Organic mental disorders II: dementias

Martin Brunovsky, MD, PhD

Prague Psychiatric Center

3rd Faculty of Medicine Charles University

Dpt. of Neurology, Faculty Hospital Bulovka

Dementia

a syndrome which is acquired and characterized by multiple impairments in cognitive functions without impairment in

consciousness

• Memory impairment, plus– Impairment in at least one other domain: language, visuospatial

skill, executive abilities, and emotion

- Representing decline- Interfering with function- Not better accounted for by a number of other conditions DSM-IV-TR; APA 2000

Definition of dementia• from Latin demens, dement =„senseless“ or de + mens = „deprived of mind“• not a specific disorder or disease – rather an acquired syndrome (group of

symptoms) characterized by loss of function in multiple cognitive domains.

DSM-IV diagnosis of Dementia: An acquired syndrome characterized by:

• MEMORY IMPAIRMENT (short-term ) and at least one of the following:

• Aphasia - language memory impair.

• Apraxia - motor memory impairments

• Agnosia - sensory memory impair.

• Executive dysfunction/ abstract think.

• Severe enough to cause impairment in social and occupational functioning

• Cognitive decline represents decline from previous functioning

• Deficits cannot be accounted for by delirium, other CNS condition, systemic condition, or substance-induced…

ICD-10 diagnosis of Dementia:• A decline in memory to an extent that it

interferes with everyday activities, or makes independent living either difficult or impossible.

• A decline in thinking, planning and organizing day-to-day things, again to the above extent.

• Initially, preserved awareness of the environ-ment, including orientation in space and time.

• A decline in emotional control, motivation, or a change in social behaviour, as shown in one or more of the following: emotional lability, irritability, apathy or coarsening of social behaviour, as in eating, dressing and interacting with others.

American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, D.C, American Psychiatric Association, 1994

World Health Organization: The ICD-10 Classification of Mental and Behavioural Disorders. Clinical Descriptions and Diagnostic Guidelines, Geneva, World Health Organization, 1992.

Every edition of DSM or ICD requires that patients with dementia have a deficit in memory...

But memory loss is often not an early or cardinal symptom in patients with: ...vascular dementia, frontotemporal dementia, or Parkinson-related dementias...

e.g. the Merck Manual of Geriatrics' definition of dementia:

„A deterioration of intellectual function and other cognitive skills, leading to a decline in the ability to perform activities of daily living…“

A Classification System for the Types of Dementia

Dementing disorders can be classified in many different ways. These classification schemes attempt to group disorders that have particular features in common, such as whether they are progressive or what parts of the brain are affected.

• Cortical dementia • Subcortical dementia • Progressive dementia • Primary dementia • Secondary dementia

Some types of dementia fit into more than one of these classifications. For example, Alzheimer's disease is considered a progressive, primary, and cortical dementia.

CORTICAL DEMENTIA refers to dementia in which brain damage primarily affects the brain's cortex, or outer layer. Cortical dementias tend to cause problems with memory, language, thinking, and social behavior.

SUBCORTICAL DEMENTIAis dementia that affects parts of the brain below the cortex. This dementia type tends to cause changes in emotions and movement in addition to problems with memory. One example of this dementia type is Binswanger's disease.

PROGRESSIVE DEMENTIAis dementia that gets worse over time, gradually interfering with more and more cognitive abilities. Lewy body dementia is an example of a progressive dementia.

PRIMARY DEMENTIA is dementia (such as Alzheimer's disease) that does not result from any other disease.

SECONDARY DEMENTIAis dementia that occurs as a result of a physical disease or injury.

Treatable Versus Untreatable DementiaAnother classification system that is used for dementia separates the causes of dementia into treatable or untreatable.

Treatable Dementia• About 10 percent of conditions that cause dementia

are treatable!!! • With treatment, the dementia can either be reversed

or at least halted. Examples of conditions that cause treatable cases of dementia include: • Normal pressure hydrocephalus • A brain tumor or brain cancer • Hypothyroidism • Vitamin B12 deficiency • Neurosyphilis• Reactions to medications • Poisoning

• a condition of pathologically enlarged ventricular size with normal opening pressures on lumbar puncture

• triad of dementia, gait disturbance, and urinary incontinence

• reversible by the placement of a ventriculoperitoneal shunt

Non-Treatable Dementia Although a number of diseases can cause dementia, Alzheimer's disease is by far the most common. More than one-half of all dementia cases are caused by Alzheimer's disease. The second most common cause of dementia is multi-infarct dementia, which is a type of vascular dementia.

Alzheimer's disease Multi-infarct dementia Lewy body dementia Binswanger's disease Frontotemporal dementia Corticobasal degeneration HIV-associated dementia Other infections within the brain, such as Creutzfeldt-Jakob

disease Huntington's disease and other rare hereditary dementias Head trauma, such as dementia pugilistica (also known as boxer's

syndrome).

Other conditions that can cause dementia or dementia-like symptoms include:

Parkinson's disease or multiple sclerosis (MS) Heart and lung problems Anoxia or hypoxia (conditions in which the brain's oxygen supply

is either reduced or cut off entirely).

Major Etiologies of Dementia

Alzheimer’s diseaseVascular dementia Dementia with Lewy

Bodies Frontotemporal Dementia

INCIDENCE OF DEMENTIA TYPES

Alzheimer's disease60%

AD in Parkinson's disease

7%

Vascular, mixed and rare15%

Frontotemporal8%

Lewy body dementia10%

1/3 - 2/3 AD VASCULAR PATHOLOGY PRESENT

The Continuum of Vascular Dementia and Alzheimer’s Disease

VaDAD

Mixed AD + Cerebrovasular

Disease

Infarcts, white matter lesions, vascular risk

factors

Post-stroke dementiaAmyloid plaques and neurofibrillary tangles

• Pure dementia is not common

• 77 % of vascular dem. also has AD

• 66% LBD also has AD

• 50% AD has other pathology

Differential Diagnosis

1. Alzheimer Disease (pure ~40%, + mixed~70%)

2. Vascular Disease, MID (5-20%)

Differential Diagnosis: Top Ten (commonly used mnemonic device: AVDEMENTIA)

1. Alzheimer Disease (pure ~40%, + mixed~70%)2. Vascular Disease, MID (5-20%)3. Drugs, Depression, Delirium4. Ethanol (5-15%)5. Medical / Metabolic Systems6. Endocrine (thyroid, diabetes), Ears, Eyes, Environ.7. Neurologic (other primary degenerations, etc.)8. Tumor, Toxin, Trauma9. Infection, Idiopathic, Immunologic10. Amnesia, Autoimmune, Apnea, AAMI

Differential Diagnosis: Top Ten (commonly used mnemonic device: AVDEMENTIA)

1. Alzheimer Disease (pure ~40%, + mixed~70%)2. Vascular Disease, MID (5-20%)

3. Drugs, Depression, Delirium4. Ethanol (5-15%)5. Medical / Metabolic Systems6. Endocrine (thyroid, diabetes), Ears, Eyes, Environ.7. Neurologic (other primary degenerations, etc.)8. Tumor, Toxin, Trauma9. Infection, Idiopathic, Immunologic10. Amnesia, Autoimmune, Apnea, AAMI

Alzheimer`s disease

ALOYSUS "ALOIS" ALZHEIMER(14 June 1864 - 19 Dec 1915)

• German psychiatrist and neuropathologist.

• In 1901, Alzheimer studied a patient in the Frankfurt asylum who had behavior disorder including disorder of short-term memory…

AUGUSTE DETER

• In the following years this patient became Alzheimer‘s obsession.

• In April 1906, Mrs. D. died and Alzheimer had sent the patient records and the brain to Münich where he was working at Kraepelin's lab.

• Together with two Italian physicians, he would use the staining techniques to identify amyloid plaques and neurofibrillary tangles.

A speech given on 3 November 1906 would be the first time the pathology and the clinical symptoms of presenile dementia would be presented together

Mrs. Auguste Deter 51-year-old patient

Alzheimer A. Ubereine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift fur Psychiatrie und Psychisch-Gerichtliche Medizin 1907; 64: 146–148.

DSM-IV DIAGNOSTIC CRITERIA FOR ALZHEIMER'S DISEASE:

Development of cognitive deficits manifested by bothimpaired memory (mainly short-term memory)aphasia, apraxia, agnosia, disturbed executive function

Significantly impaired social/occupational function and activities of daily living

Gradual onset, continuing declineNot due to CNS or other physical conditions (e.g., Parkinson’s, delirium)Not due to an Axis I disorder (e.g., schizophrenia)

Alzheimer`s disease

Characteristic pathological hallmarks:

B) Microscopic: Tau protein degeneration production of

neurofibrillary tangles (intracelular)

Production of beta-amyloid plaques, (extracelular)

A) MacroscopicBrain atrophy (temporoparietal)

C) dysfunction in the neuromediation systems mainly cholinergic system

(ncl. basalis Meynerti, septal nucl.)

Alzheimer’s disease

Chromosome 14(presenilin 1)

Chromosome 1(presenilin 2)

40-42 Amino Acid

Apolipoprotein E4 (41-47% in AD, 16% in healthy controls)

Chromosome 19 (gene for apolipoprotein E)

Activation of microglia, astrocytes, complement, production of membr. porus, vasoconstr.

Production of cytokines and O2

Peroxidation of lipids, Oxidative stress

1) Increased excitotoxicity (Glutamate --- NMDA recept.)

2) Impairment of Ca2+ homeostasis

3) Disturbance of glucose metabolism

Activation of phosphatases, phospholipases

Abnormal phosphorylation of Tau proteins

Production of amyloid plaques

Production of neurofibrillary tangles

„sterile“ inflammation

Neuronal death(mainly cholinergic neurons)

↓AchAmyloid precursor protein Chromosome 21

Disease Progression in Alzheimer’s Disease

0 1 2 3 4 5 6 7 8 9

Years from diagnosis

Cognitive ability

Functional ability

Behavioral problems

Caregiver time

0%

100%

Change indisease

progression

Clinical Progression of AD and MCIC

ognit

ive f

unct

ion

• Forgetfulness• Repetitive

questions• Daily function

mildly impaired• Progression of

cognitive deficits• Word-finding

difficulties• Supervision required • Agitation

• Altered sleep patterns

• Total dependence: dressing, feeding, bathing

MCIMMSE 26–30 Mild AD

MMSE 20–25

Moderate AD

MMSE 10–19

Severe ADMMSE 0–9

• Mild subjective/objective memory loss

• Normal function

10 y0 yTime (y)

Time?

Feldman H, GraconS. In: Clinical Diagnosis and Management of Alzheimer’s Disease. 1996:239-253.

The Progress of Alzheimer’s DiseaseThe Progress of Alzheimer’s Disease

0

5

10

15

20

25

30

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9

Years

MM

SE s

core

Early diagnosis Mild-moderate Severe

Cognitive symptoms

Loss of ADL

Behavioral problems

Nursing home placement

Death

Ashford et al., 1995

LATENT = No Cognitive Impairment MCI = Mild Cognitive ImpairmentSCI = Subjective Cognitive Impairment AD = Alzheimer’s dementia

Birth 10 20 30 40 50 60 70 80 90 100

Years

Dendritic & celldeath

“LATENT” SCI MCI AD

Hypometabolism in “AD-vulnerable” regions medial-temporal lobe atrophy elevated CSF tau/Aβ, isoprostanes

Hypometabolism in “AD-vulnerable” regions medial-temporal lobe atrophy elevated CSF tau/Aβ, isoprostanes

Evolution in the pathogenesis of ADEvolution in the pathogenesis of AD

Aggregation and misfolding of Aβ

followed by plaques and tangles

AD Progression

Abnormal

Normal TimePresymptomatic eMCI LMCI Dementia

CSF Aβ42

Amyloid imagingFDG-PETMRI hippocampal volumeCSF TauCognitive performanceFunction (ADL)

FDG-PET

MRI hippocampal volume

CSF Aβ42

Amyloid imaging

Cognitive performance

Function (ADL)

CSF Tau

Aisen PS, et al. Alzheimers Dement. 2010. In press.

Goals of Therapy in Alzheimer’s Disease

Time

Fu

nc

tio

nal

Ab

ility

Slowing of diseaseprogressionTreatment

Symptomaticbenefit

Maintenance of function

Functional restoration

Progression

Current Therapeutic Options for AD Are Symptomatic

• Approved pharmaceutical treatments for AD (neurotransmitter-based)– Cholinesterase inhibitors (donepezil, rivastigmine, galantamin)– N-methyl-D-aspartate (NMDA) receptor antagonists (memantin)

• Nonpharmacologic– Behavioral and social interventions– Physical and cognitive training– Counselling and support

• There are currently no pharmacologic treatments indicated for predementia AD– Diagnostic criteria are emerging

Waldemar G, et al. Eur J Neurol. 2007;14:e1-e26; Dubois B, et al. Lancet Neurol. 2007;6:734-746.

TREATMENT & MANAGEMENT:

Primary goals: To enhance quality of life Maximize functional performance by

improving Cognition Mood Behavior

Pharmacologic Cholinesterase inhibitors (donepezil,

rivastigmin, galantamin) NMDA receptor blockers (Memantine)

Non-pharmacologic Driving Advanced Directives and Durable Power

of Attorney Caregiver Social and Community

Alzheimer disease - History of Treatment

1950 1960 1970 1980 1990 2000 2010

Cholinesterase inhibitors

NMDA antagonist

Abeta sequenced

PS1 mutation

PS2 mutation

ACh loss described

donepezil

Rivastigmine patch

tacrine

memantine

rivastigmine

galantamine

APP (Swedish)

APP (London)

ApoE4

Acetylcholinesterase Inhibitors (AChEI)

DONEPEZIL (Aricept): 1996 Delay nursing home placement and progression 5mg q d (start) to 10mg q d

RIVASTIGMINE (Exelon): 2000 Global functioning and ADL preservation Start at 1.5mg bid to max 6mg bid, (patches:

start 4.6mg/24h increase to 9.5mg/24h) Rivastigmine approved also for Parkinson Disease

with Dementia (PDD) GALANTAMINE (Reminyl /Razadyne)

(2001/2005) Slowing progression 4mg bid to max 12 mg bid Extended release version: 8mg/day, 16mg/day, 24

mg/day

donepezil (Aricept) (5-10mg/day)

rivastigmin (Exelon) (9-12mg/day)

now also as transdermal patch

4.6mg/24h or 9.5mg/24h

galantamin (Reminyl/Razadyne) (16-24mg/day)

NMDA antagonists

MEMANTINE (Ebixa ; Namenda) Indicated for moderate to severe

dementia Friendly side-effect profile Start at 5mg daily, target dose:

20mg/day Studies suggest added benefit when

used with CIs Often used with those intolerant to

ChEIs Debate on clinical impact/timing with

use of this medication

Memantin (Ebixa) (10-20mg/day)Memantin (Ebixa) (10-20mg/day)

Magnesium PhysiologicalMagnesium Block

Depolarization Synaptic ActivityRestingState

Ca2+ Ca2+

–70 mV –50 mV –20 mV

Low to Moderate AffinityAntagonist Memantine(Ki = 0.5 µM)

Memantine

MM

Ca2+ M

M

Neuropharmacology, Vol 38, CG Parsons, W Danysz, G Quack. Memantine is a clinically well toleratedN-methyl-D-aspartate (NMDA) receptor antagonist—a review of preclinical data, s. 735-767.

-non-competitive NMDA-antagonist

-reduces abnormal glutamatergic activity

CellDeath

Oxidation Inflammation

Excitotoxicity Apoptosis

Antioxidants

NMDA receptor antagonists

Anti-apoptic agents (caspase inhibitors)

Anti-inflammatory agents

Tau Hyperphosphorylation

Tau-related agents

Mitochondrial stabilizing agents

Mechanistic Rationales for Potential Disease-Modifying Therapies

MemoryDecline

CellDeath

Transmitter Deficit

Secondary Processes• Synaptic degradation• Tau hyperphosphorylation• Oxidation• Excitotoxicity• Inflammation• Demyelination• Apoptosis

• Neurofibrillary tangles• White matter changes• Atrophy

Adapted from Salloway S, et al. Alzheimers Dement. 2008;4:65-79.

Amyloid Plaque

Amyloid Beta Peptides

Rage-Ligand Inhibitors Fibrillization Inhibitors

Immunotherapy Oligomer Neutralization

Immunotherapy

Amyloid Precursor

Protein (APP)

Inhibitors/Modulators

Gamma-secretase

Beta-secretase

BACE Inhibitors

Alzheimer disease - History of Treatment

1950 1960 1970 1980 1990 2000 2010

Cholinesterase inhibitors

NMDA antagonist

Abeta sequenced

PS1 mutation

PS2 mutation

ACh loss described

donepezil

Rivastigmine patch

tacrine

memantine

rivastigmine

galantamine

APP (Swedish)

APP (London)

ApoE4

Goals of future research and treatment in AD2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Solanezumab LY2062430 III

Passive? III

Pfizer I PF04360365 II Passive c-terminus Ab-40 III

GSK I GSK933776A II

Gantenerumab Passive IIIRoche I Hucal R1450 II

Active IIIV950 IIMerck I

Active IIIPfizer/JNJ ACC-001 II

4 trials Bapineuzumab N-terminal III

Semagacestat LY450139 III

Elan: AZD-103 II A-beta aggregation inhibitor III

PF-04494700 (TTP488) II RAGE III

IV-IG III

Initiated phase III

Immunotherapies

Oral-DM

BMS BMS 708163 II GSI Mild-Mod AD III

Prodromal AD II

Pfizer GSI-953 II Begacestat Mild-Mod AD III

Elan ELND-006 II GSI III

44

Mechanism of Action: Peripheral Sink Hypothesis

Liver clearance

CSF

Plasma

sAPP A

CTF

APP

secretase secretase

Brain

Blood-brain barrier

A

Interstitial space

A

Oligomers

Amyloid plaque

A antibody

0.1% Crosses BBBIncreased Total AβDecreased Unbound Aβ

Vascular Dementia(DSM-IV - APA, 1994)

A. Multiple Cogntive Impairments1. Memory Impairment2. Other Cognitive Disturbances

B. Deficits Impair Social/Occupational

C. Focal Neurological Signs and Symptoms or Laboratory Evidence Indicating Cerebrovascular Disease Etiologically Related to the Deficits

D. Not Due to Delirium

Factors Associated with Multi-infarct Dementia

History of stroke (especially in Nursing Home) Followed by onset of dementia within 3 months

Abrupt onset, Step-wise deterioration Cardiovascular disease - HTD, Atrial Fibr.

… Depression (left anterior strokes),

personality change More gait problems than in AD MRI evidence of T2 changes (??

Binswanger’s disease) Basal ganglia, putamen Periventricular white matter

SPECT / PET show focal areas of dysfunction

Neuropsychological dysfunctions are patchy

VASCULAR DEMENTIA CHANGE ON THE MINI-MENTAL STATE EXAM

OVERTIME

< event

< event

< event

0

10

20

30

-5 0 5 10

AVERAGE TIME OF ILLNESS (years)

SC

OR

E

Vascular Dementia: Therapy

1. P R I M A R Y P R E V E N T I O N

Stroke HT Cardiovascular risk

2. PREVENTION OF RECURRENCE

Control of risk factors HT, blood fluidity, lipids

3. SYMPTOMATIC TREATMENTVasodilatators (pentoxifyllin, naftidrofuril)Metabolic approachDrugs for Alzheimer ’s Disease

4. FUTURE DIRECTIONS

Drugs for cell deathTrophic factors

PRIMARY PREVENTION OF VASCULAR DEMENTIA

1. TREAT HT OPTIMALLY2. TREAT DIABETES3. CONTROL HYPERLIPIDAEMIA4. TOBACCO + ALCOHOL5. ANTICOAGULANTS FOR ATRIAL FIBRILLATION6. ANTIPLATELET THERAPY7. CAROTID ENDARTERECTOMY FOR SEVERE ( 70

%) STENOSIS8. DIETARY CONTROL9. LIFESTYLE (stress, weight…)10. STROKE + TIA : NMDA, Ca++, antioxidants11. REHABILITATION

Cochrane Review

Nimodipine (1992) : not recommended, no convincing evidence that nimodipine is a useful treatment for the symptoms of dementia (all subtypes)

Piracetam (1998) : not recommended - Effects found only on global impression of change (all subtypes of dementia)

Lecithin (1999) : results from randomized trials does not support the use of lecithin (all subtypes of dementia)

Aspirin (1999) : limited evidence that aspirin change cognitive outcome of VaD.

the most common dementia syndrome associated with parkinsonism

the second most common form of neurodegenerative dementia after Alzheimer disease (AD).

characterized by dementia accompanied by delirium, visual hallucinations, and parkinsonism. Other common symptoms include syncope, falls, sleep disorders, and depression.

The presence of both Lewy bodies and amyloid plaques with deficiencies in both acetylcholine and dopamine neurotransmitters suggests that dementia with Lewy bodies represents the middle of a disease spectrum ranging from Alzheimer’s disease to Parkinson’s disease

Dementia with Lewy Bodies (LBD)

Core And Supportive Features For Clinical Diagnosis Of DLB 1. The central feature required for a diagnosis of DLB is

progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational function

2. Two of the following core features are essential for a diagnosis of probable DLB, and one is essential for possible DLB. Fluctuating cognition with pronounced variations in

atten- tion and alertness Recurrent visual hallucinations that are typically

well formed and detailed. Spontaneous motor features of parkinsonism.

3. Features supportive of the diagnosis are repeated falls syncope transient loss of consciousness neuroleptic sensitivity systematized delusions hallucinations in other modalities.

FRONTOTEMPORAL DEMENTIA  characterized by focal atrophy of the frontal and

temporal lobes in the absence of Alzheimer pathology Pick's disease was the first recognized subtype of FTD, one that is characterized pathologically by the presence of Pick bodies (silver staining intracytoplas. inclusions) in the neocortex and hippocampus. occurs between the ages of 35 and 75 years, and only rarely after age 75; the mean age of onset is the sixth decade both sexes are equally affected. clinically, presents with language abnormalities and behavioral disturbances.

Frontotemporal Lobe Dementia Core Features• Insidious onset and gradual progression• Early decline in social/interpersonal conduct• Early impairment in personal conduct• Early loss of insight• Early emotional bluntingSupportive Features• Behavior disorder – hygiene, grooming, mental rigidity, dietary changes, perseverative behavior• Speech and language – perseveration, mutism, economy of speech• Physical signs – akinesis, rigidity, tremor, labile BP

Diagnosing dementia

BPSDActivities of daily living

DementiaDementia

Behavioural and Psychological Symptoms of Dementia:

A heterogeneous range of psychological reactions, psychiatric symptoms and behaviours resulting

from the presence of dementia

Cognitivedeficits

mild ………...... moderate …..…...……. severe

time course of the disease

depression anxiety

psychotic symptoms (delusions, hallucinat.) verbal aggressionagitation / apathy

Loss of independence

agitation/negativism

physical aggression

BPSD

90% of patients affected by dementia will experience Behavioral and Psychological Symptoms of Dementia (BPSD) that are severe enough to be labeled a problem at some time during the course of their illness.

(Mega et al. 1996)

J Am Ger Soc. 1996; 44(9): 1078-1081

Behavioral Disturbances in Dementia:

Five „I“ for investigating cause of behavioral symptoms in elderly

Iatrogenic? (anticholinergics, BZD, digitalis, diuretics…)

Inconsistency (change in routine, caregiver, or

environment?) Illness or pain?

Infection?

Is patient depressed?

• Caution! Drugs for urinary incontinence and benign prostatic hyperplasia!• Agents not crossing blood-brain barrier :

trospium (Spasmed), tolterodine (Detrusitol, Detrol),darifenacin (Emselex)

• Agents crossing blood-brain barrier : oxybutynin (Uroxal, Ditropan), propiverine (Mictonorm, Mictonetten)• Unclear: solifenacin (Vesicare), fesoterodine (Toviaz)

BPSD that will not respond to medication

Wandering Inappropriate urination/defecation Inappropriate dressing/undressing Annoying repetitive activities

(perseveration) or vocalization Hiding/hoarding Eating inedibles Tugging at/removal of restraints Pushing wheelchair bound co-residents

Problems that may respond to medication

Anxiety Depressive symptoms Sleep disturbance Manic-like symptoms Persistent and distressing delusions

or hallucinations Persistent verbal and physical

aggression Sexually inappropriate behavior

Jeste, Finkel 2000

Differential Diagnosis of Psychosis of AD Vs

Psychosis of Schizophrenia in the

Elderly Psychosis of AD Schizophrenia

Bizarre or complex delusions Rare Frequent

Misidentifications of caregivers Frequent Rare

Common form of hallucinations Visual Auditory

Schneiderian first-rank symptoms Rare Frequent

Active suicidal ideation Rare Frequent

Past history of psychosis Rare Frequent

BPSD:Treatment Patients with BPSD should be evaluated for delirium.

Consider changes in environment, medication, fecal impaction, pneumonia, urinary infection, etc.

Evaluate for needs that the dementia patient is unable to communicate normally e.g. pain

Behavioral management or situational manipulation are the initial strategies of choice for mild to moderate BPSD.

Pharmacological interventions are useful if symptoms are severe or do not respond to nonpharmacologic strategies alone

BPSD: Nonpharmacologic Therapy

Environmental modifications such as music, plants, animals

Speak slowly, keep commands simple and positive, use gestures, gentle touch

Behavioral management techniques Structured activities and use of schedules Massage, exercise

Rowe, Alfred 1999Gerdner, Swanson 1993

BPSD: Pharmacological Therapy Look for symptom complexes such as depression,

psychosis or anxiety to guide initial choice of agent If enlightened empiric therapy is needed, chose agents

that minimize side-effect potential and maximize chance of efficacy

In most situations, medications should be given in lower doses than are typically recommended for an adult population. However, it is noteworthy that the elderly are heterogeneous and the range of medication dosage is substantial

Ideally, use agents with demonstrable efficacy as first line agents

BPSD: PharmacotherapySYMPTOMS PHARMACOTHERAPY

Agitation, Disinhibition, Agression, Behavioral disturbances

Antipsychotics (tiaprid, melperon, haloperidol)(Second generation antipsychotics ??)

Depression Antidepressants (avoid tricyclics)

Anxiety S1A agonits: buspironShort-acting benzodiazepins (oxazepam, lorazepam)

Circadian rhythm disturbances Hypnotics:zolpidem,zopiclon (non-bzd)melatonin, trazodone, mirtazapine

Psychotic symptoms (delusions, hallucinations)

Antipsychotics (tiaprid, melperon, haloperidol)(Second generation antipsychotics ??)

AFP. 2003. 67: 2335-40.

Atypical Antipsychotics

Effectiveness of atypicals is firmly established in treating dementia-related psychosis

Includes Abilify (aripiprazole), Zyprexa (olanzapine), Seroquel (quetiapine), Risperdal (risperidone), Clozaril (clozapine) and Geodon (ziprasidone)

Risperidone now available in a disintegrating tablet in 0.25mg-4mg doses and a long acting injection (up to 50mg q 2 weeks) Continue oral therapy for three weeks to get

adequate level

FDA Public Health Advisory, April 11, 2005

Risk of Atypical Antipsychotics

Class Effect 2005 - black box warning of increased risk

of death and “not approved for use in dementia-related psychosis.” Risk of death 1.6-1.7 x that of placebo Over a 10 week trial. 4.5% rate of death vs.

2.6% for the placebo group. Mostly cardiovascular deaths or infectious

(pneumonia) Patient (caregiver) specific risk assessment

and counseling