconds, someone in US develops Alzheimer’s.
In 2050, every 33 secs an American will develop AD
Survival is an average of 4 to 8 years after diagnosis with AD, but
many live for as long as 20 years with the disease.
On average, 40 % of person’s years with AD are in the most
severe stage of the disease.
AGE IS HIGHEST RISK FACTOR FOR AD
Age 30 – 65
Early Onset
Age 65 – 74
10% of total AD pts – some autosomal dominant mutation in
ALZHEIMER’S
DISEASE
Amyloid precursor protein, presenilin 1 or presenilin 2
7% of total AD pts –
Age 75 – 84
43% of total AD pts
Age 85 & up
40% of AD pts
Total AD pts
Genetics
100% - Female:Male = 2:1 ratio
Familial 5 to 15% of cases;
APOE4  risk factor NOT dx marker – not necessary for AD
Susceptibility - polymorphism APOE-4 & earlier onset in
homozygous individuals.
Down’s syndrome (trisomy 21 gene) AD if survive to midlife
Vascular risk factors AD by cerebrovascular pathology or thru
Risk Factor / direct effects on AD pathology
Typical course 8 to 10 yrs after dx, but some live 20 years
Disease
Late stage AD become mute and bed bound
Course
Early onset more likely to survive full course
Late onset dx more complex multiple comorbidities
Death commonly due to aspiration
MILD NCD DUE TO ALZHEIMER’S DISEASE
A. Criteria met for MILD neurocognitive disorder.
B. Insidious onset & gradual progressive impairment in 1 or
more cognitive domains.
C. Not interfering with IADLs but more difficult & use
compensatory strategies.
1. May or may NOT have evidence of a causative AD genetic
mutation from family history or genetic testing, BUT
2. All 3 of the following are present:
a. Clear evidence of decline in memory & learning + at least
1 other cognitive domain (detailed history or serial
neuropsychological testing).
b. Steadily progressive, gradual decline in cognition, without
extended plateaus.
c. No evidence of mixed etiology
DSM 5 MAJOR NCD due to Alzheimer’s disease
A. Criteria met for MAJOR NCD.
B. Insidious onset & gradual progressive impairment in 2 or more
cognitive domains.
POSSIBLE AD if only one of the following are present 
PROBABLE AD if either of the following is present 
Interferes with IADLs fx
The following CRITERIA are also met:
a. Clear evidence of decline in memory & learning + at least 1
other cognitive domain (based on detailed history or serial
neuropsychological testing).
b. Gradual progressive decline in cognition w/o long plateaus.
c. NO evidence of MIXED etiology
Alzheimer's Disease
•
Estimated that 4,000,000
people in U.S. have
Alzheimer's disease.
• Estimated that 25-35% of
people over age 85 have some
time of dementia.
• After age 65 the percentage of
affected people, doubles with
every decade of life.
• Caring for patient with
Alzheimer's disease can cost
$47,000 per year (NIH).
NEUROPSYCHIATRIC FEATURES AD
~ 80% of pt with MAJOR NCD due to Alzheimer’s disease 
behavioral & psychological SX – that are also frequent at the
MILD stage.
Behavioral symptoms = or more distressing than cognitive
SX & are frequently the reason health care is sought.
MILD STAGE NCD due to AD  depression & apathy
MODERATE STAGE NCD due to AD  psychotic features,
irritability, agitation, combativeness, sundowning &
wandering
Rummaging, hiding, & hoarding
Delusions: Paranoia & persecutory themes
LATE STAGE NCD due to AD  gait disturbance, dysphagia,
incontinence, myoclonus, and seizures
tangle
plaques
Neurofibrillary Tangle
Amyloid Plaque
http://www.drugdevelopment-technology.com/projects/caprosinol/images/2-graph.jpg
.
PET scan of the brain of a person with AD showing a loss
of function in the temporal lobe.
Atrophic hippocampus in AD
Compare central sulcus of
Alzheimer’s patient with normal
81 year old woman
From Whole Brain Atlas at http://www.med.harvard.edu/AANLIB/home.html
74 year old AD patient: reduced blood flow
on SPECT in temporal areas
Depression in Dementia
• Seen in up to 40% of AD patients; may
precede onset of AD
• Signs include sadness, loss of interest in usual
activities, anxiety, and irritability
• Suspect if patient stops eating or withdraws
• May cause acceleration of decline if untreated
• Recreational programs and activity therapies
have shown positive results
Treatment Disclaimer
• Although there is currently no way to cure
Alzheimer's disease or stop its progression,
there are now encouraging advances in
Alzheimer's treatment, including medications
and non-drug approaches to improve
symptom management.
NCD pharmacological treatment for AD
Acetylcholinesterase Inhibitors
donepezil (Aricept)
rivastigmine (Exelon)
galantamine (Razadyne)
tacrine (Cognex) – less used due to side effects
memantine (Namenda) – NMDA antagonist
Cognition Enhancing Drugs
Cholinergic Agents (AChEI)
- Donepezil/Aricept
- Rivastigmine/Exelon
- Galantamine/Razadyne
NMDA Antagonist
- Memantine/Namenda
Acetylcholinesterase Inhibitors
Mechanism of Action:
• Inhibits centrally-acting acetylcholinesterase,
making more acetylcholine available
• This compensates in part for degenerating
cholinergic neurons that regulate memory
Behavioral Therapy
• Nonpharmacologic intervention
• Antidepressants
• Antipsychotics if necessary
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