British Journal of Anaesthesia, 119 (S1): i115–i125 (2017)

doi: 10.1093/bja/aex354
Neuroscience and Neuroanaesthesia

NEUROSCIENCE AND NEUROANAESTHESIA

Postoperative cognitive dysfunction and dementia:

what we need to know and do
M. J. Needham, C. E. Webb and D. C. Bryden*
Critical Care Department, Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital,
Sheffield, UK
*Corresponding author. E-mail: daniele.bryden@sth.nhs.uk

Abstract
Approximately 12% of apparently previously cognitively well patients undergoing anaesthesia and noncardiac surgery will
develop symptoms of cognitive dysfunction after their procedure. Recent articles in this Journal have highlighted the
difficulties of confirming any clear links between anaesthesia and cognitive dysfunction, in part because of the lack of con-
sistency regarding definition and diagnosis. Postoperative cognitive dysfunction (POCD) is usually self-limiting and rarely
persists in the longer term, although plausible biological mechanisms for an impact on brain protein deposition do exist.
Clinical research studies are frequently confounded by a lack of agreed definitions and consistency of testing. Preoperative
assessment of neurocognitive function and risk factor identification is imperative in order to ascertain the true extent of
POCD and any causative link to anaesthesia and surgery. At present a multidisciplinary care bundle approach to risk factor
stratification and reduction is the most attractive management plan based on evidence of slight benefit from individual
interventions. As yet no individual anaesthetic technique, drug or mode of monitoring has been proved to reduce the inci-
dence of POCD. Providing patients with appropriate and accurate information can be difficult because of conflicting evi-
dence. The Royal College of Anaesthetists’ patient liaison group has produced a useful patient information leaflet that is
designed to provide guidance in discussions of individual risks whilst considerable uncertainties remain.

Key words: cognition; dementia; perioperative period

A proportion of apparently previously cognitively well patients provision for patients considered to be at risk of postoperative
undergoing surgery and anaesthesia will develop symptoms of cognitive dysfunction (POCD).
cognitive dysfunction after their procedure. There is a sugges- Several forms of cognitive dysfunction can occur in the peri-
tion that this is most marked in those over 65 yr of age, of which operative period all of which are characterised by problems in
there are currently 10 million people in the UK and with a pro- thinking and perception. The earliest of these, delirium, occurs
jected total of 19 million by 2050, representing significant num- 24 to 96 h after a procedure and is manifest as an acute confu-
bers of people at potential risk.1 Clearly any link of cognitive sional state with disturbance in attention and reduced aware-
dysfunction with anaesthesia and surgery is of concern and ness of the environment. The National Institute for Health and
anaesthetists should be aware of the current evidence base and Care Excellence (NICE) guidance on delirium, CG103, suggests
make attempts both to counsel patients appropriately and pharmacological therapy if the patient is distressed by their
adopt techniques that minimize any further insults to high-risk symptoms or is a risk to others.2 However there is considerable
patients. This review provides an overview of current clinical benefit in pro-active management of surgical patients at risk of
and research evidence regarding considerations for anaesthesia delirium, for example reviewing the need for drugs with

C The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
V
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i115
 i116 | Needham et al.

antimuscarinic actions that are known to be triggers for delir- declining cognitive trajectory.17 18 Mild Cognitive Impairment
ium such as ranitidine and digoxin, whilst being observant for converts to dementia at a rate of 10% per yr and has been linked
the effects of nicotine and alcohol withdrawal. Delirium with both delirium and POCD.19 Detection of MCI can be difficult
increases length of stay in hospital and associated costs such as if patients are able to use compensatory mechanisms when in
use of critical care facilities, and has also been associated with familiar circumstances such as home and family environments.
increased mortality.3–8 Patients over the age of 65 yr with a hip These mechanisms have the potential to fail once the patient is
fracture or severe illness and already possessing a degree of cog- placed in an unfamiliar hospital environment particularly
nitive impairment are particularly at risk, although multiple alongside other risk factors for delirium and POCD.
tools for assessing delirium risk are in use and their agreement The National Institute of Aging-Alzheimer’s Association
as tools for risk stratification is poor.3 Although delirium has 2011 definition of MCI is summarized in Table 1.20
not however been definitively linked to long-term cognitive Unlike delirium and dementia, no formal definition of post-
impairment or dementia,4 recent studies do implicate such a operative cognitive dysfunction (POCD) has been codified.
link.5–7 Neither the DSM nor International Classification of Diseases
A persistent degree of cognitive impairment has been noted (ICD) recognises it as a distinct entity. While an international
in up to 10% of elderly patients up to three months after a surgi- panel works towards a consensus definition and to refine its
cal procedure. When this persists beyond six–12 months it may relation to other neurocognitive disorders, it remains a research
be indicative of a more persistent state that some authors con- construct.13 At best it is possible to consider POCD as a mild
sider to be a form of long-term cognitive impairment.8 For many neurocognitive disorder of unspecified aetiology within the con-
people, any persistent degree of cognitive impairment would be fines of DSM V. Further uncertainty exists as to the relationship
of concern in itself, but there have been additional suggestions between POCD and both dementia and delirium. Some studies
that the risks of developing dementia may be higher in older suggest delirium as a risk factor for both, but it is not clear
patients, particularly those who receive general anaesthesia.9–11 whether POCD is part of a continuum that culminates in
Despite these concerns, recent articles in this journal have high- dementia or a distinct entity in its own right. Furthermore evi-
lighted the difficulties of confirming any clear linkages in part dence suggests that POCD can occur in patients who did not first
because of the lack of consistency regarding definition and diag- have delirium.21 Resolving these relationships will allow better
nosis.12–14 planning of postoperative testing and produce greater diagnos-
tic certainty in future studies.

Definitions
Diagnosis and cognitive testing
Delirium is a recognisable acute confusional state representing
symptoms that may or may not be linked to organic illness.15 POCD is generally described as a form of cognitive dysfunction
The Diagnostic and Statistical Manual of Mental Disorders that begins between seven days and one year after surgery, but
(DSM) V recognises delirium and dementia as clearly defined limited understanding of the condition to date precludes further
disease entities.16 In the most recent DSM V guidance, it is categorisation. Given this, diagnosis has relied on administering
included within the category of major neurocognitive disorder batteries of neuropsychological tests to patients to observe any
and subclassified on its aetiology, for example Alzheimer’s decline in function. While diagnosis using either biomarkers22
disease. or radiological investigations23 remains under development, so
The four diagnostic criteria for a major neurocognitive disor- far the cost and mixed results of small studies has prevented
der are: widespread adoption and resulted in a situation of relatively
fluid descriptive terms. There is no consensus regimen for neu-
1. Evidence of significant cognitive decline from a previous
ropsychological testing, and this is reflected in the literature.
level of performance in one or more cognitive domains
Systematic reviews of studies involving cardiac surgery24 and
2. Interference with independence in daily activities
non-cardiac surgery patients25 both show marked differences in
3. Not exclusively in the context of delirium
the type and number of neuropsychological tests used and the
4. No other diagnosis better explains the symptoms
timing and interpretation of statistical significance of the
The diagnosis of a neurocognitive disorder requires both a results.
history of cognitive decline and a documented substantial Despite the variation in testing regimens there is growing con-
impairment in standardized neurocognitive testing. sensus as regards the best form of statistical analysis with the
Mild Cognitive Impairment (MCI) and specifically the amnes- z-score emerging as the tool of choice.24 The z-score or standard
tic subtype, is a common neuropsychiatric term encompassing score is a measure of the number of standard deviations that an
a period between normal cognitive function and dementia observation is from the mean. It is calculated by subtracting the
(DSM-V: “mild neurocognitive disorder”) thus forming part of a mean (m) from the observation (x) and dividing by the standard

Table 1 Definition of mild cognitive impairment (MCI)20

Characteristic Source

A) Concern regarding a change in cognition Patient or Informant

B) Impairment in one or more cognitive domains Neurocognitive Testing - e.g. Episodic Memory
C) Preservation of Functional Independence Patient, Informant, Home assessment
D) Absence of Dementia As per DSM-V definition
 Postoperative cognitive dysfunction and dementia | i117

deviation (r): z¼x - m/r. In assessing POCD it is the difference in Debate continues over the optimal timing of perioperative
preoperative and postoperative test scores that is of interest cognitive testing.12 Test scores can be affected by anxiety, pain
rather than a single result. To produce a population mean and and acute medications, therefore testing on the day of surgery
standard deviation, a control group should be tested at the same should ideally be avoided as a result of these confounding fac-
intervals as the patient group and the mean difference calculated. tors. Obtaining more than one episode of preoperative cognitive
Improvements resulting from performing the same test repeat- testing can be problematic12 18 and potential solutions could
edly are likely, and so the population mean is subtracted from include:
the observed difference in the patients’ test scores to control for • Memory Clinics: either for the general ageing population or
this learning effect. For any chosen neuropsychological test, the linked specifically to surgical specialties
difference in a single patient’s preoperative and postoperative • Primary Care Surgery Clinics: potentially nurse-led
test score is subtracted from the mean difference from repeated • Separate assessments at Surgical Booking (i.e. at decision to
testing on controls and divided by the control group standard proceed to surgery) and Anaesthetic Pre-assessment
deviation equals the z-score. To produce a dichotomous outcome,
a z-score two standard deviations from the mean is considered to Funding and time-constraints are clear barriers to these
be abnormal and diagnostic of POCD. potential processes, however this topic is encompassed within
An additional confounding factor is the point at which test- the NHS England Commissioning for Quality and Innovation
ing is performed, as this might give an incorrect impression of (CQUIN) guidance on Dementia/Delirium,26 and thus could be
an individual’s cognitive trajectory. Single point preoperative considered as part of this nationally funded scheme.
Optimal postoperative cognitive testing has been suggested at
testing for cognitive impairment will not distinguish between
one week and three months post procedure27 depending on the
an individual whose cognitive trajectory is worsened,
clinical picture, absence of confounding factors and a robust
unchanged or even improved by an intervention. For example,
follow-up pathway. Formal diagnosis of POCD is again impeded by
in a patient about to undergo total hip replacement, hip pain
a lack of definition and requirement for multimodal testing, but a
can impact cognition considerably such that postoperative
decline in z-scores using one of the tests below should prompt
reduction in pain and improved mobility can produce improve-
consideration for referral to an appropriate specialist for further
ment in an individual’s cognitive trajectory.12 Figure 1
assessment (e.g. care of the elderly or psychiatric services).
illustrates the difference in cognitive trajectories that can occur
Formal and appropriate testing of cognition is imperative in
and how single point testing fails to adequately distinguish
risk stratification for both delirium and POCD. Cognitive assess-
between them.
ment tools such as the Abbreviated Mental Test (AMT) and
Mini-mental state examination (MMSE) are widely used world-
wide for screening and diagnosing dementia, however both lack
the sensitivity and specificity to detect subtle cognitive impair-
Composite psychometric (z) score

A ment such as MCI.17 28 There are numerous neurocognitive tests

Surgery
Postoperative available for detecting MCI, however many are time consuming
cognitive and lack either sensitivity or specificity.17 28–30 Those that hold
B trajectories the most promise for use in a preoperative clinic environment
e include the Montreal Cognitive Assessment Tool (MoCA),
Preoperative d Addenbrooke’s Cognitive Exam (ACE-III) and the Quick MCI
cognitive Screen (Qmci). These are summarized in Table 2, and further
trajectories c details are provided in Supplement Material S1.
Both MoCA and ACE-III are used in many UK centres, partic-
ularly in stroke, care of the elderly and neuropsychiatry serv-
b ices. The Montreal Cognitive Assessment tool has been studied
a
in vascular, neurosurgical, and emergency general surgery
–24 –18 –12 –6 0 6 12 18 24 patient populations including assessment outcomes in carotid
Time (months) endarterectomy, traumatic brain injury and subarachnoid hae-
morrhage patients.34–37 The ACE-III test is the most recent ver-
sion of the examination with improved specificity for detecting
dementia, but its use in surgical patients is not established.33
Fig 1 Preoperative and postoperative cognitive trajectories. This illustrates The quick MCI screen was adapted from the AB Cognitive
possible preoperative and postoperative cognitive trajectories for a single
Screen 135 with evidence of improved ability to differentiate
patient. Curve (A) illustrates a patient experiencing cognitive decline
before surgery whilst in contrast curve (B) represents a patient with rela-
between normal cognition, mild cognitive impairment and
tively stable cognitive function. A number of postoperative trajectory dementia.38 Large scale studies are ideally required to validate
curves (a-e are possible). In patient (A), curve (b) represents a continuation use of these cognitive tests in perioperative practice. The results
of the preoperative trend. Curve (a) would be an acceleration of cognitive of these tests should be matched against age, gender, education
decline and curve (c) would be a reduction in cognitive decline, or even and cultural background of the individual being tested 12 and
cognitive improvement. Without knowing Patient A’s cognitive trajectory
should be delivered by specifically trained staff with concomi-
in the pre-op period, curves (a–c) could all be interpreted as POCD. For
patient (B), curve (c) shows POCD, curve (d) is no change from the preoper-
tant consultation with specialists in old age and neuropsychia-
ative course, and curve (e) represents a cognitive improvement. Of note try for more formal assessments where concerns arise.
curve c can be interpreted as relative cognitive improvement for patient (A)
and relative cognitive decline for patient (B), hence the importance of
knowing the preoperative cognitive trajectory for an individual.
Prevalence and incidence
Reproduced with permission from.12 Dementia disease processes are estimated to double in inci-
dence in the next 30 yr, and 48% of unplanned hospital
 i118 | Needham et al.

Table 2 Summary of MoCA, ACE-III and Qmci test characteristics.17 28–33 *Figures from original validation study,32 lower figures quote 48–68%29

MoCA (Version 8.1) ACE-III Qmci

Total Score 30 100 100

Cut Off Score for MCI 26 82–88 62
Average Time to Complete 10 mins 16 mins 5 mins
Sensitivity % 90 84–93 90
Specificity % 87* 100 87
Limitations Designed to suspect Lack of discriminatory Needs larger scale studies to
MCI rather than Dementia cut off scores between validate use in detecting MCI
MCI & Dementia
Available at www.mocatest.org dementia.ie https://academic.oup.com/ageing

admissions above 80 yr of age will have detectable disease.39 any reasonable degree of accuracy. Identification of risk factors
Similarly the incidence of delirium varies depending on patient has been beset by methodological problems but a number of
population and sampling methodologies.40 Studies for vascular case-control, retrospective and prospective studies have tried to
surgery patients quote incidences of 5–39%.41 42 Numerous stud- characterise the risk factors for developing POCD. Paredes and
ies have been carried out to estimate the prevalence of POCD in colleagues25 found that increasing age was the most common
the post-surgical population. Comparison of these reveals strik- risk factor and was identified in seven of the 24 studies analy-
ing heterogeneity in the study populations, tests and follow-up sed. Other risk factors identified in multiple studies were fewer
period used; therefore a wide range of prevalence is quoted in years of education, postoperative delirium and the use of seda-
the literature.24 25 tive drugs.13 27 46 Multiple additional risk factors were noted in
In non-cardiac surgery a systematic review identified 19 single studies namely; depression, previous stroke, postopera-
studies and aggregated their results to give an incidence of tive infection, postoperative pulmonary complications, lacunae
11.7% amongst the 6477 identified patients at three months of on brain imaging and total time spent with Bispectral Index
follow-up.25 However, many of the studies included older (BIS) readings lower than 40 as summarized in Table 3.25 46
patients undergoing higher risk surgery, and therefore the risk Screening tools for those at risk of delirium already exist but
among an unselected UK hospital cohort is likely to be very dif- are not universally used. Marcantonio and colleagues47, 48 devel-
ferent. For example the prevalence of POCD in patients under- oped and validated prediction models for delirium in both non-
going elective hip surgery has been estimated to be 22%.43 cardiac47 and cardiac48 surgical patients. The former uses seven
Amongst cardiac surgery patients the rate of POCD may be as risk factors including age>70 yr, pre-existing cognitive impair-
high as 60%. However, a systematic review that analysed 62 ment, poor functional status, self-reported alcohol abuse, elec-
studies of POCD after cardiac surgery found a 10-fold variation trolyte disturbances and major vascular surgery.47 Scores are
in quoted incidence as a result of differences in study popula- graded into low, moderate and high risk for delirium. The
tions and the protocols used to detect POCD.24 Further work is American Geriatric Society consensus statement on delirium
required but all indications are that a significant number of peo- suggests that two or more of the factors in Table 3 should
ple will be affected by POCD after surgery. prompt prevention measures.49
Another focus of ongoing study has been the follow up of Formal risk stratification for POCD is not currently possible
patients with POCD to establish whether the condition is self- because of the lack of definition and identification as discussed
limiting or progressive. A subgroup of participants in the origi- above. However use of the above named risk factors could be
nal international multicentre study on long-term postoperative used to trigger referral for more formal cognitive testing and
cognitive dysfunction (ISPOCD 1) study were followed up consideration of any preventative measures. Type of surgery
between one and two years after surgery and compared with may potentially play a role with one single centre cohort study
non-surgical controls.44 The incidence of test results indicative of 1064 patients showing increased risk of early (but not late)
of POCD was 10.4% and 10.2%, respectively, with only 0.9% of POCD with major thoracic, intra-abdominal and orthopaedic
patients consistently showing cognitive impairment at all three procedures.50
time points (one week, three months and one to two years). A
longer term follow up of the same cohort 10 yr after the initial Anaesthesia and dementia
study found no association between a subsequent diagnosis of
dementia and a prior diagnosis of POCD at either one week or Whether or not anaesthesia can lead to dementia is of increas-
three months post-surgery.45 This study suggests that POCD ing interest. It has been the subject of case-control, cohort and
developing in the postoperative period can largely be reversible prospective studies which have yet to yield a conclusive answer.
and rarely persists in the longer term. A 2011 meta-analysis of 15 case-control studies failed to find
any association between general anaesthesia and subsequent
Alzheimer’s dementia (AD).51 Encompassed within the meta-
Risk factors
analysis, two studies investigated an association between
Risk stratification to enable identification of those at high risk of regional anaesthesia and AD, but again none was found.
developing delirium and POCD does not yet exist in a robust Supporting this conclusion, a cross-sectional study of over 600
form in most UK surgical centres. Thus preoperative counselling elderly patients in Vienna failed to show a dose-dependent link
and any potential optimisation processes cannot be targeted to between number of anaesthetics received and cognitive
 Postoperative cognitive dysfunction and dementia | i119

Table 3 Comparison of perioperative risk factors for delirium and POCD

Delirium46–48 POCD13 25 27 46

Age >65 y Increasing age

Visual/Hearing Impairment Poor education (shorter time in school education)
Acute Admission/Emergency Surgery History of cerebrovascular disease with no residual impairment
Alcoholism/Substance Misuse Duration and Type of Surgery (Cardiac, Orthopaedics and Vascular)
Pre-existing Cognitive Impairment Pre-existing Cognitive Impairment
Abnormal Electrolytes/chronic kidney disease Poor functional status
Poor nutrition/Poor functional status Postoperative respiratory complications
APACHE 2 scores >16 Postoperative infections
Type of Surgery (e.g. Major Vascular/Cardiac) Time spent with BIS<40 (inconclusive)
Polypharmacy
Frailty

100

90

80
CAMCOG score

70

60

50

40

30
0 2 4 6 8 10
Time (yr)

Fig 2 Cognitive trajectories of patients with no existing cognitive impairment (blue) and existing cognitive impairment (orange) who underwent surgery (solid
lines) or no surgery (dashed lines). Over 10 yr the cognitive decline of people with existing cognitive impairment was seemingly accelerated by surgery. A cut off
of 79 in the CAMCOG is traditionally used to diagnose dementia. Reproduced with permission from.55

dysfunction.52 Subsequent published work has produced mixed decline in cognitively normal patients, in those with a degree of
results. In Taiwan a recent large case control study of 135 000 existing cognitive impairment there followed a worsening of
records from a national database gave a statistically significant function. Criticism of this study remains that there is risk of
hazard ratio of 1.99 for dementia associated with anaesthesia.53 bias and confounding that casts doubt on any clear link how-
However it was also noted that the anaesthetic cohort was older ever biologically plausible.56
and burdened to a greater extent by depression and cardiovas-
cular co-morbidities as potential confounding factors. The Biological mechanisms of POCD
Taiwan database review conflicts with the results of a large pro-
While the pathophysiology underlying dementia is the subject
spective cohort study.54 Amongst 4000 patients in the ACT of intense and ongoing study, little is yet known about the
(Adult Changes in Thought) cohort, there was no increased risk mechanism by which POCD occurs. Translational research so
of dementia in patients who had undergone an anaesthetic and far has focused on the interaction between anaesthetic agents
even amongst a group whose surgery was deemed high risk.54 and the pathological processes of Alzheimer’s disease.
Analysis of patients enrolled in the Oxford Project to Histologically Alzheimer’s disease is characterised by intra-
Investigate Memory and Ageing (OPTIMA) study suggests a neuronal neurofibrillary tangles, composed of hyperphosphory-
more nuanced picture (Fig. 2).55 Elderly people were recruited lated tau protein arranged in paired helical filaments, and
into this prospective study as either controls or with MCI, and extracellular amyloid plaques, composed of Ab40 and Ab42 pep-
394 subsequently underwent moderate or major surgery. Mixed tides that are the result of aberrant processing of the amyloid
effects modelling of their Cambridge Cognition Examination precursor protein (APP).57 The pathological effects of these
(CAMCOG) showed that whilst surgery did not precede cognitive changes are an increase in neuronal death and loss of synapses,
 i120 | Needham et al.

principally of cholinergic neurones of the basal forebrain region. Preparation and optimisation
The central cholinergic system is important in the formation
To date there are no specific treatments available for POCD, but
and regulation of consciousness, learning and memory, and
the condition is of concern to some elderly patients, and it is
therefore its degradation by amyloid plaques and neurofibrillary
important that anaesthetists and surgeons consider ways to
tangles contributes to the observed clinical picture of a global
reduce its incidence and engage in discussion of the risks with
decline in memory, reasoning, judgment and orientation.57
patients preoperatively. As POCD is likely to be multifactorial,
Studies involving clinically relevant concentrations of iso-
the approach to prevention should be multidisciplinary and
flurane, sevoflurane and desflurane all show potentiation of the
include consultation with care of the elderly specialists where
pathophysiological processes associated with Alzheimer’s dis-
appropriate. The Canadian PREHAB study, a randomized con-
ease that lead to neuronal death. For example mice exposed to
trolled trial examining the impact on clinical outcomes of pro-
2.1% sevoflurane for six h showed an increase in caspase-3 acti-
viding preoperative rehabilitation for frail elderly patients
vation (a marker of apoptosis) in brain.58 When exposed to 3%
before cardiac surgery, is ongoing.62 It may provide information
sevoflurane they also found increased levels of APP processing
about the benefits of a pre-optimisation approach as cognitive
and increased levels of Ab peptides. Transgenic Alzheimer’s dis-
function will be examined as part of the assessment process.
ease mice were also found to be more susceptible to sevoflurane Preoperative orientation programs in paediatric surgery
induced neurotoxicity when given the same dose and duration already exist and have been shown to potentially reduce anxiety
of sevoflurane. Whether this work done in cell culture and ani- levels and improve patient satisfaction.63 64 Studies into similar
mal models is clinically relevant requires further study, but evi- processes in adults suggest improvements in postoperative
dence of in vitro biological change does provide a plausible pain, negative emotion and a small reduction in length of stay,
mechanism whereby general anaesthetic agents could lead to but are too heterogeneous to reach a confident conclusion.65
cognitive dysfunction in the postoperative period.59 The orientation process can involve both verbal and written
Additional work has been done to investigate putative roles methods including group sessions and hospital tours and
for the processes of neuroinflammation and cerebral microem- ideally would involve a close family member or caregiver.
boli. In rat models both isoflurane and sevoflurane increase per-
meability of the blood-brain barrier by damaging brain vascular
Chronic disease management
endothelial cells, and this process is more pronounced in older
animals.60 This could allow cytokines and other pro- Perioperative medicine is increasingly recognized as a multidis-
inflammatory mediators to access the brain and the resulting ciplinary specialty in its own right, particularly for elderly and
cellular dysfunction might cause POCD. Cardiac surgery models frail patients undergoing major surgery.66 Involvement of care
provide additional hypothetical contributory mechanisms. of the elderly specialists is well established for hip fracture
Micro-emboli formed either from the surgical site or the cardio- patients with good results,67 but this is less common in other
surgical specialties. The Royal College of Anaesthetists 2017
pulmonary bypass circuit could cause cerebral infarctions lead-
guidelines for provision of preoperative assessment services
ing to POCD. While in population studies small lesions present
recommends that older, frail patients have access to a consul-
on diffusion weighted imaging magnetic resonance imaging
tant geriatrician, and that joint surgical, geriatric and anaes-
(MRI) scans are associated with cognitive dysfunction, their role
thetic clinics should be considered.68 The cost burden of such
in POCD remains unclear. Several perioperative studies of
an assessment process is obvious, but financial savings and
patients undergoing cardiac surgery demonstrated new postop-
improved quality of life could be anticipated as a result of the
erative lesions, but proving a temporal relationship with POCD
impact on delirium and POCD and a considerably improved care
is difficult. From 13 studies identified in a recent review, no firm
pathway. There is a need to consider health economic analyses
conclusions of a causal link could be drawn, in part because of
of these type of approaches when planning intervention
the variable timings of the MRI scans and neuropsychological
studies.
tests.18
Vascular risk factors such as hypertension, obesity, diabetes
While potentially anaesthetic-related modifiable factors
mellitus and smoking are linked with cognitive decline in the
such as hypotension, hypoxia and altered cerebral perfusion
general population.12 27 It is therefore logical that optimisation
have been postulated as contributing to POCD, the evidence to
of these features would assist in lowering the risk of POCD and
support this is weak. The ISPOCD cohort study prospectively
dementia. These are also risk factors for postoperative compli-
recruited 1218 patients aged over 60 yr of age in 13 countries cations such as wound infections and respiratory deterioration
who were undergoing major noncardiac surgery. It failed to that are also linked to delirium and POCD.
show an association between either hypotension or hypoxia Alcohol excess is strongly linked with delirium and long-
and POCD.27 However there is some suggestion that during car- term cognitive impairment and dementia via cerebral atrophy
diac surgery maintaining mean arterial pressures of 80–90 mm and vitamin B1 deficiency.69 There is some evidence that
Hg may reduce the incidence of both postoperative delirium chronic alcohol excess is also a risk factor for POCD particularly
and cognitive dysfunction. This together with studies showing in those over 55 yr old.69 70 Use of benzodiazepines is the most
suggested associations between reduced cerebral oxygenation, common form of treatment in such cases but confers potential
as measured by near infrared spectroscopy (NIRS), and POCD, additional risks including delirium itself. Thus preoperative
does suggest that cerebral hypoperfusion or hypoxia could be a counselling should include a strong emphasis on the cognitive
contributing factor to changes in cognition.61 It appears there- benefit of controlled reduction and if possible cessation of alco-
fore that current levels of knowledge regarding the impact of hol consumption.
anaesthesia and surgery on POCD are at best patchy and incom- Pre-assessment should also include evaluation and docu-
plete, and there is considerable need for focus on areas where mentation of visual and/or hearing impairments with an
we can identify and support patients at risk in the perioperative emphasis on ensuring access to aids throughout the periopera-
period. tive period. Preoperative improvement of general health may
 Postoperative cognitive dysfunction and dementia | i121

yield indirect benefits, for example correction of anaemia and Moreover the decision to proceed with surgery can be based
electrolyte abnormalities although not directly linked to cogni- on the physical burden of disease that can in itself impact on
tive dysfunction. Anaemia in isolation is associated with the patient’s cognitive function. For example, there is evidence
increased postoperative mortality and wound infections. Oral that cardiac surgery, by improving oxygen delivery, reducing
iron therapy in the elderly can be problematic as a result of poor pain and symptoms of breathlessness, can actually lead to cog-
compliance and gastrointestinal absorption, but evidence is nitive improvement81 (see Fig. 1). However, for patients with
building for use of i.v. iron preoperatively,71 although results milder disease symptoms who are at high risk for developing
from the PREVENTT trial are still pending.72 Magnesium levels delirium, POCD or dementia conservative management of their
are intrinsically linked to cognitive function with chronic defi- disease may be more a prudent decision at an individual time
ciency causing memory impairment alongside muscle weak- point.
ness and lethargy. Dietary replacement of magnesium has been
shown to help in a subset of dementia patients particularly
Intraoperative prevention
those with Alzheimer’s Disease.73 74 Oral organic magnesium
salts such as magnesium citrate have good bioavailability and Studies using processed electroencephalogram (pEEG) monitor-
replacement should aim for an intake of 4–6 mg kg1 day1.74 ing to minimize the cumulative time at low BIS levels have
Reduction in fasting times for clear fluids should be considered given mixed results, but there is growing evidence that pEEG
for those at risk of POCD and delirium, with the aim to help pre- monitoring reduces the incidence of POCD and delirium.82 83 84
vent dehydration and electrolyte disturbances and aid patient In the largest randomized study of POCD and pEEG, 921 elderly
comfort. patients undergoing major non-cardiac surgery were
Polypharmacy in the elderly is associated with postoperative randomized to receive BIS-guided anaesthesia with a target of
delirium, but the link with POCD is less robust.30 49 Evidence 40 to 60 or standard care.85 Amongst those in the BIS group
from the ISPOCD study showed an association between preoper- there was a statistically significant reduction in POCD from
ative benzodiazepines and a reduced incidence of cognitive 14.7% to 10.2% at three months postoperatively. Those in the BIS
decline postoperatively, however this study did not stipulate group spent significantly less time with BIS<40 and received
the duration or dosage of benzodiazepines, which have them- lower end-tidal anaesthetic concentrations than the usual care
selves been previously linked to delirium.27 Other studies have group. The authors estimate that if their study protocol was
failed to show similar results or any link to POCD75 76 such that used more widely, BIS-guided anaesthesia would prevent 23
benzodiazepine use cannot be recommended in the periopera- cases of POCD in every 1000 elderly patients undergoing major
tive period. Continuation of chronic psychoactive medications surgery. The use of near infrared spectroscopy (NIRS) in cardiac
such as anticholinesterase therapy is important as withdrawal surgery to avoid low cerebral oxygen saturation might also be
of drugs such as donepezil has been shown to double the risk of useful although observational studies have produced inconsis-
nursing home placement in severe Alzheimer’s dementia.77 tent results.13 86 87 Conversely the ISPOCD study27 failed to find
Medication reviews as part of a comprehensive geriatric assess- any association between hypoxia and POCD in non-cardiac
ment in the frail elderly are recommended by the British patients.
Geriatrics Society; a meta-analysis of 22 trials using such an There is no good clinical evidence that any individual anaes-
assessment approach showing increased likelihood of improved thetic agent reduces the probability of POCD, and in particular
cognition after emergency admission to hospital.78 no consistent evidence that i.v. anaesthetic techniques offer
any advantages. A study by Schoen and colleagues88 of 128
patients undergoing on-pump cardiac surgery, found signifi-
Patient counselling and surgical options cantly less POCD in the first week postoperatively when sevo-
Surgical consent processes do not yet regularly include a discus- flurane was compared with propofol for maintenance of general
sion regarding the cognitive burden of surgery and anaesthesia, anaesthesia. The opposite was found in 180 patients undergoing
although there is increasing public awareness of the issue.79 lumbar spine surgery; at two years of follow-up the group
Despite the additional concern this will inevitably place on the randomized to sevoflurane showed significant progression in
patient and family members, POCD is a material inherent risk25 MCI compared with a control group, and there was no signifi-
that alongside other surgical complications deserves discussion. cant decline in the propofol group.89 While it would seem intui-
It is generally considered appropriate in English law to inform tive that regional anaesthesia would confer cognitive
patients of “a significant risk which would affect the judgement protection, once again evidence is lacking, and the heterogene-
of a reasonable individual,” and this concept is engrained into ous nature of trials makes comparisons difficult.90 Similarly a
the General Medical Council (GMC) guidance on consent.80 81 trial of intraoperative remifentanil in elderly patients under-
However after recent case law including the case of Chester v going major abdominal surgery failed to show any benefit for its
Afshar (2004) whereby the House of Lords held that a patient use over fentanyl boluses.91
was not informed of a risk inherent to the surgery, despite a low Other developments have included a small randomized con-
probability of occurrence, the Department of Health now trolled trial suggesting the benefits of remote ischaemic precon-
advises that healthcare practitioners provide information about ditioning in patients undergoing cardiac surgery.92 Another area
all possible serious adverse events and ensure documentation of ongoing research is the use of antioxidants, and a
of such a discussion.80 An individualised approach to the proc- randomized controlled trial using N-acetylcysteine is under-
ess of consent should take place, taking into account known way.93 With such a limited evidence base, one strategy for man-
risk factors, type and urgency of surgery, and the patient’s aging patients at risk or concerned about developing POCD
wishes. It may be entirely appropriate to discuss the risks of would be to extrapolate from efforts to reduce the incidence of
POCD with a high-risk patient who is concerned about the con- postoperative delirium. Guidelines2 94 already exist for this, and
dition, even if there are no definitive methods to prevent its would be expected to yield some benefit for the earlier stages of
occurrence. POCD. Beyond this further research is required and it may be
 i122 | Needham et al.

High risk patients

Age>65y
Pre-existing cognitive impairment
Suspected cognitive impairment
Specialist
Cognitive testing Previous stroke
assessment
Poor functional status
Major surgery
Predicted anaesthetic time>1.5 h23
Risk of postoperative respiratory complications

Identification

Optimise chronic Hearing/visual/

Pharmacy review
disease other functional aids

Alcohol/smoking
Reduce fasting times Prehabilitation?
cessation

Correct anaemia &

electrolytes

Optimisation

Information & counselling Surgical options

Consent

Depth of anaesthesia Maintain blood pressure

Adequate analgesia
monitoring & oxygenation

Continue pertinent Avoid high risk

medications medications

Prevention

Fig 3 Suggested flow diagram for the perioperative process of patients at high risk of POCD. Developed by C. Webb, M. Needham, D. Bryden.
 Postoperative cognitive dysfunction and dementia | i123

that care bundles can be developed to pool together some of the 5. Sauër AC, Veldhuijzen DS, Ottens TH, Slooter AJC, Kalkman CJ,
above interventions. Figure 3 illustrates the authors’ suggested van Dijk D. The association between delirium and cognitive
approach to managing patients at high risk of POCD who are change after cardiac surgery. Br J Anaesth 2017; 119: 308–15
being considered for surgery. 6. Sprung J, Roberts RO, Weingarten TN, Nunes Cavalcante A,
Knopman DS, Petersen RC, et al. Postoperative delirium in
elderly patients is associated with subsequent cognitive
Conclusions impairment. Br J Anaesth 2017; 119: 316–23
Decline in cognitive function after a surgical event and associ- 7. Aranake-Chrisinger A, Avidan MS. Postoperative delirium
ated anaesthesia is recognized in the elderly population, how- portends descent to dementia. Br J Anaesth 2017; 119: 285–8
ever providing patients with appropriate and accurate 8. MacLullich AMJ, Beaglehole A, Hall RJ, Meagher DJ. Delirium
information can be difficult because of many uncertainties. The and long-term cognitive impairment. Int Rev Psychiatry 2009;
RCOA patient liaison group has produced a useful patient infor- 21: 30–42
mation leaflet that is designed to provide guidance in discus- 9. Tsai TL, Sands LP, Leung JM. An update on postoperative cog-
sions of individual risks.95 Considerable uncertainties remain. nitive dysfunction. Adv Anesth 2010; 28: 269–84
10. Sztark F, Le Goff M, André D, Ritchie K, Dartigues JF, Helmer
Agreed definitions for cognitive dysfunction and identification
CF. Exposure to general anaesthesia could increase the risk
of appropriate assessment tools are needed in order to ensure
of dementia in elderly. EJA 2013; 30: 245
appropriate funding and consistency of research approaches.
11. Sprung J, Jankowski CJ, Roberts RO, et al. Anesthesia and inci-
Improved perioperative patient pathways to include involve-
dent dementia: a population-based, nested, case-control
ment of care of the elderly specialists, along with increased
study. Mayo Clin Proc 2013; 88: 552–61
training of staff involved in the perioperative patient pathway,
12. Nadelson MR, Sanders RD, Avidan MS. Perioperative cogni-
are required to help address the increasing numbers of patients
tive trajectory in adults. Br J Anaesth 2014; 112: 440–51
anticipated to present to hospital with evidence of, or at risk of,
13. Brown C, Deiner S. Perioperative cognitive protection. Br J
developing cognitive decline in the perioperative period.
Anaesth 2016; 117: iii52–61
14. Slooter J. Delirium, what’s in a name? Br J Anaesth 2017; 119:
Authors’ contributions 283–85
15. Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults:
Study design/planning: D.C.B.
diagnosis, prevention and treatment. Nat Rev Neurol 2009; 5:
Study conduct: 210–20
Data analysis: 16. Neurocognitive Disorders. In Diagnostic and Statistical Manual
Writing paper: all authors of Mental Disorders, 5th Edn. Arlington, VA, USA: American
Revising paper: all authors Psychiatric Association, 2013
DCB contributed to the design, planning and writing. CEW and 17. Louie J, Tierney K, Ebmeier K. Screening for mild cognitive
MJN contributed to the writing and reviewing of the article. impairment: a systematic review. Int J Geriatr Psychiatry 2009;
24: 902–15
Supplementary material 18. Crosby G, Culley DJ, Hyman BT. Preoperative cognitive
assessment of the elderly surgical patient: a call for action.
Supplementary material is available at British Journal of Anesthesiology 2011; 114: 1265–8
Anaesthesia online. 19. Tomaszewski Farias S, Mungas D, Reed BR, Harvey D, DeCarli
C. Progression of mild cognitive impairment to dementia in
clinic- vs community-based cohorts. Arch Neurol 2009; 66:
Declaration of interest
1151–7
D.C.B. is a member of the editorial board of BJA Education, and a 20. Albert MS, DeKosky ST, Dickinson D, et al. The diagnosis of
member of HTA Emergency and Elective Specialist Care mild cognitive impairment due to Alzheimer’s disease:
Research Panel. M.J.N. and C.E.W.: none declared. recommendations from the National Institute on Aging-
Alzheimer’s Association workgroups on diagnostic guide-
lines for Alzheimer’s disease. Alzheimers Dement 2011; 7:
References
270–9
1. House of Commons Library Research. The ageing popula- 21. Rudolph JL, Marcantonio ER, Culley DJ, et al. Delirium is asso-
tion: key issues for the 2010 Parliament. Available from ciated with early postoperative cognitive dysfunction.
www.parliament.uk/business/publications/research/key- Anaesthesia 2008; 63: 941–7
issues-for-the-new-parliament/value-for-money-in-public- 22. Androsova G, Krause R, Winterer G, Schneider R. Biomarkers
services/the-ageing-population (accessed 23 May 2017) of postoperative delirium and cognitive dysfunction. Front
2. National Institute for Care and Health Excellence. Delirium: Aging Neurosci 2015; 7: 112
Prevention, Diagnosis and Management (CG103). Manchester: 23. Sun X, Lindsay J, Monsein LH, Hill PC, Corso PJ. Silent brain
NICE guideline, 2010 injury after cardiac surgery: a review: cognitive dysfunction
3. Jansen CL, Absalom AR, de Bock GH, van Leeuwen BL, Izaks and magnetic resonance imaging diffusion-weighted imag-
GJ. Performance and agreement of risk stratification instru- ing findings. J Am Coll Cardiol 2012; 60: 791–7
ments for postoperative delirium in persons aged 50 years or 24. Rudolph JL, Schreiber KA, Culley DJ, et al. Measurement of
older. PLoS One 2014; 9: e113946 post-operative cognitive dysfunction after cardiac surgery: a
4. Williamson WK, Nicoloff AD, Taylor LM Jr, Moneta GL, systematic review. Acta Anaesthesiol Scand 2010; 54: 663–77
Landry GJ, Porter JM. Functional outcome after open repair of 25. Paredes S, Cortı́nez L, Contreras V, Silbert B. Post-operative
abdominal aortic aneurysm. J Vasc Surg 2001; 33: 913–20 cognitive dysfunction at 3 months in adults after
 i124 | Needham et al.

non-cardiac surgery: a qualitative systematic review. Acta 44. Abildstrom H, Rasmussen LS, Rentowl P, et al. Cognitive dys-
Anaesthesiol Scand 2016; 60: 1043–58 function 1-2 years after non-cardiac surgery in the elderly.
26. NHS England/Contracting and Incentives Team. Commission- Acta Anaesthesiol Scand 2000; 44: 1246–51
ing for quality and innovation guidance 2015/2016. Available 45. Steinmetz J, Siersma V, Kessing LV, Rasmussen LS. Is postop-
from http://www.england.nhs.uk/wp-content/uploads/2015/ erative cognitive dysfunction a risk factor for dementia?
03/9-cquin-guid-2015-16.pdf (accessed 23 May 2017) A cohort follow-up study. Br J Anaesth 2013; 110: i92–7
27. Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term post- 46. Lloyd DG, Ma D, Vizcaychipi MP. Cognitive decline after
operative cognitive dysfunction in the elderly: ISPOCD1 anaesthesia and critical care. Contin Educ Anaesth Crit Care
study. Lancet 1998; 351: 857–61 Pain 2012; 12: 105–9
28. Jager CA, Ahmed-Ali S, Wilcock GK. A comparison of screen- 47. Marcantonio ER, Goldman L, Mangione CM, et al. A clinical
ing tools for the assessment of mild cognitive impairment. prediction rule for delirium after elective non cardiac sur-
Neurocase 2012; 18: 336–51 gery. JAMA 1994; 271: 134–9
29. O’Caoimh R, Timmons S, Molloy DW. Screening for mild cog- 48. Rudolph JL, Jones RN, Levkoff SE, et al. Derivation and valida-
nitive impairment: comparison of "MCI Specific" screening tion of a preoperative prediction rule for delirium after car-
instruments. J Alzheimers Disease 2016; 51: 619–29 diac surgery. Circulation 2009; 119: 229–36
30. Axley MS, Schenning KJ. Preoperative cognitive and frailty 49. Inouye SK, Robinson T, Blaum C, et al. Postoperative delirium
screening in the geriatric surgical patient: a narrative review. in older adults: best practice statement from the American
Clin Ther 2015; 37: 2666–75 Geriatrics Society. J Am Coll Surg 2015; 220: 136–48
31. Davis DHJ, Creavin ST, Yip JLY, Noel-Storr AH, Brayne C, 50. Monk TG, Weldon BC, Garvan CW, et al. Predictors of cogni-
Cullum S. Montreal Cognitive Assessment for the diagnosis tive dysfunction after major noncardiac surgery. Anesthesia
of Alzheimer’s disease and other dementias. Cochrane 2008; 108: 18–30
Database Syst Rev 2015; 10: CD010775 51. Seitz DP, Shah PS, Herrmann N, Beyene J, Siddiqui N.
32. Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Exposure to general anesthesia and risk of Alzheimer’s dis-
Cognitive Assessment, MoCA: a brief screening tool for mild ease: a systematic review and meta-analysis. BMC Geriatr
cognitive impairment. J Am Geriatr Soc 2005; 53: 695–9 2011; 11: 83
33. Noone P. Addenbrooke’s cognitive examination-III. Occup 52. Fischer P, Wallner H, Jungwirth S, et al. Cumulative exposure to
Med 2015; 65: 418–20 general anesthesias and cognitive dysfunction at age 75 in the
34. Koski L. Validity and applications of the Montreal cognitive Vienna Transdanube Aging “VITA” study. J Neuropsychiatry Clin
assessment for the assessment of vascular cognitive impair- Neurosci 2007; 19: 21–6
ment. Cerebrovasc Dis 2013; 36: 6–18 53. Chen PL, Yang CW, Tseng YK, et al. Risk of dementia after
35. de Guise E, LeBlanc J, Champoux M-C, et al. The mini-mental anaesthesia and surgery. Br J Psychiatry 2014; 204: 188–93
state examination and the montreal cognitive assessment 54. Aiello Bowles EJ, Larson EB, Pong RP, et al. Anesthesia expo-
after traumatic brain injury: an early predictive study. Brain sure and risk of dementia and alzheimer’s disease: a pro-
Inj 2013; 27: 1428–34 spective study. J Am Geriatr Soc 2016; 64: 602–7
36. Wong G, Lam SW, Wong A, Ngai K, Poon WS, Mok V. 55. Patel D, Lunn AD, Smith AD, Lehmann DJ, Dorrington KL.
Comparison of montreal cognitive assessment and mini- Cognitive decline in the elderly after surgery and anaesthe-
mental state examination in evaluating cognitive domain sia: results from the Oxford Project to Investigate Memory
deficit following aneurysmal subarachnoid haemorrhage. and Ageing (OPTIMA) cohort. Anaesthesia 2016; 71: 1144–52
PLoS One 2013; 8: e59946 56. Docherty AB, Shenkin SD. Cognitive decline after surgery
37. Hewitt J, Williams M, Pearce L, et al. The prevalence of cogni- and anaesthesia: correlation does not mean causation.
tive impairment in emergency general surgery. Int J Surgery Anaesthesia 2016; 71: 1131–5
2014; 12: 1031–5 57. Jiang J, Jiang H. Effect of the inhaled anesthetics isoflurane,
38. O’Caoimh R, Gao Y, McGlade C, et al. Comparison of the quick sevoflurane and desflurane on the neuropathogenesis of
mild cognitive impairment (Qmci) screen and the SMMSE in Alzheimer’s disease. Mol Med Rep 2015; 12: 3–12
screening for mild cognitive impairment. Age Ageing 2012; 58. Lu Y, Wu X, Dong Y, Xu Z, Zhang Y, Xie Z. Anesthetic sevo-
41: 624–9 flurane causes neurotoxicity differently in neonatal naı̈ve
39. Department of Health (2009). Living well with dementia: a and Alzheimer disease transgenic mice. Anesthesiology 2010;
national dementia strategy. Available from http://www.gov. 112: 1404–16
uk/government/publications/living-well-with-dementia-a- 59. Fodale V, Santamaria LB, Schifilliti D, Mandal PK.
national-dementia-strategy (accessed 8 June 2017) Anaesthetics and postoperative cognitive dysfunction: a
40. Davis DHJ, Kreisel SH, Muniz Terrera G, et al. The epidemiol- pathological mechanism mimicking Alzheimer’s disease.
ogy of delirium: challenges and opportunities for population Anaesthesia 2010; 65: 388–95
studies. Am J Geriatr Psychiatry 2013; 21: 1173–89 60. Acharya NK, Goldwaser EL, Forsberg MM, et al. Sevoflurane
41. Visser L, Prent A, van der Laan MJ, et al. Predicting postopera- and Isoflurane induce structural changes in brain vascular
tive delirium after vascular surgical procedures. J Vasc Surg endothelial cells and increase blood-brain barrier permeabil-
2015; 62: 183–9 ity: possible link to postoperative delirium and cognitive
42. Böhmer H, Hummel TC, Habel U, et al. Predicting delirium decline. Brain Res 2015; 1620: 29–41
after vascular surgery. Ann Surg 2003; 238: 149–56 61. van Harten AE, Scheeren TW, Absalom AR. A review of post-
43. Chow WB, Rosenthal RA, Merkow RP, et al. Optimal preopera- operative cognitive dysfunction and neuroinflammation
tive assessment of the geriatric surgical patient: a best prac- associated with cardiac surgery and anaesthesia. Anaesthesia
tices guideline from the American College of Surgeons 2012; 67: 280–93
national surgical quality improvement program and the 62. Stammers AN, Kehler DS, Afilalo J, et al. Protocol for the
American Geriatrics Society. J Am Coll Surg 2012; 215: 453–66 PREHAB study–Pre-operative Rehabilitation for reduction of
 Postoperative cognitive dysfunction and dementia | i125

Hospitalization After coronary Bypass and valvular surgery: your-brain-when-you-go-under-anaesthesia-a6725386.html

a randomised controlled trial. Br Med J Open 2015; 5: e007250 (accessed 22 July 2017)
63. Kain ZN, Caramico LA, Mayes LC, Genevro JL, Bornstein MH, 80. Department of Health. Reference guide to consent for exami-
Hofstadter MB. Preoperative preparation programmes in nation or treatment (Second Edition) 2009/11911. Available
children: a comparative examination. Anesth Analg 1998; 87: from http://www.gov.uk/government/uploads/system/
1249–55 uploads/attachment_data/file/138296/dh_103653__1_.pdf
64. Vaezzadeh N, Douai ZE, Hadipour A, Osia S, (accessed 21 July 2017)
Shahmohammadi S, Sadeghi R. The effect of performing pre- 81. General Medical Council. Consent: patients and doctors
operative preparation program on school age children’s making decisions together. 2008. Available from http://www.
anxiety. Iran J Pediatr 2011; 21: 461–6 gmc-uk.org/static/documents/content/GMC_Consent_0513_
65. McDonald S, Page MJ, Beringer K, Wasiak J, Sprowson A. Revised.pdf (accessed 21 July 2017)
Preoperative education for hip or knee replacement. 82. Cormack F, Shipolini A, Awad, WI, et al. A meta-analysis of
Cochrane Database Syst Rev 2014; 13: CD003526 cognitive outcome following coronary artery bypass graft
66. Braude P, Partridge JSL, Hardwick J, Shipway DJH, Dhesi JK. surgery. Neurosci Biobehav Rev 2012; 36: 211829
Geriatricians in perioperative medicine: developing subspe- 83. Palanca BJA, Avidan MS, Wildes TS, Ju Y-E, Ching S.
cialty training. Br J Anaesth 2016; 116: 4–6 Electroencephalography and delirium in the postoperative
67. Grigoryan KV, Javedan H, Rudolph JL. Orthogeriatric care period Br J Anaesth 2017; 119: 294–307
models and outcomes in hip fracture patients: a systematic 84. Escallier KE, Nadelson MR, Zhou D, Avidan MS. Monitoring
review and meta-analysis. J Orthop Trauma 2014; 28: e49–55 the brain: processed electroencephalogram and peri-
68. Guidelines for the provision of anaesthesia services (GPAS) operative outcomes. Anaesthesia 2014; 69: 899–910
for preoperative assessment and preparation 2017: Chapter 2. 85. Chan MT, Cheng BC, Lee TM, et al. BIS-guided anesthesia
Sections: 3.16–3.21. Available from http://www.rcoa.ac.uk/sys decreases postoperative delirium and cognitive decline.
tem/files/GPAS-2017-02-PREOP.pdf (accessed 31 May 2017) J Neurosurg Anesthesiol 2013; 25: 33–42
69. Hudetz JA, Iqbal Z, Gandhi SD, et al. Postoperative cognitive 86. Rogers CA, Stoica S, Ellis L, Stokes EA, Wordsworth S, Dabner
dysfunction in older patients with a history of alcohol abuse. L, et al. Randomised trial of near-infrared spectroscopy for
Anesthesiology 2007; 106: 423–30 personalized optimization of cerebral tissue oxygenation
70. Ridley NJ, Draper B, Withall A. Alcohol-related dementia: an during cardiac surgery Br J Anaesth 2017; 119: 384–93
update of the evidence. Alzheimers Res Ther 2013; 5: 3 87. Lewis C, Hogue CW. Lack of benefit of near-infrared spectro-
71. Litton E, Xiao J, Ho Kwok M. Safety and efficacy of intrave- scopy monitoring improving patient Br J Anaesth 2017
nous iron therapy in reducing requirement for allogeneic 88. Schoen J, Husemann L, Tiemeyer C, et al. Cognitive function
blood transfusion: systematic review and meta-analysis of after sevoflurane- vs propofol-based anaesthesia for on-
randomised clinical trials. Br Med J 2013; 347: 4822 pump cardiac surgery: a randomized controlled trial. Br J
72. Richards T, Clevenger B, Keidan J, et al. PEVENTT: preoperative Anaesth 2011; 106: 840–50
intravenous iron to treat anaemia in major surgery: study pro- 89. Yang CW, Fuh JL. Exposure to general anesthesia and the
tocol for a randomised controlled trial. Trials 2015; 16: 254 risk of dementia. J Pain Res 2015; 8: 711–8
73. Xu Z-P, Li L, Bao J, et al. Magnesium protects cognitive func- 90. Wu CL, Hsu W, Richman JM, Raja SN. Postoperative cognitive
tions and synaptic plasticity in streptozotocin-induced function as an outcome of regional anesthesia and analge-
sporadic Alzheimer’s model. PLoS One 2014; 9: e108645 sia. Reg Anesth Pain Med 2004; 29: 257–68
74. Gröber U, Schmidt J, Kisters K. Magnesium in prevention and 91. De Cosmo G, Sessa F, Fiorini F, Congedo E. Effect of remifen-
therapy. Nutrients 2015; 7: 8199–226 tanil and fentanyl on postoperative cognitive function and
75. Gray SL, Dublin S, Yu O, et al. Benzodiazepine use and risk of cytokines level in elderly patients undergoing major
incident dementia or cognitive decline: prospective popula- abdominal surgery. J Clin Anesth 2016; 35: 40–6
tion based study. Br Med J 2016; 352: i90 92. Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Pagel PS.
76. Rasmussen LS, Steentoft A, Rasmussen H, Kristensen PA, Remote ischemic preconditioning prevents deterioration of
Moller JT. Benzodiazepines and postoperative cognitive dys- short-term postoperative cognitive function after cardiac
function in the elderly. ISPOCD Group. International Study of surgery using cardiopulmonary bypass: results of a pilot
Postoperative Cognitive Dysfunction. Br J Anaesth 1999; 83: investigation. J Cardiothorac Vasc Anesth 2015; 29: 382–8
585–9 93. Skvarc DR, Dean OM, Byrne LK, et al. The Post-Anaesthesia
77. Howard R, McShane R, Lindesay J, et al. Nursing home place- N-acetylcysteine Cognitive Evaluation (PANACEA) trial:
ment in the Donepezil and Memantine in Moderate to study protocol for a randomised controlled trial. Trials 2016;
Severe Alzheimer’s Disease (DOMINO-AD) trial: secondary 17: 395
and post-hoc analyses. Lancet Neurol 2015; 14: 1171–81 94. American Geriatrics Society abstracted clinical practice
78. Ellis G, Whitehead MA, Robinson D, O’neill D, Langhorne P. guideline for postoperative delirium in older adults. J Am
Comprehensive geriatric assessment for older adults admit- Geriatr Soc 2015; 63: 142–50
ted to hospital: meta-analysis of randomised controlled tri- 95. Royal College of Anaesthetists England (Section 7). Risks
als. Br Med J 2011; 343: d6553 associated with your anaesthetic: becoming confused after
79. Ng K. What happens to your brain when you go under anaes- an operation. Available from http://www.rcoa.ac.uk/docu
thesia. The Independent, 2015. Available from http://www. ment-store/becoming-confused-after-operation (accessed
independent.co.uk/news/science/this-is-what-happens-to- 17 June 2017)