Older women appear to be at higher risk than older men for deterioration in neurologic and cognitive functioning as well as ventricular brain volumes following the administration of general anesthesia and surgery. That was the conclusion of a study that tracked cognitive aging in more than 500 elderly people over time.
Elderly women and men who received general anesthesia were both at higher risk for deleterious neurocognitive outcomes when compared with elderly people who did not receive anesthesia, but the declines were more pronounced in women than men.
Elderly people receive more than one-third of the over 40 million anesthetics administered annually in the United States, and women in general have an increased risk for developing Alzheimer’s disease. However, the relationship between sex, genetic factors and postoperative cognitive decline has not been well established.
“I decided to study the sex differences in postoperative cognitive decline after I learned that Alzheimer’s disease disproportionately affects women in both prevalence and severity,” said Katie Schenning, MD, MPH, assistant professor of anesthesiology at Oregon Health & Science University in Portland. She presented the results of her study at the 2015 Alzheimer’s Association International Conference (abstract 5336).
Dr. Schenning and her colleagues performed a retrospective analysis of two longitudinal studies of cognitive aging performed at Oregon Health & Science University. The first was the Oregon Brain Aging Study (Neurology 2000;54:105-113), which involved a cohort of community-dwelling men and women aged 65 and older who were generally free of confounding factors known to modify risk for cognitive decline, such as vascular disease, hypertension or diabetes (N=304).
The second was the Intelligent Systems for Assessing Aging Changes, a longitudinal study that included sensor-based monitoring of elderly men and women (N=223) to measure their daily physical activities over an average of 33 months. Participants received annual physical examinations and neuropsychological testing (J Gerontol B Psychol Sci Soc Sci 2011;66B:i180-i190).
Of the 527 participants, 182 underwent a total of 331 surgical procedures under general anesthesia. The researchers controlled for age, years of education and the Cumulative Illness Rating Scale, and used mixed-effects models to assess the relationship between exposure to general anesthesia/surgery and longitudinal change in measures of cognition, function and ventricular brain volumes. They modeled exposure to anesthesia as both a dichotomous categorical factor and a continuous variable, indicating the number of exposure events in order to evaluate the effect of repeated anesthesia applications.
Men who had undergone general anesthesia and surgery experienced a more rapid rate of decline than their unexposed counterparts as determined by validated instruments, including the Mini-Mental State Examination (P=0.009), Instrumental Activities of Daily Living Scale (P=0.024) and Clinical Dementia Rating Scale Sum of Boxes (P=0.027). Women exposed to surgery, however, experienced a significantly more rapid rate of deterioration on the Mini-Mental State Examination (P<0.001), the Clinical Dementia Rating (P=0.003) and the Clinical Dementia Rating Scale Sum of Boxes (P<0.001); in activities of daily living (P<0.001); and in delayed logical memory (P=0.011), as well as in ventricular volume (P=0.005). The differences between women and men were even more pronounced as the number of anesthetics increased.
“My hypotheses are that factors such as female sex and [the presence of] ApoE4 [apolipoprotein 4] cause an increased risk of the development of postoperative neurocognitive decline,” Dr. Schenning told Anesthesiology News. “The most significant finding was that the rate of increase in ventricular volume [measured on brain MRI] was significantly associated with surgery/anesthesia exposure in women, but there was no similar finding in men,” Dr. Schenning added.
Roderic G. Eckenhoff, MD, professor and vice chair for research at the University of Pennsylvania’s Perelman School of Medicine, in Philadelphia, noted that after controlling for ApoE4 status, the researchers found that the declines were faster in older women than in older men. He was not involved in the study. “Because the incidence of Alzheimer’s disease is also higher in women than in men, this observation provides clues that the underlying pathology accelerated by surgery and anesthesia might be similar to Alzheimer’s disease,” Dr. Eckenhoff.
This topic has been “controversial and inconsistent,” Dr. Eckenhoff continued. Retrospective studies have been divided over whether surgery and anesthesia accelerate cognitive decline or increase incident dementia. “These careful analyses of prospective longitudinal studies—of which there are now a few—seem to be revealing a significant association, in part due to more consistent data collection, and in some cases, a purposeful enrichment of vulnerability factors,” Dr. Eckenhoff said.
“Our research clearly shows an association between surgery, general anesthesia and cognitive decline in older adults,” Dr. Schenning said. “More studies are needed to confirm this observation and to identify ways to minimize the effects of surgery and general anesthesia on older adults. Future research should focus on whether certain people are more susceptible to postoperative cognitive decline by virtue of sex or genetic risk factors,” she said.