Disordered minds and
brains?
Dr Lesley Young
Sunderland Royal Hospital
A condition affecting….
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20% all hospital in-patients (40% >80yr
olds O`Regan et al 2010)
60-80% ICCU patients (50% will develop longterm cognitive deficits) Ely EDA 2008
And has……..
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20-30% in-patient mortality
(10-14% for acute GI bleed, 4-5% for ACS)
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30% institutionalized
Increased complication rate
Increased length of stay
3x increased risk developing dementia
Delirium
What I am going to tell you
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Definitions
Why does delirium happen?
– What we can learn from mice
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Recognising it
Risks and precipitants
Prevention is better than cure
Drug treatment
Prognosis and outcomes
Delirium – DSM IV
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Disturbance of consciousness
 reduced ability to focus, sustain or shift attention
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A change in cognition or the development of a
perceptual disturbance that is not due to a preexisting dementia
Develops over a short period of time and tends to
fluctuate
Evidence that disturbance is caused by the
direct physiological consequences of a general
medical condition, substance intoxication or
withdrawal.
The get out clause……
Why do old people get
delirium with a UTI?
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Aberrant stress response?
Inflammatory theory?
– Systemic infection
– Injury
– surgery

Cholinergic theory? (↓ Ach →delirium)
– Severe illness / trauma →↓ Ach
– Hypoxia/hypoglycaemia →↓ Ach
– ↑SAA →delirium
Predisposing factors
Precipitating factors
High vulnerability
Noxious insult
Low vulnerability
Mild insult
After Inouye
What we can learn from
mice (Cunningham)

Mice with neurodegenerative
dementia-type disease (ME7)
–
–
–
–
Affective (11-13 weeks)
Coginitve (12-16 weeks)
Motor (16-19 weeks)
Death (24 weeks)
Effect of inflammatory insult
on cognitive function
controls
normal+LCP
prion+LCP
Long term follow up:
accelerated decline in LCP
group
controls
prion+saline
prion+LCP
ME7 mouse studies have shown
a cognitive deficit that:
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Is induced by systemic infection
Is acute onset and transient
Occurs in “demented” but not normal
mice
Affects working memory > reference
memory
Is dependent on prior microglial cell
activation
(After Cunningham EDA 2008-10)
Aging
Dementia
Prion disease
Primed microglial
cells

Location of
activated
microglial
cells
determines
dysfunction
Infection
Injury
Surgery
Other insult
Activation of
microglial
cells
DELIRIUM
Neuronal death
Disease
progression
In clinical practice.....
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Identify those at risk
Prevent incident delirium
Recognise prevalent delirium
Identify and treat precipitants
Manage behaviour well for better
outcomes
But…..
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Delirium is under-recognised:
– In published studies only 20-50% of
cases recorded as delirium in records
(Collins Age and ageing 2010 28% prevalent delirium detected)
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Failure to recognize associated with
poor management (Young Age&Ageing 2003)
Use of cognitive screening tests can
improve recognition (Jitapunkul 1991, Anthony
Psychol Med 1982, O`Keeffe JAGS 2005, Young Age &Ageing 2003)
 72.6% cases identified when cognitive screening attempted v
42.9% when not p<0.0001 (Young 2003)
Barriers to recognition
(Davies et al to
EDA 2007)
*p<0.001
Geriatrics
experience
(n=399)
No geriatrics
experience
(n=351)
28%
14%
Acute onset
89%
88%
Inattention
32%
31%
Visual hallucinations
35%
38%
Agitation
52%
49%
Aware of poor prognosis
57%
52%
Aware under-recognised
80%
80%
Adequate training *
24%
9%
Confident of diagnostic
criteria*
Aids to recognition
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Cognitive screening
tests:
–
–
–
–
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– CAM
– CAM-ICU
– Delirium Observation
Scale
– Neecham
– DSI
AMTS
MMSE
6-CIT
Sweet 16
Measures of attention
– Serial 7`s
– Months backwards
– Digit span
(forwards/backwards)
– Trail making
– Letter cancellation tests
Delirium screening
tools
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Delirium +/- dementia?
–
–
–
–
Cognitive history
IQCODE
AD8
Visual perceptual deficits
Risk factors
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Age > 75
Dementia (2/3 cases)
Severe illness
Physical frailty
Dehydration
Infection
Visual impairment
Drugs (opiates, anticholinergics)
Surgery
Alcohol excess
Renal impairment
Precipitants
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Infection
Drugs
– opiods OR 2.5, benzodiazepines OR 3, dihydropyridines OR2.4,
antihistimines OR 1.8, Clegg and Young Age and Aging 2010
– Anticholinergic drugs (Tune REF, Pitkala 2007)
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Dehydration or electrolyte disturbance
Immobility
Malnutrition
Intercurrent illness e.g.
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Metabolic/endocrine disturbances
Organ failure (liver, renal, cardiac etc)
Neurological problems (e.g. CVA, epilepsy)
Precipitants of delirium –
prospective study General Medical in-patients
>70yrs n=87 J Laurila EDA 2009
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Infections
Drugs
Metabolic disturbance
Circulatory conditions
Neurological
Other post-op
(84%)
(46%)
(47%)
(26%)
(24%)
(18%)
Delirium is multi-factorial
Prevention

Up to 40% cases may be preventable
– Early attention to or avoidance of
precipitants in those at risk
– Adopting “HELP” approach in those at
risk (Inouye NEJM 1999; 340:669-676)
Hospital Elder Life
Program (Inouye NEJM 1999)
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Complications of hospitalisation:
– Delirium
– Functional decline
– Adverse drug events
25-60%
34-50%
54%
–
–
–
–
17%
15%
10%
3%
*HAI
*Falls
*Pressure sores
*VTE
Targeted, multi-component intervention
program
Help interventions
Cognitive impairment
Reality orientation
Therapeutic activities
Vision/hearing impairment
Vision/hearing aids
Adaptive equipment
Immobilisation
Early mobilisation
Minimising immobilising
equipment
Psychoactive medication use Non-pharmacological approaches
to sleep/anxiety
Restricted use of sleeping tablets
Dehydration
Early recognition
Volume repletion
Sleep deprivation
Noise reduction strategies
Sleep enhancement program
How HELP is delivered “High touch/low tech”
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Inclusion criteria:
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– Aged 70+
– At least one of:
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Screen (by Elder
life specialist/nurse)
– MMSE
– ADL
– Test vision and
hearing
– Usual activities
MMSE<24
Mobility or ADL
impairment
Dehydration
Vision impairment
Hearing impairment
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Program delivered
by volunteers
– (16 hours training, 1x4hr
shift/week for 6/12+)
Intervention
Control p
Cognitive
decline
8%
26%
<0.05 Inouye JAGS 2000
Physical
decline
14%
45%
33%
56%
<0.05 Inouye JAGS 2000
0.03 Vidan JAGS 2009
Reduced
incident
delirium
OR=0.60
RR↓ 35%
6%
OR= 0.4
Costs
↓$831
↓$1.25 million/yr
↓$121,425
Rizzo Med care 2001
Rubin JAGS 2006
Caplan Int Med J 2007
LOS
↓0.3 d/pt
Rubin JAGS 2006
Falls /1000 3.8
pt days
1.2
38%
11.4
4.7
0.02
0.002
0.03
0.005
Reference
Inouye NEJM 1999
Rubin JAGS 2006
Caplan Int Med J 2007
Vidan JAGS 2009
Inouye NEJM 2009
However….
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Prevention is better than cure
– HELP (targeted multi-component
intervention) can prevent up to 40%
incident delirium
– Little evidence for improved outcomes in
prevalent delirium (Laurila, Helsinki study J Geront
2006) at 6/12:
MMSE Sl better in intervention group
 QoL Sl better in intervention group
 Costs of care – no different
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How should we treat
prevalent delirium?
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Identify and treat underlying cause
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Drugs?
– Neuroleptics??
– Benzodiazepines??
– Cholinesterase inhibitors??
Investigating the cause
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Infections:
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– Cultures
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–
–
–
–
MSU, sputum,
swabs etc
FBC
CRP
CXR
LP (only if clinical picture
points to CNS cause)
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Drug review
– Stop what you can
Metabolic upsets
– U&E, LFT, Ca, TFT,
Glucose
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Circulatory
– ECG
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Neurological
– CT (often abnormal,
rarely diagnostic –
consider if likely acute
CNS cause)
– EEG (? Non-convulsive
status, HSE, dementia v
delirium)
Drugs
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Cochrane database 2009
Benzos – not recommended
 Cholinesterase inhibitors – no evidence
 Antipsychotics – effective over placebo
 Haloperidol effective over lorazepam
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Treatment trials are rare and difficult
RCTs antipsychotics
RCTs antipsychotics
Risperidone = olanzepine
Risperidone = haloperidol
Quetiapine > placebo
Dexmetomedine > haloperidol (ICU)
Olanzepine = haloperidol (ICCU)
Olanzepine > haloperidol (chinese dementia)
Amisulpiride = quetipine
Haloperidol/chlorpromazine > lorazepam
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RCP/BGS guidelines - haloperidol
EDA 2009 consensus - haloperidol
NICE 2010– haloperidol or olanzepine
Low dose, minimum duration, to alleviate distress
Cholinesterase inhibitors
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Theoretical basis why Cholinestersae
inhibitors might be helpful......BUT
Several small studies – results inconclusive
Rivastigmine does not decrease duration of
delirium and may increase mortality (Eijk 2010)
– Multicentre, double-blind placebo-controlled RCT
in ICU patients with delirium
– Trial stopped after 104 patients included
because increased mortality and trend to
increased duration of delirium in treatment group
Prognosis
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Traditional view:
– Short, transient, full recovery
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Delirium research shows:
– Poor outcomes even with full recovery
– Independent predictor of poor outcome
Recovery from delirium (cole
EDA 2008)
55% improved at 1 month
 70% improved at 6 months (i.e. 30%
not)
A substantial minority of patients don`t
recover (~10%)
Full recovery associated with good
outcomes (= no delirium)
Incomplete recovery may impair self
management
worse outcomes
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20-30% in-patient mortality
30% institutionalized
Increased complication rate
Increased length of stay
3x increased risk developing dementia
Adjusted Total 1-Year Health Care Costsa
Leslie, D. L. et al. Arch Intern Med 2008;168:27-32.
Copyright restrictions may apply.
Relation between delirium
and dementia
1.Delirium
Dementia (causal)
Delirium (marker)
2. Subclinical dementia
Dementia
3. Insult
Delirium
Dementia
Probably 1+2
Conclusion
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Delirium is common
Under-recognised and low priority
Associated with poor outcomes
Prevention is possible and cost
effective in those at risk
Prevention is better than cure
Infection control
Confusion control
Thank you