Neuropsychiatric Symptoms in Cognitive Disorders Sultzer, Page 1 The Elephant in the Room: Sensitive Subjects in Dementia Care UCI-MIND Research Conference David Sultzer, MD UCLA Semel Institute for Neuroscience and Human Behavior Auguste Deter, age 51 ‣ Confusion, delusions, hallucinations ‣ Plaques, tangles, arteriosclerosis “She screams that the doctor wants to cut her open… She fears him as a threat to her honor as a woman.” “Often she screams for many hours in a horrible voice.” - Alois Alzheimer November 1906, Frankfurt } Patient distress and compromised safety } Recurrence } Institutionalization } Caregiver burden } Increased healthcare utilization and costs 1 1 1 2.31 0.78 1.17 3.03 2.78 2 0 1 2 3 4 ED Visits Acute Hospitalization Medicare Expenditures Relative Rate or Risk No Distress Low Distress High Distress Maust 2017 Sultzer 2014, Pugh 2007, Sultzer 2017 § Delusions in AD § PET metabolic activity 0 10 20 30 2 months 5 months 10 months Offense Duration (Sec) Wildtype Transgenic § Aggression in AD mice § Genetics Amyloid transgenics vs Wildtype § Agitation in AD § PET cholinergic receptors in anterior cingulate } Prevalence: 20-40% } Delusions: paranoid/threat and misidentifications } Hallucinations less common; usually visual } Associated with: ◦ More rapid cognitive decline ◦ Agitation/aggression } Management o Consider delirium o Address sensory deficits o Reassurance and support o Med treatment - rarely o Consider if distress or behavioral impact o Re-evaluate frequently; consider d/c after 3 months } Lewy body dementia ◦ 80% with visual hallucinations ◦ Associated with cortical spread and density of Lewy bodies ◦ Cholinesterase inhibitor medications may be beneficial } Parkinson’s disease ◦ Visual hallucinations are common ◦ Dopamine replacement therapy often contributes, but is necessary for control of motor symptoms of PD ◦ Consider delirium ◦ If meds are necessary: Quetiapine Pimavanserin Clozapine
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Neuropsychiatric Symptoms in Cognitive Disorders Sultzer, Page 1
The Elephant in the Room: Sensitive Subjects in Dementia Care UCI-MIND Research Conference
David Sultzer, MD UCLA Semel Institute for Neuroscience and Human Behavior
Auguste Deter, age 51 ‣ Confusion, delusions, hallucinations ‣ Plaques, tangles, arteriosclerosis “She screams that the doctor wants to cut her open… She fears him as a threat to her honor as a woman.” “Often she screams for many hours in a horrible voice.”
- Alois Alzheimer November 1906, Frankfurt
} Patient distress and compromised safety } Recurrence } Institutionalization } Caregiver burden } Increased healthcare utilization and costs
1 1 1
2.31
0.78 1.17
3.03 2.78
2
0
1
2
3
4
ED Visits Acute Hospitalization
Medicare Expenditures
Rela
tive
Rate
or R
isk
No Distress
Low Distress
High Distress
Maust 2017 Sultzer 2014, Pugh 2007, Sultzer 2017
§ Delusions in AD § PET metabolic activity
0
10
20
30
2 months 5 months 10 months Offe
nse
Dur
atio
n (S
ec)
Wildtype Transgenic
§ Aggression in AD mice § Genetics Amyloid transgenics vs Wildtype
§ Agitation in AD § PET cholinergic receptors
in anterior cingulate
} Prevalence: 20-40% } Delusions: paranoid/threat and misidentifications } Hallucinations less common; usually visual } Associated with: ◦ More rapid cognitive decline ◦ Agitation/aggression
} Management o Consider delirium o Address sensory deficits o Reassurance and support o Med treatment - rarely
o Consider if distress or behavioral impact o Re-evaluate frequently; consider d/c after 3 months
} Lewy body dementia ◦ 80% with visual hallucinations ◦ Associated with cortical spread and density of Lewy bodies ◦ Cholinesterase inhibitor medications may be beneficial
} Parkinson’s disease ◦ Visual hallucinations are common ◦ Dopamine replacement therapy often contributes, but is necessary for
control of motor symptoms of PD ◦ Consider delirium ◦ If meds are necessary:
� Quetiapine � Pimavanserin � Clozapine
Neuropsychiatric Symptoms in Cognitive Disorders Sultzer, Page 2
} Definition ◦ Heterogeneous behaviors
� Non-aggressive physical, aggressive physical, verbal ◦ Related to anxiety, fear, confusion, irritability,
distraction, managing affect, let it go Ø Emotion-focused: support, time for themselves • Education: link to neurocognitive disorder • Address stress and depression • Respite care • Support groups
2. Patient • Repetition, redirection, reassurance • Improve communication, pleasant activities, social engagement
US - No medication is approved in the U.S. for the treatment of agitation in AD. EMA - Risperidone for short-term treatment of persistent aggression in moderate to severe AD
with risk of harm, and unresponsive to non-pharmacological approaches.
} 9-month intervention, person-centered care and: ◦ Antipsychotic review, social interaction, or exercise
} Antipsychotic review ◦ Reduced antipsychotics by 50% ◦ Non-significant decline in mortality ◦ Significant decline in mortality when combined with social
interaction (35% neither, 19% both) ◦ Total neuropsychiatric symptoms worsened
� But not significant when combined with social interaction
} Exercise ◦ Improved total neuropsychiatric symptoms ◦ No change in depression
} Implications ◦ Reducing meds alone may not be optimal ◦ Real-life, practical interventions can improve outcomes and
reduce antipsychotic use
Ballard 2016 NIA 2017
Neuropsychiatric Symptoms in Cognitive Disorders Sultzer, Page 4
} Common and persistent } Promotes disability } Central aspect of the
} Distinct, both clinically and neurobiologically } Regional cortical hypometabolism ◦ AD, n=53 ◦ Apathy vs no apathy, matched for other symptoms ◦ Depression vs no depression
Holthoff 2005
Apathy - L orbitofrontal
Depression - L lateral frontal
} Delirium or other medical contribution? } Behavioral interventions ◦ Enhanced activities: 23/26 studies found benefit ◦ WHELD study: Antipsychotic review combined with social activity or exercise
} Alzheimer’s Association Caregiver Center ◦ www.alz.org/care ◦ Approaches to individual neuropsychiatric symptoms
} Practical Dementia Care ◦ Rabins, Lyketsos, and Steele, 2006 ◦ Appendix A: Dementia Family Care Guidelines ◦ www.oup.com/us/pdc ◦ Problem-oriented; brief; not as much info on agitated behaviors
} Caregiver’s Guide to Understanding Dementia Behaviors ◦ Family Caregiver Alliance ◦ www.caregiver.org ◦ Problem-oriented, brief
Neuropsychiatric Symptoms in Cognitive Disorders Sultzer, Page 5
} Better-defined syndromes, particularly “agitation” } Biomarkers for distinct symptoms } Medication development guided by neurobiology } Prevention } Practical, effective, and safe management ◦ Integrated psychosocial and pharmacological ◦ Person-centered ◦ Practice guides and easy implementation ◦ Healthcare system alliance