Behavioral Symptoms in Alzheimer Dementia:A Guide to Evaluation and Management

December 31, 2006

An 81-year-old man presents with severe Alzheimer dementia. Hishistory includes benign prostatic hypertrophy with 2 transurethralresections. He has a remote history of tobacco use and has not used alcohol excessively. He isotherwise in good health. At the time of his original diagnosis, a cholinesterase inhibitor was notprescribed.

The patient is a retired executive who resides at home with his wife; his daughter lives nextdoor. Until now, the family had been able to provide the support and supervision necessary toallow the patient to remain at home. He has had brief periods of behavioral problems but thesewere self-limited.Recently, he has begun to demonstrate increased agitation and aggressive behavior. Hisrelationship with his wife was described as "verbally volatile." In the past 2 to 4 weeks, his behavioralsymptoms have escalated. The patient's primary care physician prescribed low-doserisperidone. The family, who wished to continue to care for the patient at home, administeredthe medication, and even exceeded the recommended dosage, because the patient's symptomsfailed to respond. He began to wander, became combative when attempts at redirection weremade, threw furniture, and struck several family members. The family finally transported himto the local emergency department for further evaluation and treatment.The patient was found to have no acute medical problems. He was admitted to the psychiatryunit and placed under the care of a geriatric psychiatrist. The patient was extremely confused,disoriented, and aphasic. Although he was generally pleasant and cooperative, he frequently becameagitated and combative when redirected by staff. He wandered into other patients' roomsand attempted to leave the unit several times. His gait was unsteady.For his safety, he was placed in a clinical recliner. He was given lorazepam as needed. Becausehe did not respond to risperidone, olanzapine, 2.5 mg qhs, was started. His agitation, aggressivebehavior, and wandering did not decrease initially, and he required a Posey restraint forsafety. Lorazepam was discontinued.An organic workup was completed to detect any reversible causes of the change in mentalstatus and behavior. This included a CT scan, without contrast, of the head; measurement of ammonia,thyroid-stimulating hormone (TSH), vitamin B12, and folate levels; a rapid plasma reagintest; and a complete metabolic profile. Most results were unremarkable. The CT scan showedcerebral atrophy without evidence of acute intracranial abnormality. The blood glucose level wasmildly elevated; the TSH level was low. An ECG showed normal sinus rhythm. Because theworkup revealed no other possible causes for the patient's behaviors, they were attributed toprogression of Alzheimer disease. Further evaluation and treatment were undertaken with dementiaas the working diagnosis.Social contact - including frequent and extended visits by the patient's family - resultedin decreased agitation. However, other attempts at nonpharmacologic intervention (activities therapy,differential reinforcement, and environmental changes, such as having the patient closer tothe nurses' station) were ineffective once the family left the unit.Use of the Posey restraint was continued because the patient's behavior had not changedsignificantly and he and others were still at risk. During an episode of increased agitation, ziprasidone,10 mg IM, was administered. The patient became less irritable and more easily directed.Olanzapine was stopped and oral ziprasidone, 20 mg/d, was initiated. A trial of donepezil was alsobegun.Despite the reduction in agitation and aggression, the patient continued to wander. ThePosey restraint was replaced with one-to-one observation. The patient responded well when staffdirected him away from the rooms of other patients.What are the most effective strategies to cope with thebehavioral problems associated with dementia?Typically, the initial approach todementia focuses on the assessmentand management of cognitive impairments.However, the cognitive declineis frequently subtle and insidious.Patients and their families oftenadapt to and accommodate deficits inmemory, judgment, or cognitive function,and they do not report them tothe physician.BEHAVIORAL SYMPTOMS:THE SCOPE OF THE PROBLEMBehavioral symptoms affectmost patients with dementia at somepoint during the course of the illness.In many cases, the clinician becomesaware of the difficulties experiencedby a patient and his or her caregiversonly after the onset of behavioralproblems. The family presents in astate of crisis. They have been able toprovide support, supervision, andstructure for the patient up to thispoint. However, as a result of the progressionof the dementia, behavioralsymptoms become more prevalentand complicate the continuous cognitivedecline.1Although caregivers are able toinstitute interventions to address thepatient's increased needs in performingactivities of daily living, behavioralsymptoms often prevent him from accepting these interventions.The behaviors put patient and caregiversat risk for physical injury aswell as psychological trauma andstress. In the hospital or other structuredsettings, inappropriate behaviorsare, at the very least, disruptive;an agitated or aggressive patient maypresent a risk of harm to himself andothers. This is the point at which thefamily struggles with the question ofwhether to consider a long-term-carefacility.EVALUATION OF BEHAVIORALDISTURBANCESThe 2 behavioral problems ofmost concern are agitation and aggression.These can occur as a responseto psychotic symptoms, suchas delusions and hallucinations. Besidespsychosis, other causes of behavioraldisturbance include frustrationthat results from failed attemptsto communicate a specific emotion,symptom, or need because of languageand/or cognitive deficits. Delirium,which has multiple possiblecauses, may also cause behavioralproblems. The diagnostic criteria forthe psychosis of Alzheimer diseaseare listed in the Table.2Initial management involves evaluationfor causes of behavioral disturbancesthat are potentially reversible.These include the "I's"3:

  • Iatrogenic causes (drug reaction/interactions).
  • Infection.
  • Illness (pain and/or worsening ofchronic medical conditions).
  • "Is the patient depressed?" (Severedepression with or without dementiais known to cause agitated or psychoticbehavior.)

Addressing any or all of thesecan result in improvement in behavioralsymptoms.Behavioral symptoms can occurat any time during the progression ofdementia. The type of dementia oftendetermines when these symptomsbecome evident. The psychosis associatedwith Alzheimer dementia is oflate onset, presenting most often inthe moderate to severe stage.In Lewy body dementia, which ischaracterized by varying degrees ofcognitive impairment, hallucinations(mainly visual), and Parkinsonism,the psychotic symptoms with behavioraldisturbances are noted beforecognitive impairment becomes obvious.It is important to differentiateLewy body dementia from Alzheimerand vascular types because patientswith Lewy body dementia are moresensitive to the effects of medication.

NONPHARMACOLOGICINTERVENTIONS

Once reversible causes of behavioralsymptoms have been evaluatedand addressed, interventions - pharmacologicor nonpharmacologic - can be implemented to decrease thedisruptiveness of these behaviors.Historically, pharmacologic therapywas instituted. However, the currentstrategy is to avoid using more medicationsfor patients who are alreadytaking multiple agents.

Therefore,nonpharmacologic interventions arerecommended as first-line therapy

.If used effectively, these interventionsmay decrease behavioral symptomsand reduce their emotional, physical,and financial costs. Other advantagesof this approach include

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:

  • Nonpharmacologic therapy addressesthe psychosocial/environmentalcauses of the behavior.
  • The complications of pharmacologicinterventions - such as adverseevents, drug-drug interactions, andlimited efficacy - are avoided.
  • When medication is effective, it maymask the patient's need by eliminatingthe behavior that serves as a signalfor the need, thereby reducingthe patient's already compromisedability to communicate and diminishingthe caregiver's ability to properlycare for him. Nonpharmacologic approachesdo not have this effect.

Nonpharmacologic interventionsinclude sensory intervention (music),social contact (pet visits), behaviortherapy (differential reinforcement),staff training, physical activity (outdoorwalks), environmental interventions(wandering areas), and medical/nursing care interventions (painmanagement). Multiple nonpharmacologicinterventions may also be combinedwith pharmacologic therapy.Although family members whocare for a patient at home can implementsome of these modalities, optimaleffectiveness is achieved in morestructured and supervised settings,such as adult day-care programs orextended-care facilities.Despite aggressive and consistentuse of nonpharmacologic interventions,behavioral symptoms maysometimes persist. Pharmacologic interventionis necessary in these situations,and referral to a geriatric psychiatristis recommended.

PHARMACOLOGICTHERAPY

Traditional antipsychotics, suchas haloperidol, are used to treat agitationand aggressive behaviors. Theyare effective and have a rapid onset ofaction; several are available in bothoral and parenteral forms. However,they may be overly sedating and cancause extrapyramidal side effects(muscle stiffness, restlessness, andParkinson-like symptoms). Short-actingbenzodiazepines (eg, lorazepam)are an alternative but they may causeexcessive sedation and an increasedrisk of falls. Their use sometimes resultsin a paradoxical increase insymptoms, possibly because of the effectsof disinhibition.Atypical antipsychotics - includingrisperidone, quetiapine, olanzapine,ziprasidone and aripiprazole - are a safer option because the risk ofextrapyramidal side effects is muchlower.

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Each of these medicationshas a unique pharmacodynamic andpharmacokinetic profile.

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As a result,they are variably effective for positivepsychotic symptoms (hallucinations,delusions, disorganized thinking,agitation); negative symptoms (socialwithdrawal, lack of affect, cognitiveimpairment); mood; and anxiety.Their sedative effects and adverseevents profiles vary as well.Two studies found that low-doserisperidone was effective for the treatmentof aggression, agitation, andpsychosis in dementia.

8,9

One of thestudies reported an increased incidenceof cerebrovascular accidents inthe risperidone-treated patients; however,these patients had significantrisk factors for stroke.

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Elevated levelsof blood glucose and lipids havebeen associated with olanzapine.If the behaviors do not constitutean emergency and nonpharmacologicinterventions remain unsuccessful,several other classes of medicationcan be considered. Theseinclude the cholinesterase inhibitors, antidepressants, anticonvulsants, andmemantine.A recent review found that theeffects of cholinesterase inhibitors onbehavioral symptoms were variable.

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However, because these agents mayslow further cognitive decline and thesubsequent increase in symptoms,and may modulate behavioral symptomsas well, their use is stronglyrecommended.In depressed patients, an antidepressantat therapeutic doses relievesdepression as well as agitatedor psychotic behaviors. The tricyclicantidepressants, such as amitriptyline,are best avoided because theymay cause anticholinergic side effects,orthostatic hypotension, andcardiac arrhythmia. Selective serotoninreuptake inhibitors are a goodoption.

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In spite of the potential fordrug-drug interactions with theseagents, most are effective and welltolerated in older patients.Anticonvulsants have been usedto treat impulse control, mood instability,agitation, and aggression. In anopen-label extension of a double-blindtrial, divalproex sodium was found todecrease agitation scores of patientswith dementia.

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Further study is ongoing.Other anticonvulsants, such ascarbamazepine, lamotrigine, gabapentin,and tiagabine, have been used toreduce behavioral symptoms.Memantine, a recently approvedN-methyl-D-aspartate receptor antagonist,can help slow the progression ofdementia; it may have an indirect benefiton behavior.

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The combination ofa cholinesterase inhibitor and memantineappears to work synergistically toimprove cognition and reduce behavioralsymptoms.

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OUTCOME OF THIS CASE

Although the family wished tohave the patient return home, it wasrecommended that he be transferredto an extended-care facility, at leastfor a period of convalescence. Unfortunately, the facility was unable to obtainziprasidone. Without the medicationand with the stress of the newenvironment, his agitation and aggressionincreased.The patient was subsequentlyreadmitted to the hospital. Duringthis rehospitalization, the family reportedthat the patient had been unableto tolerate donepezil because ofGI side effects. This agent was discontinued,and memantine, 5 mg/d,was started. Ziprasidone was reinstituted;the patient quickly improved,and he was discharged to a differentextended-care facility that was betterable to care for patients with behavioralsymptoms related to dementia.Three months after discharge,the patient is doing well at this facility.His care was assumed by thefacility psychiatrist, who discontinuedthe memantine and initiated hydroxyzine.The patient continues to takeziprasidone.

References:

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