In our study, we assessed the cognitive function of PHPT patients using the MMSE, and we discovered that PHPT patients had poor cognitive performance compared to the benign thyroid disease group with the paired sex, education, and age. In addition, we found that cognition scores showed a negative correlation with PTH levels.( Sperman= -0.42, p < 0.05) This is in general accordance with previous research findings that imply a relationship between high PTH levels and the central nervous system, especially cognition [19, 27, 28]. The expression of PTH2 receptor (PTH2R) has been found in the cerebral arteries of the central nervous system [29, 30], Studies reported that the interaction of the ligand of the PTH2R named as tuberoinfundibular peptide of 39 residues(TIP39) with PTH2R in the brain have influenced cognition [31–33].
Our study also simultaneously evaluated the sleep quality of PHPT patients using PSQI and revealed that PHPT patients had poorer sleep quality than the control group, which is consistent with the findings of Febrero. B’s investigation [34]. Meanwhile, the present result indicated that the sleep quality scores of PHPT patients were positively correlated with PTH levels, which implies that the higher the PTH of PHPT patients, the worse the sleep quality. This may be since the PTH 24-h profile is influenced by sleep processes. A trend towards higher PTH levels during sleep periods compared to waking periods has been observed [35]. Furthermore, PTH activates osteoblasts to overproduce the cytokine interleukin-6 in PHPT, which has been implicated in the inflammatory response, thereby regulating the sleep period [36, 37].
Based on the above assessment results, we observed a link between the total PSQI score and the cognitive score of PHPT patients, indicating that the poorer the sleep quality of PHPT patients, the worse their cognitive function. This may be due to decreasing sleep duration being related to an increased risk of Aβ accumulation, which aggregates as amyloid plaques and neurofibrillary tangles, respectively, triggering multidomain cognitive deficits [13, 14].
The mediation effects analysis revealed that the PTH level of PHPT patients not only directly and negatively predicted their cognitive scores, but also indirectly predicted cognitive function through sleep latency or sleep disturbance, implying that the higher the PTH of PHPT patients, the higher the sleep latency or sleep disturbance scores, and the worse their cognitive performance. Memory benefits from intact sleep architecture. The hippocampus exhibits enormous irregular activity during slow wave sleep (SWS) and quiet waking, providing synaptic bombardment for induction, which is thought to build the cellular and molecular underpinning of memory [16, 17, 38]. Delayed sleep and sleep disorders may affect memory by affecting slow-wave sleep [39].
Of the 144 patients who underwent parathyroidectomy in our hospital, we analyzed the pre-and post-operative differences and found that no significant differences were seen in preoperative and postoperative sleep levels in either the BP group, PC group, or all PHPT. It may suggest that surgery did not improve sleep quality in PHPT patients. Post-operative PTH levels and cognition were both linked with post-operative PSQI scores. (Sperman = 0.182*, p = 0.029; Sperman = -0.253**, p = 0.002) This finding might support the value of concentrating on preoperative and postoperative sleep quality for the cognition of PHPT patients. However, postoperative PTH levels did not correlate significantly with postoperative cognitive function. (Sperman = -0.105, p = 0.210) It is probable that the rapid decline in PTH post-operatively precedes cognitive enhancement and the clinical follow-up was too short.
There are some limitations to the present study. First, using self-reported assessment of sleep quality might contribute to record bias. The examination of brain electrical waves for sleep and fMRI were needed to further confirm our findings. Second, we were unable to define the mechanisms of sleep quality, PTH level, and cognition. Further studies and long-term follow-up are necessary.
Sleep latency or sleep disturbance exhibited a partial mediating effect on the association between PTH level and MMSE scores in PHPT patients. The surgery could reduce PTH levels and improve cognition, but might not improve sleep quality in PHPT patients. Therefore, we suggest that PHPT should regularly test for PTH levels, cognition, and sleep quality issues before surgery, notably sleep latency and sleep disturbance, which can be alleviated by exercise and other methods, potentially postponing the cognitive impairment. As cognitive function is influenced by multiple factors, it is worth further investigating whether interventions for PTH levels and sleep are useful in enhancing cognitive function in PHPT patients.