Alzheimer’s Disease

Alzheimer’s Disease

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Description: Prevalence and Impact of AD: AD is the most common cause of dementia in people 65 years and older, Affects 10% of people over the age of 65 and 50% of people over the age of 85, Approximately 4 million AD patients in the United States, Annual treatment costs = $100 billion, AD is the fourth leading cause of death in the United States, The overwhelming majority of patients live at home and are cared for by family and friends. Delirium vs dementia: Delirium and dementia often occur together in older hospitalized patients; the distinguishing signs of delirium are- Acute onset, Cognitive fluctuations over hours or days, Impaired consciousness and attention, Altered sleep cycles.

 
Author: Mary-Letitia Timiras M.D. (Senior) | Visits: 597 | Page Views: 944
Domain:  Medicine Category: Therapy 
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Contents:
ALZHEIMER’S DISEASE
Mary-Letitia Timiras M.D.
Overlook Hospital
Summit, New Jersey

Topics Covered







Demography
Clinical manifestations
Pathophysiology
Diagnosis
Treatment
Future trends

Prevalence and Impact of AD
AD is the most common cause of dementia in people
65 years and older
Affects 10% of people over the age of 65 and 50% of
people over the age of 85
Approximately 4 million AD patients in the United States
Annual treatment costs = $100 billion
AD is the fourth leading cause of death in the United States
The overwhelming majority of patients live at home and
are cared for by family and friends

Evans DA. Milbank Q. 1990;68:267-289.
Alzheimer’s Association. Available at: www.alz.org/hc/overview/stats.htm. Accessed 5/9/2001.

DIFFERENTIAL
DIAGNOSIS
• Alzheimer’s disease
• Vascular (multi-infarct) dementia
• Dementia associated with Lewy
bodies
• Delirium
• Depression
• Other (alcohol, Parkinson's disease
[PD], Pick’s disease, frontal lobe
dementia, neurosyphilis)

DELIRIUM vs DEMENTIA


Delirium and dementia often occur
together in older hospitalized patients; the
distinguishing signs of delirium are:

• Acute onset
• Cognitive fluctuations over hours or days
• Impaired consciousness and attention
• Altered sleep cycles

VASCULAR DEMENTIA
• Development of cognitive deficits manifested by
both
• impaired memory
• aphasia, apraxia, agnosia, disturbed executive
function

• Significantly impaired social, occupational
function
• Focal neurologic symptoms & signs or evidence
of cerebrovascular disease
• Deficits occur in absence of delirium

DEPRESSION vs
DEMENTIA

• The symptoms of depression and dementia
• often overlap; patients with primary
depression:
• Demonstrate ↓ motivation during cognitive
testing
• Express cognitive complaints that exceed
measured deficits
• Maintain language and motor skills

Projected Prevalence of AD
4 Million AD Cases Today—
Over 14 Million Projected Within a Generation
16

14.3

Millions

14

11.3

12
10

8.7

8
6
4

5.8

6.8

4

2
0
2000

2010

2020

2030
Year

2040

2050

Evans DA et al. Milbank Quarterly. 1990;68:267-289.

The Progress of Alzheimer’s Disease
30

Early diagnosis

Severe

Mild-moderate

Cognitive symptoms

MMSE score

25
20

Loss of ADL

15
10
5

Behavioral problems
Nursing home placement
Death

0
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9

Years

Alzheimer’s Disease Progresses
Through Distinct Stages
Dementia/Alzheimer’s

Stage

Symptoms

Mild
Memory loss
Language
problems
Mood swings
Personality
changes
Diminished
judgment

Moderate
Behavioral, personality
changes
Unable to learn/recall
new info
Long-term memory
affected
Wandering, agitation,
aggression, confusion
Require assistance
w/ADL

Severe
Gait, incontinence,
motor disturbances
Bedridden
Unable to perform
ADL
Placement in
long-term care
needed

WHAT IS DEMENTIA?
• An acquired syndrome of decline in memory
and other cognitive functions sufficient to
affect daily life in an alert patient
• Progressive and disabling
• NOT an inherent aspect of aging
• Different from normal cognitive lapses

Normal Lapses
• Forgetting a name
• Leaving kettle on
• Finding right word
• Forgetting date or
day

Dementia
• Not recognizing
family member
• Forgetting to serve
meal just prepared
• Substituting
inappropriate
words
• Getting lost in own
neighborhood

Normal Lapses
• Trouble balancing
checkbook
• Losing keys,
glasses
• Getting blues in
sad situations
• Gradual changes
with aging

Dementia
• Not recognizing
numbers
• Putting iron in
freezer
• Rapid mood
swings for no
reason
• Sudden, dramatic
personality change

RISK FACTORS FOR
DEMENTIA
• Age
• Family history
• Head injury
• Fewer years of education

THE GENETICS OF
DEMENTIA
• Mutations of chromosomes 1, 14, 21
• Rare early-onset (before age 60) familial
forms of dementia
• Down syndrome
• Apolipoprotein E4 on chromosome 19
• Late-onset AD
• APOE*4 allele ↑ risk & ↓ onset age in doserelated fashion
• APOE*2 allele may have protective effect

PROTECTIVE FACTORS
UNDER STUDY
• Estrogen replacement therapy
after menopause
• NSAIDs
• Antioxidants

LEWY BODY DEMENTIA
• Dementia
• Visual hallucinations
• Parkinsonian signs
• Alterations of alertness or attention

Pathology of AD
• There are 3 consistent
neuropathological hallmarks:
– Amyloid-rich senile plaques
– Neurofibrillary tangles
– Neuronal degeneration

• These changes eventually lead to
clinical symptoms, but they begin
years before the onset of symptoms

β-amyloid Plaques
Immunocytochemical
staining of senile plaques
in the isocortex of a brain
of a human with AD (antiamyloid antibody)

Neurofibrillary Tangles
Immunocytochemical
staining of neurofibrillary
tangles in the isocortex of
the brain of a human with
AD (anti-tau antibody)

Cholinergic Hypothesis
• Acetylcholine (ACh) is an important
neurotransmitter in areas of the brain
involved in memory formation
• Loss of ACh activity correlates with the
severity of AD

Bartus RT et al. Science. 1982;217:408-414.

Acetylcholinesterase Inhibitors
• Drugs used to treat Alzheimer’s disease act by
inhibiting acetylcholinesterase activity
• These drugs block the esterase-mediated
metabolism of acetylcholine to choline and
acetate. This results in:
– Increased acetylcholine in the synaptic cleft
– Increased availability of acetylcholine for
postsynaptic and presynaptic nicotinic
(and muscarinic) acetylcholine receptors
Nordberg A, Svensson A-L. Drug Safety. 1998;19:465-480.

Acetylcholinesterase Inhibition
Acetic acid

Choline AChE inhibitor

Presynaptic
nerve terminal
Muscarinic
receptor

Postsynaptic
nerve
terminal
Nicotini
c
receptor

Acetylcholine
(ACh)

Nordberg A, Svensson A-L. Drug Safety. 1998;19:465-480.

Acetylcholinestera
se
(AChE)

ASSESSMENT: HISTORY
(1 of 4)

• Ask both the patient & a reliable informant
• about the patient’s:
• Current condition
• Medical history
• Current medications & medication history
• Patterns of alcohol use or abuse
• Living arrangements

ASSESSMENT: PHYSICAL
(2 of 4)





Examine:
Neurologic status
Mental status
Functional status

• Include:
• Quantified screens for cognition
– e.g., Folstein’s MMSE, Mini-Cog
• Neuropsychologic testing

ASSESSMENT:
LABORATORY (3 of 4)

• Laboratory tests should include:
• Complete blood cell count
• Blood chemistries
• Liver function tests
• Serologic tests for:
Syphilis, TSH, Vitamin B12 level

ASSESSMENT: BRAIN
IMAGING (4 of 4)







Use imaging when:
Onset occurs at age < 65 years
Symptoms have occurred for < 2 years
Neurologic signs are asymmetric
Clinical picture suggests normal-pressure
hydrocephalus






Consider:
Noncontrast computed topography head scan
Magnetic resonance imaging
Positron emission tomography

Treatment of Alzheimer’s Disease
Patients (millions)

5

4,523,100

4
3
2,261,600

2
904,600

1

543,800

0
Prevalence Diagnosed

Treated*

* Any drug treatment, not limited to acetylcholinesterase inhibitors.
Source: Decision Resources, March 2000.

Treated
with AChEIs



TREATMENT &
MANAGEMENT

Primary goals: to enhance quality of
life & maximize functional performance
by improving cognition, mood, and
behavior
– Nonpharmacologic
– Pharmacologic
– Specific symptom management
– Resources

NONPHARMACOLOGIC
• Cognitive enhancement
• Individual and group therapy
• Regular appointments
• Communication with family,
caregivers
• Environmental modification
• Attention to safety

PHARMACOLOGIC
• Cholinesterase inhibitors: donepezil,
rivastigmine, galantamine
• Other cognitive enhancers: estrogen,
NSAIDs, ginkgo biloba, vitamin E
• Antidepressants
• Antipsychotics

SYMPTOM
MANAGEMENT
• Sundowning
• Psychoses (delusions,
hallucinations)
• Sleep disturbances
• Aggression, agitation
• Hypersexuality

RESOURCES FOR
MANAGING DEMENTIA
• Attorney for will, conservatorship, estate
planning
• Community: neighbors & friends, aging &
mental health networks, adult day care, respite
care, home-health agency
• Organizations: Alzheimer’s Association, Area
Agencies on Aging, Councils on Aging
• Services: Meals-on-Wheels, senior citizen
centers

SUMMARY (1 of 2)
• Dementia is common in older adults but is NOT
an inherent part of aging
• AD is the most common type of dementia,
followed by vascular dementia and dementia
with Lewy bodies
• Evaluation includes history with informant,
physical & functional assessment, focused
labs, & possibly brain imaging

SUMMARY (2 of 2)
• Primary treatment goals: enhance quality of
life, maximize function by improving
cognition, mood, behavior
• Treatment may use both medications and
nonpharmacologic interventions
• Community resources should be used to
support patient, family, caregivers

Future Trends





Alzheimer’s as a multifactorial syndrome
Pendulum of history
Vaccine
Genetic therapy