"Our results provide novel insights into a pathogenic process potentially linking surgery to the subsequent development of AD in vulnerable patients," write Dr. Igor Feinstein and colleagues at Stanford University School of Medicine in JAMA Neurology.
"The most important implication of our study is the finding that undergoing major surgery causes biochemical changes like those seen in Alzheimer's disease," Dr. Feinstein told Reuters Health by email.
"While it has long been suspected that undergoing major surgery may compromise neurocognitive function, this is the first time that surgery has been linked to biochemical changes that are extremely sensitive and specific for this devastating disease," Dr. Feinstein said.
"Importantly, we also showed that different types of major surgery cause different degrees of biochemical change, implying that not all surgeries may convey the same risk of neurocognitive dysfunction," he added.
The Stanford team studied five men and one woman who underwent cardiac surgery at a median age of 65 years and five men and three women who had hip replacement surgery at a median age of 76 years.
In the cardiac-surgery patients, median plasma pTau181 concentrations before surgery were 1.40 pg/mL, below the threshold (1.81 pg/mL) associated with progression to AD.
During surgery, however, pTau181 levels increased 5.1-fold to 6.75 pg/mL and plasma total tau levels rose 26.1-fold (from 2.44 to 58.74 pg/mL). Levels of pTau181 and total tau remained elevated on the first and second days following surgery, although not significantly.
In the hip-surgery patients, pTau181 levels rose 2.5-fold (from 1.25 to 3.45 pg/mL) right after surgery, while total tau levels rose 3.8-fold (from 2.05 to 9.47 pg/mL). Levels of pTau181 and total tau levels remained elevated on postop days one and two, although not significantly.
Plasma NfL levels remained unchanged through cardiac and hip surgery, but rose 2.4-fold on postop day 1 (from 13.69 to 39.40 pg/mL) and remained elevated on postop day 2 in the cardiac-surgery patients. In the hip surgery patients, NfL levels rose 1.4-fold (from 13.5 to 21.0 pg/mL) on postop day 1 and remained elevated on postop day 2, although not significantly so.
Dr. Feinstein cautioned that the current study focused only on short-term biomarker changes "which makes it difficult to speculate about their long-term significance."
"Further work is needed to fully understand whether these changes are sustained, how these biomarker profiles are linked to postoperative cognitive function and whether patient and procedure specific variables have an impact on biomarker profiles and subsequent long-term outcomes," he said.
"Thus, while there are no immediate clinical implications for vulnerable populations (e.g., older adults and those with pre-existing cognitive impairments), ongoing work will hopefully pave the way for the development of individualized care protocols focused on optimizing perioperative cognitive outcomes," Dr. Feinstein added.
The study had no commercial funding and the authors have no relevant disclosures.
SOURCE: https://bit.ly/2XDpWJR JAMA Neurology, online September 20, 2021.
By Megan Brooks
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