AAGP Position Statement: Principles of Care for Patients
With Dementia Resulting From Alzheimer Disease
Adopted by the Board of Directors of the American Association
for Geriatric Psychiatry in September 2005 (Published in the
American Journal of Geriatric Psychiatry, July 2006)
This statement was prepared by a Task Force authorized by
the AAGP Board of Directors and was then adopted by the AAGP
Board at its September 14, 2005, meeting. The Task Force consisted
of Constantine Lyketsos (Chair), Christopher Colenda, Cornelia
Beck, Karen Blank, Murali Doriaswamy, Douglas Kalunian, and
Kristine Yaffe.
POSITION
There exists currently an effective, systematic care/treatment
model for patients with dementia resulting from Alzheimer
disease (AD). This consists of a series of therapeutic interventions-pharmacologic
and nonpharmacologic-targeted at patients with AD and their
caregivers. Although these interventions do not produce a
cure of the underlying disease and do not appear to stop its
progression, they have been shown to produce benefits for
patients and their caregivers. The aims of this care model,
often referred to as "Dementia Care," are to delay
disease progression, delay functional decline, improve quality
of life, support dignity, control symptoms, and provide comfort
at all stages of AD. This evolving model is based on scientific
evidence of beneficial outcomes, with acceptable risks, and
is increasingly targeted at an improving pathophysiological
understanding of the biology of AD. Although the evidence
is limited, the existing evidence, coupled with clinical experience
and common sense, is adequate to produce a minimal set of
care principles. In this context, the American Association
for Geriatric Psychiatry (AAGP) affirms that there now exists
a minimal set of care principles for patients with AD and
their caregivers. Consequently, the detection and treatment
of AD must now be considered part of the typical care practices
for any physician and other licensed clinicians who interact
with patients with this disease. This document articulates
these principles of care.
DEFINITIONS
Cognitive Impairment No Dementia (CIND)
A clinical syndrome consisting of measurable or evident decline
in memory or other cognitive abilities with little effect
on day-to-day functioning that does not meet criteria for
dementia as defined by DSM-IV-TR.1
Mild Cognitive Impairment (MCI)
A clinical syndrome that is a subgroup of CIND with prominent
amnestic symptoms that is in all likelihood a prodrome of
AD.
Dementia
A clinical syndrome, that is not entirely the result of delirium,
consisting of global cognitive decline with memory plus one
other area of cognition affected with significant effects
on day-to-day functioning and meets DSM-IV-TR criteria.
Dementia Resulting From Alzheimer
Disease
The most common type of dementia characterized by decline
primarily in cortical aspects of cognition and following a
characteristic time course of gradual onset and progression.
Alzheimer Disease
A specific degenerative brain disease characterized by senile
plaques, neuritic tangles, and progressive neuronal loss;
also, the presumptive cause of AD.
CONTEXT OF THIS POSITION STATEMENT
The aim of this statement is to assert the position of the
AAGP regarding the existence of specific principles of care
for patients with AD for the purpose of improving care, and
access to care, for patients with AD and their caregivers.
This statement also aims to provide clinicians with guidance
about the key elements of these care principles and about
the reasons for which this care should be made available to
patients with AD and caregivers. Because this is a position
statement about treatment, it is assumed that appropriate
diagnostic confirmation of AD has been carried out before
the application of this model of care.
Being a position statement, not a practice guideline or parameter,
this statement reflects the beliefs and opinions of the members
of a professional association with special expertise in the
care of patients with AD. As much as possible, this statement
is based on the available evidence and is an effort to articulate
best principles of care by synthesizing the available evidence
with clinical judgments and practices. However, it is recognized
that available evidence is not conclusive in most cases and
that there are differing views and opinions about how to implement
dementia care. Nevertheless, it is important from time to
time to produce statements such as this as a guide to clinical
practice.
The statement is targeted at AAGP members, other physicians,
and other licensed clinicians who care for people with dementia.
Although there are similarities in the care of patients with
all types of dementia, this document is intentionally targeted
at AD, not other forms of dementia, so as to retain focus,
because most of the evidence supporting the effectiveness
of dementia care is derived from studies of patients with
AD and because AD is the most common form of dementia. The
reader is referred to other documents regarding the care of
patients with non-Alzheimer dementia. Furthermore, this document
is not targeted at "mild cognitive impairment" (MCI),
considered by many to be the earliest clinical manifestation
of AD, because the evidence base regarding the treatment of
the latter is limited and in evolution.
This position statement is intended to encompass clinical
care for patients with AD in typical clinical settings (e.g.,
primary care, specialist care, and longterm care, including
assisted living environments). Given its scope and purpose,
this document intentionally does not address nonclinical aspects
of dementia care as related to diagnostic tests, research,
policy, or reimbursement for care. The reader is referred
to other AAGP position statements involving the latter.
WHY THIS DOCUMENT NOW
Dementia is a major public health problem already that is
expected to worsen given the aging of the population. Over
4.5 million Americans have the most common form of dementia,
AD; this number will likely triple in the next 40-50 years.2
Despite the commitment of significant effort and resources
to the development of curative therapy for AD, a cure remains
many years, possibly decades, away. In the meantime, it is
important that medical professionals care for patients who
currently have the disease, and their caregivers, using the
most advanced methods available. The public has an increasing
awareness of AD and is presenting to the healthcare system
for care in ever-increasing numbers. Improvements in the diagnosis
and the understanding of the biology of AD and significant
evidence to support the effectiveness of therapies for AD
all contribute to the timeliness of this position statement.
The evidence base supports the effectiveness of the dementia
care "package," which has been shown now in a variety
of clinical settings to have wide-ranging benefits for patients
and caregivers with regard to delay of functional decline,
control of many symptoms, maximization of quality of life,
and delay of disability and institutionalization. The evidence
supporting dementia care has been extensively articulated
in a series of Practice Guidelines, Care Parameters, Consensus
Statements, Conference Proceedings, scientific papers, and
books proposed previously by AAGP, and also by the American
Psychiatric Association, the American Academy of Neurology,
the Alzheimer Association, the federal Agency for Health Care
Policy and Research (now AHRQ), and others. Despite this,
detection rates for dementia remain low overall, no better
than a decade ago,3 and the Guidelines are probably
not being followed in most settings where dementia patients
are seen, in part as a result of failure to detect.4,5
In the current climate where there is evidence of treatment
efficacy, for treatment albeit not cure, it is incumbent on
professional organizations such as AAGP to assert minimal
care principles for the medical profession in their areas
of expertise.
ORGANIZATION OF THIS DOCUMENT
The remainder of this document articulates general principles
of dementia care, encompassing the full spectrum of available
treatments, both pharmacologic and nonpharmacologic, organized
around the following key areas of therapy:
- Disease therapies for AD, targeted specifically at aspects
of the current pathophysiological understanding of the disease;
- Symptomatic therapies for cognitive symptoms;
- Symptomatic therapies for other neuropsychiatric symptoms;
- Interventions targeted at, and the provision of, supportive
care to patients; and
- Interventions targeted at, and the provision of, supportive
care to caregivers.
DISEASE THERAPIES FOR ALZHEIMER DISEASE
TARGETED SPECIFICALLY AT ASPECTS OF THE CURRENT PATHOPHYSIOLOGICAL
UNDERSTANDING OF THE DISEASE
A detailed discussion of the current understanding of the
complex pathophysiology of AD is beyond the scope of this
document. Briefly, this understanding implicates the misprocessing
of the amyloid precursor protein (APP) as the key initial
event. Processing of this protein in brain neurons through
the beta secretase pathway leads eventually to the deposition
of insoluble deposits referred to as beta amyloid plaques,
eventually leading to synaptic failure, neuronal injury, formation
of tangles of hyperphosphorylated tau protein, and apoptotic
neuronal death. The loss of neuronal systems leads to the
loss of multiple neurotransmitters, which in turn lead to
the emergence of the cognitive, other neuropsychiatric, and
functional symptoms of the disease. This process occurs over
years, perhaps even decades, before the onset of symptoms.
If the amyloid hypothesis is correct, and there are reasons
to think that it may not be the whole story, the ideal disease
therapy for Alzheimer brain disease would be one that either
prevents the deposition of beta amyloid plaques or one that
prevents the synaptic and neuronal damage caused by these
plaques. Several treatments along these lines are in development,
some in early human trial phases. The most promising are medications
that diminish the production of the toxic, insoluble forms
of beta amyloid, and "immunotherapies," both passive
and active, that are intended to remove beta amyloid from
the brain.
In addition to directly targeting amyloid deposition or clearance,
several factors have been identified as "accelerators"
of the AD progression, some of which are being or have been
considered as targets of therapy. These include:
- Postmenopausal loss of estrogen in women;
- Inflammatory response;
- Oxidative free radicals;
- Brain vascular disease;
- High cholesterol; and
- Glutamate excitoxicity.
Estrogen replacement, with and without progesterone, has
been studied extensively as a treatment or preventive for
Alzheimer dementia. Although epidemiologic studies and early
clinical trials were promising, several trials have concluded
that estrogen replacement does not attenuate dementia progression.6,7
There is some suggestion from epidemiologic studies that estrogen
replacement for a 5-10- year period soon after menopause might
delay or prevent the onset of Alzheimer decades later,8
but this hypothesis will be very difficult to test. For
now, estrogen is not an appropriate therapy for AD.
The association of brain inflammation with AD has led to
several tests of the hypothesis that antiinflammatory treatment
may delay the progression of AD dementia.9 Nonsteroidal
antiinflammatory drugs (NSAIDs) such as ibuprofen and indomethacin
have been associated with a lower risk of developing AD in
several epidemiologic studies. However, there is a long-term
risk of gastrointestinal bleeding and renal disease and now
evidence that NSAIDs are associated with rare cardiovascular
toxicity. Thus far, trials of prednisone10 and
NSAIDs11-15 have suggested that antiinflammatory
treatments are not effective for AD. At present, antiinflammatory
agents are not recommended for the treatment of AD and should
not be used for this purpose.
The association of oxygen free radicals with AD dementia
has raised the question of whether antioxidant therapy in
AD is warranted. Epidemiologic evidence supports the concept
that vitamin E, perhaps in combination with vitamin C, may
prevent AD.16 In addition, there has been one randomized
trial that suggested high-dose vitamin E, 2,000 IU/day, might
delay the progression of functional decline in AD.17
The trial, however, had methodological weaknesses that made
its findings less compelling. Nevertheless, the American Psychiatric
Association and the American Academy of Neurology treatment
guidelines for AD both recommend consideration of high-dose
vitamin E as a treatment option. This recommendation is tempered
by recent findings that vitamin E therapy did not delay progression
of MCI to AD,18 a putative precursor clinical state
to Alzheimer dementia, and by findings from a meta-analysis,
that vitamin E in very high doses increased mortality in older
people.19 Although vitamin E may still be an
option to be considered for AD, given concerns about mortality,
however small, doses above 400 IU per day should probably
be avoided.
The over-the-counter antioxidant ginkgo biloba, and its putative
active form EGB in doses of 120 mg/per day or higher, may
have some efficacy in treating dementia as some trials suggest.20
However, the effect is likely to be small, and safety concerns
have been raised about the use of over-the-counter substances
for long time periods in the absence of extensive testing
or careful manufacturing oversight for purity. Therefore,
in general the use of ginkgo is not recommended for AD.
There is now strong evidence that brain vascular disease
plays a role in the progression of Alzheimer dementia in two
ways. First, brain vascular disease may add to the cognitive
impairment of dementia for a given amount of Alzheimer pathology
in the brain.21 This should be no surprise because
two pathologic processes would be expected to worsen the clinical
syndrome of dementia. Second, brain vascular disease has been
implicated as a factor in the development of the Alzheimer
pathology,22 perhaps by accelerating amyloid deposition
and by increasing amyloid toxicity to synapses or neurons.
Therefore, the management of vascular brain disease and
its associated risk factors is now part of the care for disease
treatment for AD for patients with significant risk factors.
Control of high blood pressure is an important component of
this. The level of control is somewhat controversial, but
at least one clinical trial has suggested that maintaining
systolic below 140 mm Hg is associated with less rapid dementia
progression.23 Treatment of hypercholesterolemia,
homocystinemia, and hyperglycemia are other aspects of this
approach. Therefore, the treatment of patients with dementia
should include monitoring of blood pressure, glucose, cholesterol,
and homocysteine and the initiation or modification of appropriate
interventions when indicated. For patients with AD plus
significant brain vascular disease, initiation of low-dose
aspirin therapy or, if appropriate, of other forms of anticoagulation
should be seriously considered as a treatment that might prevent
the worsening of dementia.
Evidence is emerging that links high levels of cholesterol,
APP metabolism, and the risk for AD. The e-4 allele of apolipoprotein
E gene is involved in the central nervous system (CNS) distribution
of cholesterol among neurons. Although the exact mechanism
by which cholesterol effects Ab1-42 production is not known,
several retrospective observational studies have found that
the chronic use of 3-hydroxy- 3-methyglutaryl coenzyme A reductase
inhibitors (statins) are associated with a decreased risk
of developing AD.24 A randomized, controlled trial
using pravastatin over three years, however, did not demonstrate
a significant effect on cognitive function in elderly individuals
at risk for cardiovascular disease.25 Although
HMG-CoA reductase inhibitors ("statins") may hold
promise for prevention of AD, current data suggest they are
not indicated to treat AD other than in the context of their
use to reduce plasma cholesterol levels.
Glutamate is the main excitatory neurotransmitter in the
CNS. Glutamate excitotoxicity has been implicated in the etiopathogenesis
of AD. Injured or dying glutamate-producing neurons will under
certain conditions release large amounts of glutamate in their
synaptic clefts leading to toxicity and death in the downstream
neurons of their synaptic connections. An increase of extracellular
glutamate is believed to increase NMDA-receptor activation
that increases intracellular accumulation of Ca++.26
Increased intracellular Ca++ in turn activates a series of
intracellular systems such as the caspase system, leading
to cell death. Memantine, an NMDA noncompetitive antagonist,
protects cells from glutamate- activated excitotoxicity. Two
randomized, controlled trials have reported benefits in advanced
stages of dementia on measures of Clinical Global Impressions
of Change and behavior scales, although one study found that
the intention-to-treat analysis with last observation carried
forward revealed no difference between placebo and memantine.27,28
Memantine-donepezil combination therapy for severe AD was
superior to donepezil alone in a recent six-month randomized
trial.29 Safety data so far are very good, also
suggesting that memantine can be administered safely with
cholinesterase inhibitors such as donepezil. Recent pharmacoeconomic
analysis of memantine in moderate-to-severe AD concluded,
despite limitations of the data available for analysis, that
memantine is a cost-effective treatment at this point in time.30
Given mechanistic, clinical trial and economic data, memantine
is indicated for moderate-to- severe AD, and its use earlier
in milder dementia may be justified. In this light, a
discussion with patients of the pros and cons of memantine
is now part of the care for patients with AD with moderate
to severe dementia.
SYMPTOMATIC THERAPIES FOR COGNITIVE SYMPTOMS
One of the earliest pathologic findings associated with AD
was the loss of neurons in the nucleus basalis, the main origin
of cholinergic neurotransmission to the cortex. Although the
cholinergic hypothesis of AD has lost favor in light of the
amyloid hypothesis, overcoming this cholinergic deficit of
AD continues to be a mainstay of treatment for the cognitive
symptoms of the disease. Several lines of evidence suggest
that acetylcholine (ACh) neurotransmission is important to
the normal functioning of memory. Inhibitors of acetylcholine
such as atropine or diseases that reduce acetylcholine levels
such as AD lead to memory loss.
Approaches taken to increase acetylcholine levels in diseased
brains include increasing production by providing the chemical
precursors, directly stimulating the ACh receptor or delaying
breakdown of the ACh that is naturally produced. It is not
feasible to give ACh directly because it is very short-lived
in the body. Acetylcholine precursors such as choline and
lecithin are taken up by brain neurons to make more ACh. They
are not effective in the treatment of memory disorder or AD,
however. Direct stimulation of cholinergic postsynaptic receptors
(through nicotinic and muscarinic agonists) is still under
investigation but does not appear too promising both as a
result of safety concerns and as a result of limited efficacy.
The most successful approach has been to reduce the naturally
occurring degradation (breakdown) of acetylcholine. Acetylcholine
is normally degraded through an enzyme known as acetylcholine
esterase (AChE), which is floating outside neuronal cells
in brain tissue. Inhibition of AChE results in increased acetylcholine
levels because of reduced degradation.
The U.S. Food and Drug Administration (FDA) has approved
four drugs, tacrine, donepezil, rivastigmine, and galanthamine,
for the treatment for AD. In addition, Huperzine-A, an over-the-counter
"nutriceutical," has been shown to have cholinesterase
activity and may have efficacy as a treatment of the cognitive
symptoms of AD in some clinical trials. However, Huperzine-A
has not been adequately tested for this purpose and, given
the alternative agents, is not high on the list of possible
treatments.
In terms of the four FDA-approved cholinesterase inhibitors
(CEIs), tacrine should not be used in light of the alternatives,
its complex titration, and associated risk of hepatic toxicity.
Over a dozen controlled, 3-6-month duration trials have reported
that CEIs can improve or slow cognitive losses and improve
global functioning (relative to placebo) in mild to moderate
AD. Regarding the long-term effects of these medications,
one 12- month study marginally missed significance on its
primary end point and open studies that have been reported
are subject to biases, so that there is a need for confirmatory
long-term controlled trials. One study of donepezil (known
as "AD2000") did not report significant cognitive
or functional benefits at 36 months, but these results remain
controversial because of the study design and sampling issues.
Some preliminary data suggest that CEIs may also delay nursing
home placement, reduce caregiver stress, and yield economic
benefits.
In very mild or more severe AD, the benefits of CEI are less
well proven. One 6-month randomized, controlled trial of donepezil
in moderate to severe AD found significant benefits to both
cognition and global function. Another 6-month randomized,
controlled trial of donepezil in very mild AD reported significant
benefits on some cognitive measures but not on a global measure.
There are no published trials with rivastigmine or galanthamine
in very mild or in moderate to severe AD.
The available direct comparison studies of CEIs (12-48 weeks)
have found no consistent differences in efficacy despite some
differences in tolerability and dropout rates. To date, there
are no published long-term trials directly comparing all three
agents, and the conduct of such a study by an independent
entity will enhance the field.
Benefits of treatments in individual patients can be difficult
to judge but may manifest initially as either improvement
or stabilization. Most clinicians and experts in this area
agree that at least for some patients, albeit a small number,
CEIs make a notable clinical difference. Over longer periods,
a slowing of cognitive and functional losses is the expected
benefit. Although there is still disagreement on what should
be the minimum duration of a therapeutic trial, it is reasonable
that patients who are tolerating these agents be tried on
them for at least 6 months (which is the duration of the key
trials that showed therapeutic benefits).
The evidence regarding combined use of CEI with memantine
is better than the evidence regarding switching between agents
or combining two CEIs, although there is much need for additional
data. Both memantine and CEIs are approved for moderate AD
and hence clinicians have a choice of which agent to start
therapy based on factors such as ease of use, patient preference,
cost, and safety issues. In judging treatment response, clinicians
should always seek information from a reliable informant,
take into account dementia and general health fluctuations,
and evaluate changes in cognition, function, and behavior.
It is also important to educate the family on realistic expectations
to enhance compliance. Families should also be cautioned that
abrupt discontinuation can occasionally lead to worsening
cognition or behavior.
The CEIs are the class of drugs with the strongest evidence
supporting their efficacy in treating the cognitive symptoms
of mild to moderate AD and should be considered as part of
the care for all such patients who do not have contraindications
as long as they are used after careful education of patients
and their caregivers and with careful and ongoing assessment
of the benefit-risk after they have been initiated.
SYMPTOMATIC THERAPIES FOR OTHER NEUROPSYCHIATRIC
SYMPTOMS
General Approach
Although cognitive deficits are the clinical hallmark of
dementing diseases, including AD, noncognitive neuropsychiatric
symptoms (NPS) are nearly universal, affecting over 90% of
patients with AD, and can influence the presentation and course
of the dementia.31 These NPS of dementia include
agitation, aggression, delusions, hallucinations, repetitive
vocalizations, and wandering, among others. In addition, an
affective disturbance, referred to as "depression of
Alzheimer disease" or "Alzheimer-associated affective
disorder" affects as many as 50% of patients with AD
at all dementia severities.32 NPS, especially behavioral
disturbances, are more common in later stages and are associated
with increased hospital lengths of stay, increased nursing
home placement, as well as caregiver stress and depression.
Interventions aimed at treating NPS have a tremendous positive
impact on patients, caregivers, and society. The detection,
management, or treatment of all forms of the noncognitive
neuropsychiatric symptoms is a key part of the care of AD.
Detection can be accomplished reliably in everyday clinical
practice with high reliability using systematic interviews
of patients and caregivers such as through the use of the
Neuropsychiatric Inventory (NPI) or its questionnaire version,
the NPQ.33
Once a noncognitive NPS have been detected, a series of activities
are a critical part of the development of dementia care. These
activities include:
- Differentiating which disturbance is present, for example,
delirium, apathy, mood or affective disorder ("depression"),
psychotic disorder (hallucinations, delusions), isolated
sleep disorder, isolated resistiveness with care, or a specific
behavior problem in the absence of those mentioned (such
as wandering, restlessness, verbal agitation, or physical
aggression);
- Considering possible contributing causes and the need
for workup. For example, one or more of the following might
be contributing causes: medications, medical illness (especially,
pain, constipation, dehydration, urinary tract infection,
upper respiratory infection, or other medical illness),
cognitive symptoms, environmental precipitants, unsophisticated
caregiving, unmet physical needs, or unmet psychologic needs;
and
- Making sure contributing causes are all addressed and
that basic needs are met, and then deciding if a specific
additional treatment is needed.
Nonpharmacologic Interventions
Once NPS have been identified, differentiated, and contributing
causes sorted out, specific tailor-made treatments are often
needed. The principles of care require that nonpharmacologic
interventions be tried first. Such interventions, often delivered
through caregivers, might include cognitive interventions
(reorientation; reminders, cues, task sequencing, or prompts),
environmental modifications (adjustment of noise level; provision
of familiar objects; reduction of clutter or visual distractors;
use of pictures to provide cues), changes in activity demand
(implementation of routines and scheduling, reduction in amount
and complexity of activities), or interpersonal approaches
(simplified language; use or avoidance of touch; focus on
patient's wishes, interests, and concerns). The selection
of specific nonpharmacologic therapies should be based on
the unique characteristics of the patient, the caregiver,
the availability of the therapy, the severity of the NPS,
and the likelihood that the specific symptoms will respond
to the specific therapy.
A recent systematic review of the literature identified several
specific nonpharmacologic interventions that appear to be
effective based on controlled trials for the NPS of dementia.34
Cognitive stimulation, improved socialization (perhaps through
the use of "adult day care"), or behavioral management
techniques centered on either the patient's or the caregiver's
behavior is the most effective treatments whose benefits might
last for months. Specific education for caregivers about how
to manage NPS has similar benefits, but other caregiver interventions
do not. Music therapy, use of snoezelen rooms, and possibly
sensory stimulation are useful ways of deescalating agitation
and can reduce NPS during the treatment session but do not
seem to have longer term effects. Changing the visual environment
such as through the provision of cues and visual cues to patients
who wander may work for some patients. Clinicians taking
care of patients with dementia are behooved to become familiar
with such techniques and either to develop the knowledge allowing
them to implement these themselves or to develop referral
sources to clinicians who have such expertise.
Pharmacologic Therapies
Despite nonpharmacologic efforts, the management of noncognitive
NPS often requires the introduction of medication therapies
specifically targeted at these symptoms. There is no clear
standard regarding which medications to use for which types
of symptoms. Nevertheless, the principles of care require
the use of medications when other approaches have failed and
there continues to be a need to treat or when the clinical
situation presents sufficient urgency to require pharmacologic
intervention before other approaches can be properly instituted.
Generally speaking, a need to treat with medications exists
when the NPS constitute a problem such as causing subjective
distress to the patient or caregiver, interfering with function
or causing disability, impeding the delivery of essential
care, or posing a danger to self or others; the specific symptoms
are likely to be medication-responsive (especially if they
have failed to respond to other treatment modalities); a threshold
of symptom severity, distress, disability, interference with
care, or danger has been exceeded; and the balance between
expected benefits and known risks of medication treatment
is acceptable to the patient or surrogate decision-maker.
Medications should be used cautiously with defined targets
and under close monitoring. Certain general approaches might
be considered following a recently proposed algorithm35
in which medications are used to treat underlying causes of
delirium or distressing physical symptoms such as pain, dyspnea,
and constipation. It is also reasonable to initiate therapy
with a CEI for milder NPS, if the patient is not already on
one, because they are well tolerated and may benefit cognition
and function. Trials of CEIs have reported consistent, albeit
rather small, positive effects on NPS. However, the data supporting
this conclusion are from trials in which NPS were secondary
outcomes.
If specific psychotropic medication therapy is to be instituted
for the management of NPS, there are two reasonable approaches.
One is to identify the target symptom and choose a medication
that is known to treat a symptom most closely related to the
one the patient is exhibiting. For example, one might use
an antipsychotic for psychotic symptoms or an antidepressant
for anxiety symptoms such as repetitive vocalizations or pacing.
Although this approach is intuitive, randomized clinical trials
have not been designed to confirm that this approach is effective.
An alternative approach is more empirically based, guided
by the current state of evidence, and expert consensus in
combination with the goal of minimizing adverse effects. Although
there are multiple classes of drugs in use for treating NPS,
including antipsychotics, antidepressants, anxiolytics, mood
stabilizers, beta-adrenergic receptor blockers, blockers,
and many others, there is limited evidence regarding the use
of individual medications. Most atypical antipsychotics have
moderately convincing evidence of efficacy for treating some
NPS of dementia. There have been recent reports that newer
atypical antipsychotics have been associated with infrequent
but serious adverse events, including a small increased risk
of death.36 Typical antipsychotics such as haloperidol
also may have efficacy in this context, but they should be
used with caution as a result of concerns about side effects
and because they too may be associated with similar small
increases in risk of death.37 Analyses focused
on the number needed to harm for these adverse events must
be assessed against findings from cost-effectiveness and cost-utility
analyses of the effects of these drugs on patient and caregiver
quality of life, survival, and costs of care.38
Data from trials of other classes of drugs for NPS such as
selective serotonin reuptake inhibitors (SSRIs) and "mood
stabilizer" anticonvulsants are conflicting. At this
point, it is clear that none of the medications in use for
NPS offer a "magic pill" and the treatment effects
have been modest.
In the absence of specific evidence for efficacy of individual
medications, if nonpharmacologic interventions or ChIs have
failed, the NPS of dementia are best treated with a range
of other psychotropic medications following an empiric approach
as recommended by a recent Consensus panel of experts39
or established treatment guidelines.40
In light of a recent FDA "black box warning," physicians
considering the prescription of atypical antipsychotics to
treat the NPS of patients with AD should discuss the potential
risks and benefits of such treatment with patients and their
surrogate decision- makers, especially for patients with risk
factors for cerebrovascular disease. It is important to emphasize
that no psychoactive medication prescribed to treat NPS of
dementia should be continued indefinitely and attempts at
drug withdrawal should be made regularly. The reader is referred
to a recent AAGP commentary on the matter.41
Given the complexities and risks involved in the pharmacologic
management of NPS in AD, the principles of care require giving
serious consideration to the involvement of a specialist such
as a geriatric psychiatrist, geriatrician, or neurologist
with specific expertise in the pharmacologic treatment of
the NPS of AD.
INTERVENTIONS TARGETED AT AND THE PROVISION
OF SUPPORTIVE CARE TO PATIENTS
General Approach
A key component of the principles of care involves the provision
of proper supportive care to patients with AD. The specific
interventions that individual patients require should be tailor-made
to their condition and their circumstances and typically change
with the progression of cognitive and functional decline associated
with AD. Clinicians caring for patients with AD should become
familiar with and or develop checklists (e.g., the checklists
offered by Rabins et al.42) that will help them
address systematically the elements of supportive care that
the principles require. At a minimum, clinicians should be
prepared to review such checklists and deliver appropriate
supportive care interventions, or refer the patient to clinicians
who are able to do so, as the circumstances may require.
Critical Intervention Areas
The following is a minimal checklist of issues to be addressed.
The details involved in the specific approach to individual
issues can be obtained from multiple sources, including books,
practice guidelines, and the
Alzheimer's Association web site (www.alz.org).
- Safety Matters Should Be Addressed,
Especially With Regard to Driving, Living Alone, Medication
Administration, Environmental Hazards, Wandering, and Falls.
Many books exist that can be provided to caregivers about
how to safety-proof the home of a person with AD. An in-home
occupational therapy assessment, using a functional assessment
method such as the Assessment of Motor and Process Skills
(AMPS), can provide information about level of care needs
and medication administration and also about home safety.
Patients with AD, especially those at risk for wandering,
should be referred for enrollment in the Alzheimer's Association
Safe Return or a similar program. In more severe dementia,
fall risk should be assessed on an ongoing basis and walking
aides or physical therapy intervention should be considered
to prevent falls. Regarding driving,43 rational
recommendations can be made by clinicians provided the physician
understands the substantial limits of current information
and also the applicable local reporting laws. Department
of motor vehicle reporting requirements vary by state. Research
suggests that discontinuation of driving should be strongly
considered for all patients with AD, even in mild dementia.
Patients whose illness has progressed beyond the early stage
of dementia should be advised to terminate driving, whereas
those with very earliest manifestations should be referred
for driving performance evaluation by a qualified examiner
while noting the limitations in on road testing. Because
of the expectation of progression, clinicians should reassess
dementia severity and appropriateness of continued driving
every six months.
- The Day-to-Day Living of Patients Should Be Structured
to Maximize Their Remaining Abilities and Function.
This preserves their dignity, makes life easier for caregivers,
and possibly encourages abilities to persist for longer
periods of time. Clinicians should work with caregivers
to find settings and environments in which limitations are
minimized and remaining abilities maximized such as making
sure that patients are well nourished and hydrated, are
properly socialized, receive a minimal level of activity,
have support for the performance of activities of daily
living, and have good sleep hygiene. Setting up the environment
is one specific approach that might be used to address this
aspect of care. According to this, the environment is manipulated
to achieve a balance between objective environmental demands
and a patient's cognitive and physical competencies, in
the following layers: 1) physical: manipulation to daily
objects, structural elements or sensory aspects of environment;
2) task: manipulation to daily routines including communication,
cueing techniques, and ways in which persons interact with
objects; 3) social: manipulation to organization, composition
and interactions of social groups; and 4) combination: manipulation
to one or more of these.
- General Medical Health Should Be
Closely Monitored. Medical comorbidity is a major
source of functional and cognitive impairment for patients
with AD44 and has been associated with accelerated
cognitive and functional decline. Relatively minor medical
illness can have a major impact on patients with AD. The
prevention of delirium and the adverse effects of medical
illness is a major aspect of dementia care. The clinician
should encourage general health maintenance, including exercise,
annual influenza immunization, dental hygiene, necessary
sensory aids, and good bowel routines, and in later phases
of the disease, attend to basic requirements such as nutrition,
hydration, and skin care. This is best accomplished by ensuring
that the patient has a good primary care physician who is
mindful of the special issues that arise in the care of
patients with AD.
- Advanced Care Planning and Advanced
Directives. Because loss of decisional capacity can
be anticipated, estate wills, advance directives, and durable
powers of attorney for health care are necessary to extend
the patient's autonomous decision-making. More evidence-based
studies are needed to help determine the benefits of various
assessments for determining capacity of patients with dementia
to consent to clinical care and research participation.
All patients retaining capacity should be strongly encouraged
to complete advance directives for medical care and institutional
placement, and be educated about the potential adverse consequences
of not doing so. During the later stages, decisions about
life-extending measures such as gastrostomy and intravenous
hydration should respect advance directives by patients
and incorporate participation from surrogate decision-makers.
INTERVENTIONS TARGETED AT AND THE PROVISION
OF SUPPORTIVE CARE TO FAMILY CAREGIVERS
General Approach
A key component of the principles of care involves the provision
of proper support to the family and other informal caregivers
of patients with AD. Such interventions have been shown in
controlled trials to enhance life quality for patients and
caregivers, and to delay institutionalization for home residing
caregivers. The specific interventions that individual caregivers
require should be tailor-made to their condition and their
circumstances, and typically change with the progression of
cognitive and functional decline of the patient for whom they
care. Clinicians caring for patients with AD should become
familiar with and/or develop checklists that will help them
address systematically the elements of supportive care for
caregivers that the principles require. At a minimum, clinicians
should be prepared to review such checklists and deliver appropriate
supportive care interventions, or refer the patient to clinicians
who are able to do so, as the circumstances may require.
Critical Intervention Areas
The following is a minimal checklist of issues to be addressed.
The details involved in the specific approach to individual
issues can be obtained from multiple sources, including books,
practice guidelines, and the Alzheimer's
Association web site (www.alz.org).
- Educating Caregivers. Critical
areas for education include dementia, AD, cognitive impairment,
noncognitive functional, and NPS, how diagnosis is made,
prognosis, treatment options, and supportive care. A very
important topic is the approach to the patient and the changing
role of the caregiver from their previous role as a specific
family member to being a caregiver. Another important area
for education involves teaching caregivers how to avoid
arguing with patients and how to involve them only in decisions
appropriate to their current level of cognitive ability.
Helping caregivers identify which of the patient's symptoms
arise from the brain injury and which likely have other
causes is also an important goal of the education process.
Well-informed caregivers are best equipped to address the
problems that AD presents. How much education caregivers
need depends on their role in the caregiving situation,
their ability to learn about a very complex situation, and
their interest. Educational needs also vary over time because
most dementias are progressive. Furthermore, the caregiver's
ability to comprehend, learn, and accept information may
change over time. Most can absorb only so much information
in one hearing, and their ability to learn may be affected
by their emotional state. Caregivers learn by different
methods. Some learn best by listening, others by reading,
and most by repetition. Written material is helpful for
many people, and several organizations, including the Alzheimer's
Association (www.alz.org), provide excellent pamphlets
on specific topics.
- Teaching Problem-Solving Skills.
Patients with dementia develop many problems that neither
they nor their caregivers have faced previously. Common
sense problem-solving is frequently effective. Even when
solutions are only partially successful in resolving a problem,
they can provide tremendous support to the patient and the
caregiver. One of the benefits of focusing on common sense
problem-solving is that most individuals are able to learn
the principles and use them to address new problems when
they arise. Despite this, caregivers are often either not
adept at problem-solving or have trouble applying it when
faced with a specific situation. Teaching caregivers how
to problem-solve by role playing or detailed face-to-face
instruction is a critical and very effective aspect of providing
care to caregivers.
- Accessing Resources. Assisting caregivers
in accessing resources is a critical part of dementia care.
Helping them find alternative caregivers in the family is
an important first step. Referral to the local Alzheimer's
Association chapter or to support groups, if needed and
appropriate, may be necessary. Access to the patient's primary
clinician on a 24-hour basis to address any crisis arising
in the patient's condition is a critical aspect of good
dementia care. Other important resources may be elder care
attorneys, rehabilitation therapists (occupational therapist,
physical therapist, speech), social workers, elder "care
managers," and others.
- Long-Range Planning. Caregivers
must be encouraged to conduct long-range planning as much
as possible with regard to financial matters, planning for
assisted living or institutionalization, advanced directives,
and dealing with late-stage dementia care. This is important
both from the planning point of view and also so that decisions
that are difficult might be made in the most deliberate
way possible.
- Emotional Support. Caregivers
should be encouraged to attend to their personal health
and mental health needs and be provided with assistance
in resolving family conflicts, referrals for counseling
and mental health or physical health assessment, and emotional
support to "ventilate" and express their frustrations,
as appropriate.
- Respite. Almost all caregivers
eventually need a break from caregiving. Clinicians should
carefully monitor for signs of caregiving strain and consider
respite as early as possible. This should be encouraged
as much as possible and strongly recommended when it is
evident that the caregiver is becoming overwhelmed. Setting
the stage early after diagnosis to prepare caregivers for
the potential need of respite in the future is also very
important. With more severe dementia AD, patients often
become very dependent on and may "shadow" their
caregiver. This can be very overwhelming and may well be
preventable by the careful introduction of other caregivers
through respite earlier in the disease. Many options for
respite exist, including use of other family or informal
caregivers, adult day care, professional caregivers, weekend
(or longer) admission to an assisted living facility, and
others. The clinician should be prepared to offer advice
and appropriate referral.
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