Delirium and
Dementia
Dr. Lisa McMurray
Back to Basics
9 April 2014
Delirium and Major
Neurocognitive
Disorder
DSM-5
Acknowledgements
Several slides are taken from a 2012
lecture on dementia and delirum by Dr.
Cathy Shea
Objectives -- Delirium
Describe delirium
Describe an approach to the patient suffering from delirium
Initiate treatment of delirium, including both medication and psychosocial
approaches
Differentiate between delirium and dementia
Objectives – Dementia
(Major NC Disorder)
Describe dementia
Know the essential features of the most common dementias:
Alzheimer type
Vascular
Lewy Body
Fronto-temporal
Brain trauma
Know “potentially reversible” causes of dementia that must be ruled out and
treated (in practice, rarely reversible)
Toxins
NPH
IC masses
Infections
Endocrine (hypothyroidism, B12 deficiency)
Identify depression in an elderly person when it mimics dementia
Describe the severity of the dementia
Initiate management of dementia, including both treatment of reversible
conditions, medication, psychosocial approaches, and referral
Lau, T. Canadian Journal of Diagnosis Nov/Dec 2009
DELIRIUM
What is Delirium?
**An acute change in attention and
awareness + 1 other cognitive
domain
**due to a medical condition.
**acute onset and fluctuating course
Potentially reversible
Often unrecognized
Poor prognosis
Delirium
Key Features
Change from usual mental state!!!
Fluctuates (may appear normal at times)
Altered level of attention/awareness (somnolent
or hypervigilant)
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 Epidemiology
Prevalence
1-2% in community
15-24% in general hospital
Incidence
Hospital admission: 6-56%
Post-operative elderly: 15-53%
Elderly ICU: 70-87%
THIS IS A COMMON PROBLEM!
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
Caplan et al, 2008
Delirium is serious
Patients 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
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
CT scan brain
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, earplugs
Minimize sleep medications
Delirium – pharmacological Mgmt
Haloperidol 0.5 mg po/im q1h (im) prn agitation
Risperidone, Olanzapine, Quetiapine, and Aripiprazole
have also demonstrated efficacy
Treat hyperactive delirium only
Benzodiazepines indicated for alcohol/benzo
withdrawal
What is dementia?
Decline in cognition (history and
objective performance)
Severe enough to affect day-to-day
independence
Not due to delirum or other.
What is dementia?
It develops in the presence of a clear
level of attention
It should be differentiated from delirium,
an acute change in cognition due to a
general medical condition, with a
fluctuating level of consciousness
Alzheimer's Australia, 18 May
2012
Dementia is Common
Age related risk:
> 65: Overall Prevalence is
% Prevalence
8%
35
30
Prevalence doubles every
~5 years
34.5
25
20
15
10
Females>males
2.4
11.1
5
0
65-74
75-84
85+
Lindsay et al. Can J Psychiatry 2004;49:83-91. CSHA CMAJ
1994; 150: 899-913; CSHA. Neurology 2000; 55: 66-73
Evaluation of Possible Dementia
Universal screening not yet recommended
Evaluate 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
Evaluation of Dementia
Careful history with informant
Onset and progression
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
Rule out Less Common,
Potentially Treatable Causes
“Pseudodementia” of depression
Other 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
Cancer
e.g. primary, metastatic, paraneoplastic
These may be potentially reversible or
stopped if recognized and treated early
Depression and Dementia overlap
Depression 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
Insidious
Slow progression
Labile mood
Can enjoy things
Cognitive changes
first
Cooperative
Aphasia, wordfinding difficulties
No history of mood
disorder
Depressive
Pseudodementia
Subacute
Rapid progression
Consistently
depressed
Cannot enjoy things
Mood Changes first
Uncooperative or
does not try
No aphasia
History of mood
Disorder
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
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
Neuroimaging in workup
CT 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’s
Alzheimer Dementia
A progressive degenerative disease
Primarily medial-temporal and temporalparietal 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
http://www.nia.nih.
gov/alzheimers/alz
heimers-diseasevideo
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.
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
Genetic risk factors
Family history (1° relative with AD 3.5 x risk)
Female Gender
Down’s Syndrome
Low Education
Pre-existing lower mental ability
Normal
High Education
Apolipoprotein
E e2 or e3
Head Trauma
Depression in men: 4x risk
Smoking: 2x risk
↓ TSH: 4 x risk
Exposure to toxins (pesticides, fertilizers…): 4 x risk
Vascular:
•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
MCI
Diet: Fish, vegetables
Moderate Alcohol
All lipid lowering drugs
Statins
NSAIDs?
DementiaAge
Physical activity
Mental activities
Rich Social Networks
Alzheimer Risk and Protective Factors
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
Alzheimer’s: Retrogenesis – 7 stage decline
Age
Acquired/Lost
abilities
Hold a job
Handle simple
finances
Stage
Years
MMSE
3 incipient
4 mild
0
7
29
19
5-7
Select proper
clothing
5 moderate
9
14
5
4
4
3-4½
2-3
15 mo
1
1
6-10 mo
2-4 mo
1-3 mo
0
Put on clothes unaided
6a mod.severe
6b
6c
6d
6e
7a severe
7b
7c
7d
7e
7f
10½
5
13
0
12+
8-12
Shower unaided
Toilet unaided
Controls urine
Controls bowels
Speaks 5-6 words
Speaks 1 word
Walks
Sit up
Smile
Hold up head
Birth/Death
19
Management
Needs
None
Independent
survival still
possible
Requires parttime assistance
Requires fulltime assistance
Requires
continuous care
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 Dementia
Atrophy 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
Age of onset
Social behaviours
Memory problems
Aphasia
Visuospatial skills
FTD
Usually < 70
Inappropriate,
unconcerned
Late
PPA and SD*
Preserved
AD
Usually > 65
Appropriate,
concerned
Early
Late
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
Vascular Dementia: Epidemiology
65-74
0.6%
The prevalence of
VaD doubles every
2.4%
5 years
75-84
4.8%
85+
0%
2%
Canadian Study of Health and Aging. CMAJ, 1994
4%
6%
VaD risk factors
Demographic
Stroke factors
Previous / recurrent CVA
cerebrovascular accident
Age
Sex
Ethnicity
Vascular risk factors
•
•
•
•
•
•
•
Hypertension
Atherosclerosis
Diabetes mellitus
Low blood pressure
Coagulopathies
Peripheral vascular disease
CHF
Pratt RD. J Neurol Sci, 2002.
Skoog I. Neuroepidemiology, 1998.
•
•
•
•
•
•
•
Cigarette smoking
Hypercholesterolemia
Ischemic heart disease
Atrial fibrillation
Elevated homocysteine
Myocardial infarction (MI)/angina
CABG
Classification and etiology
Large-vessel dementia
Small-vessel dementia
Ischemic-Hypoperfusive: post
cardiac arrest
Hemorrhagic
Román et al. Lancet Neurology 2002; 1: 426–36
Embolism, thrombosis
Aging, hypertension,diabetes
Large vessel
occlusion
Small
vessel
Occlusion
Single critical
infarct
Strategic Single
Infarct Dementia
Multiple large
cortical or
subcortical
infarcts
Small infarcts
(Lacunes)
Deep white matter
lesions
Lacunar state
Binswanger’s
Multi-infarct
Dementia
Damage to critical cortical and
subcortical structures
Hypoperfusion
Sub-cortical Ischemic
Vascular Dementia (SIVD)
Final Common
Pathway
 Cholinergic
transmission
VaD
O’Brien et al. Lancet Neurology 2003; 2: 89-98
Román et al. Lancet Neurology 2002; 1: 426–36
Damage/interruption of
subcortical circuits and
projections
Dementia with Lewy-Bodies
Prevalence
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. AD
Worse:
– Attention than AD (very difficult to do 3 word repetition)
– Visuospatial abilities
Early memory OK
Relatively good verbal skills, though naming is often
impaired
Dementia with Lewy-Bodies
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 disorder
Severe 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
Behavioral & Psychological Symptoms
of Dementia (BPSD)
BPSD is an umbrella term for a heterogenous
group of non-cognitive symptoms almost
ubiquitous in dementia
Never assume a diagnosis of dementia has
been made/or is understood by the carergivers
BPSD appears at all stages & can precede the
diagnosis of dementia by 2 years or more
BPSD is less predictable than the course of
cognitive or functional decline in dementia
BPSD Symptom Clusters
Aggression
Apathy
Physical aggression
Verbal Aggression
Aggressive resistance
to care
Pacing
Repetitive actions
Dressing/undressing
Restless/anxious
Agitation
Withdrawn
Lacks interest
Amotivation
Hallucinations
Euphoria
Sad
Delusions
Pressured speech
Tearful
Misidentification
Irritable
Hopeless
Suspicious
Guilty
Mania
Psychosis
Anxious
Irritable/screaming
Suicidal
Depression
Adapted from McShane R. Int
Psychogeriatr 2000;12(suppl 1): 147
Managing Dementia
Diagnosis
Screening (MMSE, MoCA)
Differential Diagnosis
Management of
Cognitive problems
Behavioural problems
Management
Management of risk factors and primary
prevention strategies
Cognitive impairment
Behavioural and Psychological
Symptoms
Involvement of families (Care-giver
support)
Management of Risk Factors
Do: 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 NSAIDs
Patterson 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:
CCCDTD3 2006
Increased consumption of fish
Reduced consumption of dietary fat
Moderate consumption of wine
Cognitive Enhancers
Focus 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 Strategies
Higher doses work better
More noticeable benefit with more severe
disease
But -- adherence is a problem
Some suggest lower dose at early stage, then
increase to higher dose when disease progresses
to moderate
Others suggest maximizing dose from the
beginning (less tolerable)
Memantine (Namenda)
NMDA receptor antagonist
Indicated for Alzheimer's dementia, moderate to
severe
Tariot, 2004: Memantine + Donepezil
Less deterioration of cognition, behavior, function
May delay emergence of psychosis
Side effects: confusion, headache
Dosing: 5mg/day; increase q1week to 20 mg/day
Nonpharmacological Interventions
Individualized 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 caregiver
Helping 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.