Delirium and Dementia

Dr. Lisa McMurray

Back to Basics

2 April 2013

AcknowledgementsSeveral slides are taken from a 2012 lecture on dementia and delirum by Dr. Cathy Shea

Objectives in plain English:Describe dementia

Describe delirium

Describe an approach to the patient suffering from delirium

Initiate treament of delirium, including both medication and psychosocial approaches

Differentiate between delirium and dementia

Know the essential features of the most common dementias:Alzheimer typeVascularLewy BodyFronto-temporal

Know “potentially reversible” causes of dementia that must be ruled out and treated (in practice, rarely reversible)

Identify depression in an elderly person when it mimics dementia

Initiate treatment of dementia, including both medication and psychosocial approaches

Lau, T. Canadian Journal of Diagnosis Nov/Dec 2009

What is dementia?The development of significant deficits in 2 or more areas of cognition

Severe enough to affect day-to-day functioning

What is dementia?It develops in the presence of a clear state of consciousness

It should be differentiated from delirium, an acute change in cognition due to a general medical condition, with a fluctuating level of consciousness

What is Delirium?

An acute change in level of consciousness/attention and cognition due to a general medical condition. Characterized by fluctuation.

Potentially reversibleOften unrecognizedPoor prognosis

More later…

DeliriumKey Features

Change from usual mental state!!!

Fluctuates (may appear normal at times)

Altered level of consciousness (hyper/hypo or mixed)

Inattention (you must repeat questions because patients attention wanders)

Perceptual disturbances (visual hallucinations and paranoid delusions)

Disorganized thinking (rambling, tangential speech)

Psychomotor changes (hyper or hypoactive)

Delirium EpidemiologyPrevalence

1-2% in community

15-24% in general hospital

IncidenceHospital admission: 6-56%

Post-operative elderly: 15-53%

Elderly ICU: 70-87%

Delirium Pathophysiology“Acute brain failure”

Decreased neurotransmitter synthesis

CNS inflammation

Drugs

Combine to produce altered neurotransmission and confusion

Key features differentiating delirium from dementia

Feature Delirium Dementia

Onset Acute Insidious

Course Fluctuates Stable,slowly progress

Duration Hours to weeks Months to years

Attention Hypo or hyper Normal

Orientation Impaired Impaired

Memory Impaired Impaired

Thinking Disorganized Impoverished

Perception Illusions & Halluc May be normal

Sleep-wake Always disrupted May be disrupted

Physical illness or drug toxicity

Either or both Usually absent

Delirium is seriousPatients with delirium have:

- prolonged length of stay in hospital

- worse rehabilitation/functional outcomes

- higher institutionalization rates

- increased risk of cognitive decline

- higher mortality rates (10-26%)

Delayed recognition → worse outcomes

Caplan et al, 2008

Delirium Workup: Consider…CBC and differential

Electroytes

BUN/creatinine

Magnesium and phosphate

Calcium and albumin

Liver function tests

TSH

Urinalysis, Urine Culture and Sensitivity

Blood gases

Blood culture

Chest x-ray

EKG

Delirium – Non-pharm management

Supervision (1:1 if necessary)

Reorientation

Clear instructions

Eye contact

Optimize vision/hearing with glasses, hearing aids

Avoid restraints

Consistent staff/room

Low light at night

Minimize sleep medications

Delirium – pharmacological MgmtHaloperidol 0.5 mg po/im q1h (im) prn agitation

Risperidone, Olanzapine, and Quetiapine have also demonstrated efficacy

Treat hyperactive delirium only

Alzheimer's Australia, 18 May 2012

Dementia is CommonAge related risk:

> 65: Overall:Incidence: 2 %

Prevalence: 8 %

Prevalence doubles every ~5 years

Females>males

Lindsay et al. Can J Psychiatry 2004;49:83-91. CSHA CMAJ 1994; 150: 899-913; CSHA. Neurology 2000; 55: 66-73

Dementia – DSM IVCognitive deficits manifested by both

Memory impairment (Amnesia) andOne or more of

AphasiaApraxiaAgnosiaDisturbance in executive functioning

Impaired social or occupational functioningDecline from previous level of functioning

The patient with cognitive impairment, simplified

Is this a dementia or a delirium?

R/O treatable causes of dementiaDepression

Hypothyroidism

Vitamin B12 deficiency

Hypercalcemia

Other

What type of dementia is it?

Treat: Psychosocial + Meds

Dementia / Delirium /DepressionDementia: A condition of acquired cognitive deficits, sufficient to interfere with functioning, in a person without depression (pseudo-dementia) or delirium

Delirium: An acute, potentially reversible, condition characterized by fluctuating attention & level of consciousness, disorientation, disorganized thinking, disrupted sleep/wake cycle

Depression: Alteration in usual mood with sadness, despair, lack of enjoyment in previously enjoyed activities and vegetative symptoms sufficient to interfere with functioning

DSM-IV Criteria for DeliriumDisturbance of consciousness with decreased ability to focus, sustain or shift attention

Change in cognition or development of perceptual change not accounted for by dementia

Develops over a short period of time

Fluctuates during course of the day

Evidence in history, physical or lab findings that cause is physiologic consequence of General Medical Condition (GMC)

DSM IV - Major Depression 5 or more symptoms for 2 or more weeks

Depressed mood or loss of interest plus 4 of:Change in sleepChange in appetitePsychomotor changePoor energy/fatigueGuilt/WorthlessnessPoor concentration/indecisivenessSuicidal thoughts

Impaired FunctioningNot Substance/GMC/Bereavement

Depression and Dementia overlapDepression in late life may mimic dementia (depressive pseudo-dementia)

Late onset (>age 60) depressive illness may be an early manifestation of dementia.

Depression often complicates and co-exists with a previously diagnosed dementia.

Dementia Depressive Pseudodementia

Insidious SubacuteSlow progression Rapid progressionLabile mood Consistently

depressedCan enjoy things Cannot enjoy thingsCognitive changes first

Mood Changes first

Cooperative Uncooperative or does not try

Aphasia, word-finding difficulties

No aphasia

No history of mood disorder

History of mood Disorder

Screening for DementiaPerhaps best for >70-75 years of Age

If Informants/caregivers notice a change

The “Alzheimer’s test”: ask a reliable informant

Is there a memory problem?

Is it getting worse?

Has it caused a decline in usual activities, hobbies, or paying bills?

Perform a short mental-status questionnaire

e.g. MMSE, MoCA, Mini-COG

Insufficient evidence to suggest one over another

No good short test to differentiate among subtypes

Dementia: Differential Diagnosis• Alzheimer: Memory predominates• Vascular Dementia:

• Multi-infarct – multiple strokes• Subcortical ischemic – subcortical white matter changes with

vascular risk factors

• Dementia with Lewy-bodies: • Fluctuation in attention; visual hallucinations; Parkinsonism

• Frontotemporal Dementia:• Behaviour variant• Language variant (primary progressive aphasia, semantic dementia)

• Parkinson’s Dementia • Onset > 1 year after Parkinson’s

Dementia: Less Common CausesOther neurologic problems

e.g. Huntington’s disease, Normal pressure hydrocephalus, trauma, anoxia, subdural hematoma

Drugs

e.g. Alcohol, illegal drugs

Toxins

e.g. heavy metals, organic compounds

Infections

e.g. HIV, neurosyphilis, Lyme, fungal, viral, prion (Creutzfeld-Jakob)

Inflammatory Conditions

e.g. CNS vasculitis, multiple sclerosis

Endocrine, metabolic, and nutritional

e.g. hypothyroidism, vitamin B12 deficiency, hypercalcemia

Cancere.g. primary, metastatic, paraneoplastic

These may be potentially reversible or stopped if recognized and treated early

Symptoms suggesting a Medical Cause

Rapid onset and/or progression

Younger age than expected

Recent illness or chronic illness before onset

History of trauma or toxic/substance exposure

Predominant frontal symptoms/ early personality change

Onset of focal neurologic symptoms

Evaluation of Dementia

Careful history with informant

Physical with emphasis on neurologic and cardiovascular symptoms

Mental status examination with evaluation of cognition

Laboratory Work-up: CBC, TSH, Electrolytes, Ca, Fasting Glucose, B12

Folate if celiac disease or no grain in diet

Neuroimaging if indicated (see next slide)

In special cases only: LP, MRI, functional neuroimaging, EEG, neuropsychological testing

Neuroimaging in workupCT brain if:

Age < 60

Rapid decline (1-2 mo)

Dementia < 2 y

Recent and significant head trauma

Unexplained neuro symptoms

History of Ca

Anticoagulants or bleeding disorder

Early urinary incontinence and gait disorder (NPH)

New localizing sign

Atypical presentation

Gait disturbance

Gauthier et al, 2012

MOCA

Mini-Cog

Mini-mental State Examination

Copyright Marshall Folstein

Alzheimer’sAlzheimer Dementia

A progressive degenerative disease

Primarily medial-temporal and temporal-parietal cortex

Average 7-10 year duration from onset of symptoms to death

5% of population over 65*

*CSHA: Canadian Study on Health and Aging; Knopman et al. Neurology 2001; 56: 1143-53

Ballard, C et al. Lancet 2011; 377: 1019-31

Ballard, C et al. Lancet 2011; 377: 1019-31

Ballard, C et al. Lancet 2011; 377: 1019-31

Clinical picture of Alzheimer’s

Insidious onset and gradual progression in an otherwise health elderly person, e.g. 75 years old

E.g. forgetting ingredients in cooking; misplacing posessions, repeating stories/questions

Gradually worse; driving can become unpredictable and erratic.

Depressive symptoms common in early phases.

Psychosis emerges middle to late.

Alzheimer Risk and Protective Factors

Genetic risk factorsFamily history (1° relative with AD 3.5 x risk)Female GenderDown’s Syndrome

Low EducationPre-existing lower mental ability

Head TraumaDepression in men: 4x riskSmoking: 2x risk↓ TSH: 4 x riskExposure to toxins (pesticides, fertilizers…): 4 x riskVascular:

• Lacunar/deep white matter infarcts: 20 x risk• Apolipoprotein E e4 especially E4/E4• Hypertension & Hypotension• Diabetes Mellitus• Elevated homocysteine levels• Decreased folate levels• Increased lipids and/or cholesterol

Age

High Education Apolipoprotein E e2 or e3

Diet: Fish, vegetablesModerate AlcoholAll lipid lowering drugsStatinsNSAIDs?

Physical activityMental activitiesRich Social Networks

Adapted from Fratiglioni et al, Lancet Neurology 2004: 343-53; Patterson et al. Alzh & Dementia 2007; 341-7; Scalco and van Reekum. Can Fam Physician 2006; 52: 200-7

DementiaMCINormal

Adapted from Fratiglioni et al, Lancet Neurology 2004: 343-53; Patterson et al. Alzh & Dementia 2007; 341-7; Scalco and van Reekum. Can Fam Physician 2006; 52: 200-7

Age Acquired/Lost abilities

Stage Years

MMSE

Management Needs

12+ Hold a job 3 incipient

0 29 None

8-12 Handle simple finances

4 mild 7 19 Independent survival still possible

5-7 Select proper clothing

5 moderate

9 14 Requires part-time assistance

5443-4½ 2-3

Put on clothes unaidedShower unaidedToilet unaidedControls urineControls bowels

6a mod.severe6b6c6d6e

10½ 5 Requires full-time assistance

15 mo 116-10 mo2-4 mo 1-3 mo

Speaks 5-6 wordsSpeaks 1 wordWalksSit upSmileHold up head

7a severe7b7c7d7e7f

13 0 Requires continuous care

0 Birth/Death 19

Alzheimer’s: Retrogenesis – 7 stage decline

Non-Alzheimer Dementia?Hallucinations/delusions more prominent in early Lewy Body Dementia (Psychiatry)

Depressive symptoms and apathy may be more common in early Vascular Dementia (Geriatric Med/Psychiatry)

Impulsive, disinhibited behaviours more common in Fronto-Temporal Dementia (Psychiatry/ Emergency Dept./Police)

Frontotemporal DementiaAtrophy of frontal and anterior temporal cortex

Early onset: ages 45-65 (range 21-85)5.4% of those referred to Canadian dementia centre

12 % of those before age 70

2% of those after age 70

M=F or M>F

Lasts 6-8 years (3 in FTD-MND)Neary et al. Lancet Neurol 2005; 4: 771–80; ACCORD, 2003

Fronto-temporal Dementia:Clinical Picture

Late-middle age; children often involved

Personality change Disinhibited or apathetic

Language variants present with aphasia

Often misdiagnosed as psychiatric condition

Repetitive behaviours/fixations

Self-neglect

Cognitive problems begin later

Comparison of FTD and AD

FTD ADAge of onset Usually <

70Usually > 65

Social behaviours

Inappropriate,unconcerned

Appropriate, concerned

Memory problems

Late Early

Aphasia PPA and SD*

Late

Visuospatial skills

Preserved Impaired

*PPA=primary progressive aphasia; SD=semantic dementia

Vascular Dementia/Vascular Cognitive Impairment

Cognitive disorder caused by vascular or circulatory lesions

Alzheimer’s: Vascular Dementia ~ 2-5:1

Epidemiology:

10-20% of dementias

1.5% of those 65 and older*

Mixed (AD and VaD): ~20% or more of dementias

Post-stroke dementia: in 1/3 of stroke survivors

M>F

*Canadian study on health and aging

Vascular Dementia

www.emedicinehealth.com

Canadian Study of Health and Aging. CMAJ, 1994

Vascular Dementia: Epidemiology

The prevalence of VaD doubles every 5 years

DemographicAgeSex Ethnicity

Stroke factorsPrevious / recurrent CVA cerebrovascular accident

Pratt RD. J Neurol Sci, 2002.Skoog I. Neuroepidemiology, 1998.

Vascular risk factors• Hypertension • Cigarette smoking• Atherosclerosis • Hypercholesterolemia• Diabetes mellitus • Ischemic heart disease• Low blood pressure • Atrial fibrillation• Coagulopathies • Elevated homocysteine• Peripheral vascular disease • Myocardial infarction (MI)/angina• CHF • CABG

VaD risk factors

Classification and etiologyLarge-vessel dementiaSmall-vessel dementiaIschemic-Hypoperfusive: post cardiac arrestHemorrhagic

Román et al. Lancet Neurology 2002; 1: 426–36

Large vesselocclusion

Occlusion Hypoperfusion

Multiple large cortical or

subcortical infarcts

Small infarcts(Lacunes)

Deep white matter lesions

Strategic SingleInfarct Dementia

Sub-cortical IschemicVascular Dementia (SIVD)

Multi-infarctDementia

Single criticalinfarct

Embolism, thrombosis Aging, hypertension,diabetes

Small vessel

Lacunar state Binswanger’s

O’Brien et al. Lancet Neurology 2003; 2: 89-98Román et al. Lancet Neurology 2002; 1: 426–36

Final CommonPathway

VaD

Damage to critical cortical and subcortical structures

Damage/interruption of subcortical circuits and projections

Cholinergic transmission

Dementia with Lewy-BodiesPrevalence

Pathologic studies: Affects ~1/3 previously called Alzheimer’s

2nd or 3rd most common type of dementia after AD

More profound cholinergic deficit than AD

More rapid progression than AD: ~4-5 points/year on MMSE

Hippocampus relatively preserved vs. ADWorse:

– Attention than AD (very difficult to do 3 word repetition)– Visuospatial abilities

Early memory OK

Relatively good verbal skills, though naming is often impaired

Central feature: Dementia before or within 1 year of onset of parkinsonism (“rule of 1 year”)

Core features: One (possible) or two (probable) of:Fluctuations in attention and alertness (80% vs 6% AD)Recurrent Visual hallucinations (70% vs 15%)Spontaneous Parkinsonism (75% vs 20%)

Suggestive features (if 1 or more core features present too: probable DLB; if no core features too: possible DLB)

REM sleep behaviour disorderSevere neuroleptic sensitivity (50% do not react so adversely)Low DA transporter uptake in Basal Ganglia (PET or SPECT)

McKeith et al. Neurology 2005; 65: 1863-72

Dementia with Lewy-Bodies

Behavioral & Psychological Symptoms of Dementia (BPSD)

BPSD is an umbrella term for a heterogenous group of non-cognitive symptoms almost ubiquitous in dementiaNever assume a diagnosis of dementia has been made/or is understood by the carergiversBPSD appears at all stages & can precede the diagnosis of dementia by 2 years or moreBPSD is less predictable than the course of cognitive or functional decline in dementia

Adapted from McShane R. Int Psychogeriatr 2000;12(suppl 1): 147

BPSD Symptom Clusters

PacingRepetitive actions

Dressing/undressingRestless/anxious

HallucinationsDelusions

MisidentificationSuspicious

AgitationPhysical aggressionVerbal Aggression

Aggressive resistanceto care

Sad Tearful

HopelessGuilty

AnxiousIrritable/screaming

Suicidal

WithdrawnLacks interestAmotivation

Psychosis

Depression

Apathy

Aggression

EuphoriaPressured speech

Irritable

Mania

Managing DementiaDiagnosis

Screening (MMSE, MoCA)

Differential Diagnosis

Management ofCognitive problems

Behavioural problems

ManagementManagement of risk factors and primary prevention strategies

Cognitive impairment

Behavioural and Psychological Symptoms

Involvement of families (Care-giver support)

Management of Risk FactorsDo: Treat systolic hypertension > 160 mm: target BP 140 mm or less

Do for reasons other than treating dementia:ASA, statins, antithrombotic treatment, and correction of carotid artery stenosis > 60%

Treatment of type 2 diabetes, hyperlipidemia, ↑ homocysteine

Avoid: estrogens alone or with progestins

Unclear how helpful these are:Supplementation with vitamins E or C; though > 400 IU/day Vitamin E increases mortality

Higher levels of physical or mental exercise

Use of NSAIDsPatterson et al. CMAJ 2008; 178: 548-56

Management of Risk Factors and Primary Prevention Strategies

Consider despite insufficient evidence:Recommend strategies to:

Reduce head injury

For greater education

To wear appropriate clothing during administration of pesticides, fumigants, fertilizers and defoliants

Advise patients of potential advantages of:Increased consumption of fish

Reduced consumption of dietary fat

Moderate consumption of wineCCCDTD3 2006

Cognitive EnhancersFocus of importance differs for patient, caregiver and clinician

3 Cholinesterase inhibitors (donepezil, galantamine, rivastigmine) + NMDA antagonist (memantine))

Goals of treatment depend on stage of illness

Early stage: MMSE 26 - 21

Improve cognition

Slow progression and maintain quality of life

Mid-stage: MMSE 20 - 11

Preserving function (ADLs)

Maintaining safety

Delaying institutionalization

Late-stage: MMSE <10

Management of behaviours

Cholinesterase Inhibitors

Consistent modest effects on:Cognition Caregiver global impression

Delay in progression equivalent to 3-6 months

May delay emergence of apathy

Untreated Alzheimer’s: 2-4 MMSE points per year

Clinical StrategiesHigher doses work betterMore noticeable benefit with more severe diseaseBut -- adherence is a problem

Some suggest lower dose at early stage, then increase to higher dose when disease progresses to moderateOthers suggest maximizing dose from the beginning (less tolerable)

Memantine (Namenda)NMDA receptor antagonistIndicated for Alzheimer's dementia, moderate to severeTariot, 2004: Memantine + Donepezil Less deterioration of cognition, behavior, functionMay delay emergence of psychosisSide effects: confusion, headacheDosing: 5mg/day; increase q1week to 20 mg/day

Nonpharmacological InterventionsIndividualized to patient, caregiver, availability of treatment, severity

Cognitive interventions: re-orienting, reminders, cues, prompts

Environmental modifications/removal of trigger: adjust noise level, provision of familiar objects, reduction of clutter or visual distracters', use of pictures to provide cues

Limit risks: physical (stove, wandering), financial affairs, driving

Changes in activity demand: implement routines and schedules, reduce amount and complexity of activities

Interpersonal approaches: simplify language, avoid overt frustration and anger, use of or avoidance of touch, focus on patient’s wishes, interests and concerns

Educate and support caregivers/families

The role of caregiverHelping with Activities of Daily Living (ADL), the most common being:

- Getting dressed, bathing- Getting in and out of beds and chairs

Performing Instrumental Activities of Daily Living (IADL), including:- Helping with household duties, finances, transportation- Arranging for outside services

Managing BPSD in the home

Playing a significant role in the management of pharmacological treatment of the patient

Alzheimer’s Association and the National Alliance for Caregiving.Brodaty, Green. Drugs Aging 2002;19:891-8.