The Management of

Alzheimers Disease
Laurel Coleman, MD
Maine Medical Center
Portland, Maine

Management of Alzheimers Disease

Manage
cognitive
symptoms

Manage BPSD

Support
patient/family

Increased
quality of
life for
patient and
family

Pharmacologic Options for AD

Cognitive enhancers
2 classes
Cholinesterase inhibitors (ChEIs)
NMDA-receptor antagonist

Do not cure the disease or reverse cognitive

impairment
Can improve cognition and functional ability
Reduce the rate of decline 9-12 months (ChEIs)
Delay in nursing home placement was 17-21
months (ChEIs)

Management of Alzheimers Disease:

Cognitive Enhancers

*Available in generic

Drug Name

Dosage form

Dosage range

Donepezil
(Aricept)

Tablet*, orally
5 mg 23 mg QD
disintegrating tablet*

Minimum
Indication
titration interval
(as tolerated)

4 weeks
5 mg 10 mg

Mild to
severe

3 months
10 mg 23 mg

Galantamine
(Razadyne)

Tablet/oral solution*

4 mg 12 mg BID

Extended-release
capsule*

8 mg 24 mg ER QD 4 weeks

Rivastigmine
(Exelon)

Capsule*

1.5 mg 6 mg BID

2 weeks

Patch
Tablet*,
oral solution*

4.6 mg 9.5 mg QD
5 mg 10 mg QD

4 weeks
1 week

Memantine
(Namenda)

4 weeks

Aricept package insert. Razadyne package insert. Exelon package insert.

Mild to
moderate
Mild to
moderate
Mod to
severe

Pharmacologic Options for AD

Common Side Effects
NMDA-receptor
antagonist

Cholinesterase inhibitors
(Donepezil, galantamine, rivastigmine)

Nausea
Vomiting
Diarrhea
Weight loss
Loss of appetite
Muscle weakness
Vivid dreams/nightmares
(donepezil)

(Memantine)

Dizziness
Headache
Constipation
Confusion

Aricept package insert. Razadyne package insert. Exelon package insert.

Switching ChEIs
Lack or loss of
therapeutic benefit

Immediate switch
No washout needed

Tolerability issues

Washout period of
1-2 weeks before
starting another agent

Noncompliance

Try an alternate
dosage form before
switching

Discontinuation of Therapy

Data for optimal duration of treatment as disease

progresses is limited

Consider discontinuation in the following situations:

1.
2.

Modest cognitive and functional benefits associated with continued

therapy with (donepezil) in moderate to severe AD 1
Discontinuation associated with adverse behavioral changes and
reduced participation in activites2
Inability to tolerate multiple ChEIs
No improvement or greater than expected decline after one or
more therapeutic trials
End-stage dementia

Howard et al. New Engl J Med. 2012;366:893-903.

Daiello et al. Am J Geriatr Pharmacother. 2009;7:74-83.

Impact of Coexisting Medical

Conditions

2.4 conditions/pt
HTN
82%
DM
39%
CAD 21%
CHF
14%
Stroke 10%

Cognitive
Impairment

Prevalence of coexisting conditions in PWD

Schubert CC, et al. J Am Geriatr Soc. 2006;54(1):104109.

Impact of Coexisting Medical

Conditions
PWD in primary care average 5.1
medications/pt1
50% take 1 anticholinergic medications

Medications with anticholinergic activity

Impairs cognition acutely (delerium) and
chronically2
Anticholinergic burden

Interfere with the therapeutic effect of ChEIs 3

1. Schubert CC, et al. J Am Geriatr Soc. 2006;54(1):104109.
2. Campbell N, et al. Clin Interv Aging. 2009;4:225233.
3. Lu C, Tune LE. Am J Geriatr Psychiatry. 2003;11(4):458461.

Behavioral and Psychological

Symptoms of Dementia (BPSD)

Apathy
Depressive symptoms
Anxiety
Agitation/irritability/
aggression
Psychotic symptoms
Delusions
Hallucinations

Tampi et al. Clinical Geriatrics. 2011;19:41-46.

Disinhibition
Euphoria
Loss of appetite
Sleep disturbances
Stereotyped
behaviors (eg,
pacing, wandering,
rummaging, picking

Managing BPSD
Identify triggers
Observe symptom timing and frequency
Look for environmental triggers, eg noise, lighting
Investigate potentially treatable causes, eg pain

Make adjustments
Address medical causes
Adapt environment
Adapt caregiving

Modify as needed

Managing BPSD
Nonpharmacological Interventions

Use the 3 Rsrepeat, reassure, redirect

Simplify the environment, task, routine
Anticipate unmet needs
Allow adequate rest between stimulating
events
Use cues
Encourage physical activity
Other interventions

Managing BPSD:
Pharmacologic Interventions
Drug class

Chemical name

Dosage
range (mg)

Side effects of class

Antipsychotics

Aripiprazole*
Haloperidol
Risperidone*
Quetiapine*
Olanzapine*

2.5-15
0.5-5
0.25-2
25-200
2.5-15

Sedation, EPS, NMS,

metabolic syndrome, QTc
prolongations, increased
risk of CVE and mortality

Antidepressants

Fluoxetine
Citalopram
Paroxetine
Sertraline
Trazadone

10-80
10-60
10-50
25-200
25-200

Anxiety, headaches,
sedation, GI symptoms,
sexual dysfunction

Mood stabilizers

Carbamazepine
Divalproex
sodium
Oxcarbazepine

100-400
250-1000
300-600

Sedation, gait and balance

issues, falls, liver
dysfunction,
hyperammonemia,
thrombocytopenia

*2nd-generation
antipsychotics

Adapted from Tampi et al. Clin Geriatr. 2011;19:31-32.

Alzheimers Disease

Education of Patient
and Family

Education of Patient and Family

Safety issues:

Home environment
Driving
Medication adherence
Financial exploitation
Elder abuse

Address future needs: financial planning,

advanced directives, power of attorney

Education of Patient and Family

Medications
Define treatment success
Symptomatic benefit in
Cognition
Physical function and ADLs
Behavior

Increases time to nursing home placement

Discuss length of therapy

Adequate trial is 6 months
Cummings JL. Am J Geriatr Psychiatry. 2003;11(2):131145.
Doody RS, et al. Arch Neurol. 2001;58(3):427433.

Impact on Caregivers
Tasks Change Over Time
Early stage
Help with IADLS,
eg, paying bills and
preparing meals
Cope with mood
swings and
reluctance to
engage

Mid stage
Help with ADLS,
eg, dressing and
toileting
Cope with
increased memory
loss, sleep
disturbances,
wandering, loss of
driving

Late stage
Help with all personal
care
Cope with
unresponsiveness
and end-of-life issues

Education of Patient and Family

Alzheimers Association

24/7 Nationwide Helpline

www.alz.org

800.272.3900
Information and referral in 170 languages
Current reliable information for healthcare professionals, people
with dementia, family members and caregivers

300 local offices

Information and referral

Support groups
Care consultation
Safety services
Education, local conferences

Clinical Trials

>120 clinical studies in

the US are recruiting
participants

Slow recruitment is a
barrier to discovering
new treatments

Alzheimers Association
TrialMatch

Connect potential
participants with
appropriate clinical studies
Access via phone or online
Confidential
Free

Understanding prevention research

Much evidence comes from large
epidemiological studies that show
associations, not proof
Study results apply to populations, not
individuals
Large randomized studies for many
prevention strategies unlikely
Cost prohibitive

Prevention
Factors with a consistent association

Heart-head connection
Preventative drug treatments
Physical exercise
Diet
Social connections
Intellectual activity
Head trauma prevention

Prevention
Factors with a consistent association
Increased risk of AD
Conjugated equine
estrogen with
progesterone*
Diabetes
Depression
Smoking

*Moderate evidence,
all other factors had low evidence

Decreased risk of AD
Physical activity
Mediterranean diet
Cognitive engagement

The Future of Alzheimers Disease

Earlier recognition
Dependent on reliable biomarkers

New medications
Current medications only address symptoms
New medications in development
Disease-modifying therapy
Combination disease-modifying and symptomatic
therapy

Prevention

Alzheimer's Disease Progression

Beta-amyloid
Beta-amyloid and
and neurofibrillary
neurofibrillary
tangle
tangle formation
formation begins
begins in
in
pre-clinical
pre-clinical phase
phase
Pre-Clinical
Pre-Clinical

Cell death

MCI
MCI

Probable
ProbableAD
AD

TIME
Asymptomatic
A=Beta-amyloid
AD=Alzheimers disease
MCI=Mild cognitive impairment

Clear cognitive
deficits
Mild cognitive
deficits

Adapted from Shaw et al. Nature Reviews Drug Discovery. 2007;6:295-303.

Targets for Future Therapies

A
-secretase inhibitors
-secretase inhibitors
Monoclonal antibodies

Tau protein
Inflammation
Insulin resistance

Emerging Treatments for AD

A production
A aggregation
A clearance
tau aggregation
or phosphorylation
Cholinergic
drugs
Other

Clinical Trials
Failed

Phase 2

Moving to
Phase III

Phase III

AN-1792

ACC-01

Lu AE58054

Solanezumab

Bapineuzumab

Crenezumab

EVP-6124

IVIg

Dimebon
Rosiglitazone
Semagacestat
Tarenflurbil
Tramiprosate