Cognitive decline in the middle-aged after surgery and anaesthesia: results from the Wisconsin Registry for Alzheimer's Prevention cohort.

Surgery and anaesthesia might affect cognition in middle-aged people without existing cognitive dysfunction. We measured memory and executive function in 964 participants, mean age 54 years, and again four years later, by when 312 participants had had surgery and 652 participants had not. Surgery between tests was associated with a decline in immediate memory by one point (out of a maximum of 30), p = 0.013: memory became abnormal in 77 out of 670 participants with initially normal memory, 21 out of 114 (18%) of whom had had surgery compared with 56 out of 556 (10%) of those who had not, p = 0.02. The number of operations was associated with a reduction in immediate memory on retesting, beta coefficient (SE) 0.08 (0.03), p = 0.012. Working memory decline was also associated with longer cumulative operations, beta coefficient (SE) -0.01 (0.00), p = 0.028. A reduction in cognitive speed and flexibility was associated with worse ASA physical status, beta coefficient (SE) 0.55 (0.22) and 0.37 (0.17) for ASA 1 and 2 vs. 3, p = 0.035. However, a decline in working memory was associated with better ASA physical status, beta coefficient (SE) -0.48 (0.21) for ASA 1 vs. 3, p = 0.01.

Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain.

BACKGROUND: Retrospective clinical studies suggest there is a risk for neurodevelopmental impairment following early childhood exposure to anaesthesia. In the developing animal brain, including those of non-human primates (NHPs), anaesthetics induce apoptotic cell death. We previously reported that a 5 h isoflurane (ISO) exposure in infant NHPs increases apoptosis 13-fold compared with control animals. However, the majority of paediatric surgeries requiring anaesthesia are of shorter durations. We examined whether 3 h ISO exposure similarly increases neuroapoptosis in the NHP developing brain. METHODS: Six-day-old NHP infants ( Macaca mulatta ) were exposed to 3 h of a surgical plane of ISO ( n =6) or to room air ( n =5). Following exposure, NHP brains were screened for neuronal and oligodendrocyte apoptosis using activated caspase-3 immunolabelling and unbiased stereology. RESULTS: ISO treatment increased apoptosis (neurones + oligodendrocyte) to greater than four times that in the control group [mean density of apoptotic profiles: 57 (SD 22) mm -3 vs 14 (SD 5.2) mm -3 , respectively]. Oligodendrocyte apoptosis was evenly distributed throughout the white matter whereas neuroapoptosis occurred primarily in the cortex (all regions), caudate, putamen and thalamus. CONCLUSIONS: A 3 h exposure to ISO is sufficient to induce widespread neurotoxicity in the developing primate brain. These results are relevant for clinical medicine, as many surgical and diagnostic procedures in children require anaesthesia durations similar to those modelled here. Further research is necessary to identify long-term neurobehavioural consequences of 3 h ISO exposure.