The term perioperative neurocognitive disorders (PND) is derived from postoperative cognitive dysfunction (POCD), and has been renamed as PND in recent years in accordance with the latest international consensus. PND specifically refers to changes in mental, social and cognitive abilities in patients following surgery; in severe cases, personality changes and reduced social functioning may also occur. As a serious complication affecting the central nervous system (CNS), apart from surgical trauma, advanced age is widely recognized as a critical factor contributing to the development and progression of PND. Its adverse effects represent a major challenge for the rapidly growing elderly population worldwide.
It is currently believed that the decline in cognitive functions such as memory and attention observed in some patients after surgery may be associated with inflammatory responses in the brain. Surgical stress may activate supporting cells in the brain, such as astrocytes. When these cells are abnormally activated, they may fail to maintain normal neuronal function, thereby disrupting brain homeostasis and leading to cognitive impairment.
Recent studies have shown that these glial cells exert distinct effects on neurons under different phenotypes: some phenotypes promote neural repair and protection, whereas others exacerbate neural injury. Evidence suggests that in multiple neurological disorders, the pro-inflammatory phenotype of glial cells is closely associated with cognitive impairment.
Prokineticin-2 (PK2) is an endogenous signaling molecule involved in the regulation of diverse physiological processes, including inflammatory responses, energy metabolism, and neuroprotection. Previous studies have demonstrated that PK2 exerts protective effects in various neurological disease models, improving neuronal function and alleviating cognitive or motor deficits. Our preliminary animal experiments revealed reduced brain PK2 levels, especially in memory-related regions, in mice with postoperative cognitive dysfunction. Exogenous supplementation of PK2 significantly restored brain cell function and improved cognitive performance in these mice, suggesting that PK2 may play an important role in maintaining cerebral function after surgery.
However, it remains unclear whether changes in PK2 levels in clinical patients correlate with the occurrence and severity of postoperative cognitive dysfunction. This study aims to investigate changes in circulating PK2 levels and explore their association with postoperative cognitive alterations, so as to provide evidence for the improved prevention and identification of PND.
We plan to enroll elderly patients undergoing hip replacement surgery at Nanjing First Hospital. By analyzing PK2 expression levels and dynamic changes, combined with postoperative neuropsychological scale assessments, we will evaluate the correlation between serum PK2 levels and the clinical incidence of PND, and further verify the intrinsic link between PK2 levels and the pathogenesis of PND.
Age ≥ 65 years and ≤ 80 years
ASA physical status Class Ⅰ-Ⅲ
Elderly patients undergoing hip replacement surgery
Mini-Mental State Examination (MMSE) score ≤ 24
Severe cardiac, pulmonary, hepatic or renal dysfunction
Recent use of sedatives or antidepressants, or alcohol abuse
Patients with severe mental disorders including depression, schizophrenia, bipolar disorder, mental retardation, etc.
The study population consists of elderly patients aged 65 to 80 years with ASA physical status Class Ⅰ-Ⅲ who are undergoing hip replacement surgery. Patients are excluded if they have an MMSE score ≤ 24, severe cardiac, pulmonary, hepatic or renal dysfunction, recent use of sedatives/antidepressants or alcohol abuse, severe mental disorders (e.g., depression, schizophrenia, bipolar disorder, mental retardation), a history of severe craniocerebral injury, cerebrovascular disease, hydrocephalus, intracranial tumor or other neurological diseases (e.g., Parkinson's disease, Huntington's disease, epilepsy), severe visual or hearing impairment, or inability to complete cognitive function tests due to advanced age, low educational level or other factors.
Case-control
Prospective
Not listed
PK2 level
Venous blood samples will be collected from patients 1 day before surgery and on postoperative days 1 and 3 for the detection of PK2 levels
the levels of related oxidative markers including SOD
Venous blood samples will be collected from patients 1 day before surgery and on postoperative days 1 and 3 to detect the levels of related oxidative markers including SOD.
the levels of related oxidative markers including GSH
Venous blood samples will be collected from patients 1 day before surgery and on postoperative days 1 and 3 to detect the levels of related oxidative markers including GSH.
the levels of related oxidative markers including CAT
Venous blood samples will be collected from patients 1 day before surgery and on postoperative days 1 and 3 to detect the levels of related oxidative markers including CAT.
Levels of inflammatory markers TNF-α
Venous blood samples will be collected from patients 1 day before surgery and on postoperative days 1 and 3 to detect the levels of inflammatory markers TNF-α.
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