Association Between Exposure to General Versus Regional Anesthesia and Risk of Dementia in Older Adults

Clive Velkers, MSc; Miles Berger, MD, PhD; Sudeep S. Gill, MSc, MD; Roderic Eckenhoff, MD; Heather Stuart, PhD; Marlo Whitehead, MSc; Peter C. Austin, PhD; Paula A. Rochon, MPH, MD; Dallas Seitz, MD, PhD, FRCPC


J Am Geriatr Soc. 2021;69(1):58-67. 

In This Article

Abstract and Introduction


Background/Objectives: Cognitive changes are commonly observed in older adults following surgical procedures. There are concerns that exposure to general anesthesia (GA) may contribute to an increased risk of Alzheimer's disease. Our study examined the associations between exposure to GA compared with regional anesthesia (RA) administered for elective surgical procedures and the development of dementia.

Design: Population-based propensity matched retrospective cohort study.

Setting: Linked administrative databases were accessed from ICES (formerly called the Institute for Clinical Evaluative Services) in Ontario, Canada.

Participants: We included all community-dwelling individuals aged 66 and older who underwent one of five elective surgical procedures in Ontario, Canada, between April 1, 2007, and March 31, 2011. Individuals with evidence of dementia preceding cohort entry were excluded. Individuals who received GA were matched within surgical procedures to those who received RA on age, sex, cohort entry year, and a propensity score to control for potential confounders.

Measurements: The baseline characteristics of the study sample were compared before and after matching. Individuals were followed for up to 5 years following cohort entry for the occurrence of dementia using a validated algorithm. Cox proportional hazards analysis was used to determine the hazard ratio (HR) and 95% confidence interval (CI) for the association between anesthetic type and dementia. Subgroup and sensitivity analyses were undertaken.

Results: A total of 7,499 matched pairs were included in the final analysis. Overall, no difference was observed in the risk of being diagnosed with dementia for individuals who received GA when compared with RA (HR = 1.0; 95% CI = .8–1.2). There was also no association between anesthesia and dementia in most subgroup and sensitivity analyses.

Conclusion: Elective surgery using GA was not associated with an overall elevated risk of dementia when compared with RA. Future studies are required to determine whether surgery is a risk factor for dementia irrespective of anesthetic technique.


In 2015, more than 47 million people worldwide were living with Alzheimer's disease (AD) and other forms of dementia, and this number is projected to increase in the future.[1] Many risk factors for AD are nonmodifiable including age, female sex, and genetic predisposition.[2] Currently, no disease-modifying treatments are available for AD or other dementias, and there has been growing interest in the prevention of dementia through identification of potentially modifiable risk factors.[3,4]

Interest has been increasing in the possible associations between exposure to general anesthesia (GA) and the development of dementia. Cognitive changes are commonly observed following surgery and can manifest clinically in several different ways. Postoperative delirium is a typically reversible state that typically occurs within days of surgery.[5,6] Objective cognitive deficits accompanied by subjective cognitive complaints within 1 to 12 months after surgery are referred to as postoperative neurocognitive disorders (NCDs),[7,8] which, by definition, do not extend beyond 1 year following surgery. Although controversial, there are concerns about potential persistent postoperative cognitive deficits and that perioperative neurocognitive disorders (PND), an umbrella term for postoperative delirium and NCD, can be associated with long-term cognitive decline.[9] Although often symptomatically reversible, there are reports of persistence of PND and some evidence to suggest that PND can be associated with development of cognitive impairment years later.[10]

Postoperative cognitive changes in older adults are common, but the relationship between anesthesia and dementia is less certain. Some in vitro,[11–13] animal,[11,14,15] and human studies[16–18] have demonstrated increased production and aggregation of β-amyloid peptides (Aβ) and increased cerebrospinal fluid tau protein levels following exposure to different types of GA. Studies have also observed increases in cerebrospinal fluid tau-to-Aβ ratios within 24 to 48 hours following surgery in the same range observed in patients with AD.[17,18] Previous observational studies found either an increased risk of developing dementia following exposure to GA[19–21] or no increase in risk.[22–24] Few studies have compared the effect of GA with regional anesthesia (RA) on the risk of developing dementia.

Few large-scale studies have explored the relationship between surgery, anesthesia, and development of dementia.[19,20,22,23,25–27] Limitations of these studies have included the use of self-reported exposure data,[23] insufficient controlling for confounders,[20,25] and use of outcome measures other than dementia.[22,23] In addition, some studies included high-risk procedures such as cardiac surgery in which RA cannot be used alone that limits generalizability to elective surgical procedures in which there are multiple anesthetic options.[20,23,25,26] Therefore, we examined the association between exposure to GA versus RA among older adults undergoing elective surgical procedures and subsequent development of dementia.