BGS Amulree Essay Prize

Long Term Post-Operative Cognitive

Dysfunction;
A 12 month longitudinal cohort study of elderly noncardiac patients.
Nathan Gauge1

Abstract
Post-operative cognitive dysfunction (POCD) in elderly non-cardiac patients has recently been
identified as a significant risk factor for increased mortality, welfare dependence and premature
withdrawal from work over a follow up of 8.5 years. The single most important risk factor for the
development of POCD is advancing age. In the UK population ageing, coupled with an increase in the
age of patients undergoing surgery will make POCD and increasingly important condition.
Despite the significant long term impact of POCD, previous studies in the elderly have failed to
identify significant levels of POCD at one year post operatively. This essay will present the first
longitudinal cohort study to demonstrate a significantly greater level of global cognitive impairment
in surgical patients compared to controls 1 year post-operatively. The discussion will identify why
previous trials have failed to show a significant level of POCD at 1 year post operatively and has
substantial implications for future research into reducing the impact of POCD.

Nathan Gauge is a KCL final year medical student

He was involved in all aspects of the study including design, data collection and was solely responsible for the
statistical analysis and authorship of this essay. This work has been submitted for the Amulree prize with the
permission of the other authors involved in the study.

BGS Amulree Essay Prize

Epidemiology of POCD
POCD has been identified in medical literature for over 50 years[4] when Bedford noted that "Hes
never been the same since his operation" is often heard in geriatric practice and conducted a
retrospective study identifying POCD for the first time. Despite this it took a further 40 years before
the landmark study into non-cardiac POCD was conducted by the ISPOCD study group - published in
1998 demonstrating that amongst major non-cardiac surgical patients greater than 60 years old POCD
was present in 25.8% of patients at one week and 9.9% at 3 months post operatively [31].
It is important to distinguish POCD from postoperative delirium which is a temporary change in
mental status characterized by a reduced awareness of the environment and a disturbance in attention
occurring shortly after surgery[13]. Post operative delirium is associated with delayed recovery and
increased mortality[30]. POCD in contrast is a more persistent condition identified by
neuropsychological testing which demonstrate a decline in cognitive function without an alteration in
mental status or awareness[13].
Estimates of the prevalence of POCD have varied widely from no reported change up to 71% of
patients showing POCD between one week and 6 months after surgery[34]. There are two principle
reasons for the wide range of incidence; firstly variation in type of surgery and anaesthesia and
secondly variation in the definition of POCD itself. The problem of defining POCD has been
addressed by several authors [28, 34, 40] and a consensus has yet to be reached. There are several
barriers to establishing a definition of POCD.
1. POCD is currently defined on the basis of a randomly assigned statistical cut off point.
Different authors have a variety of opinions on where this cut off point should be placed.
Important consideration needs to be given to previously established definitions of cognitive
decline in the elderly and both the clinical and personal impact of any given level of decline.
2. POCD is a binary definition of cognitive decline. It is plausible that POCD is present to a
greater or lesser extent in the majority of patients and therefore represents a continuum of
cognitive dysfunction. Reduction of the continuous data produced by neuropsychological tests
to binary data may therefore be inappropriate.
3. There is little data on whether different areas of cognition are preferentially affected in
POCD. Neuropsychological testing allows isolation of several areas of cognitive function.
Authors disagree on the number and type of tests as well as which cognitive aspects should be
focussed on.
The approach taken in this study is based on evidence that individual cognitive domains have different
effects on patients activities of daily living and capacity to function independently. Price et al.
demonstrated that POCD patients suffering from executive function deficits either alone or in
combination with memory deficits have the greatest functional impairment[36]. Previous studies have
demonstrated that deficits in attentional function have a particularly significant impact on patients
activities of daily living[8].
Computerised neuropsychometric testing and in particular the Cognitive Drug Research (CDR)
computerised assessment system has been shown to reduce the learning effect caused by repeated
assessments used in the study of POCD[47]. For these reasons we have employed a computerised test
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battery which focuses on attention and executive function. We have followed the ISPOCD study
group Z score method for calculating global cognitive decline as well as including analysis of
individual neuropsychometric tests.

BGS Amulree Essay Prize

Nathan Gauge

Impact of POCD
POCD has been shown to have severe long-term consequences for patients including increased
mortality in both the short term - between three months and one year post operatively [32] - and longterm with one study demonstrating an increased mortality over a median follow-up of 8.5 years post
operatively[44]. POCD has also been associated with increased duration of hospital stay[32],
premature withdrawal from the labour market and increased duration of welfare payments[44].
Following cardiac surgery Newman et al. have shown that cognitive decline is significantly associated
with significantly reduced quality of life and a less productive working status [33].

Despite the long-term implications of POCD both for the patient and the health service very few
studies have assessed POCD one year post operatively. A literature search of the Medline database2
identified only six papers that assessed POCD over six months post operatively and incorporated a
control group for comparison [1, 3, 5, 19, 20, 22]. The papers are summarised in table 3 in the
appendix. Only one paper found a significant difference in cognitive function between patients and
controls. Ancelin et al. identified a decline in cognitive function in visuo-spacial tests whilst also
noting a simultaneous improvement in patients compared to controls in the language tests[3]. This
study failed to control for the learning effect caused by repeated psychometric testing of patients and
did not include a measure of global decline.

The failure of previous trials to identify a significant difference in global cognitive decline between
patients and controls may represent either 1) evidence that POCD is a temporary impairment that
resolves completely within one year or 2) previous trials have failed to use a sufficiently sensitive
neuropsychological test battery to detect long-term changes in cognitive function without succumbing
to the difficulties of either the ceiling effect or the learning effect. The epidemiological evidence
demonstrating long-term health and welfare consequences to POCD suggest that there are lingering
cognitive deficits that have remained undetected.

Whilst POCD is believed to be a condition that is at least in some patients - reversible many authors
have considered a link between POCD and the development of dementia in later life. The difference
in definitions between POCD and measures of early dementia such as Mild Cognitive Impairment
(MCI) and Age Associated Cognitive Decline (AACG) is only the presence of a surgical history. MCI
and AACD have been used extensively throughout the psychiatric literature and are well documented
as predictors of future dementia including Alzheimers disease amongst elderly patients [27].

Xie and Tanzi [50] have argued that there is some experimental evidence to support a link between
general anaesthesia, surgery and permanent cognitive damage. They point to studies that show
ischemic brain injury is associated with the development of dementia, and - at least in experimental
2

The literature search was based on the systematic review by Newman et al.[34] Updated using the same search
terms to cover the period 2005 to 2010.

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Nathan Gauge

models - exposure to anaesthetic substances including isoflurane and propofol has induced neuronal
cell death and altered the formation of A peptides associated with Alzheimers disease. However,
case-control studies linking Alzheimers disease with exposure to general anaesthetic, although
limited by design, have been inconclusive [6, 7]. Further research is clearly needed before a link can
be satisfactorily established.

BGS Amulree Essay Prize

Aetiology, Pathogenesis and Prevention

Several studies have identified risk factors associated with POCD. As with many diseases age is the
strongest predictor of POCD risk. In the ISPOCD1 study at three months POCD was found in 7% of
patients aged 60-69 and in 14% of patients over 69. In addition; duration of anaesthesia, respiratory
complications, infection and further operations were found to be independent risk factors for POCD
[31]. A connection has also been found between lower levels of education, depression and POCD [2].
It is suggested that these risk factors are explained by deficiencies in the test as individuals with high
level of intelligence are able to compensate for some levels of cognitive decline with their so called
cognitive reserve [16] and it is well recognised that depression can lead to a reduction in
neuropsychological test scores[42]. POCD has been associated with lower alcohol consumption in
middle aged patients thought to be a result of increased sensitivity to CNS active substances [25].
Conversely in male cardiac surgical patients a history of alcohol dependence has been associated with
increased cognitive decline [24].

A plethora of theories explaining the underlying pathogenesis of POCD have been put forward but
none have yet been satisfactorily proven. It is useful when considering an area where there are so
many possible mechanisms to construct a simple set of categories from which to explore potential
mechanisms. Assuming that POCD is genuine and is caused by part of the process of surgery there are
at least three major areas that should be considered:
Potential
Causes of
POCD

Surgical
Insult

Fat
microem boli

System ic
Inflammation

Blood loss
and anaem ia

General
Anaesthesia

Cerebral
Oxygen
Desaturation

Direct
Neurotoxicity

Cerebral and
System ic
Effects

Postoperative
Recovery

Medication

Infection

BGS Amulree Essay Prize

Nathan Gauge

Surgical Insult

The potential for microemboli to cause cognitive decline has been explored previously [15, 26]. Koch
et al. used transcranial Doppler to assess the number of microemboli in either of the middle cerebral
arteries during hip or knee replacements. Whilst microemboli were detected in both patients with and
without a venous-arterial shunt the authors were unable to correlate the number of emboli detected
with POCD. It is worth noting however that this study may have been underpowered to detect an
effect involving just 22 patients and size as well as number of emboli may play an important role.

The possibility of systemic inflammation causing POCD in cardiac surgery has been explored by
randomising the use of intra-venous ketamine during anaesthetic induction. The authors found a
significant improvement in the intervention arm in one specific cognitive domain and a significant
reduction in the levels of C-Reactive Protein postoperatively[23]. Experimentally the exposure of rats
to anaesthesia and splenectomy resulted in increased levels of CNS inflammation and cognitive
impairment [46] interestingly in rats exposed only to anaesthesia no cognitive deficit was found.

Cerebral oxygen de-saturation has been a significant area of study in cardiac and carotid artery
surgery and has been correlated with POCD[11, 43]. In non-cardiac surgery it is a more complex
picture. Significant cerebral oxygen desaturation only occurs in a minority of patients during noncardiac surgery [11], but amongst these individuals preliminary evidence indicates that monitoring to
enable intervention improves outcome [10]. Cerebral oxygen de-saturation has been shown to be
significantly correlated with blood loss in abdominal patients and a percentage fall in haemoglobin
[21]. Treatment of anaemia and vitamin B12 deficiency in patients with cognitive impairment has
been shown to significantly improve cognition [14] postoperative anaemia represents a plausible
cause of POCD.

General Anaesthetics on CNS

The possibility of General Anaesthetic (GA) agents causing long term cognitive impairment is a
controversial one and provokes strong responses amongst anaesthetists. Neurotoxicity of general
anaesthetics has been investigated both in the laboratory and the clinical context.

In a recent review article [35] considered the laboratory evidence for neurotoxicity of general
anaesthetics. In some animal models a paradoxical improvement in memory has been shown amongst
rats exposed to GA however refinement of the model showed a consistent impairment in learning
for 2-3 weeks following exposure [12]. Experiments on cells in vitro have exposed some potential
pathways for neurotoxicity of GA agents notably in the oligomerisation of A peptides linked with
Alzheimers disease [49]. The applicability of the laboratory work to clinical practice is not yet clear.

BGS Amulree Essay Prize

Nathan Gauge

Clinical assessment of the impact of GA on neurotoxicity has been addressed by studies comparing
regional anaesthesia (RA) with GA. A number of trials have looked at this with the majority finding
no significant difference between the two suggesting that GA plays only a small role in POCD,
however, methodological limitations complicates their results [38]. It is worth noting that the largest
study so far found when using per protocol analysis that there was a significant reduction in
POCD amongst patients with RA (12.7%) compared to patients receiving GA (21.2%) at one week
postoperatively [39]. Evidence from these trials is therefore still somewhat inconclusive.

An alternative assessment of the impact of GA can be achieved through the monitoring of the depth of
anaesthesia. However, this method is likely to pick up additional systemic effects of sedation as well
as any direct neurotoxicity from GA. Depth of anaesthesia monitoring using electroencephalography
has been attempted in four papers.

Three randomised control trials were reported [17, 18, 48]. Gaba et al. have not reported full analysis
of their data, however, they found no correlation between BiS values and postoperative delirium.
Wong et al randomised patients to either titration of isoflurane to Bispectral Index Scores (BiS) of 5060 or standard treatment. In the intervention group they showed a 30% reduction in use of isoflurane
(p <0.05), a reduction in time to orientation (p < 0.01) and no difference in POCD. However the
analysis of POCD was done without reference to baseline values and by repeating the
neuropsychological tests 7 times within the first 72 hours postoperatively[18]. Without a control
group for learning effect and conducting all psychometric tests within 3 days postoperatively these
results are more applicable to postoperative delirium than POCD.

Farag et al randomised patients to two different anaesthetic depths and found a significant reduction in
cognitive decline in the group randomised to deeper levels of anaesthesia (p = 0.006) in one of their
three neuropsychological tests the processing speed index at 4-6 weeks postoperatively.
Unfortunately the two anaesthetic depths were similar and both overlapped with the ideal level of
sedation (a BiS score of between 40-60 [37]). It has also been noted that there was poor compliance
with the target BiS values patients in the low BiS group were within or below the range only 54% of
the time and in the high BiS group were within or above the range for only 57% of the time[45].

Steinmetz et al. conducted an excellent correlation study using intraoperative cerebral state index
(CSI) a very similar measure to BiS - with POCD. They found no statistical difference in mean CSI,
deep hypnotic time (CSI<40) and light hypnotic time (CSI>60) between patients with POCD and
those without at 1 week postoperatively. They also found no significant correlation between the Z
scores for the 7 neuropsychological tests and mean CSI [45].

Given the mixed results found using depth of anaesthesia monitoring and issues with study design
further research is urgently needed. Any role for GA in the development of POCD is far from clear.

BGS Amulree Essay Prize

Nathan Gauge

Postoperative Recovery
A number of routine postoperative medications are known to have significant effects on patients
cognitive response especially in attention and reaction speed tasks. This effect has been monitored
only sporadically in POCD studies and has been found to be significant in some trials (see for
example opioid medication in [45]. However, a study addressing the effect of benzodiazepines in
elderly patients found no significant relationship between blood concentrations of the drug and POCD
[41]. Despite this finding the use of neurologically active drugs in studies of POCD is a potentially
important confounder. Postoperative complications including infection and respiratory difficulties
have been shown to be associated with increased risk of POCD [31]. Careful consideration of these
potential confounders is therefore essential.

Prevention

No modifiable cause of POCD in non cardiac surgery has yet been identified[38]. Several trials have
considered possible mechanisms (reviewed in (Newman et al., 2007). These include normotensive and
hypotensive anaesthesia, intravenous versus inhalation Anaesthesia, pulse oximetry monitoring,
hypocapnia and vitamin supplementation. None have found significant effects with respect to
POCD[34].

As identified previously, several trials in cardiac surgery have shown some promise in preventing
POCD[23, 43]. In non-cardiac surgery to date only one trial has shown a reduction in a sub test of
POCD[17]. This trial has been heavily criticised in the literature[45] and the results therefore need
cautious interpretation.

BGS Amulree Essay Prize

Nathan Gauge

Methods
The study protocol was approved by the local research ethics committees and all patients gave written
informed consent. Patients were taken from two UK regional teaching hospitals and were matched
based on age, gender and baseline mini mental state exam (MMSE) to control subjects taken from the
local regions. The full selection protocol for surgical patients has been published previously [29].
Patients were included if they were scheduled to undertake elective major abdominal or orthopaedic
surgery under general anaesthesia at either centre. Exclusion criteria included age under 60 years,
inability to complete or unwillingness to comply with any of the protocol or procedures and preexisting dementia (defined as a MMSE score of 23 or less).

Assessments
Patients were assessed using a combination of the MMSE and the standard computerised drug
research (CDR) battery. Assessments were carried out at baseline (preoperatively for surgical
patients) and as a minimum at 12 months following the baseline assessment.
In line with previous studies cognitive decline was classified at three levels; mild, moderate and
severe[36]. These levels correspond to measures commonly used to describe cognitive decline in
elderly subjects, specifically; age associated cognitive decline (AACD), mild cognitive impairment
(MCI) and post-operative cognitive dysfunction (POCD). The scores were calculated using the
ISPOCD Z score method described previously [31]. The change for individual subjects from baseline
was calculated and the control group was used to remove any learning effect and to provide the values
for standard deviation. The following seven cognitive tests were used; MMSE, simple reaction time,
digit vigilance accuracy, digit vigilance reaction time mean, choice reaction time accuracy, choice
reaction time mean and cognitive reaction time mean. The level of cognitive decline was defined as
follows;
Mild (AACD) = greater than 1 SD decline in at least one of the seven cognitive domains.
Moderate (MCI) = greater than 1.5 SD decline in at least one of the seven cognitive domains.
Severe (POCD) = greater than 1.96 SD decline in at least two of the seven cognitive domains.

Analysis
A sample size of 250 patients provides a 99% power to detect a difference of 25% between the two
groups with a 0.05 risk of type 1 error. Assuming a patient loss to follow up at one year of 25% this
requires an initial study population of 313. The 25% difference in proportions of decline was based on
the 3 month difference in mild cognitive decline reported previously from the London cohort i.
Analysis was conducted using SPSS software, version 17.0 (SPSS, Chicago, IL, USA). Significance
was determined as two-sided p values <005. No correction was made for multiple comparisons.

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Comparison of the baseline MMSE, age and gender of the control and surgical groups was made
using the 2 test, Students t test and MannWhitney U test as appropriate. The Kolmogorov-Smirnov
test was used to establish deviation from a normal distribution.
The primary outcome measure was predetermined as the difference in the prevalence of mild,
moderate and severe cognitive decline between surgical patients and controls assessed using the 2
test. Continuous analysis was also conducted on the individual cognitive domains using Students t
test, the MannWhitney U test as appropriate.

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Results
Cohort Analysis
Population Characteristics
330 subjects were assessed at baseline including 192 surgical patients and 138 controls. The baseline
characteristics are reported in table 1. There was no significant difference in Age (p = 0.498), baseline
MMSE (p= 0.252) or Gender (p = 0.563) between the two groups.

Age
MMSE
Male
Gender
Table 1

Group

Number

patient
control
patient
control
patient
control

192
138
192
138
192
138

Median (IQR) /
percentage
75 (9)
76 (7)
28 (2)
28 (2)
40%
37%

Test

Asymp. Sig. (2tailed)

M-W

0.498

M-W

0.252

0.563

A total of 256 (78%) subjects completed all of the 1 year assessments. There were no significant
differences with respect to Age (p = 0.910), baseline MMSE (p = 0.313) or Gender (p= 0.372)
between subjects who completed the 1 year assessment and those who did not.
Global Decline
At one year post operatively there was a significant difference between patients and controls in all
three levels of cognitive decline. Mild POCD was found in 76% of surgical patients compared to
50.4% of nonsurgical controls (Pearson 2 p = <0.001). Moderate POCD was found in 48% of
surgical patients compared to 27.5% of nonsurgical controls (Pearson 2 p = 0.001). Severe POCD
was identified in 11.2% of surgical patients compared to just 3.8% of nonsurgical controls (Pearson 2
p = 0.024). These results are displayed in figure 1.

Percentage of Subjects with POCD at 1 year

p = <0.001
p = <0.001
80.0%
70.0%
p = 0.001

60.0%
50.0%

surgical patient

40.0%

control

30.0%

p = 0.024

20.0%
10.0%
.0%
Mild

Moderate

Severe

Figure 1

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Individual Domains
Significant differences were found between surgical patients and controls with respect to simple
reaction times - median(IQR) 25.57(73.80) v 9.52(49.75) p = 0.025, cognitive reaction times median(IQR) -25.69(120.96) v -3.42(65.35)p = 0.006 and digit vigilance mean accuracy (median
(IQR) 0.00 (4.44) v 0.00 (0.00) p = 0.05). The full results of the continuous analysis are presented in
table 2.
Z

Asymp. Sig. (2tailed)

MMSE

-1.790

.073

Simple Reaction Time Mean

-2.243

.025

Digit Vigilance Mean

Accuracy

-1.940

.052

Digit Vigilance Reaction

Time Mean

-.504

.614

Choice Reaction Time Mean

Accuracy

-.896

.370

Choice Reaction Time Mean

-1.220

.223

Cognitive Reaction Time

Mean

-2.744

.006

Table 2

13

Surgical patient /
control

Median (IQR)

surgical
control
surgical
control
surgical
control
surgical
control
surgical
control
surgical
control
surgical

0.00 (2.00)
0.00 (2.00)
25.57 (73.80)
9.52 (49.75)
0.00 (4.44)
0.00 (0.00)
9.25 (59.26)
13.47 (29.80)
0.00 (3.34)
0.00 (3.33)
-5.81 (81.61)
-10.78 (57.70)
-25.69 (120.96)

control

-3.42 (65.35)

BGS Amulree Essay Prize

Nathan Gauge

Discussion
This is the first longitudinal cohort study of POCD to demonstrate a significant difference in the level
of global cognitive decline between surgical patients and controls at 12 months post operatively. It
identifies attentional and executive function as particularly sensitive neurocognitive domains in
POCD.
It is important to address the reasons why our trial has successfully identified significant differences
in the level of cognitive decline where previous trials have not. I have highlighted three possible
mechanisms for this:

The reduction of ceiling and learning effects using the CDR system
The use of multiple levels of POCD
The focus on attention and executive function

Our emphasis on computerised neuropsychometric analysis and reaction speeds substantially reduces
the learning effect observed with many other studies[47]. It is worth noting that the only other 12
month trial to demonstrate any difference between surgical patients and controls also employed a
computerised test battery[3]. Previous studies into POCD including the work of the ISPOCD study
group is substantially hampered by learning effect. Despite attempts to account for the effect using a
control group this analysis method exposes trials to 2 primary flaws.
Firstly the trial is not truly assessing cognitive decline but rather a failure to recall the
neuropsychometric tests and to demonstrate cognitive improvement. It has been previously noted that
memory function appears less significant in POCD than executive function and has a lower impact on
patients functional impairment[36].
Secondly the fixed and invariable nature of paper-based neuropsychometric tests exposes them to a
potential retest ceiling effect. This is distinct from an initial ceiling effect which will tend to
overestimate the levels of POCD[9]. Instead during repeated retesting over a short time period
subjects can achieve extremely high scores from which further improvement becomes exponentially
difficult. The normal subjects reach the test ceiling early and subsequent retesting provides impaired
subjects an opportunity to catch up. POCD
studies focusing on differences in the learning
effect will therefore tend to produce a gradual
convergence in test scores between impaired and
non-impaired subjects despite continued
cognitive deficits within the impaired group
demonstrated graphically in figure 2.
This pattern has been observed in previous
studies of POCD and has been presented as a
reduction in the level of cognitive dysfunction
with time [31]. The retest ceiling effect is
substantially reduced, though not completely
eliminated, with the CDR system employed in
our study as a result of the variability of the

Figure 2

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target, the emphasis on reaction times and the use of practice sessions prior to each test to standardise
familiarity with the tasks and equipment and has been demonstrated empirically[47].
Whilst our definition of three levels of POCD has been used previously[36] it is not widely employed
in POCD research. However, in our opinion it carries a number of advantages. Firstly it allows for the
detection of more subtle changes in cognitive function sacrificing specificity for increased
sensitivity to cognitive decline. Improving the sensitivity for decline has identified a greater
percentage difference between surgical and control populations, substantially increasing the statistical
power to detect a variation in the proportions of two populations. This method also allows for
comparison with the extensive literature on cognitive decline in the elderly with the definitions
corresponding to age associated cognitive decline and mild cognitive impairment. Finally we have
also included the classic definition of severe POCD allowing for comparison with previous literature
within this field.
Very few earlier papers assessing POCD over six months post operatively (table 4 appendix) have
incorporated measures of attention and executive function. Our emphasis on these two cognitive
domains was based on the evidence demonstrating their significance for functional impairment
associated with cognitive decline in the elderly [8, 36]. The results from this study demonstrate that
both attention and executive function are significantly affected in elderly surgical patients one year
post operatively. Given the significant impact on functional impairment caused by these specific
cognitive domains our findings may help to explain the substantial evidence demonstrating the
continued impact of POCD on patients mortality and their capacity to function within society well
beyond the 3 month cut off point previously identified[44].
As the first trial to identify significant levels of POCD a full twelve months post operatively our
findings represent an important step in bridging the gap that has emerged between the impact of
POCD on patients lives and our capacity to identify cognitive impairment beyond 3 months post
operatively. Given the recent evidence demonstrating the mortality and morbidity associated with
POCD as well as increased costs to the health service the identification of modifiable causes of POCD
is an important research challenge. This trial establishes the combination of computerised
neuropsychometric testing, a focus on attention and executive function and a multilevel approach to
scoring cognitive decline as a powerful new method for identifying the long term effects of POCD.
Our methods substantially reduce the experimental problems faced by previous trials and provide a
greater sensitivity for differences in cognitive decline with a longer duration of effect. It is our hope
that our findings will pave the way for future intervention trials.

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Appendix
Table 3

Lead
Author
Goldstein
Billig
Hall

Date
1998
1996
2005

Gilberstadt

1968

Abildstrom 2000
Ancelin

2010

follow
up
300
365
365
365 to
730
365 to
730
395

number Control
verbal
memory
of
for
and
and
attention and
subjects learning language learning concentration
108
N
x
104
N
x
122
N
63

336

270

x
x

16

visual
and
spatial

Visuomotor

numerical

executive
function

composite
screening
tools
x
x
x

Difference
None
None
None

None

x
x

None
language
visuospacial

BGS Amulree Essay Prize

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