Behavioral Changes in Persons with Alzheimers Disease

1
Behavioral Changes in Persons with Alzheimers
Disease
Alzheimers Disease International
2001 Christchurch, New Zealand

• Jeffrey L. Cummings, M.D.
• UCLA Alzheimers Disease Center
• Los Angeles, California

2
Disclosure

• Dr. Cummings has served as consultant for or
  performed research with Astra-Zenica, Bayer,
  Bristol Myers Squibb, Eisai, Janssen, Lilly,
  Merz, Novartis, Ono, Pfizer, Sanofi
  pharmaceutical companies.

3
Persons with Alzheimers DiseaseHave Behavioral
Changes

• Frequency
• Characteristics
• Impact
• Neurobiology
• Treatment

4
Behavioral Changes in Persons with Alzheimers
Disease

• Nearly all persons with AD exhibit behavioral
  changes
• Diverse behavioral symptoms occur
• Multiple symptoms occur simultaneously
• Behavioral changes become more frequent with
  disease progression
• Behaviors are recurrent after onset

5
Behavioral Changes in Persons with Alzheimers
Disease

• Behavioral changes have a neurobiological basis
• Neuroimaging
• Neuropathology
• Neurochemistry
• Behavioral changes respond to treatment
• Cholinesterase inhibitors
• Psychotropic agents

6
Neuropsychiatric Symptoms in Persons with
Alzheimers Disease
with NPI Scores
(Mega et al, Neurology 1996 46 130-135)
7
Multiple Behavioral Changes Occur Simultaneously
with 0,1,2,3 Symptoms (Psychosis, Agitation,
Depression)
(Levy et al, Am J Psychiatry, 1996)
8
Once Present, Behavioral Symptoms Commonly Recur
of Patients
Patients Re-Examined Five times in One Year
(Levy et al, Am J Psychiatry 1996 153 1438-1443)
9
Neuropsychiatric Symptoms in Persons with
Alzheimers Disease
with Sx
10
Neuropsychiatric Symptoms in Persons with
Alzheimers Disease
with Sx
11
Impact of Behavioral Changes on Persons with AD
and Their Families

• Distressing for the person with AD
• Cause persons with AD to be agitated
• Increase distress in caregivers
• Often require treatment with medication
• Lead to earlier institutionalization

12
Non-Pharmacologic Behavioral Interventions

• 3 Rs Repeat, Reassurance, Redirection
• ABCs Antecedents, Behavior, Consequences
• Support caregiver
• Alzheimers Disease International / Alzheimers
  Association

13
Psychosis in Persons with AD

• Prevalence
• 25 cross-sectional
• 50-70 longitudinal
• Features
• Theft, infidelity, misidentification
• Pathophysiology
• Decreased frontal/temporal metabolism/perfusion
• Increased neocortical neurofibrillary tangles

14
Persons with AD and Psychosis Have Significantly
More NFT in Neocortex
NFT Counts Per 1 mm
2



(Farber et al, Arch Gen Psychiatry 2000 57
1165-1173)
15
Psychosis in AD Treatment

• Atypical antipsychotics
• Risperidone
• Olanzapine
• Quetiapine
• Ziprasidone
• Conventional neuroleptics
• Haloperidol

16
Reduction of Psychosis in Persons with AD by
Olanzapine
Plac
5 mg
10 mg
15 mg
Change in NPI Psychosis Score (Del Hall)


(Street et al, Arch Gen Psychiatry 2000 57 968)
17
Reduction of Psychosis in Persons with AD by
Risperidone

Percent of Patients Whose Delusions Resolved With
Treatment

(Sx at baseline not at end of study)
(Katz et al, J Clin Psychiatry 1999 60 107)
18
Agitation in Persons with AD

• Prevalence
• 40 cross-sectional
• 60-80 longitudinal
• Features
• Aggression, vocalization, resistance to care
• Pathophysiology
• Decreased frontal/temporal metabolism/perfusion
• Increased frontal neurofibrillary tangles

19
Agitation in AD Treatment

• Atypical antipsychotics
• Conventional neuroleptics
• Anticonvulsants/mood stabilizers
• Selective serotonin reuptake inhibitors
• Trazodone
• Buspirone
• Beta-blockers

20
Reduction of Agitation in Persons with AD by
Risperidone
(p0.02)
(p0.06)
Percent of Symptomatic Patients With Scores Of 0
or 1 At Study End
(Katz et al, J Clin Psychiatry 1999 60 107)
21
Reduction of Agitation in Persons with AD by
Olanzapine
Placebo
5 mg
10 mg
Reductions On NPI Agitation Score


(Street et al, Arch Gen Psychiatry, 2000)
22
Comparative Effects of Risperidone and
Haloperidol on MMSE Scores in Persons with AD

Change In MMSE Score
Plac
Risperidone
Haloperidol
(DeDeyn et al, Neurology 1999 53 946)
23
Carbamazepine Treatment of Agitation in Persons
with AD
of Patients
(Tariot et al, Am J Psychiatry 1998 155 54-61)
24
Reduction of Occupational Disruptiveness Reported
by Caregivers of Persons with AD on Olanzapine
Placebo
5 mg
10 mg
Reductions On NPI/NH Occupational Disruptiveness S
cale Score

(Street et al, Arch Gen Psychiatry, 2000)
25
Depression in Persons with AD

• Prevalence
• 25 cross-sectional
• 50 longitudinal
• Information source influences frequency estimates
• Features
• Major depression rare
• Depressive symptoms common
• Exacerbates cognitive and functional disability

26
Depression in Persons with AD Treatment

• Selective serotonin reuptake inhibitors
• Citalopram, sertraline, fluoxetine,paroxetine
• Tricyclic agents
• Nortriptyline
• Combined serotonin and noradrenergic reuptake
  inhibitors
• Venlafaxin

27
Reduced Depression and Irritability in Persons
with AD Treated with Citalopram
Irritability
Depression
GBS Scale Score Change


(Nyth and Gottfries, Br J Psychiatry 1990 157
894)
28
Treatment of Depression in Persons with AD with
Sertraline
Cornell Scale
Hamilton Scale
ADL

Scale Scores


(Lyketsos et al, Am J Psychiatry 2000 157 1686)
29
Cholinergic Deficit in AD

• Atrophy of nucleus basalis at the base of the
  brain
• Loss of the enzyme choline acetyltransferase
• Reduced synthesis of the transmitter
  acetylcholine
• Limbic and neocortical cholinergic deficits
• Acetylcholine receptors largely intact

30
Cholinesterase Inhibitors

• Tacrine (Cognex)
• Aricept (Donepezil)
• Rivastigmine (Exelon)
• Galantamine (Reminyl)

31
Reduced Psychotropic Use in Persons on Donepezil





(Small et al, Clin Therapeutics 1998 20 838)
32
Cholinesterase Inhibitors and Behavior in Persons
with Alzheimers Disease

• Psychotropic effects
• Reduce apathy, visual hallucinations, anxiety,
  depression, aberrant motor behavior
• Less consistent effects on agitation, delusions
• Effect size of 30 over placebo
• Independent of effect on cognition
• Increase frontal and temporal perfusion

33
Treatment of Persons with Alzheimers Disease
Cholinesterase inhibitor Vitamin E
Assess residual behavioral disturbances
Specific behavioral target environmental
interventions
Pharmacologic treatment
34
The Mechanism Of Alzheimers Disease
Amyloid Production and Accumulation
Nerve Cell Death
Neurochemical Deficiency
Cognitive and Behavioral Changes
35
Amyloid Production and Accumulation
Anti-Amyloid Agents
Nerve Cell Death
Anti-Oxidants
Neurochemical Deficiency
Cholinesterase Inhibitors
Cognitive and Behavioral Changes
Psychotropic Agents
36
Behavioral Changes in Persons with Alzheimers
Disease Summary

• Behavioral changes occur in nearly all persons
  with Alzheimers disease
• Behavioral changes diminish the quality of life
  of patient and caregiver
• Behavioral symptoms reflect the pathologic and
  chemical changes in the brain
• Behavioral changes respond to treatment