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Assessment and Management of Disruptive Behaviors in Persons With Dementia

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VITAS Healthcare
VITAS Healthcare

This webinar helps physicians conduct a systematic evaluation for behavioral changes in persons with dementia. It offers approaches for developing a comprehensive care plan for disruptive behaviors. These methods incorporate caregiver education and non-pharmacologic interventions followed by pharmacologic management.

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Assessment and Management of Disruptive Behaviors in Persons with Dementia
Objectives • Describe the occurrence and impact of dementia-related behaviors • Construct a systematic evaluation for behavioral changes in persons with dementia • Develop a comprehensive care plan that incorporates caregiver education and non-pharmacologic interventions followed by pharmacologic management for disruptive behaviors
Alzheimer's Association. (2023). 2023 Alzheimer’s Disease Facts and Figures. Retrieved from https://www.alz.org/media/ Documents/alzheimers-facts-and-figures.pdf Most Common Etiologies of Dementia Cause Prevalence Pathophysiology Alzheimer’s disease 60-80% Amyloid plaques and neurofibrillary tangles Mixed pathologies >50% More than one neuropathology, more common oldest old Cerebrovascular disease 5-10% Blood vessels damaged, brain tissue injured Lewy Body disease 5% Alpha-synuclein protein Frontal Lobar Degeneration 3% Tau protein Transactive response DNA-binding protein (TDP-43)
Alzheimer's Association. (2023). 2023 Alzheimer’s Disease Facts and Figures. Retrieved from https://www.alz.org/media/ Documents/alzheimers-facts-and-figures.pdf Epidemiology • 2023 US Alzheimer’s estimate: – 6.7 million people aged 65+ – 2/3 are women, ~ 1 in 3 women develop dementia in their lifetime • More than 1 in 9 persons over the age of 65 have dementia • 1 in 3 persons over the age of 65 dies with dementia • Diagnosis of dementia cuts one’s life expectancy in half • Dementia is the fifth-leading cause of death in persons over 65 • Between 2000-2019, dementia- related deaths increased 145%
Natural History of Dementia ADL Dependency Death Low Time (Slow decline) High Hospice Eligible FAST 7a plus Disease-related complication within the last several months Disease-related complications include, but are not limited to: • UTI • Sepsis • Febrile episode • Delirium • Pneumonia • Hip fracture • Eating difficulty or dysphagia • Dehydration • Feeding tube
78 y/o with rapidly progressive Alzheimer’s and vascular dementia after sustaining a fall at home with a hip fracture that was surgically repaired. During the patient’s skilled stay, the patient has become mostly WC and/or bedbound and not participating in PT with both physical and verbal agitation and aggression, especially when trying to engage in activities or move the patient. The agitation is new since the hip fracture. The psychiatrist diagnosed the patient with depression and prescribed sertraline 50mg followed by valproic acid 250mg BID due to refractory symptoms. The patient has been more lethargic but remains agitated at times. Additional changes include 5% weight loss in 1 month due to a poor appetite, functional decline with a PPS decrease from 80 to 40, and dependency in 3/6 ADLs from 1/6 prior to the fall. After completion of skilled care, the patient was transitioned to long term care. The daughter expresses guilt as she recognizes her mom is upset and angry because she never wanted to be in a nursing home. Case
Delirium Acute Onset and Fluctuating Course AND Inattention plus either Disorganized Thinking Altered LOC DELIRIUM
Terminal Restlessness THE USUAL ROAD THE DIFFICULT ROAD
Dementia Behaviors Thought and Perceptual Disturbances • Delusions • Paranoia • Hallucination Mood Disturbances • Anxiety • Depression • Irritability Activity Disturbance • Agitation and/or aggression • Wandering • Purposeless hyperactivity • Apathy • Impulsivity • Socially inappropriate behavior • Sleep problems • Repetitive behavior
Agitation/Aggression Definition International Psychogeriatric Association convened a panel of experts with the goal of establishing principles guiding the definition of agitation in elderly populations: 1. Occurring in patients with cognitive impairment or a dementia syndrome; 2. Exhibiting behavior consistent with emotional distress; 3. Manifesting excessive motor activity, verbal aggression, or physical aggression; and 4. Evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related)
Radue, et al. (2019). Neuropsychiatric symptoms in dementia. Handbook of Clinical Neurology, 167, 437-454. Neuropsychiatric Symptoms (NPS) by Stage of Dementia 4.3% 11.2% 15.2% 44.3% 38.2% 13.3% 32.6% 30.3% 30.0% 31.4% 82.3% 56.0% 54.5% 25.7% 30.4% Normal cognition Mild cognitive impairment Mild dementia Moderate dementia Severe dementia No symptoms 1-2 symptoms 3+ symptoms 7% 16% 17% 31% 32% 34% 36% 39% 39% 40% 42% 49% 0% 10% 20% 30% 40% 50% 60% Euphoria Hallucinations Disinhibition Delusions Aberant motor behavior Appetite disorder Irrtability Sleep Disorder Anxiety Aggression Depression Apathy 80-90% of patients will develop neuropsychiatric symptoms over the course of their illness No FDA-Approved Treatment for Neuropsychiatric Symptoms in Dementia
Mitchell, et al. (2009). The clinical course of advanced dementia. New England Journal of Medicine (361), 1529-1538. Symptom Experience in Persons With Dementia in the Last Year of Life 0 5 10 15 20 25 30 35 40 Dyspnea Pain Pressure ulcers Aspiration Agitation Residents With Symptoms (%) Distressing Symptoms Months Before Death (no. of residents alive during interval) >9-12 (N=67) >6-9 (N=96) >3-6 (N=128) 0-3 (N=177)
Cummings J et al. Reduction and prevention of agitation in persons with neurocognitive disorders: An IPA consensus algorithm International Psychogeriatrics 2022: DICE International Psychogeriatric Association D Describe the behavior I Investigate the underlying contributors/causes C Create intervention: non-pharmacologic and pharmacologic E Evaluate the interventions effectiveness I Investigate behavior plus precipitants, duration, frequency, potential harm; Impact intervention P Plan intervention that reflects patient features and setting; share DM with patient/CG A Act multidisciplinary plan with psychosocial interventions and choose pharmacologic treatments if needed
O’Gorman, et al. (2020). A framework for developing pharmacotherapy for agitation in Alzheimer’s disease: recommendations of the ISCTM working group. The Journal of Prevention of Alzheimer's Disease, 7(4), 274-282. Behavior Description • Characterization • Severity or quantification • Temporal onset and course Scale Measure Cohen-Mansfield Agitation Inventory 4 behavioral categories, 29 total items, caregiver response over last 2 weeks, behavior frequency ranges from 1 to 7, higher scores more behaviors Neuropsychiatric Inventory 10 or 12 (sleep and appetite added) behaviors rated by frequency (4 categories) severity (3 categories), caregiver distress (5 categories) over a week, higher scores more behavioral burden Behavioral pathology in Alzheimer’s disease 7 behavioral categories containing 25 symptoms, each scored on a 4-point severity scale ascertained by a caregiver • Caregiver status • Context of personal, family, social, and medical history • Associated circumstances, including precipitants and alleviating factors
Impact of Disruptive Behaviors in Dementia Patient • Increased morbidity (cognitive/ functional); lower quality of life • Abuse and neglect • Increased likelihood of hospitalization with a longer length of stay • Nursing home placement • Increased mortality Caregiver • Increased burden, stress, exhaustion, and strain • Sleep disturbances, depression, and anxiety • Lower quality of life • Reduced income from employment • Increased mortality
Case (cont.) Describe the behavior and rationale to treat: • Agitation and aggression worse with movement and activity, new after fall • Verbal (yelling when trying to move or interact) and physical (resistive to daily care and strike out when try to move) • Intermittent sleeping and agitation and daughter reports a poor quality of life • Unsteady on feet, not wanting to move around much • Decreased oral intake • Potential risk to staff for physical harm
Kales HC, Gitlin LN, Lyketosis CG. Assessment and Management of behavioral and psychological symptoms of dementia. BMJ 2015; h369 DICE D Describe the behavior I Investigate the underlying contributors/ causes C Create intervention: non-pharmacologic and pharmacologic E Evaluate the interventions effectiveness
Ringman JM, Schneider L. (2019) Treatment Options for Agitation in Dementia. In Current Treatment Options Neurology (Vol 21, 30). Contributors to Agitation and Restlessness Contributor Causes Approach Physical symptom Pain, SOB, constipation Opioid or laxative Psychological symptom Depression, anxiety, bipolar disorder, delusions, hallucinations SSRI, SNRI, antipsychotic Medical condition Infection, COPD, HF, gout, hyperglycemia, electrolyte abnormality, broken bone, constipation, insomnia Treat condition Unmet need Hunger, thirst, hot, cold, boredom Attend to need Sensory impairment Poor vision/hearing Adaptive Environment Under/over stimulation, change in routine, life stressor, pt-cg relationship Modify Toxicology Anticholinergic drug, digitalis, benzodiazepine, withdrawal syndrome (ETOH, opioid cannabis), steroids Discontinue
Huesbo B, Ballard C, Sandvik R, et al.(2011) Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ Vol. 343. Atee M, Morris T, Macfarlane S et al. (2021) Pain in Dementia: Prevalence and Association with Neuropsychiatric Behaviors. J Pain Symptom Manage Vol 61, p 1215-1226. Contributors to Agitation and Restlessness Step Treatment Study Treatment 1 APAP Maximum dose 3gm 2 Morphine 5mg Twice daily 3 Buprenorphine 5mcg patch, can increase to 10mcg 4 Pregabalin 25mg up to 300mg daily
Case (cont.) Investigate • Additional PMH patient grimaces with movement and braces on the side with the hip fracture repair. The patient is not taking the as-needed acetaminophen and has no other analgesic ordered. Staff report the patient seems to alternate between agitation and over-sedation and is otherwise withdrawn. Appetite is poor but has no apparent nausea or constipation. Insomnia with difficulty falling asleep and early morning awakenings. • Patient’s other chronic medical conditions are well controlled. The patient does not have altercations with staff or her roommate unless trying to be moved. Her daughter reports mom misses her dog and home. Besides the sertraline and valproic acid, no changes in medications. • Physical exam: temporal wasting, hearing and vision seem intact, pain behaviors as described especially with ROM of repaired hip, and bloodwork is unremarkable. Considerations • Pain from hip fracture repair • Depression • Loneliness • Medication
DICE D Describe the behavior I Investigate the underlying contributors/ causes C Create intervention: non-pharmacologic and pharmacologic E Evaluate the interventions effectiveness
Ayalon, et al. (2006). Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Archives of Internal Medicine, 166(20), 2182-2188. Dementia Behavior Models • Person with dementia – Unmet need: behavior as an underlying need – Agitation etiology culmination from present abilities, level of cognition and function, and past/present interests with physical, psychological, social, and spiritual needs • Caregiver – Learning and behavioral (ABC) – Antecedent to behavior behavior consequence reinforces behavior • Environment – Environmental vulnerability and reduced stress thresholds: a mismatch between the setting and the patient’s ability to deal with it
Watt JA et al. Comparative Efficacy of Interventions for Aggressive and Agitated Behaviors in Dementia: A Systematic Review and Network Meta-analysis. Ann Intern Med 2019;171:633-642. Non-Pharmacologic: Persons With Dementia Treatment Studies (N) Network Meta-analysis Meta-analysis Standardized Mean Difference CMAI Re-expressed as mean difference on CMAI Massage and Touch 6 (385) -0.75 (-1.12,-0.38) -0.90 (-1.28,-0.518) -10.67 Multidisciplinary Care Plan 4 (552) -0.50 (-0.99,-0.01) -0.44 (-1.0,0.12) -7.11 Music + Massage/Touch 1 (34) -0.91 (-1.75,-0.07) -1.71 (-2.36,-1.05) -12.94 Recreational Therapy 8 (474) - 0.29 (-0.57,-0.01) -0.26 (-0.64,0.12) -4.12 Bold text indicates treatment efficacy across all types of agitation and/or aggression, clinically important difference 5.69 (aggression) and 7.11 (agitation)
Leng, et al. (2020). Comparative efficacy of non-pharmacological interventions on agitation in people with dementia: A systematic review and Bayesian network meta-analysis. International Journal of Nursing Studies, 102, 103489. Non-Pharmacologic: Persons With Dementia Treatment Standardized Mean Difference Massage −5.22 ( −8.21,−2.49) Light Therapy −5.25 (−9.90,−0.61) Music Therapy −3.61 (−7.29, −0.23) Reminiscence Therapy −4.59 (−8.97 to −0.51) Animal-Assisted Intervention −3.14 (−5.89 to −0.46) Personally Tailored Intervention −2.98 (−5.18 to −0.85) For network meta-analysis, demonstrated the following rank probability: • Massage therapy - 1 (43%) • Animal-assisted intervention - 2 (16%) • Personally tailored intervention - 3 (18%) • Pet robot intervention - 4 (11%)
Hughes, et al. (2017). Research on supportive approaches for family and other caregivers. Research summit on dementia care: Building evidence for services and supports. Non-Pharmacologic: Caregiver Interventions • Elements of caregiver support –Education and skills training (conflict avoidance, problem solving, support, environmental modification ADL, and communication skills) –Care coordination –Counseling and support groups –Respite and self-care • Example Programs –REACH II and REACH VA –The Tailored Activity Program (TAP) - Occupational Therapy and Skills2Care –Savvy Caregiver –New York University Caregiver Intervention • A meta-analysis of 23 randomized clinical trials, involving almost 3,300 community-dwelling patients and their caregivers – Significantly reduced behavioral symptoms (effect size 0.34, p<0.01) and negative caregiver reaction (effect size 0.15, p<0.006) – Similar to antipsychotics for behavior and cholinesterase inhibitors for memory – Interventions with multiple components and specific to the caregiver and person with dementia with regular follow-up had greatest success
Responses to Non-Pharmacologic Interventions Greater Response • Higher levels of cognitive function • Fewer difficulties with ADLs • Speech • Communication • Responsiveness Less Response • Staff barriers (refuse to participate) • Patient in pain
Case (cont.) Describe behavior and rationale to treat • Agitation and aggression worse with movement and activities • Risk to patient and staff Investigate • Pain • Depression and anxiety • Loneliness • Medication Create: Non-pharmacologic • Initiate animal-assisted intervention as patient misses her dog • Recreational therapy tailored to the patient’s needs • Consider what additional services hospice could offer • Pain: APAP 1,000mg every 8 hours, morphine 5mg prior to bathing and at night and prn. Bowel regimen • Medication: Wean off valproic acid and optimize depression treatment
Dementia Behaviors and Pharmacologic Treatment Helpful • Psychosis – Delusions – Hallucinations – Paranoia • Depression, anxiety, and irritability • Agitation and aggression Not Helpful • Day/night reversal • Calling out • Repetitive behaviors • Apathy • Resistive to care • Wandering
Therapeutic Class Trial Side Effects Trazodone + RTC Sedation, hypotension SSRI (citalopram) + RCT Nausea, diarrhea, QTc inc >20mg daily Antipsychotics + RCT Stroke, infection, seizure, QTc inc, DM, death Lorazepam + RCT Sedation, falls, ataxia, agitation Dextromethorphan/quinidine + RCT Falls, dizziness, diarrhea, UTIs Carbamazepine Valproic acid - RCT - RCT Sedation, anemia, liver toxicity, sedation NMDA antagonist - RCT/+obs Constipation, dizziness ACheI - /+RCT/+obs Nausea, dizziness, weight loss Cannabinoids - RCT Low dose used, oral form Radue, et al. (2019). Neuropsychiatric symptoms in dementia. Handbook of Clinical Neurology, 167, 437-454. Ringman, J. et al. (2019). Treatment options for agitation in dementia. Current Treatment Options in Neurology, 21(7), 1-14. Pharmacologic Treatment of Agitation Comparative Effectiveness, Sequential Administration, or Concomitant Use Data Scarce
Trazadone • Several small randomized controlled trials indicate benefit – Cochrane review inconclusive evidence – Often used for “Sundowning” • Dosing: – 25-100mg BID-TID and q 2hrs prn, maximum dose 300mg daily (150mg in frail older adults) • Adverse effects: – Orthostasis, syncope, hypotension, dizziness – Priapism – SIADH – Somnolence – QTc prolongation
Antonsdottir, et al. (2015). Advancements in the treatment of agitation in Alzheimer’s disease. Expert Opinion on Pharmacotherapy, 16(11), 1649-1656. Dementia-Related Agitation and Citalopram Neurobehavioral Rating Scale (NBRS) - Agitation Subscale No. of participants Citalopram 94 87 85 86 Placebo 92 84 84 81
Citalopram Considerations • Starting dose 10mg, up to 40mg daily • QTc prolongation, which is dose-dependent above does of 20mg • Confusion increased at doses of 30mg daily or higher • Consider 2x daily dosing – 10mg daily for 2 weeks – 10mg 2x daily thereafter • Other SSRI side effects • Onset of action within a week in one study
Antipsychotics • Most-studied pharmacologic intervention for dementia-related agitation • Moderate efficacy across trials and agents (18% respond above placebo response) – Typical antipsychotics – Atypical antipsychotics • Substantial side effects • Black box warning: cerebrovascular events and death (1% difference) • Lowest dose possible for the shortest duration feasible
Antipsychotics (cont.) Antipsychotic Recommended Dose Formulations Frequency Characteristics Risperidone 0.5-2.0mg Tab, liquid, IM 2x daily Extrapyramidal symptoms Olanzapine 2.5-15mg tab Daily Wt gain, inc sugar Quetaipine 25-400mg tab 3x daily (unless ER) Sedating, least extrapyramidal Aripiprazole 5-30mg Tab, liquid, IM Daily Less QT Haloperidol 0.5-5mg Tab, liquid, IM, IV, sub q 2-4x daily Chlorpromazine 10-200mg Tab, liquid, IV, rectal 2-3x daily Very sedating
Schneider, L. S., et al. (2008) Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. The New England Journal of Medicine; 355(15), 1525-1538. CATIE-AD Greatest benefits in persons demonstrating anger, aggression, and paranoia
Devanand, et al. (2012). Relapse risk after discontinuation of risperidone in Alzheimer's disease. New England Journal of Medicine, 367(16), 1497-1507. Relapse Risk With Antipsychotic Discontinuation Severe baseline symptoms at initiation, increases likelihood of worsening symptoms with discontinuation
Watt, et al. (2019). Comparative efficacy of interventions for aggressive and agitated behaviors in dementia: a systematic review and network meta-analysis. Annals of Internal Medicine, 171(9), 633-642. Antipsychotic Summary • Modest efficacy for treatment of agitation and aggression in dementia • Studies usually short duration: 6 to 12 week • Large placebo effect: 30% or higher on average • No difference in efficacy between typical and atypical antipsychotics • Typical antipsychotics–greater side effects – Somnolence, urinary tract infection, incontinence – Extrapyramidal symptoms and abnormal gait and falls – Anticholinergic effects, postural hypotension, prolonged QT – Weight gain, diabetes, and metabolic syndrome – Cognitive worsening; seizures – Stroke (NNH 99) and death (NNH 47)
*Cholinesterase inhibitors: Nausea, vomiting, diarrhea, dizziness, and agitation FDA-Approved Medications for Alzheimer’s Disease Medication Severity Dose Side Effects Donepezil (Aricept) Mild to severe 5-10mg; 23mg *Nightmares Rivastigmine (Exelon) Mild to moderate 4.6 & 9.5mg (13mg) patch *Weight loss Galantamine (Razadyne) Mild to moderate 8-24mg * Memantine (Namenda XR) Moderate to severe 28mg QD Constipation, dizziness, HA Rivastigmine improves apathy, anxiety, delusions, and hallucinations in LBD All cholinesterase inhibitors may delay onset/reduce behavioral symptoms in Alzheimer’s/LBD
Benzodiazepines • Binds to GABA receptor in CNS • Anxiolytic, sedative, and hypnotic effects (anterograde memory) • Some evidence lorazepam and alprazolam to reduce agitation • Increased risk of adverse events – Cognitive impairment/ confusion/delirium – Falls – Hip fracture – Sedation – Paradoxical agitation Benzodiazepine Half-life Dosage range Diazepam 20-50 hours Over 100 OA 2-10mg 2-4x day Lorazepam 12 hours 0.5-2mg 2-3x day Alprazolam 16 hours (9-27 range) 0.25-3mg 2-4x day Clonazepam 30-40 hours 0.25-5mg 2-3x day
Pimavanserine • 5-HT2A antagonist indicated for hallucinations and delusions associated with Parkinson’s disease • Three trials for agitation or psychosis in dementia, all of which were essentially negative • Black box warning for increased mortality in dementia and is associated with QT prolongation, peripheral edema, and confusion
Cummings, et al. (2015) Effect of dextromethorphan-quinidine on agitation in persons with Alzheimer’s disease dementia. A randomized clinical trial. JAMA vol 314(12), 1242-54. Dextromethorphan-Quinidine for Dementia Agitation in Alzheimer’s Disease • FDA approved for the treatment of pseudobulbar affect • Modulates glutamate, serotonin, and norepinephrine • Only one randomized, controlled trial to date for dementia related agitation • Side effects include – Falls – UTIs – Diarrhea – Dizziness • QTc prolongation
Phenobarbital • No data available • Many clinicians, health systems, and long-term care facilities leverage its use • 30 to 120mg TID and q2 prn • Adverse Reactions – Respiratory depression – Stevens-Johnsons – Anemia, TTP, and blood dyscrasias – Withdrawal symptoms with abrupt withdrawal – Lethargy and drowsiness – Nausea, vomiting, and hepatitis
DICE D Describe the behavior I Investigate the underlying contributors/ causes C Create intervention: non-pharmacologic and pharmacologic E Evaluate the interventions effectiveness
Describe behavior and rationale to treat • Agitation and aggression worse with movement and activities • Risk to patient and staff Investigate • Pain • Depression and anxiety • Loneliness • Medication Case (cont.) Create Contributors APAP 1,000mg every 8 hours, morphine 5mg every 8 hours, plus bowel regimen; stop sertraline and initiate citalopram Non-pharmacologic Animal-assisted intervention/recreational therapy Pharmacologic Citalopram and wean off valproic acid; trazadone 25mg as needed
Case (cont.) Describe behavior and rationale to treat • Agitation and aggression worse with movement and activities. • Risk to patient and staff Investigate • Pain • Depression and anxiety • Loneliness • Medication Create Contributors APAP 1,000mg every 8 hours, morphine 5mg every 8 hours plus bowel regiment; Citalopram 10mg twice daily Non-pharmacologic Animal assisted intervention/recreational therapy Pharmacologic Citalopram 10mg twice daily, off valproic acid; trazadone 50mg nightly and able to discontinue as needed
Al Ghassani, et al. (2021). Agitation in people with dementia: A concept analysis. Nursing Forum, 56(4), 1015-1023). Alzheimer's Association. (2023). 2023 Alzheimer’s Disease Facts and Figures. Retrieved from https://www.alz.org/ media/Documents/alzheimers-facts-and-figures.pdf Antonsdottir, et al. (2015) Advancements in the treatment of agitation in Alzheimer’s disease. Expert Opinion on Pharmacotherapy, vol 16(11), 1649-1656. Gaugler, et al. (2021). Alzheimer’s Association. 2021 Alzheimer’s Disease Facts and Figures. Alzheimer’s Dementia: Chicago, IL, USA, 17. Atee et al. (2021) Pain in Dementia: Prevalence and Association with Neuropsychiatric Behaviors. Journal of Pain Symptom Manage Vol 61, p 1215-1226. Ayalon, et al. (2006). Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Archives of Internal Medicine, 166(20), 2182-2188. Ballard, C. et al. (2009). Management of agitation and aggression associated with Alzheimer disease. Nature Reviews Neurology, 5(5), 245-255. Cohen-Mansfield, et al. (2014). Predictors of the impact of nonpharmacologic interventions for agitation in nursing home residents with advanced dementia. The Journal of Clinical Psychiatry, 75(7), 15076. Cummings, J. (2015). Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA, 314(12), 1242-1254. References
Devanand, et al. (2012). Relapse risk after discontinuation of risperidone in Alzheimer's disease. New England Journal of Medicine, 367(16), 1497-1507. Husebo, et al. (2011). Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ, 343. Hughes, et al. (2017). Research on supportive approaches for family and other caregivers. Research summit on dementia care: Building evidence for services and supports. Leng, et al. (2020). Comparative efficacy of non-pharmacological interventions on agitation in people with dementia: A systematic review and Bayesian network meta-analysis. International Journal of Nursing Studies, 102, 103489. Mitchell, et al. (2009). The clinical course of advanced dementia. New England Journal of Medicine (361), 1529-1538. O’Gorman, et al. (2020). A framework for developing pharmacotherapy for agitation in Alzheimer’s disease: recommendations of the ISCTM working group. The Journal of Prevention of Alzheimer's Disease, 7(4), 274-282. Radue, et al. (2019). Neuropsychiatric symptoms in dementia. Handbook of Clinical Neurology, 167, 437-454. Ringman, J. et al. (2019). Treatment options for agitation in dementia. Current Treatment Options in Neurology, 21(7), 1-14. Schneider, L. S., et al. (2008) Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. The New England Journal of Medicine; 355(15), 1525-1538. Watt, et al. (2019). Comparative efficacy of interventions for aggressive and agitated behaviors in dementia: a systematic review and network meta-analysis. Annals of Internal Medicine, 171(9), 633-642. References

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Assessment and Management of Disruptive Behaviors in Persons With Dementia

  • 1. Assessment and Management of Disruptive Behaviors in Persons with Dementia
  • 2. Objectives • Describe the occurrence and impact of dementia-related behaviors • Construct a systematic evaluation for behavioral changes in persons with dementia • Develop a comprehensive care plan that incorporates caregiver education and non-pharmacologic interventions followed by pharmacologic management for disruptive behaviors
  • 3. Alzheimer's Association. (2023). 2023 Alzheimer’s Disease Facts and Figures. Retrieved from https://www.alz.org/media/ Documents/alzheimers-facts-and-figures.pdf Most Common Etiologies of Dementia Cause Prevalence Pathophysiology Alzheimer’s disease 60-80% Amyloid plaques and neurofibrillary tangles Mixed pathologies >50% More than one neuropathology, more common oldest old Cerebrovascular disease 5-10% Blood vessels damaged, brain tissue injured Lewy Body disease 5% Alpha-synuclein protein Frontal Lobar Degeneration 3% Tau protein Transactive response DNA-binding protein (TDP-43)
  • 4. Alzheimer's Association. (2023). 2023 Alzheimer’s Disease Facts and Figures. Retrieved from https://www.alz.org/media/ Documents/alzheimers-facts-and-figures.pdf Epidemiology • 2023 US Alzheimer’s estimate: – 6.7 million people aged 65+ – 2/3 are women, ~ 1 in 3 women develop dementia in their lifetime • More than 1 in 9 persons over the age of 65 have dementia • 1 in 3 persons over the age of 65 dies with dementia • Diagnosis of dementia cuts one’s life expectancy in half • Dementia is the fifth-leading cause of death in persons over 65 • Between 2000-2019, dementia- related deaths increased 145%
  • 5. Natural History of Dementia ADL Dependency Death Low Time (Slow decline) High Hospice Eligible FAST 7a plus Disease-related complication within the last several months Disease-related complications include, but are not limited to: • UTI • Sepsis • Febrile episode • Delirium • Pneumonia • Hip fracture • Eating difficulty or dysphagia • Dehydration • Feeding tube
  • 6. 78 y/o with rapidly progressive Alzheimer’s and vascular dementia after sustaining a fall at home with a hip fracture that was surgically repaired. During the patient’s skilled stay, the patient has become mostly WC and/or bedbound and not participating in PT with both physical and verbal agitation and aggression, especially when trying to engage in activities or move the patient. The agitation is new since the hip fracture. The psychiatrist diagnosed the patient with depression and prescribed sertraline 50mg followed by valproic acid 250mg BID due to refractory symptoms. The patient has been more lethargic but remains agitated at times. Additional changes include 5% weight loss in 1 month due to a poor appetite, functional decline with a PPS decrease from 80 to 40, and dependency in 3/6 ADLs from 1/6 prior to the fall. After completion of skilled care, the patient was transitioned to long term care. The daughter expresses guilt as she recognizes her mom is upset and angry because she never wanted to be in a nursing home. Case
  • 7. Delirium Acute Onset and Fluctuating Course AND Inattention plus either Disorganized Thinking Altered LOC DELIRIUM
  • 8. Terminal Restlessness THE USUAL ROAD THE DIFFICULT ROAD
  • 9. Dementia Behaviors Thought and Perceptual Disturbances • Delusions • Paranoia • Hallucination Mood Disturbances • Anxiety • Depression • Irritability Activity Disturbance • Agitation and/or aggression • Wandering • Purposeless hyperactivity • Apathy • Impulsivity • Socially inappropriate behavior • Sleep problems • Repetitive behavior
  • 10. Agitation/Aggression Definition International Psychogeriatric Association convened a panel of experts with the goal of establishing principles guiding the definition of agitation in elderly populations: 1. Occurring in patients with cognitive impairment or a dementia syndrome; 2. Exhibiting behavior consistent with emotional distress; 3. Manifesting excessive motor activity, verbal aggression, or physical aggression; and 4. Evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related)
  • 11. Radue, et al. (2019). Neuropsychiatric symptoms in dementia. Handbook of Clinical Neurology, 167, 437-454. Neuropsychiatric Symptoms (NPS) by Stage of Dementia 4.3% 11.2% 15.2% 44.3% 38.2% 13.3% 32.6% 30.3% 30.0% 31.4% 82.3% 56.0% 54.5% 25.7% 30.4% Normal cognition Mild cognitive impairment Mild dementia Moderate dementia Severe dementia No symptoms 1-2 symptoms 3+ symptoms 7% 16% 17% 31% 32% 34% 36% 39% 39% 40% 42% 49% 0% 10% 20% 30% 40% 50% 60% Euphoria Hallucinations Disinhibition Delusions Aberant motor behavior Appetite disorder Irrtability Sleep Disorder Anxiety Aggression Depression Apathy 80-90% of patients will develop neuropsychiatric symptoms over the course of their illness No FDA-Approved Treatment for Neuropsychiatric Symptoms in Dementia
  • 12. Mitchell, et al. (2009). The clinical course of advanced dementia. New England Journal of Medicine (361), 1529-1538. Symptom Experience in Persons With Dementia in the Last Year of Life 0 5 10 15 20 25 30 35 40 Dyspnea Pain Pressure ulcers Aspiration Agitation Residents With Symptoms (%) Distressing Symptoms Months Before Death (no. of residents alive during interval) >9-12 (N=67) >6-9 (N=96) >3-6 (N=128) 0-3 (N=177)
  • 13. Cummings J et al. Reduction and prevention of agitation in persons with neurocognitive disorders: An IPA consensus algorithm International Psychogeriatrics 2022: DICE International Psychogeriatric Association D Describe the behavior I Investigate the underlying contributors/causes C Create intervention: non-pharmacologic and pharmacologic E Evaluate the interventions effectiveness I Investigate behavior plus precipitants, duration, frequency, potential harm; Impact intervention P Plan intervention that reflects patient features and setting; share DM with patient/CG A Act multidisciplinary plan with psychosocial interventions and choose pharmacologic treatments if needed
  • 14. O’Gorman, et al. (2020). A framework for developing pharmacotherapy for agitation in Alzheimer’s disease: recommendations of the ISCTM working group. The Journal of Prevention of Alzheimer's Disease, 7(4), 274-282. Behavior Description • Characterization • Severity or quantification • Temporal onset and course Scale Measure Cohen-Mansfield Agitation Inventory 4 behavioral categories, 29 total items, caregiver response over last 2 weeks, behavior frequency ranges from 1 to 7, higher scores more behaviors Neuropsychiatric Inventory 10 or 12 (sleep and appetite added) behaviors rated by frequency (4 categories) severity (3 categories), caregiver distress (5 categories) over a week, higher scores more behavioral burden Behavioral pathology in Alzheimer’s disease 7 behavioral categories containing 25 symptoms, each scored on a 4-point severity scale ascertained by a caregiver • Caregiver status • Context of personal, family, social, and medical history • Associated circumstances, including precipitants and alleviating factors
  • 15. Impact of Disruptive Behaviors in Dementia Patient • Increased morbidity (cognitive/ functional); lower quality of life • Abuse and neglect • Increased likelihood of hospitalization with a longer length of stay • Nursing home placement • Increased mortality Caregiver • Increased burden, stress, exhaustion, and strain • Sleep disturbances, depression, and anxiety • Lower quality of life • Reduced income from employment • Increased mortality
  • 16. Case (cont.) Describe the behavior and rationale to treat: • Agitation and aggression worse with movement and activity, new after fall • Verbal (yelling when trying to move or interact) and physical (resistive to daily care and strike out when try to move) • Intermittent sleeping and agitation and daughter reports a poor quality of life • Unsteady on feet, not wanting to move around much • Decreased oral intake • Potential risk to staff for physical harm
  • 17. Kales HC, Gitlin LN, Lyketosis CG. Assessment and Management of behavioral and psychological symptoms of dementia. BMJ 2015; h369 DICE D Describe the behavior I Investigate the underlying contributors/ causes C Create intervention: non-pharmacologic and pharmacologic E Evaluate the interventions effectiveness
  • 18. Ringman JM, Schneider L. (2019) Treatment Options for Agitation in Dementia. In Current Treatment Options Neurology (Vol 21, 30). Contributors to Agitation and Restlessness Contributor Causes Approach Physical symptom Pain, SOB, constipation Opioid or laxative Psychological symptom Depression, anxiety, bipolar disorder, delusions, hallucinations SSRI, SNRI, antipsychotic Medical condition Infection, COPD, HF, gout, hyperglycemia, electrolyte abnormality, broken bone, constipation, insomnia Treat condition Unmet need Hunger, thirst, hot, cold, boredom Attend to need Sensory impairment Poor vision/hearing Adaptive Environment Under/over stimulation, change in routine, life stressor, pt-cg relationship Modify Toxicology Anticholinergic drug, digitalis, benzodiazepine, withdrawal syndrome (ETOH, opioid cannabis), steroids Discontinue
  • 19. Huesbo B, Ballard C, Sandvik R, et al.(2011) Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ Vol. 343. Atee M, Morris T, Macfarlane S et al. (2021) Pain in Dementia: Prevalence and Association with Neuropsychiatric Behaviors. J Pain Symptom Manage Vol 61, p 1215-1226. Contributors to Agitation and Restlessness Step Treatment Study Treatment 1 APAP Maximum dose 3gm 2 Morphine 5mg Twice daily 3 Buprenorphine 5mcg patch, can increase to 10mcg 4 Pregabalin 25mg up to 300mg daily
  • 20. Case (cont.) Investigate • Additional PMH patient grimaces with movement and braces on the side with the hip fracture repair. The patient is not taking the as-needed acetaminophen and has no other analgesic ordered. Staff report the patient seems to alternate between agitation and over-sedation and is otherwise withdrawn. Appetite is poor but has no apparent nausea or constipation. Insomnia with difficulty falling asleep and early morning awakenings. • Patient’s other chronic medical conditions are well controlled. The patient does not have altercations with staff or her roommate unless trying to be moved. Her daughter reports mom misses her dog and home. Besides the sertraline and valproic acid, no changes in medications. • Physical exam: temporal wasting, hearing and vision seem intact, pain behaviors as described especially with ROM of repaired hip, and bloodwork is unremarkable. Considerations • Pain from hip fracture repair • Depression • Loneliness • Medication
  • 21. DICE D Describe the behavior I Investigate the underlying contributors/ causes C Create intervention: non-pharmacologic and pharmacologic E Evaluate the interventions effectiveness
  • 22. Ayalon, et al. (2006). Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Archives of Internal Medicine, 166(20), 2182-2188. Dementia Behavior Models • Person with dementia – Unmet need: behavior as an underlying need – Agitation etiology culmination from present abilities, level of cognition and function, and past/present interests with physical, psychological, social, and spiritual needs • Caregiver – Learning and behavioral (ABC) – Antecedent to behavior behavior consequence reinforces behavior • Environment – Environmental vulnerability and reduced stress thresholds: a mismatch between the setting and the patient’s ability to deal with it
  • 23. Watt JA et al. Comparative Efficacy of Interventions for Aggressive and Agitated Behaviors in Dementia: A Systematic Review and Network Meta-analysis. Ann Intern Med 2019;171:633-642. Non-Pharmacologic: Persons With Dementia Treatment Studies (N) Network Meta-analysis Meta-analysis Standardized Mean Difference CMAI Re-expressed as mean difference on CMAI Massage and Touch 6 (385) -0.75 (-1.12,-0.38) -0.90 (-1.28,-0.518) -10.67 Multidisciplinary Care Plan 4 (552) -0.50 (-0.99,-0.01) -0.44 (-1.0,0.12) -7.11 Music + Massage/Touch 1 (34) -0.91 (-1.75,-0.07) -1.71 (-2.36,-1.05) -12.94 Recreational Therapy 8 (474) - 0.29 (-0.57,-0.01) -0.26 (-0.64,0.12) -4.12 Bold text indicates treatment efficacy across all types of agitation and/or aggression, clinically important difference 5.69 (aggression) and 7.11 (agitation)
  • 24. Leng, et al. (2020). Comparative efficacy of non-pharmacological interventions on agitation in people with dementia: A systematic review and Bayesian network meta-analysis. International Journal of Nursing Studies, 102, 103489. Non-Pharmacologic: Persons With Dementia Treatment Standardized Mean Difference Massage −5.22 ( −8.21,−2.49) Light Therapy −5.25 (−9.90,−0.61) Music Therapy −3.61 (−7.29, −0.23) Reminiscence Therapy −4.59 (−8.97 to −0.51) Animal-Assisted Intervention −3.14 (−5.89 to −0.46) Personally Tailored Intervention −2.98 (−5.18 to −0.85) For network meta-analysis, demonstrated the following rank probability: • Massage therapy - 1 (43%) • Animal-assisted intervention - 2 (16%) • Personally tailored intervention - 3 (18%) • Pet robot intervention - 4 (11%)
  • 25. Hughes, et al. (2017). Research on supportive approaches for family and other caregivers. Research summit on dementia care: Building evidence for services and supports. Non-Pharmacologic: Caregiver Interventions • Elements of caregiver support –Education and skills training (conflict avoidance, problem solving, support, environmental modification ADL, and communication skills) –Care coordination –Counseling and support groups –Respite and self-care • Example Programs –REACH II and REACH VA –The Tailored Activity Program (TAP) - Occupational Therapy and Skills2Care –Savvy Caregiver –New York University Caregiver Intervention • A meta-analysis of 23 randomized clinical trials, involving almost 3,300 community-dwelling patients and their caregivers – Significantly reduced behavioral symptoms (effect size 0.34, p<0.01) and negative caregiver reaction (effect size 0.15, p<0.006) – Similar to antipsychotics for behavior and cholinesterase inhibitors for memory – Interventions with multiple components and specific to the caregiver and person with dementia with regular follow-up had greatest success
  • 26. Responses to Non-Pharmacologic Interventions Greater Response • Higher levels of cognitive function • Fewer difficulties with ADLs • Speech • Communication • Responsiveness Less Response • Staff barriers (refuse to participate) • Patient in pain
  • 27. Case (cont.) Describe behavior and rationale to treat • Agitation and aggression worse with movement and activities • Risk to patient and staff Investigate • Pain • Depression and anxiety • Loneliness • Medication Create: Non-pharmacologic • Initiate animal-assisted intervention as patient misses her dog • Recreational therapy tailored to the patient’s needs • Consider what additional services hospice could offer • Pain: APAP 1,000mg every 8 hours, morphine 5mg prior to bathing and at night and prn. Bowel regimen • Medication: Wean off valproic acid and optimize depression treatment
  • 28. Dementia Behaviors and Pharmacologic Treatment Helpful • Psychosis – Delusions – Hallucinations – Paranoia • Depression, anxiety, and irritability • Agitation and aggression Not Helpful • Day/night reversal • Calling out • Repetitive behaviors • Apathy • Resistive to care • Wandering
  • 29. Therapeutic Class Trial Side Effects Trazodone + RTC Sedation, hypotension SSRI (citalopram) + RCT Nausea, diarrhea, QTc inc >20mg daily Antipsychotics + RCT Stroke, infection, seizure, QTc inc, DM, death Lorazepam + RCT Sedation, falls, ataxia, agitation Dextromethorphan/quinidine + RCT Falls, dizziness, diarrhea, UTIs Carbamazepine Valproic acid - RCT - RCT Sedation, anemia, liver toxicity, sedation NMDA antagonist - RCT/+obs Constipation, dizziness ACheI - /+RCT/+obs Nausea, dizziness, weight loss Cannabinoids - RCT Low dose used, oral form Radue, et al. (2019). Neuropsychiatric symptoms in dementia. Handbook of Clinical Neurology, 167, 437-454. Ringman, J. et al. (2019). Treatment options for agitation in dementia. Current Treatment Options in Neurology, 21(7), 1-14. Pharmacologic Treatment of Agitation Comparative Effectiveness, Sequential Administration, or Concomitant Use Data Scarce
  • 30. Trazadone • Several small randomized controlled trials indicate benefit – Cochrane review inconclusive evidence – Often used for “Sundowning” • Dosing: – 25-100mg BID-TID and q 2hrs prn, maximum dose 300mg daily (150mg in frail older adults) • Adverse effects: – Orthostasis, syncope, hypotension, dizziness – Priapism – SIADH – Somnolence – QTc prolongation
  • 31. Antonsdottir, et al. (2015). Advancements in the treatment of agitation in Alzheimer’s disease. Expert Opinion on Pharmacotherapy, 16(11), 1649-1656. Dementia-Related Agitation and Citalopram Neurobehavioral Rating Scale (NBRS) - Agitation Subscale No. of participants Citalopram 94 87 85 86 Placebo 92 84 84 81
  • 32. Citalopram Considerations • Starting dose 10mg, up to 40mg daily • QTc prolongation, which is dose-dependent above does of 20mg • Confusion increased at doses of 30mg daily or higher • Consider 2x daily dosing – 10mg daily for 2 weeks – 10mg 2x daily thereafter • Other SSRI side effects • Onset of action within a week in one study
  • 33. Antipsychotics • Most-studied pharmacologic intervention for dementia-related agitation • Moderate efficacy across trials and agents (18% respond above placebo response) – Typical antipsychotics – Atypical antipsychotics • Substantial side effects • Black box warning: cerebrovascular events and death (1% difference) • Lowest dose possible for the shortest duration feasible
  • 34. Antipsychotics (cont.) Antipsychotic Recommended Dose Formulations Frequency Characteristics Risperidone 0.5-2.0mg Tab, liquid, IM 2x daily Extrapyramidal symptoms Olanzapine 2.5-15mg tab Daily Wt gain, inc sugar Quetaipine 25-400mg tab 3x daily (unless ER) Sedating, least extrapyramidal Aripiprazole 5-30mg Tab, liquid, IM Daily Less QT Haloperidol 0.5-5mg Tab, liquid, IM, IV, sub q 2-4x daily Chlorpromazine 10-200mg Tab, liquid, IV, rectal 2-3x daily Very sedating
  • 35. Schneider, L. S., et al. (2008) Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. The New England Journal of Medicine; 355(15), 1525-1538. CATIE-AD Greatest benefits in persons demonstrating anger, aggression, and paranoia
  • 36. Devanand, et al. (2012). Relapse risk after discontinuation of risperidone in Alzheimer's disease. New England Journal of Medicine, 367(16), 1497-1507. Relapse Risk With Antipsychotic Discontinuation Severe baseline symptoms at initiation, increases likelihood of worsening symptoms with discontinuation
  • 37. Watt, et al. (2019). Comparative efficacy of interventions for aggressive and agitated behaviors in dementia: a systematic review and network meta-analysis. Annals of Internal Medicine, 171(9), 633-642. Antipsychotic Summary • Modest efficacy for treatment of agitation and aggression in dementia • Studies usually short duration: 6 to 12 week • Large placebo effect: 30% or higher on average • No difference in efficacy between typical and atypical antipsychotics • Typical antipsychotics–greater side effects – Somnolence, urinary tract infection, incontinence – Extrapyramidal symptoms and abnormal gait and falls – Anticholinergic effects, postural hypotension, prolonged QT – Weight gain, diabetes, and metabolic syndrome – Cognitive worsening; seizures – Stroke (NNH 99) and death (NNH 47)
  • 38. *Cholinesterase inhibitors: Nausea, vomiting, diarrhea, dizziness, and agitation FDA-Approved Medications for Alzheimer’s Disease Medication Severity Dose Side Effects Donepezil (Aricept) Mild to severe 5-10mg; 23mg *Nightmares Rivastigmine (Exelon) Mild to moderate 4.6 & 9.5mg (13mg) patch *Weight loss Galantamine (Razadyne) Mild to moderate 8-24mg * Memantine (Namenda XR) Moderate to severe 28mg QD Constipation, dizziness, HA Rivastigmine improves apathy, anxiety, delusions, and hallucinations in LBD All cholinesterase inhibitors may delay onset/reduce behavioral symptoms in Alzheimer’s/LBD
  • 39. Benzodiazepines • Binds to GABA receptor in CNS • Anxiolytic, sedative, and hypnotic effects (anterograde memory) • Some evidence lorazepam and alprazolam to reduce agitation • Increased risk of adverse events – Cognitive impairment/ confusion/delirium – Falls – Hip fracture – Sedation – Paradoxical agitation Benzodiazepine Half-life Dosage range Diazepam 20-50 hours Over 100 OA 2-10mg 2-4x day Lorazepam 12 hours 0.5-2mg 2-3x day Alprazolam 16 hours (9-27 range) 0.25-3mg 2-4x day Clonazepam 30-40 hours 0.25-5mg 2-3x day
  • 40. Pimavanserine • 5-HT2A antagonist indicated for hallucinations and delusions associated with Parkinson’s disease • Three trials for agitation or psychosis in dementia, all of which were essentially negative • Black box warning for increased mortality in dementia and is associated with QT prolongation, peripheral edema, and confusion
  • 41. Cummings, et al. (2015) Effect of dextromethorphan-quinidine on agitation in persons with Alzheimer’s disease dementia. A randomized clinical trial. JAMA vol 314(12), 1242-54. Dextromethorphan-Quinidine for Dementia Agitation in Alzheimer’s Disease • FDA approved for the treatment of pseudobulbar affect • Modulates glutamate, serotonin, and norepinephrine • Only one randomized, controlled trial to date for dementia related agitation • Side effects include – Falls – UTIs – Diarrhea – Dizziness • QTc prolongation
  • 42. Phenobarbital • No data available • Many clinicians, health systems, and long-term care facilities leverage its use • 30 to 120mg TID and q2 prn • Adverse Reactions – Respiratory depression – Stevens-Johnsons – Anemia, TTP, and blood dyscrasias – Withdrawal symptoms with abrupt withdrawal – Lethargy and drowsiness – Nausea, vomiting, and hepatitis
  • 43. DICE D Describe the behavior I Investigate the underlying contributors/ causes C Create intervention: non-pharmacologic and pharmacologic E Evaluate the interventions effectiveness
  • 44. Describe behavior and rationale to treat • Agitation and aggression worse with movement and activities • Risk to patient and staff Investigate • Pain • Depression and anxiety • Loneliness • Medication Case (cont.) Create Contributors APAP 1,000mg every 8 hours, morphine 5mg every 8 hours, plus bowel regimen; stop sertraline and initiate citalopram Non-pharmacologic Animal-assisted intervention/recreational therapy Pharmacologic Citalopram and wean off valproic acid; trazadone 25mg as needed
  • 45. Case (cont.) Describe behavior and rationale to treat • Agitation and aggression worse with movement and activities. • Risk to patient and staff Investigate • Pain • Depression and anxiety • Loneliness • Medication Create Contributors APAP 1,000mg every 8 hours, morphine 5mg every 8 hours plus bowel regiment; Citalopram 10mg twice daily Non-pharmacologic Animal assisted intervention/recreational therapy Pharmacologic Citalopram 10mg twice daily, off valproic acid; trazadone 50mg nightly and able to discontinue as needed
  • 46. Al Ghassani, et al. (2021). Agitation in people with dementia: A concept analysis. Nursing Forum, 56(4), 1015-1023). Alzheimer's Association. (2023). 2023 Alzheimer’s Disease Facts and Figures. Retrieved from https://www.alz.org/ media/Documents/alzheimers-facts-and-figures.pdf Antonsdottir, et al. (2015) Advancements in the treatment of agitation in Alzheimer’s disease. Expert Opinion on Pharmacotherapy, vol 16(11), 1649-1656. Gaugler, et al. (2021). Alzheimer’s Association. 2021 Alzheimer’s Disease Facts and Figures. Alzheimer’s Dementia: Chicago, IL, USA, 17. Atee et al. (2021) Pain in Dementia: Prevalence and Association with Neuropsychiatric Behaviors. Journal of Pain Symptom Manage Vol 61, p 1215-1226. Ayalon, et al. (2006). Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Archives of Internal Medicine, 166(20), 2182-2188. Ballard, C. et al. (2009). Management of agitation and aggression associated with Alzheimer disease. Nature Reviews Neurology, 5(5), 245-255. Cohen-Mansfield, et al. (2014). Predictors of the impact of nonpharmacologic interventions for agitation in nursing home residents with advanced dementia. The Journal of Clinical Psychiatry, 75(7), 15076. Cummings, J. (2015). Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA, 314(12), 1242-1254. References
  • 47. Devanand, et al. (2012). Relapse risk after discontinuation of risperidone in Alzheimer's disease. New England Journal of Medicine, 367(16), 1497-1507. Husebo, et al. (2011). Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ, 343. Hughes, et al. (2017). Research on supportive approaches for family and other caregivers. Research summit on dementia care: Building evidence for services and supports. Leng, et al. (2020). Comparative efficacy of non-pharmacological interventions on agitation in people with dementia: A systematic review and Bayesian network meta-analysis. International Journal of Nursing Studies, 102, 103489. Mitchell, et al. (2009). The clinical course of advanced dementia. New England Journal of Medicine (361), 1529-1538. O’Gorman, et al. (2020). A framework for developing pharmacotherapy for agitation in Alzheimer’s disease: recommendations of the ISCTM working group. The Journal of Prevention of Alzheimer's Disease, 7(4), 274-282. Radue, et al. (2019). Neuropsychiatric symptoms in dementia. Handbook of Clinical Neurology, 167, 437-454. Ringman, J. et al. (2019). Treatment options for agitation in dementia. Current Treatment Options in Neurology, 21(7), 1-14. Schneider, L. S., et al. (2008) Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. The New England Journal of Medicine; 355(15), 1525-1538. Watt, et al. (2019). Comparative efficacy of interventions for aggressive and agitated behaviors in dementia: a systematic review and network meta-analysis. Annals of Internal Medicine, 171(9), 633-642. References