Cognitive Function and General Anesthesia Exposure: A Cognitive Impairment Stage- Dependent Inverse Relationship

Cognitive Function and General Anesthesia Exposure: A Cognitive Impairment Stage- Dependent Inverse Relationship | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Cognitive Function and General Anesthesia Exposure: A Cognitive Impairment Stage- Dependent Inverse Relationship Kayoung Song, Min-Seung Park, Seong Yoon Kim This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6621562/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract The relationship between general anesthesia (GA) exposure and cognition remains controversial. Using data from the Korea Dementia Research Center’s Trial Ready Registry, we examined the associations between a history of GA after the age of 50 and cognitive function, as measured using the Clinical Dementia Rating-Sum of Boxes (CDR-SB) and Global Deterioration Scale (GDS) scores, across the normal, mild cognitive impairment (MCI), and dementia groups. Ordinal logistic regression and subgroup analyses were performed on 688 participants (258 cognitively normal, 245 with MCI, and 185 with dementia). In the normal group, a history of GA was associated with higher CDR-SB (odds ratio [OR] = 2.20, P = 0.031) and GDS scores (OR = 1.87, P = 0.053). However, in the dementia group, GA was associated with lower CDR-SB (OR = 0.43, P = 0.032) and GDS scores (OR = 0.40, P = 0.022). Participants with a history of GA had higher CDR-SB and GDS scores in the normal group, but lower scores in the dementia group. No significant associations were observed in the MCI group. Thus, the relationship between GA exposure and cognitive function may differ depending on the stage of cognitive impairment, highlighting the need for stage-specific approaches in future research. Health sciences/Diseases/Neurological disorders/Dementia Health sciences/Neurology/Neurological disorders/Neurodegenerative diseases/Alzheimers disease General anesthesia Cognitive impairment Dementia Clinical Dementia Rating Global Deterioration Scale Figures Figure 1 Introduction Dementia is a progressive neurodegenerative disorder characterized by cognitive decline and impaired daily functioning 1 . Its global prevalence is rising rapidly, with an estimated 55 million people being affected in 2020, and is projected to increase to 78 million by 2030 and 139 million by 2050 2 . This dramatic increase presents a notable challenge to healthcare systems and societies worldwide. The clinical evaluation of dementia typically involves the use of standardized cognitive assessment tools, such as the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS). These instruments assess the cognitive, functional, and behavioral aspects of dementia severity across various stages of cognitive decline 3 – 5 and are essential for early disease detection, monitoring of disease progression, and evaluation of the effectiveness of therapeutic interventions 6 , 7 . Numerous risk factors have been implicated in the development and progression of dementia. Aging remains the most critical determinant, with the prevalence doubling approximately every five years after the age of 65 8 . Other factors include genetic predisposition (e.g., E4 variant of apolipoprotein E [APOE4]), cardiovascular disease, diabetes mellitus, obesity, smoking, and low educational attainment 9 – 11 . However, the roles of certain potential risk factors remain controversial. For instance, previous studies have reported conflicting findings regarding the association between hypertension and dementia 12 and that between general anesthesia (GA) exposure and subsequent cognitive decline or dementia. Although some studies have suggested a positive association 13 , 14 , others have reported no significant relationship 15 , 16 . In the present study, we aimed to examine the factors associated with cognitive impairment, as assessed by the CDR and GDS scores, across distinct cognitive diagnostic groups. Results Comparison of participant characteristics between the diagnostic groups A total of 688 participants were enrolled in the present study, of whom 433 (62.9%) were women, with a median age of 74 years (Table 1 ). Among the participants, 258 (37.5%), 245 (35.6%), and 185 (26.9%) were classified as normal subjects, participants with mild cognitive impairment (MCI), and participants with dementia, respectively. The median number of years of education was 12 across all groups; however, the distribution differed significantly among the groups ( P = 0.013). There was no significant difference in the prevalence of a family history of dementia. A total of 186 participants (26.6%) had a history of GA after 50 years of age, 135 (19.6%) had diabetes mellitus, 313 (45.5%) had hypertension, 294 (42.7%) had dyslipidemia, 72 (10.5%) had a history of malignancy, and 258 (37.5%) were APOE4carriers. Variables that showed significant differences among the normal, MCI, and dementia groups ( P < 0.05) included age, years of education, presence of diabetes mellitus, and APOE4 carrier status. The MMSE scores decreased progressively from the MCI to the dementia group, whereas both the CDR-SB and GDS scores increased significantly ( P < 0.001). In addition, the proportion of amyloid Positron Emission Tomography (PET) positivity and the standardized uptake value ratios (SUVRs) were significantly higher in the dementia group ( P < 0.001). Table 1 Demographic, clinical, and neuroimaging characteristics of study participants among the different diagnostic groups. Total participants (N = 688) P -value Normal (N = 258, 37.5%) MCI (N = 245, 35.6%) Dementia (N = 185, 26.9%) Demographics Age, years (Median [range]) 73 (50–90) 74 (51–87) 74 (51–87) 0.013 Female, N (%) 156 (60.5%) 156 (63.7%) 121 (65.4%) 0.544 Education, years (Median [IQR]) 12 (9.0–16.0) 12 (6.0–16.0) 12 (6.0–14.0) < 0.001 Family history of dementia, N (%) 77 (29.8%) 88 (35.9%) 61 (33.0%) 0.349 Medical history, N (%) GA history 59 (22.9%) 71 (29.0%) 53 (28.6%) 0.229 Diabetes mellitus 37 (14.3%) 59 (24.1%) 39 (21.1%) 0.019 Hypertension 132 (51.2%) 100 (40.8%) 81 (43.8%) 0.057 Dyslipidemia 115 (44.6%) 113 (46.1%) 66 (35.7%) 0.072 Malignancy 20 (7.8%) 31 (12.7%) 21 (11.4%) 0.180 APOE4 carrier 48 (18.6%) 113 (46.1%) 97 (52.4%) < 0.001 Clinical assessment measures (Median [IQR]) MMSE, score 28 (27.0–29.0) 26 (23.0–28.0) 18 (15.0–22.0) < 0.001 MMSE, Z-score 0.46 (-0.14–1.02) -0.75 (-1.90–0.08) -4.26 (-6.63– -2.21) < 0.001 CDR total 0.0 (0.0–0.0) 0.5 (0.5–0.5) 1.0 (0.5–1.0) < 0.001 CDR-SB 0.0 (0.0–0.0) 1.0 (0.5–2.0) 5.0 (3.5–7.0) < 0.001 GDS a 1.0 (1.0–2.0) 3.0 (3.0–3.0) 4.0 (4.0– 5.0) < 0.001 Amyloid PET Positive for amyloid 45 (17.4%) 129 (52.7%) 150 (81.1%) < 0.001 SUVR (Median [IQR]) 0.64 (0.56–0.92) 1.06 (0.78–1.37) 1.37 (1.13–1.56) < 0.001 a GDS data were unavailable for nine participants who were excluded from the GDS-related analysis. Abbreviations: MCI, mild cognitive impairment; IQR, interquartile range; GA, general anesthesia; APOE4, E4 variant of apolipoprotein E; MMSE, Mini-Mental State Examination; CDR-SB, Clinical Dementia Rating-Sum of Boxes; GDS, Global Deterioration Scale; PET, positron emission tomography; SUVR, standardized uptake value ratio. Variables associated with the CDR-SB scores In the normal group, multivariate analysis revealed that a history of GA was significantly associated with higher CDR-SB scores (OR = 2.20 [95% confidence interval (CI): 1.07–4.51, P = 0.031]; Table 2 ). Dyslipidemia and amyloid PET positivity were independently associated with increased CDR-SB scores (dyslipidemia: odds ratio (OR) = 2.04, P = 0.040; amyloid PET: OR = 8.62, P < 0.001). Although the education level showed a protective effect in the univariate analysis (OR = 0.91, P = 0.002), this association was not found to be statistically significant in the multivariate model. Table 2 Ordinal logistic regression analysis of variables associated with CDR-SB scores among the different diagnostic groups. Variables Univariate analysis Multivariate analysis OR (95% CI) P -value OR (95% CI) P -value Normal participants Age 1.03 (1.00–1.08) 0.084 1.01 (0.97–1.06) 0.571 Sex (female) 1.69 (0.94–3.16) 0.088 1.74 (0.87–3.60) 0.127 Education, year 0.91 (0.85–0.96) 0.002 0.95 (0.89–1.02) 0.192 Family history of dementia 1.52 (0.83–2.77) 0.170 1.47 (0.74–2.88) 0.266 GA history 2.33 (1.24–4.31) 0.007 2.20 (1.07–4.51) 0.031 Diabetes mellitus 1.16 (0.49–2.54) 0.717 1.02 (0.40–2.41) 0.966 Hypertension 1.15 (0.65–2.03) 0.630 0.74 (0.38–1.43) 0.374 Dyslipidemia 1.82 (1.03–3.24) 0.039 2.04 (1.04–4.07) 0.040 Cancer history 1.42 (0.49–3.66) 0.486 1.10 (0.32–3.36) 0.872 APOE4 carrier 1.89 (0.94–3.67) 0.065 0.86 (0.37–1.90) 0.722 PET-amyloid+ 8.58 (4.43–16.88) < 0.001 8.62 (4.09–18.64) < 0.001 MCI group Age 1.02 (0.99–1.05) 0.277 1.02 (0.98–1.06) 0.347 Sex (female) 1.25 (0.76–2.09) 0.380 1.23 (0.68–2.23) 0.495 Education, year 0.95 (0.90–0.99) 0.030 0.94 (0.88–0.99) 0.032 Family history of dementia 1.13 (0.68–1.87) 0.628 0.99 (0.57–1.72) 0.972 GA history 0.66 (0.38–1.13) 0.134 0.57 (0.31–1.04) 0.070 Diabetes mellitus 1.10 (0.62–1.91) 0.750 1.30 (0.69–2.45) 0.418 Hypertension 1.16 (0.70–1.90) 0.561 1.08 (0.60–1.92) 0.803 Dyslipidemia 0.98 (0.60–1.59) 0.920 0.95 (0.54–1.66) 0.847 Cancer history 0.58 (0.25–1.24) 0.172 0.79 (0.31–1.89) 0.601 APOE4 carrier 2.12 (1.29–3.49) 0.003 1.61 (0.88–2.93) 0.121 PET-amyloid+ 3.43 (2.05–5.81) < 0.001 3.12 (1.73–5.73) < 0.001 Dementia group Age 1.00 (0.97–1.04) 0.925 1.01 (0.97–1.05) 0.808 Sex (female) 1.34 (0.69–2.64) 0.388 1.17 (0.52–2.66) 0.703 Education, year 0.97 (0.91–1.03) 0.367 0.96 (0.89–1.04) 0.345 Family history of dementia 0.60 (0.30–1.18) 0.138 0.88 (0.42–1.80) 0.718 GA history 0.41 (0.20–0.84) 0.015 0.43 (0.20–0.92) 0.032 Diabetes mellitus 1.18 (0.54–2.61) 0.681 1.62 (0.69–3.85) 0.267 Hypertension 0.55 (0.28–1.05) 0.074 0.60 (0.29–1.24) 0.170 Dyslipidemia 0.50 (0.25–0.98) 0.046 0.55 (0.27–1.12) 0.102 Cancer history 0.76 (0.29–2.05) 0.583 1.15 (0.41–3.29) 0.790 APOE4 carrier 0.74 (0.38–1.40) 0.350 0.64 (0.32–1.27) 0.208 PET-amyloid+ 1.55 (0.70–3.40) 0.277 1.89 (0.78–4.61) 0.159 Abbreviations: CDR-SB, Clinical Dementia Rating-Sum of Boxes; OR, odds ratio; CI, confidence interval; MCI, mild cognitive impairment; GA, general anesthesia; APOE4, E4 variant of apolipoprotein E; PET, positron emission tomography. In the MCI group, education level and amyloid PET positivity were significantly associated with CDR-SB scores in the multivariate analysis (education, OR = 0.94, P = 0.032; amyloid PET, OR = 3.12, P < 0.001). In the dementia group, a history of GA was significantly associated with lower CDR-SB scores in multivariate analysis (OR = 0.43 [95% CI: 0.20–0.92, P = 0.032]). Variables associated with the GDS Scores In the normal group, a history of GA was associated with higher GDS scores in the univariate analysis (OR = 2.34 [95% CI: 1.32–4.11, P = 0.003]), with borderline significance in the multivariate model (OR = 1.87 [95% CI: 0.99–3.51, P = 0.053]; Table 3 ). Amyloid PET positivity was independently associated with higher GDS scores (OR = 6.49, P < 0.001). While age, education level, and cancer history were significantly associated with GDS scores in the univariate analysis (age: OR = 1.04, P = 0.016; education: OR = 0.91, P = 0.001; cancer history: OR = 2.39, P = 0.039), these associations were not significant after adjustment. Table 3 Ordinal logistic regression analysis of variables associated with GDS scores among the different diagnostic groups. Variables Univariate analysis Multivariate analysis OR (95% CI) P -value OR (95% CI) P -value Normal participants Age 1.04 (1.01–1.08) 0.016 1.03 (0.99–1.07) 0.223 Sex (female) 1.66 (0.98–2.86) 0.063 1.65 (0.90–3.06) 0.107 Education, year 0.91 (0.86–0.96) 0.001 0.95 (0.90–1.01) 0.131 Family history of dementia 1.34 (0.78–2.30) 0.287 1.40 (0.77–2.52) 0.262 GA history 2.34 (1.32–4.11) 0.003 1.87 (0.99–3.51) 0.053 Diabetes mellitus 1.70 (0.83–3.39) 0.135 1.42 (0.66–2.95) 0.356 Hypertension 1.43 (0.86–2.39) 0.169 0.90 (0.50–1.61) 0.714 Dyslipidemia 1.69 (1.02–2.82) 0.044 1.60 (0.89–2.89) 0.115 Cancer history 2.39 (1.03–5.46) 0.039 2.13 (0.82–5.42) 0.113 APOE4 carrier 1.55 (0.81–2.93) 0.180 0.84 (0.39–1.74) 0.651 PET-amyloid+ 6.79 (3.5–13.46) < 0.001 6.49 (3.14–13.75) < 0.001 MCI group Age 1.02 (0.98–1.05) 0.385 1.01 (0.97–1.05) 0.725 Sex (female) 1.01 (0.57–1.77) 0.973 1.16 (0.61–2.20) 0.657 Education, year 1.00 (0.94–1.05) 0.882 0.98 (0.92–1.05) 0.566 Family history of dementia 1.39 (0.78–2.49) 0.269 1.15 (0.61–2.16) 0.665 GA history 1.13 (0.62–2.07) 0.693 0.96 (0.48–1.89) 0.896 Diabetes mellitus 1.10 (0.59–2.08) 0.776 1.27 (0.64–2.55) 0.499 Hypertension 1.79 (1.02–3.20) 0.046 2.03 (1.08–3.90) 0.030 Dyslipidemia 1.09 (0.63–1.89) 0.759 0.76 (0.40–1.44) 0.405 Cancer history 1.23 (0.56–2.77) 0.619 1.35 (0.54–3.43) 0.519 APOE4 carrier 3.77 (2.07–7.15) < 0.001 2.25 (1.13–4.63) 0.024 PET-amyloid+ 7.16 (3.71–14.83) < 0.001 5.43 (2.64–11.87) < 0.001 Dementia group Age 1.02 (0.98–1.06) 0.377 1.03 (0.99–1.08) 0.161 Sex (female) 1.21 (0.58–2.54) 0.609 1.30 (0.53–3.20) 0.563 Education, year 1.00 (0.94–1.07) 0.992 1.01 (0.93–1.10) 0.817 Family history of dementia 0.71 (0.34–1.50) 0.372 1.07 (0.48–2.39) 0.868 GA history 0.40 (0.18–0.87) 0.022 0.44 (0.19–1.00) 0.052 Diabetes mellitus 1.34 (0.56–3.35) 0.520 1.76 (0.69–4.65) 0.243 Hypertension 0.52 (0.25–1.07) 0.081 0.54 (0.24–1.20) 0.137 Dyslipidemia 0.63 (0.30–1.33) 0.225 0.67 (0.30–1.48) 0.325 Cancer history 0.48 (0.17–1.43) 0.171 0.59 (0.20–1.87) 0.363 APOE4 carrier 0.60 (0.29–1.23) 0.168 0.54 (0.24–1.15) 0.113 PET-amyloid+ 1.35 (0.55–3.24) 0.510 1.75 (0.65–4.65) 0.265 Abbreviations: GDS, Global Deterioration Scale; OR, odds ratio; CI, confidence interval; MCI, mild cognitive impairment; GA, general anesthesia; APOE4, E4 variant of apolipoprotein E; PET, positron emission tomography In the MCI group, hypertension, APOE4 carrier status, and amyloid PET positivity were significantly associated with higher GDS scores in the multivariate model (hypertension, OR = 2.03, P = 0.030; APOE4 carrier, OR = 2.25, P = 0.024; amyloid PET, OR = 5.43, P < 0.001), whereas history of GA showed no significant relationship. In the dementia group, a history of GA was associated with lower GDS scores in the univariate analysis (OR = 0.40 [95% CI: 0.18–0.87, P = 0.022]) and showed a borderline significance towards an inverse association in the multivariate model (OR = 0.44 [95% CI: 0.19–1.00, P = 0.052). Comparison of CDR-SB and GDS scores by history of GA within each diagnostic group Within each diagnostic group, the CDR-SB and GDS scores were compared between participants with and without a history of GA (Fig. 1 ). In the normal group, the mean CDR-SB and GDS scores were higher for participants with, than for those without, a history of GA (0.47 vs. 0.23 for CDR-SB, 1.66 vs. 1.40 for GDS; all, P 0.05). In contrast, in the dementia group, the mean CDR-SB and GDS scores were lower for participants with, than for those without, a history of GA (4.78 vs. 5.71 for CDR-SB, 4.06 vs. 4.36 for GDS; all, P < 0.05). Discussion In the present study, we explored the relationship between GA exposure and cognitive function in three diagnostic groups: the cognitively normal, MCI, and dementia groups. Contrary to the assumption that GA exacerbates cognitive decline, our findings reveal a stage-specific pattern. In cognitively normal individuals, a history of GA was associated with higher CDR-SB and GDS scores. In contrast, no significant relationship was observed in the MCI group, and intriguingly, a history of GA was associated with lower CDR-SB and GDS scores in individuals with dementia. The observed association between GA and higher cognitive burden (as measured by the CDR-SB and GDS) in the normal group is consistent with previous studies reporting that GA exposure may accelerate subtle cognitive changes or unmask the underlying neuropathological processes 17 , 18 . Such processes can involve inflammation, disruption of the blood–brain barrier, or exacerbation of preclinical neurodegenerative changes 17 . These effects may vary depending on the type of anesthetic agent used; a recent study has indicated that the use of desflurane and midazolam may be linked to a higher risk of dementia, whereas propofol appears to have no significant association 19 . However, in the dementia group, the inverse association between a history of GA and dementia severity was unexpected; several possible explanations for this occurrence may be considered. First, certain anesthetic regimens or perioperative management strategies may help preserve or stabilize cognitive function in patients with advanced neurodegenerative diseases. Some studies have suggested that anesthetic protocols may attenuate the postoperative systemic inflammatory response 20 and that perioperative administration of agents such as dexmedetomidine may notably suppress the production of pro-inflammatory cytokines, such as IL-6, IL-8, and TNF-α 21 . However, in our study, we did not collect information regarding the specific indications for GA or the types of surgical procedures performed; this limited our ability to assess the potential role of cancer- or other disease-specific factors in these associations. Second, the inverse association may reflect improvements in cognition following the surgical treatment of an underlying condition. For example, cognitive improvement after coronary artery bypass grafting (CABG) surgery may occur because of improved general health, enhanced quality of life, and a reduction in the number of previously prescribed medications. In such cases, surgical intervention may alleviate the underlying pathology that caused the cognitive impairment; the resulting improvement in the quality of life may contribute to the improvement of cognitive outcomes 22 . Therefore, this hypothesis may not reflect the effects of GA itself, but rather, the impact of treating the primary pathology through surgery. Moreover, the observed inverse association may have been influenced by selection or survivorship bias. Individuals with dementia who undergo GA may systematically differ from those who do not, possibly having fewer comorbidities, better general health, or greater healthcare access. While our findings raise intriguing possibilities, the above interpretations remain speculative and warrant further investigation through prospective studies with detailed anesthetic and surgical data. Therefore, future studies should assess potential modifiers, such as GA type (e.g., inhalational vs. intravenous), the type and duration of surgery, and perioperative complications to better characterize these divergent outcomes. Additionally, prospective studies incorporating not only neuroimaging modalities (e.g., amyloid or tau PET) but also blood-based biomarkers of Alzheimer’s disease, inflammatory biomarkers, and more comprehensive medical records, could also help elucidate the mechanisms whereby GA exerts variable effects on cognitive function 23 , 24 . This study has a few limitations. First, the retrospective design of our study and reliance on an anonymized database limited our ability to establish definitive causal relationships. Second, detailed information on the type of GA, its duration, and intraoperative management was not available; all these parameters may have independently influenced the cognitive outcomes. Third, the temporal relationship between GA exposure and assessment of cognitive function (CDR and GDS scores) was not clearly defined. Because the dataset merely indicated whether the participants had undergone GA after the age of 50, we were unable to evaluate the potential risk of cognitive impairment in relation to the specific timing of GA. Despite these limitations, the relatively large sample size enabled us to identify statistically significant associations between GA exposure and cognitive measures across the diagnostic groups. Unlike previous studies, our analysis stratified participants according to their cognitive status and incorporated a wide range of relevant covariates, including educational level, family history of dementia, APOE4 carrier status, and amyloid PET findings; this enhanced the robustness and clinical relevance of our findings. In conclusion, our findings suggest that the association between GA exposure and dementia severity differs depending on the stage of cognitive impairment. While GA may contribute to a higher cognitive burden among individuals who are cognitively normal, it appears to have an inverse relationship with the CDR-SB and GDS scores in those with established dementia. Our findings call for further prospective investigations, with an emphasis on mechanistic studies and stratified analyses that consider disease stage, GA type, and comorbidities. Methods Study participants and exclusion criteria The data for this study were provided by the Korea Dementia Research Center’s Trial Ready Registry (KDRC TRR), supported by the Ministry of Health and Welfare and Ministry of Science and ICT, Republic of Korea 25 . The registry contains comprehensive anonymized clinical information, including that regarding demographic characteristics, diagnostic classifications, medical history, clinical assessments, laboratory results, and neuroimaging findings. MCI and dementia were diagnosed in accordance with the National Institute on Aging–Alzheimer’s Association (NIA-AA) criteria 26 . The following exclusion criteria were applied in this platform: individuals with psychiatric disorders, major neurological or severe systemic illnesses potentially affecting cognitive function, and/or severe visual or hearing impairments that could interfere with neuropsychological evaluation were excluded. Participants who were unable to undergo brain Magnetic Resonance Imaging (MRI) or PET imaging were also excluded from the study. In addition, individuals with secondary causes of cognitive impairment were identified via findings of laboratory tests, such as those for vitamin B12 deficiency, positive syphilis serology, or abnormal thyroid, renal, or hepatic function. Patients with structural brain abnormalities evident on MRI, including territorial infarctions, multiple lacunar infarcts, intracranial hemorrhages, more than five cerebral microbleeds, large hemorrhages (≥ 10 mm), brain tumors, hydrocephalus, or severe white matter hyperintensities (assessed using the modified Fazekas scale), were also excluded. All experimental protocols were approved by the Institutional Review Board of Veterans Health Service Medical Center, Seoul, Republic of Korea (Approval No. 2024-02-019), in accordance with relevant guidelines and regulations. This study was conducted in compliance with the Declaration of Helsinki. The initial IRB approval included a waiver of the requirement to obtain informed consent due to the retrospective nature of the study. Variables for analysis of cognitive function The following variables were extracted for analysis: age, sex, years of education, family history of dementia, history of GA after the age of 50 years, medical history of diabetes mellitus, hypertension, dyslipidemia, and/or cancer, APOE4 carrier status, MMSE, CDR-Sum of Boxes (CDR-SB), and GDS scores, and amyloid PET results (the amyloid status and SUVR). Both the CDR-SB and GDS scores were categorized into three ordinal levels — low, intermediate, and high — based on the diagnostic group (normal, MCI, and dementia groups) for statistical analysis. In the normal group, a CDR-SB score of 0 was classified as low, 0.5 as intermediate, and any value above 0.5 as high. In the MCI group, scores ≤ 1.0 were considered low, 1.5 to 2.5 as intermediate, and > 2.5 as high. In the dementia group, scores ≤ 3.0 were classified as low, 3.5 to 10.0 as intermediate, and > 10.0 as high. For GDS, a score of 1 in the normal group was considered low, 2 as intermediate, and > 2 as high. In the MCI group, scores ≤ 2 were low, 3 was intermediate, and > 3 was high. In the dementia group, scores ≤ 3 were low, 4 to 5 were intermediate, and > 5 were high. Nine participants lacked GDS measurements and were excluded from the GDS-based analysis. Statistical analysis Group comparisons among the normal subjects and patients with MCI and dementia were performed using the Kruskal–Wallis tests for continuous variables (age, years of education, MMSE, CDR-SB, and GDS scores, and SUVRs) and chi-square tests for categorical variables (sex, family history of dementia, history of GA, diabetes mellitus, hypertension, dyslipidemia, cancer history, APOE4 carrier status, and amyloid PET results). Univariate and multivariate ordinal logistic regression analyses were performed using the categorized CDR-SB and GDS scores as dependent variables. The covariates included in the models were selected from the same set of demographic and clinical variables used for the group comparisons. The MMSE scores and SUVRs were excluded as predictors because the MMSE score is closely correlated with both the CDR-SB and GDS scores and the SUVRs were derived from the amyloid PET results. The ORs and corresponding 95% CIs were reported. Subgroup analyses were performed for each diagnostic category to explore the potential effects of GA on cognitive function. The CDR-SB and GDS scores of the participants with and without a history of GA were compared and the score distributions were visualized using box plots. Intergroup differences were assessed using the Wilcoxon rank-sum test. All statistical analyses and data visualizations were performed using R software (version 4.3.0). Abbreviations MCI mild cognitive impairment IQR interquartile range GA general anesthesia APOE4 E4 variant of apolipoprotein E MMSE Mini-Mental State Examination CDR-SB Clinical Dementia Rating-Sum of Boxes GDS Global Deterioration Scale PET positron emission tomography SUVR standardized uptake value ratio. Declarations Acknowledgements None Funding This study was supported by a VHS Medical Center Research Grant (VHSMC 24023) from the Republic of Korea. Author contributions Song K, Conceptualization, Methodology, Writing – review and editing, and Project administration; Park M-S, Formal analysis, writing–original draft and Visualization; Kim S-Y, Supervision, Writing – review, and editing Competing Interests The authors have no potential conflicts of interest to disclose References DeTure, M. A. & Dickson, D. W. The neuropathological diagnosis of Alzheimer's disease. Mol Neurodegener 14 , 32, doi:10.1186/s13024-019-0333-5 (2019). Shin, J. H. Dementia Epidemiology Fact Sheet 2022. Ann Rehabil Med 46 , 53-59, doi:10.5535/arm.22027 (2022). Arevalo-Rodriguez, I. et al. Mini-Mental State Examination (MMSE) for the early detection of dementia in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev 7 , CD010783, doi:10.1002/14651858.CD010783.pub3 (2021). Dauphinot, V. et al. Reliability of the assessment of the clinical dementia rating scale from the analysis of medical records in comparison with the reference method. Alzheimers Res Ther 16 , 198, doi:10.1186/s13195-024-01567-9 (2024). Stella, F., Laks, J., Govone, J. S., de Medeiros, K. & Forlenza, O. V. Association of neuropsychiatric syndromes with global clinical deterioration in Alzheimer's disease patients. Int Psychogeriatr 28 , 779-786, doi:10.1017/S1041610215002069 (2016). Arevalo-Rodriguez, I. et al. Mini-Mental State Examination (MMSE) for the detection of Alzheimer's disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev 2015 , CD010783, doi:10.1002/14651858.CD010783.pub2 (2015). Reisberg, B. Global measures: utility in defining and measuring treatment response in dementia. Int Psychogeriatr 19 , 421-456, doi:10.1017/S1041610207005261 (2007). Arvanitakis, Z. The need to better understand aging and risk factors for dementia. Front Dement 2 , 1346281, doi:10.3389/frdem.2023.1346281 (2023). Rashtchian, A. et al. Diabetes mellitus and risk of incident dementia in APOE varepsilon4 carriers: an updated meta-analysis. BMC Neurosci 25 , 28, doi:10.1186/s12868-024-00878-9 (2024). Hwang, P. H. et al. Examination of potentially modifiable dementia risk factors across the adult life course: The Framingham Heart Study. Alzheimers Dement 19 , 2975-2983, doi:10.1002/alz.12940 (2023). Hwangbo, S. et al. Relationships between educational attainment, hypertension, and amyloid negative subcortical vascular dementia: The brain-battering hypothesis. Front Neurosci 16 , 934149, doi:10.3389/fnins.2022.934149 (2022). Sierra, C. Hypertension and the Risk of Dementia. Front Cardiovasc Med 7 , 5, doi:10.3389/fcvm.2020.00005 (2020). Sohn, J. H. et al. Longitudinal Study of the Association between General Anesthesia and Increased Risk of Developing Dementia. J Pers Med 11 , 1215, doi:10.3390/jpm11111215 (2021). Li, W., Jiang, J., Zhang, S., Yue, L. & Xiao, S. Prospective association of general anesthesia with risk of cognitive decline in a Chinese elderly community population. Sci Rep 13 , 13458, doi:10.1038/s41598-023-39300-5 (2023). Hussain, M., Berger, M., Eckenhoff, R. G. & Seitz, D. P. General anesthetic and the risk of dementia in elderly patients: current insights. Clin Interv Aging 9 , 1619-1628, doi:10.2147/CIA.S49680 (2014). Yang, C. W. & Fuh, J. L. Exposure to general anesthesia and the risk of dementia. J Pain Res 8 , 711-718, doi:10.2147/JPR.S55579 (2015). Maniaci, A. et al. Neurological and Olfactory Disturbances After General Anesthesia. Life (Basel) 15 , doi:10.3390/life15030344 (2025). Schulte, P. J. et al. Association between exposure to anaesthesia and surgery and long-term cognitive trajectories in older adults: report from the Mayo Clinic Study of Aging. Br J Anaesth 121 , 398-405, doi:10.1016/j.bja.2018.05.060 (2018). Lee, S. H. et al. The Risk of Dementia after Anesthesia Differs according to the Mode of Anesthesia and Individual Anesthetic Agent. Clin Psychopharmacol Neurosci 23 , 65-75, doi:10.9758/cpn.24.1181 (2025). Alhayyan, A. et al. The effect of anesthesia on the postoperative systemic inflammatory response in patients undergoing surgery: A systematic review and meta-analysis. Surg Open Sci 2 , 1-21, doi:10.1016/j.sopen.2019.06.001 (2020). Li, B. et al. Anti-inflammatory Effects of Perioperative Dexmedetomidine Administered as an Adjunct to General Anesthesia: A Meta-analysis. Sci Rep 5 , 12342, doi:10.1038/srep12342 (2015). Berger, M. et al. Postoperative Cognitive Dysfunction: Minding the Gaps in Our Knowledge of a Common Postoperative Complication in the Elderly. Anesthesiol Clin 33 , 517-550, doi:10.1016/j.anclin.2015.05.008 (2015). Grande, G. et al. Blood-based biomarkers of Alzheimer's disease and incident dementia in the community. Nat Med , doi:10.1038/s41591-025-03605-x (2025). Yun, J., Youn, Y. C. & Kim, H. R. Association Between Clonal Hematopoiesis of Indeterminate Potential and Brain beta-Amyloid Deposition in Korean Patients With Cognitive Impairment. Ann Lab Med 44 , 576-580, doi:10.3343/alm.2024.0086 (2024). Kim, H. J. et al. Establishing the Trial Ready Registry and Dementia Platform Korea system to advance AD research in Korea [poster]. Alzheimer's & Dementia 19 , doi:10.1002/alz.079375 (2023). Jack, C. R., Jr. et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement 14 , 535-562, doi:10.1016/j.jalz.2018.02.018 (2018). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 29 Nov, 2025 Reviewers agreed at journal 19 Nov, 2025 Reviewers invited by journal 22 Aug, 2025 Editor invited by journal 23 May, 2025 Editor assigned by journal 21 May, 2025 Submission checks completed at journal 13 May, 2025 First submitted to journal 13 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6621562","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":504266250,"identity":"9da8c43e-1612-4cac-a03f-2afdcd7704be","order_by":0,"name":"Kayoung Song","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYJACxgYGBjl+diDJYGBBhHo2iBZjyZ4DIC0SxGtJNJiRAOISoUV+fvOzjzNztiUYSD6/uuFHgQQDf3t3Al4tBsfYjGdu3HY7z1w6p+xmD9BhEmfObsCvhY3BmPHhttvFlrNz0m7wALUYSOTi1yLfxv4ZpCVxw80zaTf/EKOF4RiPMeNGkJYb7MduE2WLwbGcYsaZ224DAzmH7baMgQQPQb/INx/fzNi77TYwKo8/u/nmj40cf3svAYchAI8BmCRWOQiwPyBF9SgYBaNgFIwgAABH1ErHIgJfZwAAAABJRU5ErkJggg==","orcid":"","institution":"Veteran Health Service Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Kayoung","middleName":"","lastName":"Song","suffix":""},{"id":504266251,"identity":"84b73dfa-7d83-4045-b62d-8604fdf60192","order_by":1,"name":"Min-Seung Park","email":"","orcid":"","institution":"Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Min-Seung","middleName":"","lastName":"Park","suffix":""},{"id":504266252,"identity":"8cb09c88-f7d8-4362-b156-93bb7003dad3","order_by":2,"name":"Seong Yoon Kim","email":"","orcid":"","institution":"University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Seong","middleName":"Yoon","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2025-05-08 14:23:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6621562/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6621562/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90317240,"identity":"af5504ea-8763-4c94-bb59-eab8443548c3","added_by":"auto","created_at":"2025-09-01 10:26:23","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":425450,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of CDR-SB (A) and GDS (B) scores between participants with (Y) and without (N) a history of general anesthesia, stratified by diagnostic group. Box plots display the median (horizontal line), interquartile range (box), and mean (asterisk).\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6621562/v1/7230aeb661423baacdc8a477.jpeg"},{"id":90318569,"identity":"14cf4836-c6ef-4a98-b3da-94f2e46162ad","added_by":"auto","created_at":"2025-09-01 10:34:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1599625,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6621562/v1/33db9a66-0567-4e65-9c1d-518845c4f3a8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cognitive Function and General Anesthesia Exposure: A Cognitive Impairment Stage- Dependent Inverse Relationship","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDementia is a progressive neurodegenerative disorder characterized by cognitive decline and impaired daily functioning\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Its global prevalence is rising rapidly, with an estimated 55\u0026nbsp;million people being affected in 2020, and is projected to increase to 78\u0026nbsp;million by 2030 and 139\u0026nbsp;million by 2050\u003csup\u003e2\u003c/sup\u003e. This dramatic increase presents a notable challenge to healthcare systems and societies worldwide.\u003c/p\u003e\u003cp\u003eThe clinical evaluation of dementia typically involves the use of standardized cognitive assessment tools, such as the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS). These instruments assess the cognitive, functional, and behavioral aspects of dementia severity across various stages of cognitive decline\u003csup\u003e\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e and are essential for early disease detection, monitoring of disease progression, and evaluation of the effectiveness of therapeutic interventions\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eNumerous risk factors have been implicated in the development and progression of dementia. Aging remains the most critical determinant, with the prevalence doubling approximately every five years after the age of 65\u003csup\u003e8\u003c/sup\u003e. Other factors include genetic predisposition (e.g., E4 variant of apolipoprotein E [APOE4]), cardiovascular disease, diabetes mellitus, obesity, smoking, and low educational attainment\u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. However, the roles of certain potential risk factors remain controversial. For instance, previous studies have reported conflicting findings regarding the association between hypertension and dementia\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e and that between general anesthesia (GA) exposure and subsequent cognitive decline or dementia. Although some studies have suggested a positive association\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e, others have reported no significant relationship\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn the present study, we aimed to examine the factors associated with cognitive impairment, as assessed by the CDR and GDS scores, across distinct cognitive diagnostic groups.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eComparison of participant characteristics between the diagnostic groups\u003c/h2\u003e\u003cp\u003eA total of 688 participants were enrolled in the present study, of whom 433 (62.9%) were women, with a median age of 74 years (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Among the participants, 258 (37.5%), 245 (35.6%), and 185 (26.9%) were classified as normal subjects, participants with mild cognitive impairment (MCI), and participants with dementia, respectively. The median number of years of education was 12 across all groups; however, the distribution differed significantly among the groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013). There was no significant difference in the prevalence of a family history of dementia. A total of 186 participants (26.6%) had a history of GA after 50 years of age, 135 (19.6%) had diabetes mellitus, 313 (45.5%) had hypertension, 294 (42.7%) had dyslipidemia, 72 (10.5%) had a history of malignancy, and 258 (37.5%) were APOE4carriers. Variables that showed significant differences among the normal, MCI, and dementia groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) included age, years of education, presence of diabetes mellitus, and APOE4 carrier status. The MMSE scores decreased progressively from the MCI to the dementia group, whereas both the CDR-SB and GDS scores increased significantly (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In addition, the proportion of amyloid Positron Emission Tomography (PET) positivity and the standardized uptake value ratios (SUVRs) were significantly higher in the dementia group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic, clinical, and neuroimaging characteristics of study participants among the different diagnostic groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eTotal participants (N\u0026thinsp;=\u0026thinsp;688)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;258, 37.5%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMCI\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;245, 35.6%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDementia\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;185, 26.9%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDemographics\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years (Median [range])\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73 (50\u0026ndash;90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e74 (51\u0026ndash;87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e74 (51\u0026ndash;87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.013\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e156 (60.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e156 (63.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e121 (65.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.544\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation, years (Median [IQR])\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (9.0\u0026ndash;16.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (6.0\u0026ndash;16.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (6.0\u0026ndash;14.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFamily history of dementia, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e77 (29.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88 (35.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e61 (33.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.349\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedical history, N (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGA history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59 (22.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e71 (29.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e53 (28.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.229\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (14.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59 (24.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e39 (21.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.019\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e132 (51.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100 (40.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e81 (43.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.057\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e115 (44.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e113 (46.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66 (35.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.072\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMalignancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31 (12.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21 (11.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.180\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPOE4 carrier\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48 (18.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e113 (46.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e97 (52.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClinical assessment measures (Median [IQR])\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMMSE, score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (27.0\u0026ndash;29.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (23.0\u0026ndash;28.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (15.0\u0026ndash;22.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMMSE, Z-score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.46 (-0.14\u0026ndash;1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.75 (-1.90\u0026ndash;0.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-4.26 (-6.63\u0026ndash; -2.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCDR total\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0 (0.0\u0026ndash;0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.5 (0.5\u0026ndash;0.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.0 (0.5\u0026ndash;1.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCDR-SB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0 (0.0\u0026ndash;0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.0 (0.5\u0026ndash;2.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.0 (3.5\u0026ndash;7.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGDS\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.0 (1.0\u0026ndash;2.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.0 (3.0\u0026ndash;3.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.0 (4.0\u0026ndash; 5.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAmyloid PET\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePositive for amyloid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45 (17.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e129 (52.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e150 (81.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSUVR (Median [IQR])\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.64 (0.56\u0026ndash;0.92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.06 (0.78\u0026ndash;1.37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.37 (1.13\u0026ndash;1.56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003eGDS data were unavailable for nine participants who were excluded from the GDS-related analysis.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAbbreviations: MCI, mild cognitive impairment; IQR, interquartile range; GA, general anesthesia; APOE4, E4 variant of apolipoprotein E; MMSE, Mini-Mental State Examination; CDR-SB, Clinical Dementia Rating-Sum of Boxes; GDS, Global Deterioration Scale; PET, positron emission tomography; SUVR, standardized uptake value ratio.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eVariables associated with the CDR-SB scores\u003c/h3\u003e\n\u003cp\u003eIn the normal group, multivariate analysis revealed that a history of GA was significantly associated with higher CDR-SB scores (OR\u0026thinsp;=\u0026thinsp;2.20 [95% confidence interval (CI): 1.07\u0026ndash;4.51, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031]; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Dyslipidemia and amyloid PET positivity were independently associated with increased CDR-SB scores (dyslipidemia: odds ratio (OR)\u0026thinsp;=\u0026thinsp;2.04, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.040; amyloid PET: OR\u0026thinsp;=\u0026thinsp;8.62, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Although the education level showed a protective effect in the univariate analysis (OR\u0026thinsp;=\u0026thinsp;0.91, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), this association was not found to be statistically significant in the multivariate model.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOrdinal logistic regression analysis of variables associated with CDR-SB scores among the different diagnostic groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eUnivariate analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eMultivariate analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNormal participants\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.03 (1.00\u0026ndash;1.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.084\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.01 (0.97\u0026ndash;1.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.571\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.69 (0.94\u0026ndash;3.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.088\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.74 (0.87\u0026ndash;3.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.127\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation, year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.91 (0.85\u0026ndash;0.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.95 (0.89\u0026ndash;1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.192\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFamily history of dementia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.52 (0.83\u0026ndash;2.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.170\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.47 (0.74\u0026ndash;2.88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.266\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGA history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.33 (1.24\u0026ndash;4.31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.20 (1.07\u0026ndash;4.51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.16 (0.49\u0026ndash;2.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.717\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.02 (0.40\u0026ndash;2.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.966\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.15 (0.65\u0026ndash;2.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.630\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.74 (0.38\u0026ndash;1.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.374\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.82 (1.03\u0026ndash;3.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.039\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.04 (1.04\u0026ndash;4.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.040\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.42 (0.49\u0026ndash;3.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.486\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.10 (0.32\u0026ndash;3.36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.872\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPOE4 carrier\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.89 (0.94\u0026ndash;3.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.065\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.86 (0.37\u0026ndash;1.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.722\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePET-amyloid+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8.58 (4.43\u0026ndash;16.88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e8.62 (4.09\u0026ndash;18.64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMCI group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.02 (0.99\u0026ndash;1.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.277\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.02 (0.98\u0026ndash;1.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.347\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.25 (0.76\u0026ndash;2.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.380\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.23 (0.68\u0026ndash;2.23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.495\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation, year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.95 (0.90\u0026ndash;0.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.030\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.94 (0.88\u0026ndash;0.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFamily history of dementia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.13 (0.68\u0026ndash;1.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.628\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.99 (0.57\u0026ndash;1.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.972\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGA history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.66 (0.38\u0026ndash;1.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.134\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.57 (0.31\u0026ndash;1.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.070\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.10 (0.62\u0026ndash;1.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.750\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.30 (0.69\u0026ndash;2.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.418\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.16 (0.70\u0026ndash;1.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.561\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.08 (0.60\u0026ndash;1.92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.803\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.98 (0.60\u0026ndash;1.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.920\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.95 (0.54\u0026ndash;1.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.847\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.58 (0.25\u0026ndash;1.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.172\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.79 (0.31\u0026ndash;1.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.601\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPOE4 carrier\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.12 (1.29\u0026ndash;3.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.61 (0.88\u0026ndash;2.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.121\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePET-amyloid+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.43 (2.05\u0026ndash;5.81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.12 (1.73\u0026ndash;5.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDementia group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.00 (0.97\u0026ndash;1.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.925\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.01 (0.97\u0026ndash;1.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.808\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.34 (0.69\u0026ndash;2.64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.388\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.17 (0.52\u0026ndash;2.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.703\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation, year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.97 (0.91\u0026ndash;1.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.367\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.96 (0.89\u0026ndash;1.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.345\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFamily history of dementia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.60 (0.30\u0026ndash;1.18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.88 (0.42\u0026ndash;1.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.718\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGA history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.41 (0.20\u0026ndash;0.84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.43 (0.20\u0026ndash;0.92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.18 (0.54\u0026ndash;2.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.681\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.62 (0.69\u0026ndash;3.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.267\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.55 (0.28\u0026ndash;1.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.074\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.60 (0.29\u0026ndash;1.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.170\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.50 (0.25\u0026ndash;0.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.046\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.55 (0.27\u0026ndash;1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.102\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.76 (0.29\u0026ndash;2.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.583\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.15 (0.41\u0026ndash;3.29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.790\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPOE4 carrier\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.74 (0.38\u0026ndash;1.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.350\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.64 (0.32\u0026ndash;1.27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.208\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePET-amyloid+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.55 (0.70\u0026ndash;3.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.277\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.89 (0.78\u0026ndash;4.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.159\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: CDR-SB, Clinical Dementia Rating-Sum of Boxes; OR, odds ratio; CI, confidence interval; MCI, mild cognitive impairment; GA, general anesthesia; APOE4, E4 variant of apolipoprotein E; PET, positron emission tomography.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn the MCI group, education level and amyloid PET positivity were significantly associated with CDR-SB scores in the multivariate analysis (education, OR\u0026thinsp;=\u0026thinsp;0.94, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032; amyloid PET, OR\u0026thinsp;=\u0026thinsp;3.12, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In the dementia group, a history of GA was significantly associated with lower CDR-SB scores in multivariate analysis (OR\u0026thinsp;=\u0026thinsp;0.43 [95% CI: 0.20\u0026ndash;0.92, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032]).\u003c/p\u003e\n\u003ch3\u003eVariables associated with the GDS Scores\u003c/h3\u003e\n\u003cp\u003eIn the normal group, a history of GA was associated with higher GDS scores in the univariate analysis (OR\u0026thinsp;=\u0026thinsp;2.34 [95% CI: 1.32\u0026ndash;4.11, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003]), with borderline significance in the multivariate model (OR\u0026thinsp;=\u0026thinsp;1.87 [95% CI: 0.99\u0026ndash;3.51, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.053]; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Amyloid PET positivity was independently associated with higher GDS scores (OR\u0026thinsp;=\u0026thinsp;6.49, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). While age, education level, and cancer history were significantly associated with GDS scores in the univariate analysis (age: OR\u0026thinsp;=\u0026thinsp;1.04, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016; education: OR\u0026thinsp;=\u0026thinsp;0.91, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001; cancer history: OR\u0026thinsp;=\u0026thinsp;2.39, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039), these associations were not significant after adjustment.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOrdinal logistic regression analysis of variables associated with GDS scores among the different diagnostic groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eUnivariate analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eMultivariate analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNormal participants\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.04 (1.01\u0026ndash;1.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.03 (0.99\u0026ndash;1.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.223\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.66 (0.98\u0026ndash;2.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.063\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.65 (0.90\u0026ndash;3.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.107\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation, year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.91 (0.86\u0026ndash;0.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.95 (0.90\u0026ndash;1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.131\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFamily history of dementia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.34 (0.78\u0026ndash;2.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.287\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.40 (0.77\u0026ndash;2.52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.262\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGA history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.34 (1.32\u0026ndash;4.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.87 (0.99\u0026ndash;3.51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.70 (0.83\u0026ndash;3.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.42 (0.66\u0026ndash;2.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.356\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.43 (0.86\u0026ndash;2.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.169\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.90 (0.50\u0026ndash;1.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.714\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.69 (1.02\u0026ndash;2.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.044\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.60 (0.89\u0026ndash;2.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.115\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.39 (1.03\u0026ndash;5.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.039\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.13 (0.82\u0026ndash;5.42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.113\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPOE4 carrier\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.55 (0.81\u0026ndash;2.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.180\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.84 (0.39\u0026ndash;1.74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.651\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePET-amyloid+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6.79 (3.5\u0026ndash;13.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6.49 (3.14\u0026ndash;13.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMCI group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.02 (0.98\u0026ndash;1.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.385\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.01 (0.97\u0026ndash;1.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.725\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.01 (0.57\u0026ndash;1.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.973\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.16 (0.61\u0026ndash;2.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.657\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation, year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.00 (0.94\u0026ndash;1.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.882\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.98 (0.92\u0026ndash;1.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.566\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFamily history of dementia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.39 (0.78\u0026ndash;2.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.269\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.15 (0.61\u0026ndash;2.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.665\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGA history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.13 (0.62\u0026ndash;2.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.693\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.96 (0.48\u0026ndash;1.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.896\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.10 (0.59\u0026ndash;2.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.776\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.27 (0.64\u0026ndash;2.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.499\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.79 (1.02\u0026ndash;3.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.046\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.03 (1.08\u0026ndash;3.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.030\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.09 (0.63\u0026ndash;1.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.759\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.76 (0.40\u0026ndash;1.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.405\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.23 (0.56\u0026ndash;2.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.619\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.35 (0.54\u0026ndash;3.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.519\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPOE4 carrier\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.77 (2.07\u0026ndash;7.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.25 (1.13\u0026ndash;4.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.024\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePET-amyloid+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7.16 (3.71\u0026ndash;14.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5.43 (2.64\u0026ndash;11.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDementia group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.02 (0.98\u0026ndash;1.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.377\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.03 (0.99\u0026ndash;1.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.161\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.21 (0.58\u0026ndash;2.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.609\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.30 (0.53\u0026ndash;3.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.563\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation, year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.00 (0.94\u0026ndash;1.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.992\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.01 (0.93\u0026ndash;1.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.817\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFamily history of dementia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.71 (0.34\u0026ndash;1.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.372\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.07 (0.48\u0026ndash;2.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.868\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGA history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.40 (0.18\u0026ndash;0.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.44 (0.19\u0026ndash;1.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.052\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.34 (0.56\u0026ndash;3.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.520\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.76 (0.69\u0026ndash;4.65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.243\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.52 (0.25\u0026ndash;1.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.081\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.54 (0.24\u0026ndash;1.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.137\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.63 (0.30\u0026ndash;1.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.225\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.67 (0.30\u0026ndash;1.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.325\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.48 (0.17\u0026ndash;1.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.171\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.59 (0.20\u0026ndash;1.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.363\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPOE4 carrier\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.60 (0.29\u0026ndash;1.23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.168\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.54 (0.24\u0026ndash;1.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.113\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePET-amyloid+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.35 (0.55\u0026ndash;3.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.510\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.75 (0.65\u0026ndash;4.65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.265\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: GDS, Global Deterioration Scale; OR, odds ratio; CI, confidence interval; MCI, mild cognitive impairment; GA, general anesthesia; APOE4, E4 variant of apolipoprotein E; PET, positron emission tomography\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn the MCI group, hypertension, APOE4 carrier status, and amyloid PET positivity were significantly associated with higher GDS scores in the multivariate model (hypertension, OR\u0026thinsp;=\u0026thinsp;2.03, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030; APOE4 carrier, OR\u0026thinsp;=\u0026thinsp;2.25, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024; amyloid PET, OR\u0026thinsp;=\u0026thinsp;5.43, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas history of GA showed no significant relationship. In the dementia group, a history of GA was associated with lower GDS scores in the univariate analysis (OR\u0026thinsp;=\u0026thinsp;0.40 [95% CI: 0.18\u0026ndash;0.87, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.022]) and showed a borderline significance towards an inverse association in the multivariate model (OR\u0026thinsp;=\u0026thinsp;0.44 [95% CI: 0.19\u0026ndash;1.00, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.052).\u003c/p\u003e\n\u003ch3\u003eComparison of CDR-SB and GDS scores by history of GA within each diagnostic group\u003c/h3\u003e\n\u003cp\u003eWithin each diagnostic group, the CDR-SB and GDS scores were compared between participants with and without a history of GA (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In the normal group, the mean CDR-SB and GDS scores were higher for participants with, than for those without, a history of GA (0.47 vs. 0.23 for CDR-SB, 1.66 vs. 1.40 for GDS; all, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the MCI group, the mean CDR-SB and GDS scores of participants with and without a history of GA showed no significant differences (1.24 vs. 1.49 for CDR-SB, 2.88 vs. 2.86 for GDS; all, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIn contrast, in the dementia group, the mean CDR-SB and GDS scores were lower for participants with, than for those without, a history of GA (4.78 vs. 5.71 for CDR-SB, 4.06 vs. 4.36 for GDS; all, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, we explored the relationship between GA exposure and cognitive function in three diagnostic groups: the cognitively normal, MCI, and dementia groups. Contrary to the assumption that GA exacerbates cognitive decline, our findings reveal a stage-specific pattern. In cognitively normal individuals, a history of GA was associated with higher CDR-SB and GDS scores. In contrast, no significant relationship was observed in the MCI group, and intriguingly, a history of GA was associated with lower CDR-SB and GDS scores in individuals with dementia.\u003c/p\u003e\u003cp\u003eThe observed association between GA and higher cognitive burden (as measured by the CDR-SB and GDS) in the normal group is consistent with previous studies reporting that GA exposure may accelerate subtle cognitive changes or unmask the underlying neuropathological processes\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Such processes can involve inflammation, disruption of the blood–brain barrier, or exacerbation of preclinical neurodegenerative changes\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. These effects may vary depending on the type of anesthetic agent used; a recent study has indicated that the use of desflurane and midazolam may be linked to a higher risk of dementia, whereas propofol appears to have no significant association\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eHowever, in the dementia group, the inverse association between a history of GA and dementia severity was unexpected; several possible explanations for this occurrence may be considered. First, certain anesthetic regimens or perioperative management strategies may help preserve or stabilize cognitive function in patients with advanced neurodegenerative diseases. Some studies have suggested that anesthetic protocols may attenuate the postoperative systemic inflammatory response\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e and that perioperative administration of agents such as dexmedetomidine may notably suppress the production of pro-inflammatory cytokines, such as IL-6, IL-8, and TNF-α\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. However, in our study, we did not collect information regarding the specific indications for GA or the types of surgical procedures performed; this limited our ability to assess the potential role of cancer- or other disease-specific factors in these associations. Second, the inverse association may reflect improvements in cognition following the surgical treatment of an underlying condition. For example, cognitive improvement after coronary artery bypass grafting (CABG) surgery may occur because of improved general health, enhanced quality of life, and a reduction in the number of previously prescribed medications. In such cases, surgical intervention may alleviate the underlying pathology that caused the cognitive impairment; the resulting improvement in the quality of life may contribute to the improvement of cognitive outcomes\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Therefore, this hypothesis may not reflect the effects of GA itself, but rather, the impact of treating the primary pathology through surgery.\u003c/p\u003e\u003cp\u003eMoreover, the observed inverse association may have been influenced by selection or survivorship bias. Individuals with dementia who undergo GA may systematically differ from those who do not, possibly having fewer comorbidities, better general health, or greater healthcare access. While our findings raise intriguing possibilities, the above interpretations remain speculative and warrant further investigation through prospective studies with detailed anesthetic and surgical data. Therefore, future studies should assess potential modifiers, such as GA type (e.g., inhalational vs. intravenous), the type and duration of surgery, and perioperative complications to better characterize these divergent outcomes. Additionally, prospective studies incorporating not only neuroimaging modalities (e.g., amyloid or tau PET) but also blood-based biomarkers of Alzheimer’s disease, inflammatory biomarkers, and more comprehensive medical records, could also help elucidate the mechanisms whereby GA exerts variable effects on cognitive function\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThis study has a few limitations. First, the retrospective design of our study and reliance on an anonymized database limited our ability to establish definitive causal relationships. Second, detailed information on the type of GA, its duration, and intraoperative management was not available; all these parameters may have independently influenced the cognitive outcomes. Third, the temporal relationship between GA exposure and assessment of cognitive function (CDR and GDS scores) was not clearly defined. Because the dataset merely indicated whether the participants had undergone GA after the age of 50, we were unable to evaluate the potential risk of cognitive impairment in relation to the specific timing of GA. Despite these limitations, the relatively large sample size enabled us to identify statistically significant associations between GA exposure and cognitive measures across the diagnostic groups. Unlike previous studies, our analysis stratified participants according to their cognitive status and incorporated a wide range of relevant covariates, including educational level, family history of dementia, APOE4 carrier status, and amyloid PET findings; this enhanced the robustness and clinical relevance of our findings.\u003c/p\u003e\u003cp\u003eIn conclusion, our findings suggest that the association between GA exposure and dementia severity differs depending on the stage of cognitive impairment. While GA may contribute to a higher cognitive burden among individuals who are cognitively normal, it appears to have an inverse relationship with the CDR-SB and GDS scores in those with established dementia. Our findings call for further prospective investigations, with an emphasis on mechanistic studies and stratified analyses that consider disease stage, GA type, and comorbidities.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003eStudy participants and exclusion criteria\u003c/h2\u003e\u003cp\u003eThe data for this study were provided by the Korea Dementia Research Center’s Trial Ready Registry (KDRC TRR), supported by the Ministry of Health and Welfare and Ministry of Science and ICT, Republic of Korea\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. The registry contains comprehensive anonymized clinical information, including that regarding demographic characteristics, diagnostic classifications, medical history, clinical assessments, laboratory results, and neuroimaging findings. MCI and dementia were diagnosed in accordance with the National Institute on Aging–Alzheimer’s Association (NIA-AA) criteria\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe following exclusion criteria were applied in this platform: individuals with psychiatric disorders, major neurological or severe systemic illnesses potentially affecting cognitive function, and/or severe visual or hearing impairments that could interfere with neuropsychological evaluation were excluded. Participants who were unable to undergo brain Magnetic Resonance Imaging (MRI) or PET imaging were also excluded from the study. In addition, individuals with secondary causes of cognitive impairment were identified via findings of laboratory tests, such as those for vitamin B12 deficiency, positive syphilis serology, or abnormal thyroid, renal, or hepatic function. Patients with structural brain abnormalities evident on MRI, including territorial infarctions, multiple lacunar infarcts, intracranial hemorrhages, more than five cerebral microbleeds, large hemorrhages (≥ 10 mm), brain tumors, hydrocephalus, or severe white matter hyperintensities (assessed using the modified Fazekas scale), were also excluded.\u003c/p\u003e\u003cp\u003eAll experimental protocols were approved by the Institutional Review Board of Veterans Health Service Medical Center, Seoul, Republic of Korea (Approval No. 2024-02-019), in accordance with relevant guidelines and regulations. This study was conducted in compliance with the Declaration of Helsinki. The initial IRB approval included a waiver of the requirement to obtain informed consent due to the retrospective nature of the study.\u003c/p\u003e\u003ch3\u003eVariables for analysis of cognitive function\u003c/h3\u003e\u003cp\u003eThe following variables were extracted for analysis: age, sex, years of education, family history of dementia, history of GA after the age of 50 years, medical history of diabetes mellitus, hypertension, dyslipidemia, and/or cancer, APOE4 carrier status, MMSE, CDR-Sum of Boxes (CDR-SB), and GDS scores, and amyloid PET results (the amyloid status and SUVR).\u003c/p\u003e\u003cp\u003eBoth the CDR-SB and GDS scores were categorized into three ordinal levels — low, intermediate, and high — based on the diagnostic group (normal, MCI, and dementia groups) for statistical analysis. In the normal group, a CDR-SB score of 0 was classified as low, 0.5 as intermediate, and any value above 0.5 as high. In the MCI group, scores ≤ 1.0 were considered low, 1.5 to 2.5 as intermediate, and \u0026gt; 2.5 as high. In the dementia group, scores ≤ 3.0 were classified as low, 3.5 to 10.0 as intermediate, and \u0026gt; 10.0 as high. For GDS, a score of 1 in the normal group was considered low, 2 as intermediate, and \u0026gt; 2 as high. In the MCI group, scores ≤ 2 were low, 3 was intermediate, and \u0026gt; 3 was high. In the dementia group, scores ≤ 3 were low, 4 to 5 were intermediate, and \u0026gt; 5 were high. Nine participants lacked GDS measurements and were excluded from the GDS-based analysis.\u003c/p\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eGroup comparisons among the normal subjects and patients with MCI and dementia were performed using the Kruskal–Wallis tests for continuous variables (age, years of education, MMSE, CDR-SB, and GDS scores, and SUVRs) and chi-square tests for categorical variables (sex, family history of dementia, history of GA, diabetes mellitus, hypertension, dyslipidemia, cancer history, APOE4 carrier status, and amyloid PET results).\u003c/p\u003e\u003cp\u003eUnivariate and multivariate ordinal logistic regression analyses were performed using the categorized CDR-SB and GDS scores as dependent variables. The covariates included in the models were selected from the same set of demographic and clinical variables used for the group comparisons. The MMSE scores and SUVRs were excluded as predictors because the MMSE score is closely correlated with both the CDR-SB and GDS scores and the SUVRs were derived from the amyloid PET results. The ORs and corresponding 95% CIs were reported.\u003c/p\u003e\u003cp\u003eSubgroup analyses were performed for each diagnostic category to explore the potential effects of GA on cognitive function. The CDR-SB and GDS scores of the participants with and without a history of GA were compared and the score distributions were visualized using box plots. Intergroup differences were assessed using the Wilcoxon rank-sum test. All statistical analyses and data visualizations were performed using R software (version 4.3.0).\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emild cognitive impairment\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003einterquartile range\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003egeneral anesthesia\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAPOE4\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eE4 variant of apolipoprotein E\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMMSE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMini-Mental State Examination\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCDR-SB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eClinical Dementia Rating-Sum of Boxes\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGDS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGlobal Deterioration Scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePET\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003epositron emission tomography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSUVR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003estandardized uptake value ratio.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by a VHS Medical Center Research Grant (VHSMC 24023) from the Republic of Korea.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSong K, Conceptualization, Methodology, Writing – review and editing, and Project administration; Park M-S, Formal analysis, writing–original draft and Visualization; Kim S-Y, Supervision, Writing – review, and editing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no potential conflicts of interest to disclose\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDeTure, M. 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H.\u003cem\u003e et al.\u003c/em\u003e Longitudinal Study of the Association between General Anesthesia and Increased Risk of Developing Dementia. \u003cem\u003eJ Pers Med\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 1215, doi:10.3390/jpm11111215 (2021).\u003c/li\u003e\n\u003cli\u003eLi, W., Jiang, J., Zhang, S., Yue, L. \u0026amp; Xiao, S. Prospective association of general anesthesia with risk of cognitive decline in a Chinese elderly community population. \u003cem\u003eSci Rep\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 13458, doi:10.1038/s41598-023-39300-5 (2023).\u003c/li\u003e\n\u003cli\u003eHussain, M., Berger, M., Eckenhoff, R. G. \u0026amp; Seitz, D. P. General anesthetic and the risk of dementia in elderly patients: current insights. \u003cem\u003eClin Interv Aging\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, 1619-1628, doi:10.2147/CIA.S49680 (2014).\u003c/li\u003e\n\u003cli\u003eYang, C. W. \u0026amp; Fuh, J. L. Exposure to general anesthesia and the risk of dementia. \u003cem\u003eJ Pain Res\u003c/em\u003e \u003cstrong\u003e8\u003c/strong\u003e, 711-718, doi:10.2147/JPR.S55579 (2015).\u003c/li\u003e\n\u003cli\u003eManiaci, A.\u003cem\u003e et al.\u003c/em\u003e Neurological and Olfactory Disturbances After General Anesthesia. \u003cem\u003eLife (Basel)\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, doi:10.3390/life15030344 (2025).\u003c/li\u003e\n\u003cli\u003eSchulte, P. J.\u003cem\u003e et al.\u003c/em\u003e Association between exposure to anaesthesia and surgery and long-term cognitive trajectories in older adults: report from the Mayo Clinic Study of Aging. \u003cem\u003eBr J Anaesth\u003c/em\u003e \u003cstrong\u003e121\u003c/strong\u003e, 398-405, doi:10.1016/j.bja.2018.05.060 (2018).\u003c/li\u003e\n\u003cli\u003eLee, S. H.\u003cem\u003e et al.\u003c/em\u003e The Risk of Dementia after Anesthesia Differs according to the Mode of Anesthesia and Individual Anesthetic Agent. \u003cem\u003eClin Psychopharmacol Neurosci\u003c/em\u003e \u003cstrong\u003e23\u003c/strong\u003e, 65-75, doi:10.9758/cpn.24.1181 (2025).\u003c/li\u003e\n\u003cli\u003eAlhayyan, A.\u003cem\u003e et al.\u003c/em\u003e The effect of anesthesia on the postoperative systemic inflammatory response in patients undergoing surgery: A systematic review and meta-analysis. \u003cem\u003eSurg Open Sci\u003c/em\u003e \u003cstrong\u003e2\u003c/strong\u003e, 1-21, doi:10.1016/j.sopen.2019.06.001 (2020).\u003c/li\u003e\n\u003cli\u003eLi, B.\u003cem\u003e et al.\u003c/em\u003e Anti-inflammatory Effects of Perioperative Dexmedetomidine Administered as an Adjunct to General Anesthesia: A Meta-analysis. \u003cem\u003eSci Rep\u003c/em\u003e \u003cstrong\u003e5\u003c/strong\u003e, 12342, doi:10.1038/srep12342 (2015).\u003c/li\u003e\n\u003cli\u003eBerger, M.\u003cem\u003e et al.\u003c/em\u003e Postoperative Cognitive Dysfunction: Minding the Gaps in Our Knowledge of a Common Postoperative Complication in the Elderly. \u003cem\u003eAnesthesiol Clin\u003c/em\u003e \u003cstrong\u003e33\u003c/strong\u003e, 517-550, doi:10.1016/j.anclin.2015.05.008 (2015).\u003c/li\u003e\n\u003cli\u003eGrande, G.\u003cem\u003e et al.\u003c/em\u003e Blood-based biomarkers of Alzheimer\u0026apos;s disease and incident dementia in the community. \u003cem\u003eNat Med\u003c/em\u003e, doi:10.1038/s41591-025-03605-x (2025).\u003c/li\u003e\n\u003cli\u003eYun, J., Youn, Y. C. \u0026amp; Kim, H. R. Association Between Clonal Hematopoiesis of Indeterminate Potential and Brain beta-Amyloid Deposition in Korean Patients With Cognitive Impairment. \u003cem\u003eAnn Lab Med\u003c/em\u003e \u003cstrong\u003e44\u003c/strong\u003e, 576-580, doi:10.3343/alm.2024.0086 (2024).\u003c/li\u003e\n\u003cli\u003eKim, H. J.\u003cem\u003e et al.\u003c/em\u003e Establishing the Trial Ready Registry and Dementia Platform Korea system to advance AD research in Korea [poster]. \u003cem\u003eAlzheimer\u0026apos;s \u0026amp; Dementia\u003c/em\u003e \u003cstrong\u003e19\u003c/strong\u003e, doi:10.1002/alz.079375 (2023).\u003c/li\u003e\n\u003cli\u003eJack, C. R., Jr.\u003cem\u003e et al.\u003c/em\u003e NIA-AA Research Framework: Toward a biological definition of Alzheimer\u0026apos;s disease. \u003cem\u003eAlzheimers Dement\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 535-562, doi:10.1016/j.jalz.2018.02.018 (2018).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"General anesthesia, Cognitive impairment, Dementia, Clinical Dementia Rating, Global Deterioration Scale","lastPublishedDoi":"10.21203/rs.3.rs-6621562/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6621562/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe relationship between general anesthesia (GA) exposure and cognition remains controversial. Using data from the Korea Dementia Research Center\u0026rsquo;s Trial Ready Registry, we examined the associations between a history of GA after the age of 50 and cognitive function, as measured using the Clinical Dementia Rating-Sum of Boxes (CDR-SB) and Global Deterioration Scale (GDS) scores, across the normal, mild cognitive impairment (MCI), and dementia groups. Ordinal logistic regression and subgroup analyses were performed on 688 participants (258 cognitively normal, 245 with MCI, and 185 with dementia). In the normal group, a history of GA was associated with higher CDR-SB (odds ratio [OR]\u0026thinsp;=\u0026thinsp;2.20, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031) and GDS scores (OR\u0026thinsp;=\u0026thinsp;1.87, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.053). However, in the dementia group, GA was associated with lower CDR-SB (OR\u0026thinsp;=\u0026thinsp;0.43, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032) and GDS scores (OR\u0026thinsp;=\u0026thinsp;0.40, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.022). Participants with a history of GA had higher CDR-SB and GDS scores in the normal group, but lower scores in the dementia group. No significant associations were observed in the MCI group. Thus, the relationship between GA exposure and cognitive function may differ depending on the stage of cognitive impairment, highlighting the need for stage-specific approaches in future research.\u003c/p\u003e","manuscriptTitle":"Cognitive Function and General Anesthesia Exposure: A Cognitive Impairment Stage- Dependent Inverse Relationship","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-01 10:18:19","doi":"10.21203/rs.3.rs-6621562/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-11-30T02:54:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"309160572583252728233898662310209791885","date":"2025-11-20T04:03:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-22T07:10:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-23T08:12:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-21T18:31:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-14T01:20:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-05-14T01:19:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"19d3df0b-7ee3-44c9-b699-c218eadc55a9","owner":[],"postedDate":"September 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":53578267,"name":"Health sciences/Diseases/Neurological disorders/Dementia"},{"id":53578268,"name":"Health sciences/Neurology/Neurological disorders/Neurodegenerative diseases/Alzheimers disease"}],"tags":[],"updatedAt":"2025-09-01T10:18:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-01 10:18:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6621562","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6621562","identity":"rs-6621562","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}