2008

California Guideline for Alzheimer’s

Disease Management

Debra Cherry, PhD Alzheimer’s Association,

California Southland

Brad Williams, PharmD, CGP USC School of

Pharmacy

Objectives

• Describe the process utilized to update the California Guideline for AD Management

• Review the Guideline’s recommendations• Apply the recommendations to patients and

caregivers• Use the Guideline to implement a quality

improvement project

History of California AD Management Guideline

• 1995: California Workgroup on Guideline for Alzheimer’s Disease Management formed

• 1998 Publication of the first Guideline

• 2002 Guideline updated & published in The American Family Physician

• 2008 Third update completed.

Composition of the California Workgroup

Representatives from throughout the State:• Healthcare providers• Consumers• Academicians• Professional and volunteer organizations

Purpose of the Guideline

Represents core care recommendations for AD management which are:

• Based on scientific evidence• Supplemented by expert consensus• General guide to post-diagnostic

care• Intended for Primary Care

Practitioners including:– Physicians– Nurse Practitioners/Nurses– Physician Assistants

•Also defines a role for:–Social Workers–Care Managers

Mrs. R. L.

Mrs. R. L. is a retired librarian who visits her physician for a routine follow-up for her osteoarthritis, GERD, and glaucoma. She has enjoyed her 3 years of retirement, but reports that recently her husband has been worried about her memory. Mrs. L. states that she had started writing reminder notes, “which don’t always help.” She admits to reading less than she used to; she also drives less because “traffic is such a problem.”

Mrs. R. L.

Mr. L. reports that his wife often returns from grocery shopping having forgotten to pick up several things that she intended to buy. At other times she will wander through the house, looking in drawers or closets for items that she had put away for safe-keeping. Although they used to go out to dinner at least once a week, they now go much less frequently because Mrs. L. states that “I just never know what to order, and it’s not as much fun as it used to be.”

Dementia Warning Signs

Task Example

Memory decline Forgetfulness

Difficulty performing familiar tasks

Bill paying, shopping

Disorientation Getting lost in familiar places

Impaired judgment Inviting strangers into the home

Impaired abstract thinking, problem-solving

Driving skills

Dementia Warning Signs

Task Example

Misplacing things Losing valuable items in the home

Mood or behavior change

New-onset irritability, unusual habits or activities

Personality change Withdrawn, increased socialization

Problems with language Word finding difficulties

What signs and symptoms are present in Mrs. R. L. that suggest that she may have a dementia?

Guideline for AD Management

• Assessment• Treatment• Patient & Family Education & Support• Legal Considerations

Assessment

• Cognitive status• Daily function• Concurrent medical conditions• Medications• Behavior symptoms and mood• Living arrangements• Support system

Assessing Cognition

Test Items/Score Domains

Folstein Mini-Mental Status Exam

19 items

30 points

Multi-dimensional

Mini-Cog 2 items

5 points

3-item recall

Clock drawing

Blessed Orientation-Concentration-Memory

6 items

28 points

Orientation, concentration, recall

Cognitive Assessment Screening Instrument

25 items

100 points

Multi-dimensional

Assessment: Function Activities of Daily Living (ADL)

• Self-feeding• Dressing• Ambulation• Toileting

• Bathing• Transfer from bed to

toilet• Continence• Grooming• Communication

Assessment: FunctionInstrumental ADL (IADL)

• Writing• Reading• Cooking• Cleaning• Shopping• Doing laundry

• Climbing stairs• Using telephone• Managing medication• Managing money• Ability to perform outside

work• Ability to travel (public

transportation)

Assessment: Concurrent Conditions

• Chronic disease– Ability to manage

• Acute Conditions– Delirium– Infection/UTI/Influenza

Assessment: Medications & Cognition

• Anticholinergics• Benzodiazepines• Sleep aids• Antipsychotics• Narcotics• Muscle relaxants

• NSAIDs• Anti-arrhythmics• Antihypertensives• Cimetidine• Corticosteroids• Hypoglycemic agents

Assessment: Behavior & Mood

• Agitation– Restlessness

– Irritability

– Aggression

• Psychosis– Delusions

– Paranoia

– Hallucinations

• Depression– Withdrawal

– Sleep disturbances

– Appetite changes

• Apathy– Loss if interest

Assessment: Living Arrangements

• Declining ability for self-care– Patient autonomy vs. need for care

• Safety issues– Rugs, appliances– Driving

• Abuse and neglect– Dependence– Caregiver stress

Assessment: Support System

• Family’s ability to care for patient• Community supports

– Alzheimer’s Association– Caregiver Resource Center– Religious or other groups

• Community resources – day care, in-home care• Health care resources• Advance directives

Mrs. R has come to the USC Alzheimer’s Disease Center and been thoroughly assessed. She has been determined to have a diagnosis

of Alzheimer’s disease. What next?

Treatment: Develop a Treatment Plan

• Improve cognitive function

• Increase level of function

• Delay disease progression

• Manage behavior disturbances

• Ease caregiver burden

Treatment: Improve Cognitive Function

• Cholinergic manipulation– Cholinesterase inhibitors

• All agents block acetylcholinesterase activity• Rivastigmine also blocks butyrylcholinesterase• Galantamine stimulates cholinergic receptors

• NMDA antagonist– Reduces glutamate activity– Regulates calcium entry into cells

Donepezil (Aricept®)

• Approved for all stages of AD

• Availability– 5 & 10 mg tablets

– 5 & 10 mg ODT

– 1 mg/mL solution

• Dosing– 5 mg is therapeutic

– May increase to 10 mg after 4-6 weeks

• May be given without regard to food

• CYP1A2 substrate

Galantamine (Razadyne®)

• Approved for mild, moderate AD

• Availability– 4, 8, 12 mg tablets

– 8, 16, 24 mg ER capsules

– 4 mg/mL solution

• Will be first ChEI to go generic

• Dosing– Initial daily dose of 8 mg is not

therapeutic

– Dose escalation is 8 mg/day in 4-6 week intervals

– Maximum is 24 mg/day

• Give with meals

• Elimination– 50% renal

– 2D6/3A4 substrate

Rivastigmine (Exelon®)

• Approved for mild, moderate AD

• Availability– 1.5, 3, 4.5, 6 mg

capsules

– 4.6, 9.5 mg/24 hr transdermal patch

– 2 mg/mL solution

• Dosing– Initial dose of 1.5 mg twice daily is

not therapeutic

– Dose escalation is 1.5 mg twice daily in 4-6 week intervals

– Maximum is 12 mg/day

– Initial patch dose of 4.6 mg/24 hours is therapeutic

• Must give with meals

• Renal excretion

Principles for ChEI Use

• Initial treatment upon diagnosis or 6-months duration of AD symptoms

• Evaluate for ADR after 2-4 weeks

• Evaluate for effectiveness every 6 months– Switch if poor

tolerance, or continued decline

• Discontinue prior to surgery

Counseling Points

• Effects on cognition are very mild– May stabilize or slow decline for 6-12 months

• May improve independence, self-care• Gastrointestinal effects are prominent• May slow heart rate

The Evidence Suggests…

-Kaduszkiewicz, et al., BMJ 2005;331:321-327

Conclusion Because of flawed methods and small clinical benefits, the scientific basis for recommendations of cholinesterase inhibitors for the treatment of Alzheimer’s disease is questionable.

Memantine (Namenda®)

• Approved for use in moderate, severe AD– Monotherapy

– With ChEI

• Availability– 5 & 10 mg tablets

– 10 mg/5 mL solution

• Dosing– 5 mg/day for 1 week

– Increase by 5 mg/day in weekly intervals to 10 mg twice daily

– 10 mg/day maximum with renal impairment

• May be taken without regard to meals

• Renal elimination as unchanged drug

Memantine Adverse Effects

• > 5% incidence in clinical trials– Agitation (less than for placebo)– Diarrhea– Insomnia

• 5% incidence– Dizziness– Headache– Hallucinations

Memantine

• Effects in moderate AD– Slower decline in overall function and in loss of

activities of daily living– No significant effect on cognition

• Systematic reviews have reported small to no clinically relevant effect

TREATMENTRecommendations (cont.)

• Treat behavioral symptoms and mood disorders using:

– Non-pharmacologic approaches, such as environmental modification, task simplification, appropriate activities, etc.

• IF non-pharmacological approaches prove unsuccessful, THEN use medications, targeted to specific behaviors, if clinically indicated. Note that side effects may be serious and significant.

Treatment: Behavior Symptoms

• Most difficult for both patients and caregivers

• Behavior symptoms contribute to:– Patient distress– Caregiver burnout– Excess disability– Institutionalization

Treatment: Increase level of function and delay disease progression

• Behavioral Interventions• Medications• Adult Day Services• Exercise and Recreation

Jost BC, Grossberg GT. J Am Geriatr Soc. 1996;44:1078-1081.

Agitation

Diurnal Rhythm

Irritability

Wandering Aggression

Hallucinations

Mood Change

Socially Unacceptable

Delusions

Sexually InappropriateAccusatorySuicidal

Ideation

Paranoia

Depression

100

80

60

40

20

0–40 –30 –20 –10 0 10 20 30

Months Before Diagnosis Months After Diagnosis

Pre

vale

nce

(%

of

pat

ien

ts)

AnxietySocial Withdrawal

Behavioral Symptoms as AD Progresses

Mrs. R. L.

Some time has passed and Mr. L. is concerned about changes in his wife’s behavior. She becomes agitated, especially in the late afternoon and leaves the house. She says she is going home and gets more agitated when he reminds her that she is in her home.

Evaluating Behaviors

• Rapid onset requires search for medical cause– Pain, infection, adverse drug effect

• Identify problema. Behavior triggers

b. Specific Behaviors

c. Consequences

Common Causes of Behaviors

• Health problems

• Difficult tasks

• Confusing environment

• Communication breakdown

• Patient’s perceptions of the situation

What may be triggering Mrs. L.’s behavior?

What does this behavior mean to her?

How should these symptoms be managed?

Behavior Management Principles

• Non-drug management generally provides better results

• Assess likelihood that pharmacotherapy will be beneficial– Target medication to specific behavior– Avoid caregiver interpretation of PRN orders– Consider the patient's health status– Consider drug pharmacokinetic and

pharmacodynamic properties

Mrs. R. L.

Mrs. R. L. has begun a daily exercise program and late afternoon agitation is now less of an issue. However, at night she awakens and becomes agitated. She believes someone is trying to break into the house. When her husband tries to reassure her, she gets angry and strikes out at him.

What non-drug strategies are appropriate to manage Mrs. L.’s current behaviors?

Is drug therapy appropriate, and if so, how should it be initiated?

PATIENT and FAMILY EDUCATION & SUPPORT

Recommendations

• Integrate medical care with education & support by connecting patient & caregiver to support organizations

- Alzheimer’s Association 1-800-272-3900 www.alz.org

- Family Caregiver Alliance 1-800-445-8106

www.caregiver.org- or your own social service department.

PATIENT and FAMILY EDUCATION & SUPPORT

Early Stages

Pay particular attention to the special needs of early-stage patients, involving them in care planning, heeding their opinions and wishes, and referring them to community resources, including the Alzheimer’s Association.

LEGAL CONSIDERATIONSRecommendations

• Include a discussion of the importance of basic legal and financial planning as part of the treatment plan as soon as possible after the diagnosis of AD.

• Monitor for evidence of and report all suspicions of abuse as required by law.

• Report the diagnosis of AD in accordance with local laws.

Using the Guideline in a Health Care Setting

Health care organizations are challenged to care

for the growing number of older adults with

chronic health conditions

How to use Guidelines for a QI project:

• Set quality goals derived from guideline

• Train practitioners

• Add case management

• Evaluate

Implementation Support Tools

Provider Tool Kit

• Medical Record Checklist

• List of Reversible Medical Conditions

• Signs/Symptoms of Elder Abuse

• Mental Status Exam

• Safe Return / ID Bracelet Program Application

• Dementia and Driving Reporting Law

• Prescription Pad

QI Projects Using Guidelines

• Kaiser Permanente – Metro L.A.

• ACCESS – Kaiser, Scripps &

U.C.S.D. Healthcare

• HealthCare Partners Medical Group

• SCAN HealthPlan

Establishing Partnerships Replication Manual

Based on Alzheimer’s Association – Kaiser Permanent Metropolitan Los Angeles Dementia Care Project

www.alz.org/californiasouthland Click on Professional Training then Replication Manual

Got Guideline?2008 California Guideline for Alzheimer’s Disease

Management

Available at:

www.caalz.org(you can put your own website information here)

or contactAmy.Landers@alz.org

323-930-6289(you can put your own contact person here)