This study reviews the available evidence on the potential link between olfactory dysfunction and POCD, comprehensively evaluating seven studies that explored this relationship across different surgical settings and patient populations. The findings collectively suggest that olfactory dysfunction may be a useful preoperative marker for postoperative cognitive decline, particularly in vulnerable populations. However, the results across studies varied, and several critical gaps warrant further exploration.
The relationship between olfactory dysfunction and POCD has gained attention in recent years due to the increasing recognition of the olfactory system’s role in cognitive and emotional processing, particularly in the aging population. Several studies in this review, particularly prospective cohort studies, found that impaired olfactory function before surgery was associated with a higher risk of postoperative cognitive outcomes, including delirium and dNCR. For example, Brown et al. demonstrated a robust association between baseline olfactory impairment and an increased risk of POD, with a risk ratio (RR) of 1.90 (95% CI: 1.17 - 3.09) for delirium in patients with poor olfactory function (
16). Similarly, Zhang et al. identified a significant correlation between baseline olfactory function and delayed cognitive recovery, with a notable increase in the risk of dNCR in patients with impaired olfaction (
19). Le et al. found that impaired olfactory function before surgery predicts POD and cognitive decline, suggesting that olfactory testing could be a risk stratification tool (
21).
While several studies corroborate the notion that olfactory dysfunction is associated with POCD and delirium, there is considerable variability in the results. For instance, Rentowl and Hanning found no direct correlation between olfactory dysfunction and POCD in a cohort of elderly non-cardiac surgery patients (
15). Similarly, Lan et al. observed a decline in olfactory function post-surgery but failed to find a significant association with cognitive outcomes measured by the MMSE and HVLT-R (
3). These contrasting findings suggest that various factors, such as the type of surgery, patient demographics, and cognitive assessment tools used, may influence olfactory dysfunction and cognitive outcomes. It is possible that the effects of olfactory impairment on cognition are subtle and may only become apparent in specific patient populations, such as the elderly or those with pre-existing neurological conditions like PD (
19).
A common challenge in interpreting the findings of these studies is the potential influence of confounding factors, such as age, baseline cognitive function, comorbidities, and anesthesia protocols. For instance, Brown et al. showed that when baseline cognitive status was included in the analysis, the relationship between olfactory dysfunction and postoperative cognitive decline was significantly influenced by baseline cognitive scores, suggesting that pre-existing cognitive impairment might exacerbate the impact of olfactory dysfunction on post-surgical outcomes (
16). This underscores the importance of controlling for confounding variables to isolate the specific effect of olfactory impairment on postoperative cognitive function.
Similarly, Van Regemorter et al. demonstrated that anosmia (complete loss of smell) was a significant predictor of cognitive impairment on the CDT one year after surgery, even after controlling for education level, a common confounder in studies of cognitive function (
18). These findings emphasize the need for studies that account for multiple potential confounders and use well-defined cognitive assessment tools to capture the full spectrum of cognitive changes after surgery.
One of the most compelling findings across the studies was the association between olfactory dysfunction and an increased risk of POD, a common form of acute cognitive dysfunction after surgery. Kim et al. found that olfactory dysfunction was a significant predictor of delirium in PD patients undergoing elective surgery (
17). This suggests that olfactory dysfunction may be a marker of broader cognitive vulnerability in populations with pre-existing neurological conditions. Furthermore, studies such as Kamath et al. demonstrated that olfactory impairment could be an early warning sign of post-surgical cognitive disturbances, particularly in the context of frail or elderly patients (
20).
The mechanisms underlying the relationship between olfactory dysfunction and POCD remain speculative. Still, they may be rooted in the close connection between the olfactory and limbic systems, which play a crucial role in memory and emotional regulation (
22). Disruptions in the olfactory system may reflect broader neurological disturbances, including those in areas responsible for cognitive function. Moreover, olfactory dysfunction could serve as an early indicator of neurodegenerative processes, such as Alzheimer’s disease or PD, which are common in older adults (
23,
24). Fatuzzo et al.’s study showed that olfactory deficits are early indicators of neurodegenerative diseases, linking them to cognitive decline (
25). Zhang et al. reported that increased levels of interleukin-6 (IL-6) in the blood and nasal epithelium post-surgery are linked to olfactory and cognitive impairments (
19). Additionally, Bothwell et al. demonstrated that olfactory dysfunction is associated with reduced volumes in brain regions like the hippocampus and olfactory-related areas, which are vital for cognitive processing (
26).
Inflammation, anesthesia, and other surgical stressors are also believed to contribute to both olfactory dysfunction and cognitive decline after surgery. For example, a systematic review conducted by Brown et al. suggested that diminished olfactory function might be a marker of heightened vulnerability to inflammation or other stress responses, which could exacerbate postoperative cognitive decline (
16). This reasoning underscores the importance of exploring inflammatory and neurological pathways as potential links between olfactory dysfunction and POCD.
This systematic review suggests that olfactory impairment could serve as a useful preoperative predictor of the development of POCD and POD, particularly in older patients and neurologically vulnerable groups. Therefore, routine preoperative olfactory assessments using simple and reasonably priced tests like the BSIT or sniffin’ sticks could help clinicians identify high-risk patients and implement appropriate preventive measures. However, various obstacles to implementation should be considered. These include the need to validate olfactory screening methods in perioperative populations, the absence of standardized olfactory assessment procedures in surgical environments, and insufficient awareness among healthcare practitioners regarding the prognostic relevance of olfactory dysfunction.
Although this systematic review offers valuable insights, certain limitations must be acknowledged. First, the heterogeneity among studies — variations in olfactory assessment tools, cognitive evaluation methods, and follow-up durations — may have affected the comparability of their results. Furthermore, although we accounted for essential confounders, including age and baseline cognitive performance, other potential confounders, such as anesthesia type, surgical time, and perioperative medications, could influence postoperative cognitive outcomes. The lack of consistent reporting of these elements across studies limits our ability to systematically evaluate their impact.
5.1. Conclusions and Future Directions
The present systematic review provides valuable insights into the role of olfactory dysfunction as a potential predictor of postoperative cognitive decline. While the evidence supports a relationship between olfactory impairment and POCD, particularly in vulnerable populations such as older adults and those with neurological conditions, the variability in study findings underscores the need for more robust and homogeneous studies. Future research should aim to standardize assessment tools for both olfactory function and cognitive outcomes, control for confounding factors, and explore potential underlying mechanisms linking these two conditions. Additionally, more extensive multicenter studies and randomized controlled trials are needed to better establish the causal relationship between olfactory dysfunction and postoperative cognitive outcomes.
Exploring the potential for olfactory testing as a preoperative screening tool could have significant clinical implications, offering a simple and cost-effective way to identify patients at higher risk for cognitive complications following surgery. Lastly, therapeutic interventions to improve olfactory function or mitigate its effects on cognition could offer new avenues for enhancing postoperative recovery and quality of life in vulnerable patient populations. Future research could address these gaps and provide more precise guidance on how olfactory dysfunction may be leveraged in clinical practice to reduce the burden of POCD.
References