INSERM EPI-9930, Montpellier
Service d'Orhtopédie III, Hôpital Lapeyronie, Montpellier, France
Correspondence: Dr Marie L. Ancelin, INSERM EPI-9930, Epidemiology and Clinical Research in Nervous System Pathologies, CRLC Val d'Aurelle, Bat. Rech. Rdc, Parc Euromédecine, 34298 Montpellier Cedex 5, France
Declaration of interest None. Funding detailed in Acknowledgements.
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ABSTRACT |
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Aims To evaluate anaesthesia effects on the incidence of cognitive dysfunction after orthopaedic surgery in elderly patients.
Method A total of 140 patients over the age of 64 years completed a full range of computerised cognitive tests. The study takes into account effects of pre-operative cognitive dysfunction, depressive symptomatology and ability to perform activities of daily living.
Results Postoperative cognitive decline persisted for up to 3 months in 56% of subjects. Dysfunction was limited to verbal, visuo-spatial and semantic abilities and secondary and implicit memory. Age, low educational level, pre-operative cognitive impairment or depression are risk factors.
Conclusions Cognitive functions are not equally affected, type of impairment being determined by the risk factors described above and anaesthesia type.
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INTRODUCTION |
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METHOD |
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Cognitive evaluation
Each subject was examined pre-operatively at 9 days (mean=9 days, s.d.=4)
and at 3 months (mean=97 days, s.d.=17) using a comprehensive computerised
cognitive battery. This examination, the ECO (Examen Cognitif par Ordinateur),
was used to assess working memory, verbal and visuo-spatial secondary memory,
implicit memory, language skills (word and syntax comprehension, naming,
verbal fluency, articulation), visuo-spatial performance (ideational,
ideo-motor and constructive apraxia, functional and semantic categorisation of
visual data, visual reasoning and form perception) and focused and divided
attention (visual and auditory modalities)
(Ritchie et al,
1993).
Twenty-one summary scores were derived from the 159 ECO variables representing six cognitive domains (see Table 1):
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In addition to cognitive assessment at the time of admission, pre-existing cognitive deterioration is established by an informant questionnaire completed by caregivers (DECO, Détérioration Cognitive Observée) that measures changes in cognitive performance over the past year. Previous validation studies in both clinical and population settings have shown this instrument to be highly sensitive to early modifications in cognitive functioning due to multiple causes (Ritchie & Fuhrer, 1995). DECO scores range from a maximum of 38 (no change over the past year) down to zero (significant change over the 19 areas of cognitive performance examined). A score lower than 30 is generally considered to indicate a high probability of senile dementia within a general population sample.
Depressive symptomatology
Depressive symptomatology is described by reference to the French version
of the Center for Epidemiological Studies Depression Scale (CES-D,
Fuhrer & Rouillon, 1989).
This questionnaire has been validated both in the USA and in France as a
measure of clinical depression.
Adaptation and behaviour scale
Ability to perform activities of daily living was assessed by the
adaptation and behaviour scale ECA (Echelle de Comportement et d'Adaptation)
developed by Ritchie & Ledésert
(1991). This questionnaire is
completed by relatives and has been constructed with reference to the
disability classifications given by the World Health Organization
(1988). The scale has high
interrater and retest reliability and is highly sensitive to small changes in
activity level due to cognitive impairment.
General questionnaire
A general questionnaire was administered in order to obtain
socio-demographic information, current pathology and treatment, surgery
antecedents and to note details of the surgical procedures, type of
anaesthesia, duration of hospitalisation and management after discharge.
Statistical analysis
Significant alteration in cognitive decline was defined as the modification
of more than one standard deviation on one of the 21 summary ECO scores from
baseline to postoperative levels. Formal criteria for subclinical cognitive
impairment have uniformly used this one standard deviation criterion, for
example in the definition of ageing-associated cognitive decline
(Blackford & La Rue, 1989), mild cognitive decline (World Health
Organization, 1993) and mild neurocognitive disorders
(American Psychiatric Association,
1994).
Relative risk for cognitive decline in each cognitive domain at 3 months was calculated from decline scores, which were obtained by subtracting scores at 3 months from scores obtained pre- operatively. The decline score is positive for subjects showing decline and negative for those showing improvement.
All statistical analyses were performed with SPSS for Windows NT, version 8.01F (SPSS, 1998).
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RESULTS |
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Using separate CES-D cut-off points for depressive illness established for
men (> 17) and women ( 23) in France
(Fuhrer & Rouillon, 1989) it was found that depressive symptomatology was common in the sample, with 21%
of subjects reaching the level of major depressive episode as compared with an
observed 14% within the general elderly population
(Fuhrer et al,
1992).
The pre-existing cognitive deterioration mean score (DECO) of the sample was 33.8 (s.d.=5.9). Fifteen per cent of subjects were at risk of having early-stage senile dementia (i.e. DECO score < 30).
Participation rates
Of the 140 subjects who completed the pre-operative interview, 133 were
re-examined at 9 days postoperatively. Of these, 98 were again examined at 3
months post-operatively. Examination of the socio-demographic characteristics,
depression and ECA scores of subjects retained and lost at 3 months showed no
significant differences. By contrast, DECO scores appeared significantly lower
for subjects who withdrew at 9 days (31.4, s.d.=8.2) compared with those
retained at 3 months (34.7, s.d.=4.7) (P=0.005). Of the 21 subjects
at high risk of having early-stage senile dementia at entry into the study, 11
were lost at 3 months.
Ability to perform activities of daily living
Mean ECA score at entry was 68.0 (s.d.=7.2), which did not differ
significantly from that at 3 months (mean 67.7, s.d.=7.9). Detailed
examination of the 15 individual ECA variables also showed no significant
difference between initial and 3-month scores, except for one item (ability to
put oneself to bed) (P=0.046), probably related to surgery type.
Initially, ECA scores were significantly lower for the oldest group (> 75 years) (P=0.014) and for subjects with high risk of having early-stage senile dementia at entry (P=0.002). After 3 months, the same pattern was observed without any further significant ECA score alteration in each of these groups.
The ECA score after 3 months (but not pre-operatively) was significantly lower for subjects with high risk of depression (P<0.03). There was no correlation between initial and 3-month postoperative ECA and CES-D scores.
Cognitive evaluation
According to the cognitive domain considered, 5.8-70.3% of subjects showed
a drop in performance 9 days postoperatively
(Table 1). Deterioration of
more than one standard deviation was observed to occur in 25.4% of subjects on
a test of visuospatial reasoning (logical series). After 3 months a similar
pattern of alteration was observed, with a decrease in subjects experiencing
deterioration (3.4-66.3%). Among the various cognitive domains investigated,
no subject showed significant deterioration after 3 months in attention tasks,
and less than 5% of subjects showed a significant deterioration in primary
memory, which was affected only in the immediate postoperative period. With
regard to visuo-spatial ability, significant deterioration was principally
observed in visuospatial reasoning (19.1%) and visual analysis with semantic
cues (12.5%). Secondary verbal memory, implicit memory and language were
altered significantly over a wide range of items (from 1.1-14.6% of
subjects).
Altogether, 29% of subjects showed no significant alteration after 9 days, on any of the ECO test scores listed in Table 1, and this increased to 44% after 3 months (Fig. 1). Among those who deteriorated after 9 days, 19% of subjects showed a significant deterioration in at least four test scores at 9 days and 11% after 3 months. Among the 29% of subjects for whom no significant deterioration was noted after 9 days, 21% had the same level after 3 months as pre-operatively and 8% showed a late cognitive decline. Among the 71% of subjects with significant early cognitive decline, 15% did not experience any modification between 9 days and 3 months, 38% showed improvement in one to four cognitive tests (with 23% returning to their pre-operative level and 15% remaining below) whereas 18% continued to deteriorate in one to three tests.
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Subjects showing the greatest degree of deterioration tended to be the most elderly, those with the lowest educational level and those with a recent history of cognitive deterioration before surgery. A high rate of cognitive impairment in subjects refusing follow-up has undoubtedly led to an underestimation of actual impairment rates at 3 months.
Effect of anaesthesia type
Fifty-two subjects were exposed to general anaesthesia with sedation and 88
to local anaesthesia. In this latter group, 77 subjects submitted to peridural
anaesthesia (or rachianaesthesia), of whom 22 received additional sedation.
After general anaesthesia, 38% of sub- jects showed no alteration in cognitive
performance 9 days after the operation, compared with 24% after peridural
anaesthesia without sedation. After 3 months, regardless of anaesthesia type,
half of the subjects showed no significant cognitive change compared with
pre-operative levels. The same proportion of subjects (17-20%) continued to
deteriorate between 9 days and 3 months for both general and peridural
anaesthesia without sedation. The proportion of subjects with improved
performance was higher in the peridural group (49%) compared with the general
anaesthesia group (26%).
For subjects undergoing general anaesthesia, there was an increase in the relative risk (RR) for cognitive decline on tasks of visuo-spatial analysis (RR=2.8; 95% CI 1.1-6.9) and also on verbal fluency (RR=1.7; 95% CI 1.1-2.6). For peridural anaesthesia and in the absence of sedation, the risk increase was related principally to implicit memory (RR=1.7; 95% CI 1.2-2.2) and primary or short-term verbal memory (RR=5.4; 95% CI 1.2-24.2). Adding sedation to peridural anaesthesia led to a decline in verbal secondary memory (RR=3.8; 95% CI 1.0-14.5). There was no significant difference in the anaesthesia duration between the groups, which contributed only to a slight decline on tasks of implicit memory (RR=1.4; 95% CI 1.0-2.0).
Depressive symptomatology
The global depression score (CES-D) was 13.9 (s.d.=9.9) and did not differ
between men and women. Regardless of gender, after 3 months there was no
modification either in the global depression score (14.5, s.d.=10.7) or in
specific symptoms. In the patients depressed before surgery, 88% were still
depressed at 3 months. In the non-depressed group before operation, 9.7% were
depressed at 3 months. After 3 months there was no modification of global
CES-D score whether subjects were initially depressed or not, indicating that
depression status was not modified by undergoing the operation. Pre-operative
depression is thus a good predictor of post-operative depression, as has been
previously observed (Mckhann et
al, 1997).
Interactive effects between depressive symptomatology and
pre-existing cognitive deterioration
The depressed group showed decreased performance in visual secondary memory
(RR=3.3; 95% CI 1.2-8.9). The subjects at higher risk of having a high rate of
pre-operative cognitive impairment at entry into the study showed decreased
performance in constructional apraxia (RR=3.9; 95% CI 1.4-11.2) and secondary
visual recall (RR=3.8; 95% CI 1.4-10.2). No significant correlation was found
between CES-D score pre-operatively and the DECO score.
Performance on each ECO variable across the three examinations was examined by multivariate analysis of variance with corresponding univariate F tests. Subjects without depressive symptomatology improved significantly in visual secondary memory tests up to 9 days and continued to improve after 3 months (F=4.6, P=0.035), whereas the depressed group showed no learning effect. Subjects at risk of depression also experienced deterioration between 9 days and 3 months in the performance of a complex attention task, whereas the non- depressed group did not modify its performance (F=4.4, P=0.044). Pre-existing cognitive deterioration precluded any learning effect in various tasks, namely language word comprehension (F=6.2, P=0.016), episodic secondary memory (F=6.1, P=0.016), visuo-spatial analysis (F=4.6, P=0.036), and visuo-spatial primary memory (F=5.5, P=0.022), whereas the group not at risk improved at 9 days, or at 3 months in the case of visuo-spatial primary memory.
Effects of age and education level
Significant improvement in language from pre-operative levels to 9 days
postoperatively is seen in the younger age group as compared with the over 75
group in which no such learning effect was observed (semantic fluency,
F=9.0, P=0.004). With regard to visuo-spatial analysis
(F=11.9, P=0.001), the younger age group also showed a
learning effect from pre-operative levels to 9 days postoperatively, whereas
in the older group improvement was significant only after 3 months.
A learning effect was also observed only up to 9 days in secondary visual memory (F=10.6, P=0.002) for the high education group, whereas in the low education group the improvement was progressive up to 3 months postoperatively. Education effects are also evident on implicit memory (F=4.5, P=0.036), with deterioration observed between 9 days and 3 months in the low education group, whereas no modifications were observed for the high education group.
Regression model
A regression model was used to evaluate the relative contribution of the
above-identified risk factors (age, education, initial depressive
symptomatology, pre-operative cognitive decline, type of anaesthesia) to
postoperative cognitive decline. The latter dependent variable is the decline
score. Type of anaesthesia was found to be the most significant determinant of
decline in verbal fluency scores (phonetic, P=0.047; semantic prompt,
P=0.025), visuo-spatial analysis (P=0.02) and implicit
memory (P=0.03), with greater decline being observed for general
anaesthesia. Peridural anaesthesia in the absence of sedation appeared as a
significant determinant of decline in primary (P=0.032) and secondary
(P=0.031) verbal memory and implicit memory (P=0.003).
Applying sedation during peridural anaesthesia led to a significant decline in
secondary memory on tasks of narrative recall (P=0.025). Poor
pre-operative levels of cognitive performance were found to contribute
significantly to decline on face recall (P < 0.025), irrespective
of the anaesthesia type, and on visuo-spatial analysis after general
anaesthesia (P=0.03).
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DISCUSSION |
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Postoperative cognitive change across time
At 9 days 71% of subjects show significant alteration in at least one
cognitive test score, and 56% at 3 months. Because the same test battery was
used on all three test occasions, repeated examination could have led to an
underestimation of the proportion of subjects with cognitive decline,
considering that subjects who did not decline could be those for whom a
learning effect did not occur. Such rapid cognitive deterioration affecting a
large number of subjects is evidently far greater than the rates observed in
the general population (Ritchie et
al, 1996; Dodds &
Allison, 1998). The high proportion of declining patients detected
in the present study probably results both from the use of a wide range of
sensitive neurological tests and also from the absence of exclusion criteria
concerning the initial health status of the patients.
It should be noted that systematically the same cognitive domains were found to be significantly altered at 9 days and 3 months for more than 72% of the subjects showing persistent decline (only 6% of subjects experienced slight deterioration for which quite distinct domains were altered between 9 days and 3 months). This strongly argues for acute detection of a real postoperative cognitive decline. This also provides a partial basis for attributing the observed cognitive deficit at 3 months postoperatively to central nervous system trauma occurring during surgery and anaesthesia, although the lack of a control group does not permit us to estimate to what extent it may have been due to associated factors such as stress and pain.
Improvement between 9 days and 3 months (for 38% of subjects) can result either from a learning effect and/or from a reversibility of the deleterious effect of the anaesthesia or complete elimination of residual anaesthetics.
Risk factors
Four groups appear to be at particularly high risk of postoperative
cognitive decline in that either they do not show the benefit of previous
learning or they deteriorate: the very old (over 75 years); those with low
levels of education; subjects with high pre-operative levels of depressive
symptomatology; and those with a recent history of cognitive impairment.
Age frequently has been reported as a risk factor for cognitive alteration after anaesthesia. This is probably related to the important changes in both physiology and pharmacokinetics occurring with ageing and the possible interaction of anaesthetic drugs with current medication in the elderly (Parikh & Chung, 1995; Jones & Hunter, 1996).
Age also has been found to have an interactive effect with educational level in determining the degree of cognitive decline over time. Increased neuronal reserves in the more educated appears to compensate temporarily for any cognitive loss (Touchon & Ritchie, 1999). Elderly persons with a high level of education show greatest resistance to changes on tests with a high learned component (language and secondary memory), whereas level of education makes relatively little difference to the rate of change for cognitive functions such as attention, implicit memory and visuo-spatial analysis, which are hypothesised to be less influenced by environmental effects (Leibovici et al, 1996).
Depression is known to influence some specific area of cognition, notably attention (Cassens et al, 1990), and it appears partly and variably involved in the decline in cognitive performance after anaesthesia (Savageau et al, 1982; Williams-Russo et al, 1995; McKhann et al, 1997).
Recent history of cognitive decline has not been investigated to date as a risk factor for cognitive decline after anaesthesia because such subjects are usually excluded from most studies, although they represent a significant proportion of the elderly population (15% in the present study).
Possible biases and limitations
Although the relatively high drop-out rate between 9 days and 3 months
(28%) in this study was a cause for concern, analysis of the various
demographic variables suggested that the non-returners did not differ from the
returners and there was no interaction between return/no return and
anaesthetic choice. The only difference concerned pre-existing cognitive
deterioration, which was greater in the non-returner group. Hence, the
differential drop-out rate could have biased the results of this study. This
probably did not affect the evolution pattern between 9 days and 3 months
because the subjects at cognitive deterioration risk retained after 3 months
partitioned roughly equally between the improving, declining and no change
groups. This is likely to have minimised the number of subjects showing a
persistently high number of deteriorated scores at 3 months, especially in the
peridural anaesthesia group (see below). A high drop-out rate is common when
conducting a thorough assessment with an elderly population owing to problems
of transportation and high illness rates. Furthermore, elderly persons are
frequently concerned about their diminishing mental abilities, commonly
refusing to go through personally irrelevant mental gymnastics. This is
especially true for people suffering from pre-existing cognitive alteration
(Blumenthal et al,
1995).
It should be noted also that subjects were not assigned randomly to general or local anaesthesia groups, and the preponderance of local anaesthesia in this series reflects the existing concerns of anaesthetists and patients as to the possible effects of general anaesthesia. The proportion of subjects at risk (older and low educational level, depressive symptomatology or pre-existing cognitive deterioration) was in fact 1.6- to 2-fold higher in the peridural group than in the general anaesthesia group. This is an important bias both in our study and previous observations, making hazardous a comparative evaluation of both practices in the absence of any randomisation. On the other hand, the design of the present study permitted the evaluation of cognitive change under externally valid conditions, reflecting fairly well the real-life situation of the geriatric orthopaedic surgery population. It also demonstrates that subgroups of elderly subjects are at higher risk and that cognitive domains are differentially affected according to age and pre-existing disabilities.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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Received for publication March 31, 2000. Revision received September 7, 2000. Accepted for publication September 8, 2000.