Background: Postoperative cognitive dysfunction (POCD) presents a risk factor after general anesthesia, especially for old or cognitively impaired patients. Hence, strategies to identify possible patients at risk could help to decrease the rate of POCD. In this case report we relate the occurrence of electroencephalographic burst suppression and low bispectral indices to the development of neurocognitive decline after 12 months in one homozygous twin, whereas the other twin exhibited neither burst suppression nor neurocognitive decline. Case presentation: Two 68-year-old homozygous twins underwent the same surgical procedure with the same anesthetic regimens in comparable concentrations. For cognitive assessment, we applied a battery of neurocognitive tests at baseline (one day before surgery), at hospital discharge (three days after surgery), and 12 months after the procedure. The twins performed similarly in preoperative and discharge testing, but one twin showed worse test performance after 12 months. During surgery, we tested for possible connected consciousness by applying the isolated forearm technique (IFT). For assessment of the level of anesthesia and visual inspection of the EEG, we used the bispectral index (BIS). Neither of the twins showed signs of connected consciousness during anesthesia and the emergence tone to the return of a positive IFT response were similar. We observed lower intraoperative BIS indices for one twin. Furthermore, this twin also had two episodes of Burst Supppression. Vital parameters, particularly mean blood pressure, were stable and comparable during the entire duration of anaesthesia. The twin who exhibited Burst Suppression and lower BIS indices showed distinctly worse cognitive test scores after 12 months compared to baseline and discharge testing, indicating serious neurocognitive decline. The other twin’s cognitive performance did not decrease. Conclusions: We present findings from a unique scenario of homozygous twins with comparable lifestyles undergoing the same surgical intervention. The twin with neurocognitive decline had lower BIS values and multiple episodes of BSupp. These findings suggest that EEG monitoring under general anesthesia could help to identify frail brains that may be at increased risk of developing cognitive impairments.