Delirium in older adults is

associated with
development of new
dementia: a systematic
review and meta‐analysis
Jarett Vanz‐Brian Pereira, May Zin Aung
Thein, Anita Nitchingham, Gideon A. Caplan
Abstract
01 Introducti
on
 Increased
Delirium definition :
Delirium risk of
dementia
“Acute fluctuating syndrome with
features of inattention, altered
consciousness and cognitive
disturbance”
Affecting up to Prevalence : 5% of the world's
50% of post­ elderly population
operative
older persons Global annual cost of dementia
and 80% of is estimated to be US $818
older intensive billion
care unit (ICU)
patients

By elucidating and understanding the relationship between delirium and dementia, we

may be able to mobilise resources towards prevention strategies for both conditions in
our patients
Objecti Our study aims to obtain a pooled effect
size for the odds of dementia after delirium

ve through meta‐analysis
02 METH
ODS
 MEDLINE, EMBASE and
PsycINFO were searched using a
combina­tion of MeSH terms and
Data
keywords
sources
and
Keywords : ‘delirium’, ‘acute
confusion’, ‘prognos* or course* or
sequalae or outcome*’, ‘mortality’,
‘nursing homes’, ‘institution*’,

Search
‘dementia’ and ‘cognition disorders’.

Criteria : English language, article

published between 1981 and 2018 strategy
 Inclusion Criteria Exclusion Criteria

Studies on patients with hepatic

Age ≥65 years
encephalopathy and delirium tremens

Article Hospital inpatient setting including

rehabilitation hospitals
Patients in palliative care, hospice, termina
cancer setting, or specifically mentioned to
have brain metastasis.

Selection Delirium diagnosed using a validated

delirium diagnostic instrument and

Assessment of mortality, nursing home

placements and new dementia in delirium
group versus no‐delirium group.
 Definition of
New dementia that
outcome
New-onset
has been clinically dementia
diagnosed by a
physician after an
episode of delirium,
in patients where Dementia Must be assessed
premorbid dementia outcome after patients have
was excluded.
been discharged
purchase from hospital to
prevent
misdiagnosis of
delirium as
dementia.
 Study
Participant’s
Characteristi
baseline
cs
Study design, As age, sex,
provenance, control for pre-
Data- follow‐up
duration and
existing
dementia;
extracti exclusion criteria

on Outcome
Data
Total number of patients, number who
developed dementia, method of delirium and
dementia diagnosis, delirium subtype, delirium
severity and delirium duration
 Risk of bias and quality
assessment

A score of 0–3 stars was

The Newcastle‐
deemed to be ‘low quality’ and
Ottawa Quality Each article was at high risk of bias, four to six
Assessment Scale scored on a scale stars ‘moderate quality’ and
(NOS) was used for from 0 to 8. moderate risk of bias, and
risk of bias seven to eight stars indicated
assessment
‘high quality’ and low risk of
bias.t
 Statistical analysis

Assessment
Primary sensitivity
of
analysis analysis
publication
bias
Comprehensive Fixed‐effects model aimed to Observational studies, which
Meta‐Analysis test the robustness of findings are used in this study, are more
(CMA) V3 software from the random effects model susceptible to publication bias
was used for and determine if a similar which can jeopardise the
statistical analysis. result was produced. validity of meta‐analyses.
03 Results
The article screening process is highlighted in the
PRISMA flow diagram provided. A total of 446 articles
were obtained

Identification
of Studies
Description of included studies
 Patient Demographics

All six studies were conducted on older adults over 65, and the method of
reporting participants' age varied between the studies.

Most of our included studies were conducted on surgical cohorts

The study by Olofsson et al. (2018) showed that participants who

developed delirium were older than participants who did not

One study did not compare the ages of participants between groups, and
only broadly stated that participants over 65 were recruited.
Diagnosis of delirium and
dementia
Delirium was diagnosed using the Confusion Assessment Method in one study, the Diagnostic and Statistical Manual
of Mental Disorders DSM IV criteria in four studies and the modified Organic Brain Syndrome Scale in one study.

In Krogseth et al. (2011), Lingehall et al. (2017) and Rockwood et al (1999), dementia was diagnosed based on a
combination of clinical history and validated cognitive tests including the Mini ‐Mental State Examination (MMSE).

Dementia was diagnosed through extensive chart review in Luger et al (2014)

Olofsson et al (2018) diagnosed dementia clinically based on DSM ‐IV criteria.

Exclusion of additional confounding
factors
In all six studies, researchers screened participants for the presence of
pre‐existing dementia on enrolment, and excluded those with baseline
dementia

Only two out of six studies explicitly reported the exclusion of patients with head trauma, neurological
conditions (e.g., aphasia) and documented psychiatric illness. Of the remaining four studies, two assessed
participants for depressive illness perioperatively and two did not report any depression assessments
The association between delirium and dementia
—results from individual studies.
Krogseth et al. (2011) Olofsson et al. (2011)
• This study found significantly more patients in the • Postoperative delirium (POD) independently
delirium group developed dementia, compared to predicted the develop­ment of new dementia
the no‐delirium group. Delirium was also a strong within 3 years.
predictor of dementia after 6 months

Lundstrom et al. (2003) Lingehall et al. (2017)

• The study found that delirious patients in the • A multivariable logistic regression showed
study were more likely to develop dementia that postoperative delirium was significantly
associated with development of dementia (

Luger et al. (2014) Rockwood et al. (1999)

• Patients in the delirium group 10/18 (55.6%) • Participants with delirium were at increased
were more likely to develop dementia compared risk of developing dementia compared to non‐
to patients in the no ‐delirium delirious participants
Qualitative analysis of pooled
studies
Primary analysis of the association of delirium on new dementia included all six studies, with a
combined sample size of 901

Delirium was significantly associated with development of new dementia when analysed with a
random‐effects model (six studies, OR = 11.9, 95% CI: [7.29–19.6], p < 0.001), with no significant
statistical heteroge¬neity between the studies according to I2 estimates (I2 = 11.4, p = 0.343).
Sensitivity analysis
Repeating the meta‐analysis using a fixed‐effects model produced the exact
same effect size as the random effects model (OR = 11.9 [95% CI: 7.51,
19.0]), reflecting the stability of our effect size estimates.

Using a random effects model, we found that delirium continued to be

significantly associated with development of new dementia (Five studies,
OR = 9.67. 95% CI: [5.80–16.2], p < 0.001), with no significant heterogeneity
between studies (I2 = 0, p = 0.728).
Risk of bias assessment
All included studies were determined to be of low to moderate risk of bias, with NOS scores ranging from 6 to 8 and a
mean score of 7.3. All six included studies scored maximum points for the ‘selection’ parameter.
04 Discussi
on
We found that delirium increases the odds of developing dementia by approximately twelve‐fold (OR = 11.9 [95% CI
7.3–19.6], p < 0.001), strongly emphasising that delirium is a significant risk factor for incident dementia.

Our findings confirm the results from previous studies that have suggested a similar
relationship between delirium and dementia

Our findings also underscore the need for greater public health awareness about the long ‐term
cognitive outcomes of delirium.
The pathophysiological mechanism linking delirium and de­mentia remains
incompletely understood
Direct Relationship

Permanent
Neuroinflammation
neuronal damage

Delirium

Acute Progression of the

exacerbation underlying chronic disease

Indirect Relationship

Delirium drugs ;
Cognitive
Delirium antipsychotics/sedative/
impairment
physical restraints
Delirium is a common complication among post hip fracture surgery
patients, with incidence rates estimated to be from 13% to 70%

However, it is unclear whether the findings can be generalised to other

populations such as medical ward and ICU patients with delirium

Most of the studies included were also conducted in Scandinavian

populations, and the findings may have limited generalisability to healthcare
systems outside Scandinavia or Europe, due to potential differences in long‐
term post‐delirium management of patients

the low I2 values in analysis suggests low statistical heterogeneity

between the studies,
The average time it takes to develop dementia after an episode of delirium
has not been established

The time to dementia after delirium may be influenced by factors such as :

- Delirium durat ion
- Severit y
- Subt ype

However, the duration, subtype and severity of delirium were not measured
by the studies

Additional research into this area is warranted as it may have important

implications on the way we diagnose and treat delirium.
In assessing the relationship between delirium and dementia, it is
important to ensure that potential confounders are controlled for.
Age is a significant risk factor for dementia; however, our small sample size precluded stratification of
studies by age and a sepa­rate sensitivity analysis on the effect of age on the risk of devel­oping dementia
after delirium

It is plausible that older patients have a greater risk of subsequently developing dementia after an episode
of delirium compared to younger patients.

Other potential factors that may influence the relationship between delirium
and dementia were less well‐reported, these included :
- durat ion of delirium
- severit y of delir ium
- document ed psychiat ric illness
05 Conclus
ion
Older adult inpatients with delirium are twelve times as likely
to go on to develop dementia compared to patients without
delirium

Delirium must be viewed as a serious cognitive disorder

necessitating effective prevention strategies in hospitalised
patients.

Future studies on medical and ICU patients are needed to

confirm the association between delirium and dementia in
these populations,
 Thankyou for
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