April 1, 2014 Volume 78, Number 4
SEE Question

A recent study compared previous anesthetic exposure in adults with and without dementia in a case-control manner. Which statement about the results of this study is most likely true?


(A) Isoflurane was more likely than nitrous oxide to be associated with subsequent development of dementia.

(B) People with dementia were no more likely to have had a general anesthetic than those without dementia.

(C) People with dementia were more likely than those without dementia to have had longer cumulative exposure to general anesthesia.

(D) The results of this study differed markedly from previous studies of association between anesthesia exposure and later dementia.


Anesthetic exposure and subsequent cognitive impairment is a hot topic within anesthesia research circles as well as with the general public. Studies are ongoing into the potential links between anesthetic exposure in pediatric patients and subsequent learning and behavioral problems. Postoperative cognitive dysfunction (POCD) has been observed in many elderly patients, and the association between POCD and specific anesthetic agents or techniques and specific surgical procedures is the subject of ongoing research. It has been observed, however, that most POCD clears with time.


The association between anesthetic exposure and subsequent dementia is controversial. Studies of rats exposed to halogenated inhalational agents have shown histological changes similar to those noted in Alzheimer disease (e.g., formation of neurofibrillary tangles, accumulation of β-amyloid in neural structures). Numerous population studies in the past, including meta-analyses, have found no association between anesthetic exposure and dementia in humans, however these studies were limited by factors such as small sample size, variation in definition of dementia/cognitive dysfunction, unclear documentation of anesthetic technique and agents, and selection bias of both dementia and case control groups.


The authors of a recent article designed a study to address the shortcomings of previous studies and to test the hypothesis that there was an association between exposure to general anesthesia after 45 years of age and subsequent development of dementia.


The Rochester Epidemiology Project (REP) is an ongoing registry that examines the medical records of all residents of Olmsted County in southeastern Minnesota regardless of where they obtain their medical care. The investigators, utilizing REP, designed a retrospective, population-based, nested, case-control study. They identified all patients with a diagnosis of dementia between January 1, 1985 and December 31, 1994. Age- and sex-matched controls that were dementia-free in the year that the matched case was diagnosed were randomly chosen from the REP. The diagnosis of dementia was confirmed by chart review by a neurologist investigator using formalized definitions of dementia and Alzheimer disease. Detailed records of anesthetic exposure after age 45 for all cases and controls were collected, including anesthetic agents, duration of exposure, and type of surgery.


The authors found 908 cases of dementia for which a matched control was assigned. Thirty-one matched sets were eliminated for various reasons. In all, 877 matched case-control sets were analyzed in detail.


Authors of the study found that patients with and without dementia had no difference in exposure to anesthesia, number of anesthetics, or cumulative exposure time to anesthetic agents. Subgroup analysis for the patients with the specific diagnosis of Alzheimer disease showed the same lack of association.


They also determined that there was no increased likelihood of dementia associated with any one of the inhaled or I.V. anesthetic agents studied.


Areas of shortcomings in earlier studies that were addressed by this study include:

• A large sample set of cases/controls was used.

• Geographic-based setting of patients minimized the selection bias that may come from simply studying a tertiary care center’s experience.

• Details of the anesthetic exposure time and agents were analyzed.

• All patients with diagnosis of dementia were labeled using standardized definitions of dementia and Alzheimer disease and results were confirmed by a neurologist investigator.


In conclusion, this robust retrospective case-control study found no association between exposure to general anesthesia after 45 years of age and subsequent development of dementia.


Answer: B



• Sprung J, Jankowski CJ, Roberts RO, et al. Anesthesia and incident dementia: a population-based, nested, case-control study. Mayo Clin Proc. 2013; 88(6):552-561.


The Self-Education and Evaluation (SEE) Program is a self-study CME program that highlights “emerging knowledge” in the field of anesthesiology.The program presents relevant topics from more than 40 of today’s leading international medical journals in an engaging question-discussion format. SEE can be used to help fulfill the CME requirements of MOCA®. To learn more and to subscribe, visit see.asahq.org.