behavioral decompensation in alzheimer s disease a systematic and multimodal approach to patient management

1. Behavioral Decompensation in Alzheimer’s Disease

3. Peak Frequency ofBehavioral Symptoms as AD Progresses Behavioural symptoms appear at all stages of AD, sometimes 2 years prior to diagnosis (Jost and Grossberg, 1996). Peak frequencies of disturbances are indicated on a time line of disease progression. Social withdrawal occurred an average of 33 months before diagnosis and was the earliest recognisable psychiatric symptom observed. Suicidal ideation, depression, paranoia, and diurnal rhythm disturbances also occurred early in the course of the disease, whereas agitation, hallucinations, and aggression were documented an average of 1–2 years after diagnosis. Behavioural symptoms appear at all stages of AD, sometimes 2 years prior to diagnosis (Jost and Grossberg, 1996). Peak frequencies of disturbances are indicated on a time line of disease progression. Social withdrawal occurred an average of 33 months before diagnosis and was the earliest recognisable psychiatric symptom observed. Suicidal ideation, depression, paranoia, and diurnal rhythm disturbances also occurred early in the course of the disease, whereas agitation, hallucinations, and aggression were documented an average of 1–2 years after diagnosis.

4. “DOCTOR, WE’VE GOT A PROBLEM...”

5. Keys To Evaluation Of BehavioralProblems In Dementia Identify the problem behavior (WHAT) Timing / frequency of the behavior (WHEN) Surroundings / environment (WHERE) Others involved? (WITH WHOM) Very troubling / dangerous? Evaluation: physical & cognitive status Recommendations

6. The Delicate Balance of ClinicalDecision-making

7. Behavioral and Psychological Symptoms in Dementia: BPSD General descriptive term for heterogeneous group of non-cognitive symptoms & behaviors occurring in dementia Symptom Clusters within BPSD include: Depressive 20% - 40% Psychotic 30% - 40% Agitation/aggressive 50% - 80%

8. Criteria for Depression of Alzheimer’s Disease A. (Need 3 or more over 2 wks...) Depressed mood and/or Decreased positive affect or pleasure Appetite disruption Sleep disruption Psychomotor retardation / agitation Irritability Fatigue or loss of energy Worthlessness, hopelessness, guilt Thoughts of death or suicidal ideation B. All criteria met for dx of AD C. Sx cause clinically significant distress or disruption in fxn

9. TREAT Depression ofAlzheimer’s Disease!

10. AAN Practice Parameters 2001Guideline-Reaffirmed 10/18/2003 AAN practice parameters support the use of first-line nonpharmacologic strategies for agitation, especially when identifiable causes such as pain or environmental triggers are responsible , Neurology. 2001 May 8;56(9):1154-66. Related Articles, Links Comment in: ACP J Club. 2001 Nov-Dec;135(3):94. Evid Based Nurs. 2002 Jan;5(1):20. Neurology. 2001 May 8;56(9):1131-2.   Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.Doody RS, Stevens JC, Beck C, Dubinsky RM, Kaye JA, Gwyther L, Mohs RC, Thal LJ, Whitehouse PJ, DeKosky ST, Cummings JL.Department of Neurology, Baylor College of Medicine, Houston, TX, USA.OBJECTIVE: To define and investigate key issues in the management of dementia and to make literature-based treatment recommendations. METHODS: The authors searched the literature for four clinical questions: 1) Does pharmacotherapy for cognitive symptoms improve outcomes in patients with dementia? 2) Does pharmacotherapy for noncognitive symptoms improve outcomes in patients with dementia? 3) Do educational interventions improve outcomes in patients and/or caregivers? 4) Do other nonpharmacologic interventions improve outcomes in patients and/or caregivers? RESULTS: Cholinesterase inhibitors benefit patients with AD (Standard), although the average benefit appears small; vitamin E likely delays the time to clinical worsening (Guideline); selegiline, other antioxidants, anti-inflammatories, and estrogen require further study. Antipsychotics are effective for agitation or psychosis in patients with dementia where environmental manipulation fails (Standard), and antidepressants are effective in depressed patients with dementia (Guideline). Educational programs should be offered to family caregivers to improve caregiver satisfaction and to delay the time to nursing home placement (Guideline). Staff of long-term care facilities should also be educated about AD to minimize the unnecessary use of antipsychotic medications (Guideline). Behavior modification, scheduled toileting, and prompted voiding reduce urinary incontinence (Standard). Functional independence can be increased by graded assistance, skills practice, and positive reinforcement (Guideline). , Neurology. 2001 May 8;56(9):1154-66. Related Articles, Links

11. Principles ofNonpharmacologic Management Safety Control risk: physical, financial, driving Serenity Manage affects: avoid overt frustration and anger Structure Increase organization: maintain schedules, facilitate good habits Sanity Reduce caregiver strain: seek social support, use respite services Clin Geriatr Med. 2004 Feb;20(1):69-82. Related Articles, Links Managing agitation and difficult behavior in dementia.Gray KF.Departments of Psychiatry and Neurology, University of Texas Southwestern medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-9070, USA. Kevin.Gray@med.va.gov Nonpharmacologic management for dementia caregivers should include the "4-S" elements of Safety, Serenity, Structure, and Sanity (Table 2). Safety measures similar to "child-proofing" include making sure access to potentially lethal poisons and medications is carefully controlled; firearms, weapons, and "sharps" should be unavailable. Kitchen appliances and power tools are best left unplugged and out of sight. Smoke alarms must be kept in good working order, electric or gas stoves can have "cut-off" switches installed, and water heater temperature should be lowered so that a cognitively impaired bather cannot suffer severe burns, even if only the hot water faucet is operated. Secure locks and fences can limit wandering, and some type of identification for clothes and/or person such as an ID bracelet help with locating a lost dementia patient. The Alzheimer's Association sponsors Safe Return, a national, government-funded program that assists in the identification and safe, timely return of individuals with dementia who wander off, sometimes far from home, and become lost; caregivers may register their loved ones by phoning 888.572.8566. Financial safety is enhanced by limiting access to unscrupulous telemarketers; telephones can be silenced, and important messages can be retrieved remotely by caregivers. Similarly, mail can be diverted to a post-office box to avoid endless solicitations, while regular monthly bills are converted to automatic or direct pay. Consider limiting television channels to a few favorites, and ensuring that shopping channels are blocked. Finally, physicians should ask about and actively discourage driving by demented persons, as a recent evidence-based review found that even mildly demented Alzheimer victims pose a significant traffic safety problem both from crashes and from driving performance measurements (11). Serenity begins with deliberate and practiced management of affect on the part of the caregiver. As verbal communication becomes increasingly unreliable, the ability to display a pleasant countenance and employ a pleasant tone of voice - regardless of the situation - will serve the caregiver well and convey an overall sense of benign circumstance to the demented patient. Speaking directly to the patient in a calm, clear voice accompanied by gentle touching sends unambiguous signals via multiple sensory routes. Communicate affection, provide reassurance, and employ simple distractions such as ice cream when levels of tension increase. Regular reminders in the earliest phases of caregiving should stress that logic is increasingly unavailable to the dementia victim, so elaborate explanations and arguments must be avoided. In general, efforts to limit stimuli and avoid sensory overload are important; many demented individuals prefer a certain quiet place with a favorite chair and favorite music. Tapping into available remote memories via reminiscence can be helpful, and may allow younger family members more comfortable communications with a demented relative. The office visit is a splendid time for both physician and staff to model appropriate interactions for family caregivers. Structure and organization of the caregiving routine exploit the capacity of dementia patients to develop and retain new procedural or "habit" memories. Making the environment as regular, predictable, and familiar as possible allows the less impaired implicit memory systems to work in the caregiver's favor (12). Patience is key, and allows new habits - like males urinating while sitting - to be practiced and entrained over time. Scheduled voiding every 2-3 hours avoids accidents and allows demented persons and their caregivers to delay the inconvenience of diapering. The physician should emphasize that establishing a routine is a critical, first step for every dementia caregiver; once a consistent routine is in place, the family may make changes gradually, as needed. Finally, preserving the caregiver's Sanity allows for optimal patient care, as caregiver "burnout" is a major determinant of nursing home placement (13). In addition to the added burden of care responsibilities, caregivers often struggle to cope with the loss of intimacy in their relationship with the dementia victim. Social isolation must be avoided, and the physician may need to foster the enlistment of adult children to relieve burden from an aged spouse, who may feel overwhelmed by the caregiving duties and angered by the criticism implied by family or physician suggestions that changes in care technique might be beneficial. Helping caregivers set limits and reasonable goals, along with regular reminders that "heroic" efforts are neither expected nor desirable, keeps family morale high. Benevolent physician and staff support reinforces caregivers learning to work smarter, not harder, and to ignore benign behaviors; family members must learn to avoid personalizing hurtful or insensitive comments that arise out of the dementia. Imaginative solutions, combined with common sense and loving concern, should always be encouraged.  Clin Geriatr Med. 2004 Feb;20(1):69-82. Related Articles, Links

12. Educational programs should be offered to family caregivers to improve caregiver satisfaction and to delay the time to NH placement (Guideline). Staff of long-term care facilities should also be educated about AD to minimize the unnecessary use of antipsychotic medications (Guideline). Behavior modification, scheduled toileting, and prompted voiding reduce urinary incontinence (Standard). Functional independence can be increased by graded assistance, skills practice, and positive reinforcement (Guideline). AAN Practice Parameters 2001Guideline-Reaffirmed 10/18/2003

13. Medication Considerations ForNon-urgent/Emergent “Agitation”

14. NPI Scores Following Treatment with Different ChEIs In addition to their effects on the cognitive and functional domains of AD, cholinergic drugs may be considered psychotropic agents and are useful in the treatment of specific disorders with cholinergic deficits such as AD, which is characterized by progressive cognitive deterioration, neuropsychological or behavioral disturbances, and eventual elementary neurological dysfunction. In addition to their effects on the cognitive and functional domains of AD, cholinergic drugs may be considered psychotropic agents and are useful in the treatment of specific disorders with cholinergic deficits such as AD, which is characterized by progressive cognitive deterioration, neuropsychological or behavioral disturbances, and eventual elementary neurological dysfunction.

16. Memantine in Moderate to SevereAD Study: Impact on Behavior - NPI At End Point There was no statistically significant difference between the 2 groups for total NPI scores There was a statistically significant difference between the treatment groupsin favor of memantine in the following domains Delusions P = .0386* Agitation/aggression P = .0083*4 Purpose: To review the behavioral outcomes, using the 12-item Neuropsychiatric Inventory (NPI) scale, which assesses neuropsychiatric disturbances based on information from the caregiver regarding the patient’s behavior and the associated distress felt by the caregiver. Scores range from 0-144, with higher scores indicating greater impairment Key Points: While there was no significant effect on total NPI score, there was a significant effect of memantine on the domains of delusions and agitation/aggression. Additional Information: Based on the LOCF analysis, there was a statistically significant difference between the treatment groups for the following NPI domains: Delusions (P = .0386) and Agitation/Aggression (P = .0038). Agitation/Aggression was the only significant item based on OC analysis Delusion Domain: Placebo Memantine Baseline 1.26 1.83 End point 1.74 1.48 Agitation/Aggression Baseline 1.9 1.98 End point 2.83 2.06 AChEIs have mixed results on behavioral disturbances in AD. Note also that the responsive items on the NPI have varied across studies.Purpose: To review the behavioral outcomes, using the 12-item Neuropsychiatric Inventory (NPI) scale, which assesses neuropsychiatric disturbances based on information from the caregiver regarding the patient’s behavior and the associated distress felt by the caregiver. Scores range from 0-144, with higher scores indicating greater impairment Key Points: While there was no significant effect on total NPI score, there was a significant effect of memantine on the domains of delusions and agitation/aggression. Additional Information: Based on the LOCF analysis, there was a statistically significant difference between the treatment groups for the following NPI domains: Delusions (P = .0386) and Agitation/Aggression (P = .0038). Agitation/Aggression was the only significant item based on OC analysis Delusion Domain: Placebo Memantine Baseline 1.26 1.83 End point 1.74 1.48 Agitation/Aggression Baseline 1.9 1.98 End point 2.83 2.06 AChEIs have mixed results on behavioral disturbances in AD. Note also that the responsive items on the NPI have varied across studies.

17. Memantine + Donepezil in Moderate toSevere AD Study: Impact on Behavior Purpose: To illustrate results on other ancillary outcome measures, including the NPI and the BGP-Care The Neuropsychiatric Inventory (NPI) score assesses neuropsychiatric disturbances using a 12-item scale based on information from the caregiver regarding the patient’s behavior and associated distress felt by the caregiver. Scores range from 0-144, with higher scores indicating greater impairment. The BGP-Care dependency subscale reflects cognitive and functional characteristics associated with increased need for care. For each item, raters scored patients either a 0, 1, or a 2, with a higher score reflecting greater Disability. Key Points: Orientation to the scale: positive changes in score indicate clinical deterioration. Memantine treatment resulted in significant differences on the BGP-Care dependency subscale compared to placebo. On the NPI scale, the total score was significantly lower for the memantine + donepezil treatment group compared with the placebo + donepezil group, representing fewer overall behavioral disturbances and psychiatric symptoms for patients. LOCF NPI single-item analyses show that memantine + donepezil treatment significantly reduced the frequency and/or severity of agitation/aggression (P<.001), irritability/lability (P = .005), and appetite/eating changes (P = .045) compared with placebo + donepezil treatment. OC NPI single-item analyses show that memantine + donepezil treatment significantly reduced the frequency and/or severity of agitation/aggression (P<.0001) and irritability/lability (P = .003) compared with placebo + donepezil treatment.Purpose: To illustrate results on other ancillary outcome measures, including the NPI and the BGP-Care The Neuropsychiatric Inventory (NPI) score assesses neuropsychiatric disturbances using a 12-item scale based on information from the caregiver regarding the patient’s behavior and associated distress felt by the caregiver. Scores range from 0-144, with higher scores indicating greater impairment. The BGP-Care dependency subscale reflects cognitive and functional characteristics associated with increased need for care. For each item, raters scored patients either a 0, 1, or a 2, with a higher score reflecting greater Disability. Key Points: Orientation to the scale: positive changes in score indicate clinical deterioration. Memantine treatment resulted in significant differences on the BGP-Care dependency subscale compared to placebo. On the NPI scale, the total score was significantly lower for the memantine + donepezil treatment group compared with the placebo + donepezil group, representing fewer overall behavioral disturbances and psychiatric symptoms for patients. LOCF NPI single-item analyses show that memantine + donepezil treatment significantly reduced the frequency and/or severity of agitation/aggression (P<.001), irritability/lability (P = .005), and appetite/eating changes (P = .045) compared with placebo + donepezil treatment. OC NPI single-item analyses show that memantine + donepezil treatment significantly reduced the frequency and/or severity of agitation/aggression (P<.0001) and irritability/lability (P = .003) compared with placebo + donepezil treatment.

18. AAN Practice Parameters 2001(Reaffirmed 10-18-03) Treat agitation, psychosis and depression The patient's paranoia, suspiciousness, combativeness or resistance to maintaining personal hygiene can seem overwhelming to families and caregivers and significantly impact quality of life. Evidence indicates that several strategies can decrease problem behaviors. If environmental manipulation fails to eliminate agitation or psychosis, use antipsychotics…

19. Diagnostic Criteria forPsychosis of AD Diagnosis of Alzheimer’s dementia Exclusion of schizophrenia or other causes of psychotic symptoms Hallucinations and/or delusions Late-onset Present intermittently for ?1 month Disruptive to patient functioning Associated agitation, negative symptoms, and depression Disturbances do not correlate exclusively with delirium

20. ANTIPSYCHOTIC USE FOR “AGITATION”

21. The Delicate Balance of ClinicalDecision-making

22. Antipsychotic Documentation Severity of symptoms Danger to patient and others Lack of response to alternative approaches Awareness of risks of treatment Judgment that potential benefits outweigh risks Previous benefit? Previous tolerability? Discussion with family Monitoring plan Plan for dose reduction when stable

23. Atypical Antipsychotic Treatment for Psychosis & Dangerous Behavioral Dyscontrol in Dementia: Olanzapine 2.5 – 10 mg, oral “loading” pts in urgent settings [15-20 mg 1st 24 hr]; IM* Risperidone 0.5 – 2 mg, caution w/ doses > 1 mg‡ Quetiapine 25-150 mg, especially w/ parkinsonism, Lewy Body Dementia† Aripiprazole 5-10 mg, non-urgent use§ Ziprasidone 20-60 mg BID, emerging option; IM¶

24. Efficacy and Adverse Effects of Atypical Antipsychotics for Dementia:Meta-analysis of Randomized, Placebo-controlled Trials Efficacy on rating scales was observed by meta-analysis for aripiprazole and risperidone, but not for olanzapine There were smaller effects for less severe dementia, outpatients, and patients selected for psychosis Approx 1/3 dropped out w/o overall differences between Rx & placebo Adverse events mainly somnolence & UTI or incontinence across Rx, and EPS or abnormal gait with risperidone or olanzapine

25. Efficacy and Adverse Effects of Atypical Antipsychotics for Dementia: (con’t) Meta-analysis of Randomized, Placebo-controlled Trials Cognitive test scores worsened with drugs There was no evidence for increased injury, falls, or syncope Significant risk for cerebrovascular events, especially with risperidone Increased risk for death overall was reported elsewhere The modest efficacy and uncertain response rates combined with the risks detailed here suggest that antipsychotics should be used with more deliberate consideration

26. Antipsychotic EquivalenciesBased On D2 Receptor Occupancy & Expert Consensus Guidelines Quetiapine = 300-400 mg Chlorpromazine = 100 mg Ziprasidone » 80 mg Aripiprazole = 10 mg Loxapine = 15 mg Olanzapine = 10 mg Risperidone = 2.5 mg Haloperidol = 2 mg

27. Non-neuroleptic OptionsFor “Agitation” ??

28. Alternative Rx FOR “Agitation” SSRI REDUCE IRRITABILITY: non-psychotic pts, psychosis? TRAZODONE (25-50 mg BID-TID) during day, qHS BUSPIRONE (10-60 mg/day): may take 2-4 wks DIVALPROEX, CARBAMAZEPINE, GABAPENTIN ADJUNCTIVE BENZODIAZEPINES HORMONES for SEXUAL AGGRESSION: (medroxyprogesterone acetate 150 mg IM q4wks)

29. Behavioral Decompensation in AD Medications do not work alone Fewer expectations late in day Distract with tasks or food Remind and assist; don’t take over! Be willing to compromise Back off and let patient relax; redirect as appropriate “They can’t resist if you don’t insist”