Introduction
Acute appendicitis is an inflammation of the vermiform appendix, it is a main cause of acute abdomen and requires surgical intervention [1]. It has an incidence of 100 new cases per 100.000 people annually in the world [2]. Although the vermiform appendix was thought to be a vestigial organ [3], recent research suggests its role in the immune system, acting as a reservoir of beneficial intestinal bacteria and contributing to the immune response [4, 5].
The standard treatment is appendectomy, either through open or laparoscopic surgery. Although it is highly effective, in advanced cases complications such as perforation of the appendix may arise, requiring more aggressive treatments. Research has found that appendectomy can have long-term effects on health, including cognition. Studies in animal and human models have revealed alterations in memory and learning after surgery, as well as associations with neurological diseases and psychiatric disorders [6—8].
A Chinese investigation in mice showed alterations in spatial learning memory after appendectomy, particularly in aged mice [8]. Research in humans has revealed long-term postoperative cognitive dysfunction, with evidence suggesting that elderly patients are more susceptible [9]. Other studies have associated appendectomy with more severe symptoms in patients with Parkinson’s disease and with an increased risk of psychiatric disorders later in life [10, 11].
Given the high volume of appendectomies globally, it is imperative to understand their potential long-term repercussions. Although current evidence is limited, the physiological basis suggests that it could be a risk factor for cognitive decline in adults. This research could transform healthcare, better informing patients and guiding prevention and treatment strategies for potential risks associated with appendectomy.
Material and methods
Study design
An observational, retrospective analysis was carried out based on a case-control design.
Study population
The target population included 270 adult patients aged 50 to 70 years who were seen between May and July 2023. Cases were defined as those patients with cognitive impairment while controls as those without impairment. Cognitive impairment was identified through the Montreal Cognitive Assessment (MoCA). Exclusion criteria included psychiatric diseases and HIV/AIDS diagnosis. The sample size was calculated through a case-control formula with a proportion of 2:1 ratio, where 90 patients with cognitive impairment and 180 patients without cognitive impairment were designated (10).
Procedure
Sociodemographic variables were recorded, as well as the presence of the dependent variable «Cognitive Impairment» measured with the Montreal Cognitive Assessment (MoCA) and the independent past appendectomy. MoCA is a cognitive screening tool that evaluates 8 cognitive domains, including attention, concentration, short-term and working memory, visuospatial abilities, verbal fluency, language, and executive functions. The maximum score on the MoCA is 30 points, and the proposed cutoff score for this study was <26 points for rule in cognitive impairment. Data collection consisted of the presence of data on medical history of interest, as well as the MoCA Score. Once collected, the data were processed with SPSS V.28 software for subsequent statistical analysis.
Statistical analysis
The data are presented in tables, comparing qualitative variables using chi square and quantitative variables using Student’s t-distribution. The OR with 95% CI was calculated and logistic regression was performed to evaluate the independent influence of appendectomy on cognitive impairment.
Table 1. Distribution of adult patients according to clinical characteristics and cognitive impairment
| Clinical characteristics | Cognitive imparment | OR IC 95% | Valor p | |
| Yes (n=90) | No (n=180) | |||
| Age (years) | 62.30±5.83 | 56.42±5.31 | — | 0.001 |
| Sex | 1.45 [0.87—2.43] | 0.157 | ||
| Male | 40 (44.44%) | 64 (35.56%) | ||
| Female | 50 (55.56%) | 116 (64.44%) | ||
| Body mass index (Kg/m2) | 27.66±5.33 | 27.89±4.04 | — | 0.699 |
| Hypertension | 2.79 [1.64—4.74] | 0.001 | ||
| Yes | 44 (48.89%) | 46 (25.56%) | ||
| No | 46 (51.11%) | 134 (74.44%) | ||
| Diabetes Mellitus 2 | ||||
| Yes | 22 (24.44%) | 24 (13.33%) | 2.10 [1.10—4.01] | 0.022 |
| No | 68 (75.56%) | 156 (86.67%) | ||
| Smoking | ||||
| Yes | 26 (28.89%) | 10 (5.56%) | 6.91 [3.15—15.13] | 0.001 |
| No | 64 (71.11%) | 170 (94.44%) | ||
| Score MoCA | 19.59 ± 3.49 | 26.41 ± 0.74 | — | 0.001 |
Abreviattions. t student = c2. MoCA = Montreal Cognitive Assesment.
Table 2. Distribution of adult patients according to surgical history and cognitive impairment
| Surgical History | Deterioro cognitivo | OR IC 95% | Valor p | |
| Si (n=90) | No (n=180) | |||
| Past appendectomy | 13.10 [5.18—33.13] | 0.001 | ||
| Yes | 28 (31.11%) | 6 (3.33%) | ||
| No | 62 (68.89%) | 174 (96.67%) | ||
| Years of appendectomy | 25±11.02 | 30.86±10.21 | — | 0.211 |
| Past cholecystectomy | ||||
| Yes | 36 (40%) | 15 (8.33%) | 7.33 [3.73—14.42] | 0.001 |
| No | 54 (50%) | 165 (91.67%) | ||
| Years after cholecystectomy | 15.86±9.13 | 22.06±11.22 | — | 0.040 |
| Other abdominal surgeries | 13.39 [4.44—40.43] | 0.001 | ||
| Yes | 21 (23.33%) | 4 (2.22%) | ||
| No | 69 (76.67%) | 176 (97.78%) | ||
| Years of other surgeries | 9.38±8.81 | 13.75±7.85 | — | 0.366 |
Abreviattions. t student = c2.
Ethical aspects
Approval of the Bioethics Committee of the Antenor Orrego Private University, recommendations of the CIOMS and the Declaration of Helsinki of the World Medical Association were followed [12, 13].
Results
We identified 90 cases and 180 controls. Among patients with cognitive impairment, higher proportions of men, hypertensive patients, type 2 diabetics, and smokers were observed compared to the control group.
A detailed analysis revealed that 31.11% of the patients with deterioration had undergone appendectomy with an average of 25 years post-procedure. While 40% reported past cholecystectomy and 23.33% other surgeries, with averages of 15.86 and 9.38 years post-procedure, respectively. Differences in surgical history between groups were statistically significant for appendectomy and other surgeries.
Logistic regression analysis identified several variables associated with cognitive impairment. Age showed a significant association with an Adjusted Odds Ratio (ORa) of 1.20 (95% CI: 1.12—1.28). Past surgeries, including appendectomy (aOR: 12.91, 95% CI: 4.11—40.57), cholecystectomy (aOR: 7.17, 95% CI: 2.99—17.21) and other interventions (ORa: 13.10, 95% CI: 3.32—51.61), were associated with cognitive deterioration. In addition, smoking also had a significant relationship with an aOR of 7.76 (95% CI: 2.75—21.90). All these variables had a p-value less than 0.001, emphasizing their strong association with cognitive impairment.
Table 3. Logistic regression of variables associated with cognitive impairment in the adult population
| B | Wald | p Value | ORa | IC 95% | ||
| inferior | superior | |||||
| Age | 0.18 | 29.36 | <0.001 | 1.20 | 1.12 | 1.28 |
| Past appendectomy | 2.56 | 19.16 | <0.001 | 12.91 | 4.11 | 40.57 |
| Past cholecystectomy | 1.97 | 19.44 | <0.001 | 7.17 | 2.99 | 17.21 |
| Other surgeries | 2.57 | 13.52 | <0.001 | 13.10 | 3.32 | 51.61 |
| Smoking | 2.05 | 15.01 | <0.001 | 7.76 | 2.75 | 21.90 |
| Constant | –12.90 | |||||
Abreviations. ORa = Adjusted Odds Ratio.
Discussion
Cognitive impairment in the adult population has been established as a growing concern in the field of global public health. As life expectancy increases and populations age, the prevalence of cognitive impairment, has intensified, affecting the quality of life of individuals and significantly burdening health systems [14].
Epidemiological studies suggest that various factors, such as age, chronic comorbidities (such as hypertension and diabetes mellitus), lifestyle habits and surgical history, are intrinsically linked to the probability of developing cognitive impairment [15, 16]. Furthermore, regional variations in prevalence are observed, reflecting possible genetic, socioeconomic, and environmental influences [17]. Given its multifactorial complexity, it is imperative that research on cognitive impairment is done from a holistic and multidisciplinary approach, in order to develop effective prevention and management strategies in the adult population.
The present observational study revealed several potential associations between different factors and cognitive impairment in an adult population. The results showed that those with cognitive impairment had higher prevalence of arterial hypertension, type 2 diabetes mellitus and smoking compared to those without impairment. A systematic review by Y. Lin et al [18] in China showed that glycemic control significantly reduced the deterioration of cognitive function assessment scores; another study by C. Lalithambika et al [19], in India, evaluated 70 patients with type 2 diabetes mellitus using the Montreal Cognitive Assessment (MoCA) test to determine the prevalence of previously unknown mild cognitive impairment (MCI). The results revealed that more than half (54.29%) of these patients had MCI. Additionally, MCI patients showed significantly higher levels in key measures such as HbA1c, fasting and postprandial blood glucose levels. As can be seen, chronic diseases are associated with cognitive deterioration.
On the other hand, the most relevant finding is the strong relationship between a history of appendectomy and cognitive impairment. A significant 31.11% of individuals with impairment reported having undergone an appendectomy in the past, in contrast to only 3.33% in the group without impairment. Although cholecystectomy also showed a markedly higher prevalence in those with impairment, it did not reach the same degree of statistical significance as appendectomy and other surgeries. Possible explanations between past appendectomy and cognitive impairment can be explained in relation to the function of the appendix in immunity and the microbiome, as is known, the appendix has been recognized as a reservoir for beneficial bacteria. An appendectomy could alter the composition of the gut microbiome, which in turn could have an impact on brain health. Relatedly, there is emerging evidence to suggest that the gut microbiome may influence brain health through the gut-brain axis [20].
Another mechanism to consider is that surgical interventions, including appendectomy, can trigger a systemic inflammatory response and chronic inflammation has been implicated in neurodegenerative diseases and cognitive decline [21].
Logistic regression analysis strengthened these associations, especially with appendectomy, which showed a high aOR. Age, as expected, also had a significant association, underscoring its known role as a risk factor for cognitive decline.
Based on our results, it would be advisable that, in future studies, different topics be addressed that are a follow-up of cognitive deterioration in the adult population. Given the finding of the association between appendectomy and cognitive deterioration, it would be essential to carry out longitudinal studies that follow patients from the time of appendectomy over several decades. These studies could determine whether there is a progressive increase in the risk of cognitive impairment after surgery and what the underlying pathophysiological mechanisms could be. On the other hand, although the exact mechanism remains unknown, some future research proposals could focus on identifying possible biological mechanisms, for example, could removal of the appendix affect the gut microbiota in a way that has repercussions on brain health? Or could postoperative immune or inflammatory responses have long-term effects on the brain?
Like any observational study, this research presents some methodological limitations. Although a relationship was found between appendectomy and cognitive impairment, we cannot conclude that appendectomy causes the impairment; on the other hand, although the study showed significant associations even after taking into account factors such as high blood pressure, type 2 Diabetes Mellitus, smoking, there is always a risk that not all potential confounders were considered. The sample was limited to patients who attended an outpatient clinic at a specific hospital during a specific period, therefore this could introduce selection bias, as these patients may not be representative of the general population. These limitations do not invalidate the findings of the study, but should be taken into account when interpreting the results and considering directions for future research.
In conclusion, it was shown that certain conditions and clinical history have a significant relationship with cognitive impairment in adults. The surgical history stands out, particularly the appendectomy, which showed a high association with this deterioration. In addition to surgical history, clinical factors, lifestyle habits and age were shown to be determining factors. These results underscore the relevance of taking surgical history and clinical conditions into account when evaluating and preventing cognitive decline. The prevailing need to deepen research that allows us to fully understand the causes of these associations and, thereby, design more effective interventions is also highlighted.
Ethical aspects: All authors certify that they meet the current authorship criteria of the International Committee of Medical Journal Editors (ICMJE).