Increased risk of dementia after transient global amnesia: a nationwide population-based, longitudinal follow-up study in South Korea.

INTRODUCTION: The long-term cognitive outcomes after transient global amnesia (TGA) have been contradictory in the literature. Our study aimed to longitudinally investigate the association between TGA and incident dementia using long-term data from a nationwide population-based cohort in South Korea. METHODS: The study population was recruited between 2002 and 2020 using the International Classification of Diseases (tenth revision; ICD-10) codes from the Korean National Health Insurance Service database. The cumulative incidence curve was plotted to compare the incidence of dementia between the TGA (ICD-10 code G45.4; n = 10,276) and non-TGA (n = 27,389) groups, determined using 1:3 propensity score matching. Using Cox proportional hazard regression models, we obtained crude and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the incident dementia in patients with TGA compared to non-TGA controls. To examine independent variables determining dementia in the TGA group, logistic regression analysis was performed, and adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: The TGA group had a significantly higher cumulative incidence of dementia than the non-TGA group (p <0.001, log-rank test). TGA was significantly associated with incident dementia in the univariate and multivariate Cox models (HR 1.34, 95% CI 1.28-1.39 and aHR 1.40, 95% CI 1.34-1.46, respectively). The adjusted logistic regression for incident dementia in the TGA group showed that age (per 1 year, aOR 1.09, 95% CI 1.09-1.10), female sex (aOR 1.31, 95% CI 1.18-1.45), diabetes (aOR 1.21, 95% CI 1.08-1.35), stroke (aOR 1.30, 95% CI 1.16-1.46), depression (aOR 1.53, 95% CI 1.33-1.76), anxiety (aOR 1.24, 95% CI 1.01-1.39), and rural residence (aOR 1.24, 95% CI 1.10-1.41) were independently associated with incident dementia. CONCLUSION: Our results suggest a longitudinal association of TGA with incident dementia.

Body mass index at baseline directly predicts new-onset diabetes and to a lesser extent incident cardio-cerebrovascular events, but has a J-shaped relationship to all-cause mortality.

OBJECTIVE: The prevalence of diabetes mellitus (DM), cardio-cerebrovascular diseases (CCVDs) has increased during recent decades. We aimed to investigate the relationship between body mass index (BMI) and each of several outcomes (DM, CCVDs, or mortality) based on the Korean National Health Insurance Service-Health Screening cohort. METHODS: BMI was categorized as appropriate for Asian populations, into underweight (< 18.5 kg/m2), normal (18.5-< 23 kg/m2), overweight (23-< 25 kg/m2), grade 1 obesity (25-< 30 kg/m2), grade 2 obesity (30-< 35 kg/m2), and grade 3 obesity (≥35 kg/m2). In addition, BMI was further stratified into one unit. Multivariate Cox proportional hazards regression analyses were conducted to examine the association between BMI category and the primary outcomes (DM, CCVDs, or mortality). RESULTS: A total of 311,416 individuals were included. The median follow-up was 12.5 years. Compared to normal BMI, underweight, overweight, and grade 1-3 obese individuals had a higher risk of the primary outcomes (hazard ratio [95% confidence intervals] 1.293 [1.224-1.365], 1.101 [1.073-1.129], 1.320 [1.288-1.353], 1.789 [1.689-1.897], and 2.376 [2.019-2.857], respectively, in men and 1.084 [1.010-1.163], 1.150 [1.116-1.185], 1.385 [1.346-1.425], 1.865 [1.725-2.019], and 2.472 [2.025-3.028], respectively, in women). Setting the reference BMI to 20-< 21 kg/m2 and categorizing into one unit increment, BMI was associated with the primary outcomes in a J-shaped manner in both sexes. The risk of DM increased with higher BMI in both sexes, while all-cause mortality decreased in men with a BMI 21-< 31 kg/m2 and women with BMI 22-< 30 kg/m2. CONCLUSIONS: BMI was associated with all-cause mortality in a J-shaped manner in both sexes, while it was associated with risk of DM in a dose-response relationship. The relationship between BMI and the primary outcomes was J-shaped.

Metformin usage and the risk of colorectal cancer: a national cohort study.

PURPOSE: This study aimed to investigate the association between metformin usage and the risk of colorectal cancer (CRC) using data from the Korean National Health Insurance Service-National Health Screening Cohort database. METHODS: Data from the NHIS-HEALS cohort between 2002 and 2015 were longitudinally analyzed. Subjects were divided into three groups: metformin non-users with diabetes mellitus (DM), metformin users with DM, and no DM group. CRC was defined using the ICD-10 code (C18.0-C20.0) at the time of admission. Cox proportional hazard regression models were adopted after stepwise adjustment for confounders to investigate the association between metformin usage and colorectal cancer risk. RESULTS: During the follow-up period, of the total 323,430 participants, 2341 (1.33%) of the 175,495 males and 1204 (0.81%) of the 147,935 females were newly diagnosed with CRC. The estimated cumulative incidence of CRC was significantly different among the three groups based on Kaplan-Meier's survival curve (p values < 0.05 in both sexes). Compared with metformin non-users, hazard ratios (95% CIs) of metformin users and the no DM group were 0.66 (0.51-0.85) and 0.72 (0.61-0.85) in males and 0.59 (0.37-0.92) and 0.93 (0.66-1.29) in females, respectively, after being fully adjusted. CONCLUSIONS: Metformin users with diabetes appear to have a significantly lower risk of CRC compared with metformin non-users.

Metformin use reduced the risk of stomach cancer in diabetic patients in Korea: an analysis of Korean NHIS-HEALS database.

BACKGROUND: Diabetes mellitus (DM) increases atherosclerotic cardiovascular complications and cancer risks. Stomach cancer is the most common cancer in Korea. Although the survival rate of stomach cancer has improved, the disease burden is still high. METHODS: This retrospective study investigated the association between metformin use and stomach cancer incidence in a Korean population using the National Health Insurance Service-National Health Screening Cohort database. Participants aged 40-80 years old at the baseline period (2002-2003) were enrolled. The study population was categorized into three groups of metformin non-users with DM, metformin users with DM, and individuals without DM (No DM group). RESULTS: A total of 347,895 participants (14,922 metformin non-users, 9891 metformin users, and 323,082 individuals without DM) were included in the final analysis. The median follow-up duration was 12.70 years. The estimated cumulative incidence of stomach cancer was highest in metformin non-users and lowest in the No DM group (men vs. women: 3.75 vs. 1.97% in metformin non-users, 2.91 vs. 1.53% in metformin users, and 2.54 vs. 0.95% in the No DM group). Compared with metformin non-users, the hazard ratios (95% confidence intervals) for stomach cancer incidence of metformin users and the No DM group were 0.710 (0.579-0.870) and 0.879 (0.767-1.006) in men and 0.700 (0.499-0.981) and 0.701 (0.544-0.903) in women, respectively, after full adjustment. CONCLUSIONS: Metformin users with DM in the Korean population were at lower risk of stomach cancer incidence after controlling for potential confounding factors.

Metformin use reduced the overall risk of cancer in diabetic patients: A study based on the Korean NHIS-HEALS cohort.

BACKGROUND AND AIM: Several studies have reported the preventive effect of metformin on cancer development. This study aimed to investigate the relationship between use of metformin and risk of cancer in Koreans. METHODS AND RESULTS: This study was designed retrospectively using the National Health Insurance Service-National Health Screening Cohort conducted between 2002 and 2015. 40 to 69-year-old subjects who received a health screening examination from 2002 to 2003 were enrolled. Hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer were estimated in a multivariate Cox proportional regression analysis. A total of 323,430 subjects was enrolled (301,905 individuals without diabetes [No DM], 8643 diabetic patients with metformin treatment [metformin users], and 12,882 diabetic patients without metformin treatment [metformin non-users]). The median follow-up period was 12.7 years. Cumulative incidence of overall cancer was 7.9% (7.7, 10.3, and 11.1% in No DM, metformin users and non-users, respectively). Compared to metformin non-users, the fully adjusted HRs (95% CIs) of metformin users and No DM for overall cancer incidence were 0.73 (0.66-0.81) and 0.75 (0.64-0.88), respectively, in men and 0.83 (0.78-0.89) and 0.81 (0.72-0.92) in women. CONCLUSIONS: Diabetic patients receiving metformin treatment, and individuals without diabetes were at lower risk for cancer incidence than diabetic patients without metformin treatment.

Increased risk of epilepsy after transient global amnesia: A population-based study in South Korea.

PURPOSE: This study aimed to investigate the risk of epilepsy after transient global amnesia (TGA). METHODS: Study population was recruited using the International Classification of Diseases codes from the Korean National Health Insurance Service database between 2002 and 2020. The incidence of epilepsy was compared between the TGA (n=12,390) and non-TGA (n=33,868) groups, determined using 1:3 propensity score matching. Using Cox proportional hazard regression model, we obtained adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident epilepsy in the TGA compared with non-TGA group. Logistic regression was performed to examine the independent variables determining incident epilepsy in the TGA group, and adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: The TGA group had a significantly higher cumulative incidence of epilepsy than controls (p <0.001, log-rank test). TGA was significantly associated with incident epilepsy in the Cox model (adjusted HR 1.46, 95% CI 1.36-1.56). The adjusted logistic regression showed that age (per 1 year, aOR 1.02, 95% CI 1.01-1.02), female sex (aOR 0.68, 95% CI 0.60-0.77), hypertension (aOR 1.14, 95% CI 1.00-1.30), diabetes (aOR 1.26, 95% CI 1.10-1.44), stroke (aOR 1.22, 95% CI 1.06-1.40), depression (aOR 1.44, 95% CI 1.22-1.69), anxiety (aOR 1.31, 95% CI 1.14-1.51), alcohol-related disease (aOR 1.96, 95% CI 1.38-2.78), low income (aOR 1.18, 95% CI 1.02-1.36) and rural residence (aOR 1.20, 95% CI 1.02-1.42) were associated with incident epilepsy. CONCLUSIONS: Our results suggest a longitudinal association of TGA with incident epilepsy.

The role of ambulatory blood pressure monitoring in enhancing medication adherence among patients with newly diagnosed hypertension: an analysis of the National Health Insurance cohort database.

BACKGROUND: Improving adherence to antihypertensive medication (AHM) is a key challenge in hypertension management. This study aimed to assess the impact of ambulatory blood pressure monitoring (ABPM) on AHM adherence. METHODS: We utilized the Korean National Health Insurance Service database. Among patients newly diagnosed with hypertension who started AHM between July 2010 and December 2013, we compared clinical characteristics and adherence between 28,116 patients who underwent ABPM prior to starting AHM and 118,594 patients who did not undergo ABPM. Good adherence was defined as a proportion of days covered (PDC) of 0.8 or higher. RESULTS: The total study population was 146,710, with a mean age of 50.5 ± 6.4 years; 44.3% were female. Co-morbidities were noted in 4.2%. About a third of patients (33.1%) showed good adherence. The ABPM group had a notably higher PDC (total PDC: 0.64 ± 0.35 vs. 0.45 ± 0.39; P < 0.001), irrespective of the number of medications, dosing frequency, or prescription duration. After adjusting for significant clinical variables, ABPM was still closely linked with good adherence (odds ratio, 2.35; 95% confidence interval, 2.28-2.41; P < 0.001). CONCLUSIONS: In newly diagnosed hypertension, undergoing ABPM prior to AHM prescription appears to enhance adherence to AHM. The exact mechanisms driving this association warrant further exploration.

The Long-Term Impact of 5-alpha Reductase Inhibitors on the Development of Bladder Cancer and the Need for Radical Cystectomy: A Nationwide Observational Study.

PURPOSE: To investigate the long-term effects of taking 5-alpha reductase inhibitors (5ARIs) on the development of bladder cancer (BC) and the implementation of radical cystectomy (RC), a standard procedure for advanced BC. MATERIALS AND METHODS: From the National Health Insurance Sharing Service database, males aged over 40 years who underwent serum prostate-specific antigen testing from 2006 through 2017 were identified, which is required for the prescription of 5ARIs. The association between the administration duration of 5ARIs and the practice for BC was analyzed. RESULTS: Of the 3,843,968 subjects, 1,514,713 (39.4%) took 5ARIs for an average of 1.53 years, remaining 2,329,255 (60.6%) as non-5ARI counterparts. The incidence of BC was higher in the non-5ARI than in the 5ARI group (1.25% vs. 0.87%, p<0.001), as was the implementation rate of RC (11.1% vs. 10.4%, p=0.037). In a multivariate analysis, the non-5ARI group had a significant risk of BC (hazard ratio [HR]=2.289, 95% confidence interval [CI]=2.241-2.338) and RC (HR=2.199, 95% CI=2.061-2.348) than the 5ARI group. Among the 5ARIs group, though the incidence of BC was maintained (slope=-0.002 per year, p=0.79) after an initial increase for two years, the rate of RC decreased (slope=-1.1, p<0.001) consistently for ten years during the administration. CONCLUSIONS: Compared to the untreated group, 5ARIs use was associated with lower rates of BC and RC. In contrast to the increase in BC seen with short-term use of less than two years, long-term use of 5ARIs decreased the rate of RC in a duration-dependent manner for ten years, suggesting a strategy to prevent disease progression.

Adherence and clinical outcomes for twice-daily versus once-daily dosing of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: Is dosing frequency important?

BACKGROUND: Twice-daily dosing of non-vitamin K antagonist oral anticoagulants (NOACs) may reduce drug adherence compared with once-daily dosing of NOACs in patients with atrial fibrillation (AF), thus worsening clinical outcomes. We evaluated adherence to apixaban and dabigatran requiring twice-daily dosing compared with edoxaban or rivaroxaban with a once-daily dosing regimen and the subsequent clinical outcomes in patients with AF. METHODS: Adherence to each NOAC and outcomes were compared between patients who were diagnosed with AF and initiated NOACs between 2016 and 2017 using Korean claims data. High adherence was defined as the proportion of days covered (PDC) of the index NOAC ≥80%. The clinical outcomes included stroke, acute myocardial infarction, death, and composite outcome. RESULTS: A total of 33,515 patients were analyzed (mean follow-up, 1.7 ± 1.3 years). The proportion of patients with high adherence to NOACs was 95%, which did not significantly differ according to the dosing regimen. The mean PDC for NOACs was as high as ~96%, which was the highest for apixaban users, intermediate for edoxaban or rivaroxaban users, and lowest for dabigatran users, regardless of the dosing regimen. Adverse outcomes in low adherence patients for each NOAC were higher than that of high adherence patients, regardless of the dosing frequency. CONCLUSIONS: Adherence between once- and twice-daily dosing NOACs in patients with AF was high and similar among both dosing regimens. Patients with low NOAC adherence had poorer clinical outcomes, regardless of the dosing frequency.

Weight maintenance and gain were significantly associated with lower risk of all-cause and cancer-related mortality in Korean adults who were newly diagnosed with cancer based on the Korean NHIS-HEALS cohort.

The burden of malignant neoplasms is increasing worldwide. Healthy lifestyles such as maintaining a healthy body weight are important to improve survival rate in cancer patients. This study was aimed to test the hypothesis that weight change affects mortality in patients newly diagnosed with cancer. This study was retrospectively designed based on the National Health Insurance Service-National Health Screening Cohort. A total of 1856 subjects aged at least 40 years who received a national health checkup within 6 months before cancer diagnosis was included. Study subjects were classified into 3 categories based on weight change before and after cancer diagnosis: weight loss, maintenance, and gain. Cox proportional hazards regression models were adopted to examine the association between weight change and mortality after adjusting for confounders. Compared to those experiencing weight loss, the adjusted hazards ratios (HRs) (95% confidence intervals [CIs]) for those experiencing weight maintenance were 0.327 (0.189-0.568) for all-cause mortality and 0.431 (0.215-0.867) for cancer-related mortality. The adjusted HRs (95% CIs) for those experiencing weight gain were 0.149 (0.044-0.505) for all-cause mortality and 0.289 (0.080-1.045) for cancer-related mortality. After stratifying according to baseline body mass index (BMI), weight maintenance and gain were negatively associated with all-cause mortality (0.286 [0.138-0.592] for weight maintenance and 0.119 [0.027-0.533] for weight gain) among those with a BMI < 25 kg/m2. Weight maintenance and gain reduced the risk of all-cause mortality in patients newly diagnosed with any cancer. In addition, weight maintenance was significantly related to cancer-related mortality.

Metformin Use May Increase Risk of Pancreatic Cancer in Diabetic Women: An Analysis of the Korean National Health Insurance Service-National Health Screening Cohort Database.

BACKGROUND: In addition to its antidiabetic effects, metformin has pleiotropic effects, such as the inhibition of carcinogenesis. This study aimed to investigate the association between metformin use and pancreatic cancer risk in the Korean National Health Insurance Service (NHIS)-National Health Screening Cohort (HEALS). METHODS: Of the individuals in the Korean NHIS-HEALS, 29,271 men and 19,091 women were included in the final analysis after propensity score matching based on age, body mass index, and smoking status. The study population was categorized into three groups: metformin non-users with diabetes mellitus (DM), metformin users with DM, and non-diabetic users. A Cox proportional hazards regression model was used to examine the association between metformin use and pancreatic cancer. RESULTS: The median follow-up period was 12.9 years. The estimated pancreatic cancer incidence was highest in metformin users with DM, regardless of sex (P<0.001), and lowest in non-diabetic men and female metformin non-users (P=0.053). The hazard ratios (95% confidence interval) for pancreatic cancer incidence in metformin users and non-diabetic individuals were 1.116 (0.648-1.923) and 0.447 (0.259-0.771) in men and 2.769 (1.003-7.642) and 1.451 (0.529-3.984) in women, respectively, after full adjustment. CONCLUSION: Women with diabetes using metformin are at a higher risk of pancreatic cancer than women with diabetes not using metformin. Meanwhile, men with DM using metformin have a similar risk of pancreatic cancer as men with DM not using metformin.

Increased Risk of Cardio-Cerebrovascular Diseases in Migraine Patients: A Nationwide Population-Based, Longitudinal Follow-Up Study in South Korea.

BACKGROUND AND PURPOSE: Migraine is reportedly associated with several cardio-cerebrovascular diseases (CCDs), but some of these diseases have not received sufficient attention. We thus attempted to determine the associations of migraine with peripheral arterial disease (PAD), ischemic heart disease (IHD), atrial fibrillation/flutter (AF), ischemic stroke (IS), and hemorrhagic stroke (HS). METHODS: The study population was recruited by applying International Classification of Diseases, Tenth Revision (ICD-10) codes to the database of the Korean National Health Insurance Service from 2002 to 2018. Cumulative incidence curves were plotted to compare the incidence rates of CCDs between the migraine (ICD-10 code G43; n=130,050) and nonmigraine (n=130,050) groups determined using 1:1 propensity-score matching. Cox proportional-hazards regression models were used to obtain adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CCDs in patients with any migraine, migraine with aura (n=99,751), and migraine without aura (n=19,562) compared with nonmigraine controls. RESULTS: For all CCDs, the cumulative incidence rates were higher in the migraine group than the nonmigraine group (p<0.001 in log-rank test). Any migraine, irrespective of the presence of aura, was associated with PAD (aHR 2.29, 95% CI 2.06-2.53), IHD (aHR 2.17, 95% CI 2.12-2.23), AF (aHR 1.84, 95% CI 1.70-1.99), IS (aHR 2.91, 95% CI 2.67-3.16), and HS (aHR 2.46, 95% CI 2.23-2.71). aHR was higher in female than in male migraineurs for all of the CCDs. CONCLUSIONS: Associations of migraine with CCDs have been demonstrated, which are stronger in females than in males.

Severe hypoglycemia and risk of hospitalization for heart failure in adults with diabetes treated with oral medications with or without insulin: A population-based study.

AIMS: We aimed to determine if severe hypoglycemia (SH) independently increases the risk of hospitalization for heart failure (hHF) in type 2 diabetes, regardless of the prevalent or incident cardiovascular disease (CVD). METHODS: This was a nationwide population-based propensity score-matched study using Korean National Health Insurance Service data (2002-2018). The hazards of hHF were compared in individuals who experienced SH (n = 8,965) and 1:3 matched controls, among adults with diabetes using oral anti-diabetes medications (OADs) with or without insulin and without previous hHF at baseline. RESULTS: During 236,417 person-years, 1,189 cases of hHF occurred. The hazard of hHF was higher in individuals with SH compared to matched controls (adjusted hazard ratio [aHR] 1.503, 95 % confidence interval [CI] 1.324-1.707). The increase in aHR remained significant when excluding participants with prevalent or incident major adverse cardiovascular events (MACE; aHR 1.352, 95 % CI 1.228-1.622) and any CVD (aHR 1.342, 95 % CI 1.025-1.756). Two or more SH events were associated with further increase in hHF risk. CONCLUSION: SH was associated with increased risks of hHF among adults with diabetes using OAD with or without insulin. The increased risk was attenuated but remained significant in those without prevalent or incident MACE or CVDs.

The ratio of triglycerides to high-density lipoprotein cholesterol is associated with the risk of chronic kidney disease in Korean men.

Dyslipidemia is nephrotoxic and can result in the development of chronic kidney disease (CKD). The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) (TG/HDL-C ratio) is well-correlated with insulin resistance and cardiovascular events. The aim of this study is to examine the association between the TG/HDL-C ratio and CKD in Korean adults. This study was retrospectively designed based on the National Health Insurance Service-National Health Screening cohort. Seventy three thousand and fifty-two participants aged between 40 and 79 years old at baseline (2009-2010) were included in the final analyses. The study population was classified into three tertile groups (T1 , T2 , and T3 ) according to the TG/HDL-C ratio by sex. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD were calculated using Cox proportional hazard regression models. The median follow-up duration was 5.9 years. Higher tertile groups of the TG/HDL-C ratio had lower estimated glomerular filtration rates in both sexes. The cumulative incidence of CKD of T1 , T2 , and T3 was 11.89%, 12.90%, and 12.91%, respectively, in men and 10.17%, 10.61%, and 14.87%, respectively, in women (all p values < 0.001). Compared with T1 of the TG/HDL-C ratio, the HRs (95% CIs) of T2 and T3 for CKD were 1.212 (1.118-1.315) and 1.183 (1.087-1.287), respectively, in men and 0.895 (0.806-0.994) and 1.038 (0.937-1.150), respectively, in women after being fully adjusted. Higher TG/HDL-C ratios were positively associated with CKD development in men, while middle levels of TG/HDL ratios reduced the CKD incidence in women.

Metformin use in cancer survivors with diabetes reduces all-cause mortality, based on the Korean National Health Insurance Service between 2002 and 2015.

ABSTRACT: Malignant neoplasms are the leading cause of death in Korea. We aimed to examine if metformin use in cancer survivors reduces all-cause mortality. This study was retrospectively designed based on data from the Korean National Health Insurance Service-National Health Screening Cohort (HEALS) between 2002 and 2015. The Kaplan-Meier estimator and log-rank test was performed to estimate the survival function according to metformin usage (3721 metformin non-users with diabetes, 5580 metformin users with diabetes, and 24,483 non-diabetic individuals). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were calculated using Cox proportional hazards regression models.The median follow-up duration was 4.2 years. The HRs (95% CIs) for all-cause mortality of metformin users and the non-diabetic group were 0.762 (0.683-0.850) and 1.055 (0.966-1.152) in men and 0.805 (0.649-0.999), and 1.049 (0.873-1.260) in women, respectively, compared with metformin non-users among diabetic cancer survivors, in a fully adjusted model. After stratifying metformin users into pre- and post-diagnosis of cancers, adjusted HRs (95% CIs) of pre- and post-diagnosis metformin users for all-cause mortality were 0.948 (0.839-1.071) and 0.530 (0.452-0.621) in men and 1.163 (0.921-1.469) and 0.439 (0.323-0.596) in women, respectively.Metformin use in cancer survivors with diabetes reduced overall mortality rates. In particular, metformin use after cancer diagnosis, not before cancer diagnosis, was inversely associated with overall mortality.Active treatment with metformin for diabetic cancer survivors after cancer diagnosis can improve their survival rates.

Metformin use in elderly population with diabetes reduced the risk of dementia in a dose-dependent manner, based on the Korean NHIS-HEALS cohort.

AIMS: The aim of this study is to investigate the association between metformin usage and dementia in an elderly Korean population. METHODS: Participants were divided into five groups: metformin non-users with diabetes mellitus (DM), metformin users with DM (low-, mid-, and high-users), and non-diabetic Individuals. Dementia was defined with primary diagnostic dementia codes according to the 10th edition of the International Classification of Diseases. To compare the incidence rate of dementia among the five groups, Kaplan-Meier estimates and log-rank test were employed. Also, to control the confounding factors, Cox proportional hazards regression models were fitted in a sequential adjustment. RESULTS: The median follow-up was 12.4 years. The overall incidence rate of dementia was 11.3% (8.4% in men and 13.9% in women). Compared with metformin non-users, hazard ratios (95% confidence intervals) of low-, mid-, and high-users and non-diabetic individuals for dementia were 0.97 (0.73-1.28), 0.77 (0.58-1.01), 0.48 (0.35-0.67), and 0.98 (0.84-1.15), respectively, in men, respectively, and 0.90 (0.65-0.98), 0.61 (0.50-0.76), 0.46 (0.36-0.58), and 0.92 (0.81-1.04), respectively, in women, after full adjustment of confounding variables. CONCLUSIONS: Metformin use in an elderly population with DM reduced dementia risk in a dose-response manner.