This article and its accompanying editorial have been selected for the ANESTHESIOLOGYCME Program. After reading both articles, go to http://www.asahq.org/journal-cme to take the test and apply for Category 1 credit. Complete instructions may be found in the CME section at the back of this issue. Background: The authors designed a prospective longitudinal study to investigate the hypothesis that advancing age is a risk factor for postoperative cognitive dysfunction (POCD) after major noncardiac surgery and the impact of POCD on mortality in the first year after surgery. Methods: One thousand sixty-four patients aged 18 yr or older completed neuropsychological tests before surgery, at hospital discharge, and 3 months after surgery. Patients were categorized as young (18‐39 yr), middle-aged (40‐59 yr), or elderly (60 yr or older). At 1 yr after surgery, patients were contacted to determine their survival status. Results: At hospital discharge, POCD was present in 117 (36.6%) young, 112 (30.4%) middle-aged, and 138 (41.4%) elderly patients. There was a significant difference between all age groups and the age-matched control subjects (P < 0.001). At 3 months after surgery, POCD was present in 16 (5.7%) young, 19 (5.6%) middle-aged, and 39 (12.7%) elderly patients. At this time point, the prevalence of cognitive dysfunction was similar between age-matched controls and young and middle-aged patients but significantly higher in elderly patients compared to elderly control subjects (P < 0.001). The independent risk factors for POCD at 3 months after surgery were increasing age, lower educational level, a history of previous cerebral vascular accident with no residual impairment, and POCD at hospital discharge. Patients with POCD at hospital discharge were more likely to die in the first 3 months after surgery (P 0.02). Likewise, patients who had POCD at both hospital discharge and 3 months after surgery were more likely to die in the first year after surgery (P 0.02). Conclusions: Cognitive dysfunction is common in adult patients of all ages at hospital discharge after major noncardiac surgery, but only the elderly (aged 60 yr or older) are at significant risk for long-term cognitive problems. Patients with POCD are at an increased risk of death in the first year after surgery. POSTOPERATIVE cognitive dysfunction (POCD) is often associated with cardiac surgery, but less is known about the prevalence of this problem after other types of surgery. 1,2 In 1998, the International Study of Postoperative Cognitive Dysfunction (ISPOCD1) evaluated cognitive decline in 1,218 elderly patients, aged 60 yr or older, who had undergone major noncardiac surgery, and found that cognitive dysfunction was present in 26% of older patients 1 week after surgery and in 10% 3 months after surgery. 3 However, this study had significant differences in the incidence of early POCD at the 13 participating hospitals, placing this finding in question. Research evaluating cognitive decline after cardiac and noncardiac surgery has primarily focused on older patients, who might have an increased vulnerability to neurologic deterioration. 1,3,4 However, the cognitive effects of surgery and anesthesia in younger adults are poorly understood, making it difficult to determine whether advancing age is the primary risk factor for this complication. Studies on normal aging have shown that abrupt declines in cognitive function in older adults are associated with early death. 5,6 The relation between POCD and mortality has not been reported. To investigate the hypothesis that advancing age is a risk factor for POCD, we designed a prospective cohort study evaluating the incidence of early (hospital discharge) and late (3 months after surgery) cognitive dysfunction in adults of all ages undergoing elective, major noncardiac surgery. This study used the same neuropsychological methodology as the ISPOCD1 study in an attempt to replicate its results at a single institution. 3 Patients were also followed to determine the impact of POCD on survival in the first year after major surgery. A companion article analyzes the type and severity of cognitive impairment in the elderly patients in this study. 7

https://www.medpagetoday.com/upload/2007/12/27/00000542-200801000-00007.pdf

Predictors of Cognitive Dysfunction after Major Noncardiac Surgery

Statins and the risk of dementia

This article describes a systematic review on the research into postoperative cognitive dysfunction (POCD) in noncardiac surgery to ascertain the status of the evidence and to examine the methodologies used in studies. The review demonstrated that in the early weeks after major noncardiac surgery, a significant proportion of people show POCD, with the elderly being more at risk. Minimal evidence was found that patients continue to show POCD up to 6 months and beyond. Studies on regional versus general anesthesia have not found differences in POCD. Many studies were found to be underpowered, and a number of other methodologic difficulties were identified. These include the different types of surgery in studies and variations in the number and range of neuropsychological tests used. A particular issue is the variety of definitions used to classify individuals as having POCD.

https://chguv.san.gva.es/docro/hgu/document_library/servicios_de_salud/servicios_y_unidades/Servicio_anestesia/Sesiones_clinicas/2007-2008/080715_Protocolo.pdf

Postoperative cognitive dysfunction after noncardiac surgery: a systematic review.

Delirium is a common neurobehavioral syndrome that occurs across health care settings which is associated with adverse outcomes, including death. There are limited data on long-term cognitive outcomes following delirium. This report reviews the literature regarding relationships between delirium and cognitive impairment. Psych Info and Medline searches and investigation of secondary references for all English language articles on delirium and subsequent cognitive impairment were carried out. Nine papers met inclusion criteria and documented cognitive impairment in patients following delirium. Four papers reported greater cognitive impairment among patients with delirium than matched controls. Four papers reported higher incidence of dementia in patients with a history of delirium. One study found 1 of 3 survivors of critical illness with delirium developed cognitive impairment. The evidence suggests a relationship between delirium and cognitive impairment, although significant questions remain regarding the nature of this association. Additional research on delirium-related effects on long-term cognitive outcome is needed.

The association between delirium and cognitive decline: a review of the empirical literature.

Background: The majority of surgical patients receive inhaled anesthetics, principally small haloalkanes and haloethers. Long-term cognitive problems occur in the elderly subsequent to anesthesia and surgery, and previous surgery might also be a risk factor for neurodegenerative disorders like Alzheimer and Parkinson disease. The authors hypothesize that inhaled anesthetics contribute to these effects through a durable enhancement of peptide oligomerization. Methods: Light scattering, filtration assays, electron microscopy, fluorescence spectroscopy and size-exclusion chromatography was used to characterize the concentration-dependent effects of halothane, isoflurane, propofol, and ethanol on amyloid β peptide oligomerization. Pheochromocytoma cells were used to characterize cytotoxicity of amyloid oligomers with and without the above anesthetics. Results: Halothane and isoflurane enhanced amyloid beta oligomerization rates and pheochromocytoma cytotoxicity in vitro through a preference for binding small oligomeric species. Ethanol and propofol inhibited oligomerization at low concentration but enhanced modestly at very high concentration. Neither ethanol nor propofol enhanced amyloid β toxicity in pheochromocytoma cells. Conclusions: Inhaled anesthetics enhance oligomerization and cytotoxicity of Alzheimer disease-associated peptides. In addition to the possibility of a general mechanism for anesthetic neurotoxicity, these results call for further evaluation of the interaction between neurodegenerative disorders, dementia, and inhalational anesthesia.

Inhaled Anesthetic Enhancement of Amyloid-β Oligomerization and Cytotoxicity

Background Anaesthesia could provoke persistent alterations in specific cognitive domains in the elderly where ageing-related neuronal changes may exacerbate pharmacotoxic effects.

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.

/pdf/exposure-to-anaesthetic-agents-cognitive-functioning-and-3upvodeoyt.pdf

Exposure to anaesthetic agents, cognitive functioning and depressive symptomatology in the elderly

Cognitive dysfunction in the elderly commonly observed following anesthesia has been attributed to age-related neuronal changes exacerbated by pharmacotoxic effects. However, the extent to which these changes may persist following recovery from surgery is still largely unknown. This study investigates the long-term effects of anesthesia on cognitive functioning after orthopedic surgery in 270 elderly patients over the age of 65 who completed a computerized cognitive battery before and 8 days, 4 and 13 months after surgery. Their performance was compared to those of 310 elderly controls who completed the same neuropsychiatric evaluation at baseline and one-year interval. Multivariate analyses adjusted for socio-demographic variables, depressive symptomatology, vascular pathology as well as baseline cognitive performance. We found early and transient post-operative decline in reaction time and constructional praxis. With regard to long-term changes we observed improvement compared to controls in most verbal tasks (probably due to learning effects). On the other hand, a clear dissociation effect was observed for several areas of visuospatial functioning which persisted up to the 13-month follow-up. This specific pattern of visuospatial deficit was found to be independent of apolipoprotein E genotype and closely resembles what has recently been termed vascular mild cognitive impairment, in turn associated with subtle sub-cortical vascular changes. The observation of only minor differences between persons operated by general and regional anesthesia makes it difficult to attribute these changes directly to the anesthetic agents themselves, suggesting that cognitive dysfunction may be attributable at least in part to peri-operative conditions, notably stress and glucocorticoid exposure.

https://www.hal.inserm.fr/inserm-00524226/document

François Bonnel

Papers

Exposure to anaesthetic agents, cognitive functioning and depressive symptomatology in the elderly

Long-term post-operative cognitive decline in the elderly: the effects of anesthesia type, apolipoprotein E genotype, and clinical antecedents.