Anaesthesia and cognitive

disturbance in the elderly

Daniel P Fines
Andrew M Severn

Delirium
Delirium is the acute onset of disturbed mental
function; it is surprisingly common in elderly
hospitalized patients and the time course is
often short. Alteration of consciousness may
be a feature. Visual hallucinations may occur
with fleeting delusional thoughts. Anxiety and
distress are common. There is a diurnal variation of symptoms with a variety of behaviours,
from aggression to withdrawal (leading to a
mistaken diagnosis of depression).
There may be a predisposing cause, such
as urinary tract or chest infection, or it may
be related to drugs including alcohol or caffeine
withdrawal. In particular, drugs with anticholinergic actions are implicated in delirium.
Many drugs, including digoxin, thiazide
diuretics, and corticosteroids have mild anticholinergic actions that may, when used in
combination with other drugs with similar
effects, contribute to delirium. Opioids, sedatives and disturbances of calcium, sodium, and
glucose homeostasis are also associated factors. Failure of communication may be a consequence of loss of dentures, glasses or hearing
aids; this may lead to a mistaken diagnosis.

Dementia
Dementia refers to a series of chronic organic
brain syndromes associated with irreversible

pathology; delirium is frequently mistaken

for dementia. Many of the causes of dementia
are associated with a failure of cholinergic
transmission; therefore, patients are very
sensitive to anticholinergic drugs. Anticholinesterases are used in some patients to
improve cognitive function. In its most easily
recognized form, dementia presents as a global
deterioration of cognitive ability in the
absence of clouding of consciousness, that is,
the patient who responds appropriately when
introduced but who clearly is mistaken as to
where he or she is when asked a few simple
questions during the preoperative visit.
The very nature of hospital admission,
particularly for emergency or trauma surgery,
means that delirium may occur in the patient
with dementia. Indeed, the latter is considered
a risk factor for the former. However, it is
important that due consideration is given to
the potentially reversible part (delirium) of
the symptom complex before assuming that
the patients problems are an inevitable consequence of dementia. In practice, it is important that a confident diagnosis of dementia is
made by the community services (e.g. general
practitioner, nursing home), rather than in an
acute postoperative situation.
The diagnosis and clinical features of the
dementias are beyond the scope of this
article. Suffice to say that there are a number
of diseases in which dementia is a feature.
Alzheimers disease is one of the most important examples of a progressive chronic condition associated with cognitive decline. Chronic
decline also occurs in Parkinsons disease and
widespread cerebrovascular disease.

Anaesthetic assessment
It is important to assess the severity of cognitive
disturbance. The Mini-Mental State Examination (MMSE) is a test of global cognitive
function2 that can be performed at the bedside.
It consists of a series of questions on orientation and simple commands to assess comprehension (Table 1). Variations in MMSE allow
comparison to be made with time and measure

doi 10.1093/ceaccp/mki066
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Key points
Perioperative delirium and longer
term cognitive disturbance are
common and disabling
consequences of anaesthesia and
surgery in the elderly.
Evidence is emerging that the risk
of postoperative delirium can be
predicted by preoperative
screening of otherwise
asymptomatic patients.
The risk of prolonged
postoperative cognitive
dysfunction (POCD) is 10%
following major surgery in
patients of more than 60 yr of age.
Increasing age is a risk factor and
the incidence in patients of more
than 80 yr of age may be as high as
one in three.
Regional anaesthesia reduces the
risk of cognitive impairment in the
immediate postoperative period
but appears to have no effect on
the incidence of prolonged
POCD.
The risks of cognitive decline
should always be considered and
discussed when major surgery is
contemplated in elderly patients.

Daniel P Fines
Consultant
Department of Anaesthesia
Royal Manchester Childrens Hospital
Hospital Road
Pendlebury
Manchester M27 4HA
Andrew M Severn
Consultant
Department of Anaesthesia
Royal Lancaster Infirmary
Ashton Road
Lancaster LA1 4RP
Tel: 01524 583528
Fax: 01524 583519
E-mail:
[email protected]
(for correspondence)

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Decline in cognitive functioning after surgery,

particularly in the elderly, has been anecdotally
appreciated by the profession and public for
many years. It is a well established phenomenon after cardiopulmonary bypass and recent
research reveals it to be a surprisingly common
outcome after other types of major surgery.
Much remains unknown about its aetiology,
but the implications for anaesthesia and surgery in an increasingly long-lived population
are considerable.
Three clinical conditions are worthy of discussion and need to be distinguished from each
other, that is, delirium, dementia, and postoperative cognitive dysfunction (POCD).1

Cognitive disturbance in the elderly

Table 1 Aspects of cognitive function tested by the MiniMental State Examination

Orientation in time
Orientation in place
Repetition of named objects
Repetition of simple phrase
Ability to undertake simple arthmetic
Recall of objects named earlier in the interview
Naming of objects shown by examiner
Execution of simple tasks by written and spoken command
Writing a simple sentence
Copying a simple design

Postoperative cognitive dysfunction

POCD has been defined for research purposes as deterioration in
performance in a battery of neuropsychological tests that would
be expected in <3.5% of controls. This dry statistical statement
equates to a catastrophic loss of cognitive ability; it is the difference between a person who is capable of living independently and
one who is not. POCD can be usefully defined as a long term,
possibly permanent, disabling deterioration in cognitive function
following surgery. The statement that Granddad was never the
same after his operation is occasionally heard and may reflect

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Possible causes of POCD

Emboli
There is much evidence to suggest that multiple cerebral emboli
are the cause of cognitive deterioration following cardiopulmonary bypass. Whilst many other types of surgery do not carry such
a direct risk of cerebral embolization it seems nevertheless
plausible as a causative factor.

Perioperative physiological disturbances

Biochemical disturbances, notably hyponatraemia, are a well
recognized cause of postoperative delirium. There is no evidence,

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progress following illness or surgery. The MMSE is scored out of a

total of 30, with points being awarded for correct answers in the
various aspects of function tested. An MMSE score of <23 is not
diagnostic of dementia but does offer supporting evidence. Lesser
degrees of impairment of MMSE scores (e.g. 2629) imply a degree
of cognitive deficit which, while not indicative of dementia, may
have implications for postoperative management. It is becoming
apparent that, even in the absence of dementia, MMSE scores of
28 or less are associated with more than a 2-fold increased risk
of developing postoperative delirium compared with scores of
29 or 30. Specific deficits of attention appear to be associated
with an even higher level of increased risk.3
Performance of a complete MMSE may be difficult to justify in
an asymptomatic preoperative patient. However, it is reasonable
to assume that a patient who is unable to recall simple information pertaining to time and place (e.g. date or hospital) will score
significantly less than the maximum 30 points. Such information may be of serious clinical significance when it comes to
predicting the possibility of postoperative confusion.
The time course of acute cognitive dysfunction, as assessed
with serial MMSE measurements following major surgery, has
been described. Duggleby and Lander4 assessed 66 patients
after hip arthroplasty for several days, undertaking serial
MMSE examinations. Four patients failed to complete the
study, for reasons that might arguably be attributable to
confusion, and no details of anaesthetic technique are recorded.
However, the data are striking. More than a quarter of these
patients had MMSE scores <26 on the third postoperative day
and, even by day 5, MMSE scores in a few patients failed to return
to preoperative levels. These patients were relatively young (mean
age 64.8, range 5080).

the lay persons view of POCD. It is difficult to get a reliable

estimate of how prevalent and disabling such conditions are.
Hence the approach used by the investigators in the International
Study of Postoperative Cognitive Dysfunction to define the
condition in terms of a statistical abnormality, rather than any
particular clinical features.
Research into POCD is fraught with problems. Observed over
time, a proportion of the elderly population will suffer cognitive
decline in any event, and some studies are hampered by the lack
of an appropriate control group. Also, the development of other
pathologies within the study period may affect the results. The
tests used to detect POCD vary among studies, making comparison difficult. The level of difficulty of the tests themselves is
importanttoo easy and they fail to detect more subtle degrees
of impairment, too difficult and they discourage the subject, thus
influencing performance in the tests. Furthermore, performance
in cognitive testing is sensitive to the environment in which it is
carried out, the manner in which it is administered, the mood of
the subject at the time, and the number of times it is administered. Allowance must be made for all of these factors when
interpreting the data. Recruiting patients to take part in studies
of POCD is not easy. Patients who feel they may be vulnerable
to cognitive decline may elect not to take part, or withdraw
subsequently if they feel that their cognitive performance has
worsened. Postoperative depression and coping mechanisms
may also play a part; subjective reporting of cognitive decline is
more common than that detected by testing.5
Despite these difficulties, some research has been carried out in
this area. The largest study of POCD carried out to date, in a
cohort of more than 1200 patients of more than 60 yr of age,
found an incidence of POCD of 25% at 1 week and 10% at
3 months postoperatively.6 Further follow up of the affected
patients showed that the incidence of cognitive problems eventually fell towards that in matched controls but that 1% had unresolved POCD up to 2 yr after operation. The older patients
within the study showed a higher incidence, approaching one in
three in the relatively small group of more than 80 yr of age,
and further studies have shown a correspondingly smaller risk
in younger patients.7 It is clear that increasing age is in itself a
risk factor for developing POCD.

Cognitive disturbance in the elderly

however, that biochemical disturbances cause prolonged POCD.

Perhaps more surprisingly, there is no evidence that perioperative
hypoxaemia or hypotension, even quite profound or prolonged, is
associated with POCD.6

Pre-existing cognitive impairment

Studies of POCD exclude patients who are already cognitively
impaired, but it is possible to demonstrate a lower risk of
POCD in patients with a higher level of intellectual performance
preoperatively. It is likely that the converse is true and a preexisting dysfunction increases the risk of POCD.

Other factors

Anaesthetic technique and postoperative

cognitive impairment
Good perioperative anaesthetic care is regarded as one of the key
means of reducing postoperative complications in any group of
patients, and it seems reasonable to assume that this also applies
to POCD in elderly patients. Therefore, it is surprising and
disappointing that fundamental parameters such as oxygenation and blood pressure do not seem to influence the incidence.
Nevertheless, there are important considerations for the
anaesthetist which can affect postoperative cognitive function.

Premedication
Benzodiazepines may cause disorientation and confusion in the
elderly. Surprisingly, however, the use of preoperative benzodiazepines is associated with an apparent 2-fold reduction in pro-

Conduct of anaesthesia
There is no strong evidence to support the use of any particular
drugs. However, there are significant associations between early
POCD, and both increasing duration of anaesthesia and respiratory complications; therefore attention can be directed to the
avoidance of these factors where possible.
Recent research has focussed more particularly on the possible
benefits of regional over general anaesthesia. Many anaesthetists
actively promote the use of regional anaesthetic techniques in
the elderly. Lower limb joint replacement, for instance, is commonly performed under regional anaesthesia alone. There may be
a number of good medical reasons in a given individual for
recommending regional above general anaesthesia but, even in
the absence of these, it is often felt that elderly patients recover
more quickly and with less cognitive disturbance following
regional anaesthesia. Available evidence from patients randomized to receive either regional or general anaesthesia shows that,
in the first week after surgery, the incidence of cognitive impairment is indeed reduced where regional techniques were used
(12.7% vs 21.2%); however, this difference does not persist at
3 months. Regional anaesthesia does not appear to be superior
to general anaesthesia in preventing prolonged POCD.8 The
reduced risk of early POCD may have important implications
for physical recovery, cooperation with postoperative therapy,
and length of hospital stay.
Recent evidence suggesting that patients are at risk from
POCD as a consequence of admission to hospital supports the
concept of day case surgery. Obviously, this can only be undertaken where support services (e.g. competent relatives, practice
nurses, social services) are involved and investigations completed
before admission.

Future developments
Table 2 Predisposing factors for POCD
Early POCD
Increasing age
General rather than regional anaesthesia
Increasing duration of anaesthesia
Respiratory complication
Lower level of education
Re-operation
Postoperative infection
Prolonged POCD (months postoperatively)
Increasing age only

The precise aetiology of POCD remains obscure and the subject

of further research. What is known can nevertheless be applied to
clinical practice in an effort to reduce the incidence. It is clear that
cognitive dysfunction in the immediate postoperative period
and that persisting for months or years are two distinct entities.
Although early postoperative delirium does not have the implications for long term care attached to prolonged POCD, its presence
can impair recovery and prolong hospitalization in a vulnerable
group of patients. Recognition of the special challenges of
perioperative care in elderly patients have made this an emerging
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Serum concentrations of known markers of brain damage such as

neurone specific enolase and S-100 beta protein do not appear to
correlate with the development of POCD. Many other factors
have been considered as possibly contributing to the risk. They
include variations in the handling of anaesthetic and other drugs,
changes in the normal adrenal response to surgery in old age, and
the possibility of a risk gene for POCD in a manner analogous to
Alzheimers disease. There is currently no good evidence to support any of these theories.
The known predisposing factors for early and late POCD are
summarized in Table 2.

longed POCD (from 9.9 to 5%). This is thought to be the result of

a deterioration in patients who have such medication withdrawn
acutely, rather than a direct protective effect of the drug. Certainly
patients who are taking drugs to support their cognitive function,
including the anticholinesterase drugs such as donezepil, should
not have them stopped perioperatively. There are grounds to
believe that sudden stopping of anticholinesterases may precipitate cognitive failure that may be difficult to reverse.

Cognitive disturbance in the elderly

References
1. Gosney M. Acute confusional states and dementias: perioperative
considerations. Curr Anaesth Crit Care 2005; 16: 349
2. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method
for grading the cognitive state of patients for the clinician. J Psychiatr Res
1975, 12: 18998
3. Lowery, D. Neuropsychological Markers of Post-Operative Delirium.
PhD Thesis, University of Newcastle upon Tyne, 2004
4. Duggleby W, Lander J. Cognitive status and postoperative pain: older adults.
J Pain Symptom Manage 1994, 9: 1927
5. Dijkstra JB, Jolles J. Postoperative cognitive dysfunction versus complaints:
a discrepancy in long-term findings. Neuropsychol Rev 2002; 12: 114
6. Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative
cognitive dysfunction in the elderly: ISPOCD1 study. Lancet 1998; 351:
85761
7. Johnson T, Monk T, Rasmussen LS, et al. Postoperative cognitive dysfunction
in middle-aged patients. Anesthesiology 2002; 96: 13517

Acknowledgement

8. Rasmussen LS, Johnson T, Kuipers HM, et al. Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus
general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand 2003;
47: 2606

The authors would like to thank Professor Clive Ballard of Kings

College, London for his assistance with this paper.

Please see multiple choice questions 3030.

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subspecialty of anaesthesia, within which an awareness of the

importance of cognitive outcome is most important.
It appears that a subset of the elderly population stands at
the top of a slippery slope, vulnerable to prolonged or permanent
cognitive decline after surgery. It is not currently possible to
identify which patients are at particular risk, or which elements
of the process of hospitalization, anaesthesia, surgery, and postoperative care may be precipitating the deterioration. At present
it is incumbent upon anaesthetists, surgeons, and all involved in
the perioperative care of elderly patients to consider the risk of
POCD whenever surgery is contemplated and to discuss the issue
with patients and their families. For some patients and some procedures, consideration of these risks may move the goalposts
such that they no longer consider the proposed operation to be
in their best interests.