Incidence Of Dementia In Patients Research Articles

The effect of oral anticoagulants on the incidence of dementia in patients with atrial fibrillation: a systematic review and meta-analysis

Abstract Background Atrial fibrillation (AF) is a common cardiac arrhythmia, with dementia being an increasingly recognised complication of this. Treatment with oral anticoagulant (OAC) therapy may be protective in developing this complication. Purpose This meta-analysis aims to investigate the validity of this hypothesis, whilst additionally exploring the effect of specific OAC medication subtypes on the incidence of dementia. Methods A comprehensive search of MEDLINE and Embase for relevant studies reporting the efficacy of OAC therapy for the incidence of dementia in patients with AF was conducted from its inception until March 2023. This included observational studies that reported odds ratio, risk ratio and hazard ratio for adult AF patients. Studies including patients with prior OAC use or prior history of dementia were excluded. Statistical analysis was performed using a random-effects model to calculate the pooled hazard ratio and their corresponding 95% confidence interval for all outcomes. Subgroup analyses were also performed according to the study design, presence of observational window, and prior history of stroke in patients. Results A total of 13 studies were included in the study. Although the heterogeneity was high in all comparisons, we demonstrated that OAC usage lowered the risk of developing dementia in AF patients when compared to the non-OAC cohort. Looking more specifically at medication subtypes, direct oral anticoagulants (DOACs) and vitamin K agonists (VKA) were both effective in reducing the likelihood of AF patients developing dementia when compared to non-OAC treatments. Conclusion Our meta-analysis confirms that administration of OAC and its subtypes (VKA and DOAC) are effective pharmacotherapies in managing dementia in patients with AF. These findings have important clinical implications for the management of AF patients and highlight the need for further investigation of the protective effects of OAC therapy on cognitive decline. Future research should explore the long-term effects of OAC therapy on cognitive function in AF patients.

Dementia in patients with early cardiovascular complications following ischaemic stroke: A neglected complication of the stroke-heart syndrome

Abstract Background Early cardiovascular complications may occur in 20-30% of patients following following ischaemic stroke (stroke-heart-syndrome, SHS). The risk of dementia in patients with SHS remains unexplored. We aimed to quantify the risk of incident dementia in patients with SHS. Methods We conducted a retrospective analysis using a global federated health care network (TriNetX). We included patients who were discharged alive post-ischaemic stroke from 2000 to 2022. These individuals were classified into two cohorts based on the incidence of cardiovascular complications within 30 days post-stroke (acute heart failure [HF], acute myocardial infarction [AMI], ventricular fibrillation or flutter [VFF], or Takotsubo disease [TTS]), ie. those with SHS (Group 1) and those with stroke-only (without SHS; Group 2). The primary outcome was the five-year risk of dementia (vascular dementia [F01], dementia in other disease [F02], unspecified dementia [F03], Alzheimer’s disease [G30]). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression analysis after 1:1 propensity score matching (PSM). Results We identified 70,113 patients with SHS (age 67.3±14.0; 42.2% females) and 1,092,540 patients with stroke-only (age 65.2±14.9, 48.1% females). Prior to PSM, patients with SHS were generally older and had a higher prevalence of cardiovascular treatments compared to those without SHS. Following PSM, 70,111 well-balanced patients were considered in each group, however, patients with SHS had a higher risk of dementia compared to patients with stroke-only (HR 1.25, 95%CI 1.20-1.30). Among the SHS complications, the highest dementia risks were associated with acute HF (HR 1.28, 95%CI 1.21-1.36) and AMI (HR 1.24, 95%CI 1.17-1.30), with no significant associations were found for TTS, and VFF. The increased risk of dementia in patients with SHS compared to patients with stroke-only was independent of oral anticoagulant (OAC) use, sex, and age (> or < 75 years) [Figure 1]. Conclusion Stroke-heart syndrome is associated with increased risk of dementia. Innovative strategies to identify and to prevent SHS complications would improve long-term prognosis in patients with recent stroke.

Association Between Antipsychotic Medication Use and Dementia Risk in Patients With Schizophrenia or Schizoaffective Disorder.

To determine the association between antipsychotic prescriptions and incident dementia in patients with schizophrenia or schizoaffective disorder. In this retrospective cohort study, Cox Proportional hazard models estimated the association between antipsychotic prescriptions and incident dementia in participants ≥50 years of age with a schizophrenia/schizoaffective disorder diagnosis over 12years. Confounding was controlled by E-balance. Cumulative dementia incidence was significantly greater among those with an antipsychotic prescription compared to those without (7.9% vs 5.5%, P < 0.0001). After controlling for confounding, antipsychotic prescriptions were associated with a 92% increased risk for dementia (HR = 1.92; 95% CI:1.13-3.27). This association was not significant among those aged ≥65 years. Antipsychotic prescription type (eg, first generation, yes or no) did not affect dementia risk but prescription number did. Antipsychotic prescriptions were associated with almost twice the incidence of dementia compared to patients without in those with schizophrenia/schizoaffective disorder.

Sodium-glucose Cotransporter-2 Inhibitors versus Dipeptidyl Peptidase IV Inhibitors and Risk of Dementia Among Patients with Type 2 Diabetes and Comorbid Mental Disorders: A Population-based Cohort Study

AimTo evaluate whether the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors which have shown potential neuroprotective effects, is associated with lower risk of dementia in patients with type 2 diabetes (T2D) and comorbid mental disorders, who are considerably more susceptible to dementia. MethodsUsing the nationwide healthcare data of South Korea between 2010 and 2022, we conducted a retrospective cohort study among patients with T2D and comorbid mental disorders initiating SGLT2 inhibitors versus active comparator (Dipeptidyl Peptidase IV (DPP4) inhibitors). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years of incident dementia were estimated after weighting by propensity score fine stratification method. ResultsOver a 4.8-year median follow-up, SGLT2 inhibitors were associated with a 12% lower risk of dementia compared with DPP4 inhibitors (11.31 vs. 12.86 events per 1000 person years; HR 0.88, 95% CI 0.84 to 0.92; RD -1.55, -2.13 to -0.97). The results were consistent when stratified by age, sex, individual component, severe mental disorders, presence of insulin, history of cardiovascular disease, or history of hypertension. ConclusionsSGLT2 inhibitors versus DPP4 inhibitors were associated with a lower risk of incident dementia in patients with T2D and comorbid mental disorders. Further randomized controlled trials are required to confirm our findings.

Impact of Helicobacter pylori eradication on age-specific risk of incident dementia in patients with peptic ulcer disease: a nationwide population-based cohort study.

The impact of peptic ulcer disease (PUD) and Helicobacter pylori (H. pylori) eradication therapy on dementia risk in high H. pylori prevalence populations remains uncertain. This study investigates the relationship between PUD, H. pylori eradication, and dementia risk, including Alzheimer's disease (AD), in an elderly South Korean cohort, considering age and eradication timing. Data from the Korean National Health Insurance Service (2002-2015) for individuals aged 55-79 were analyzed. Participants were divided based on PUD and H. pylori therapy status. Propensity score matching was used to evaluate dementia incidence and hazard ratios over 5 and 10 years, alongside the timing of eradication therapy. PUD is linked to higher dementia risk at 5 and 10 years, more for overall dementia than AD, with eradication status not significantly altering the risk. Age-specific analysis showed increased AD risk in the 60s and 70s age groups. Late eradication therapy is correlated with a higher dementia risk. PUD is a risk factor for dementia in elderly South Koreans, particularly with delayed H. pylori therapy. The findings emphasize timely H. pylori management and its potential role in neurodegenerative disease prevention.

Early Rhythm Control and Incident Dementia in Patients With Atrial Fibrillation and Prior Stroke

BackgroundAlthough early rhythm control (ERC) in patients with atrial fibrillation (AF) reduces the risk of stroke, there is no evidence thus far on whether ERC reduces the risk of developing dementia in patients with AF and prior stroke. ObjectivesThis study sought to evaluate whether ERC reduces the risk of developing dementia in patients with new-onset AF and prior stroke. MethodsUsing the Korean nationwide claims database, we identified patients with new-onset AF and prior stroke between 2010 and 2016. Patients who received rhythm control therapy within 1 year after AF onset were defined as the ERC group, otherwise patients were categorized as the usual care group. A propensity score weighting method was used to balance the 2 groups. Incident dementia defined by relevant diagnostic codes was evaluated. ResultsA total of 41,370 patients were included (mean age 70 ± 11 years; mean CHA2DS2-VASc score 5.3 ± 1.6): 10,213 in the ERC group and 31,157 in the usual care group. Compared with usual care, ERC was associated with lower risks of all dementia, Alzheimer’s dementia, and vascular dementia (weighted HR: 0.825 [95% CI: 0.776-0.876], 0.831 [95% CI: 0.774-0.893], and 0.800 [95% CI: 0.702-0.913], respectively, all P < 0.001). The benefit of ERC was slightly accentuated in the younger age group (<65 years). The beneficial effect of ERC in reducing the risk of dementia was consistent regardless of the characteristics of prior stroke. ConclusionsERC might be beneficial in the prevention of dementia in patients with AF and prior stroke. To prevent the progression of cognitive dysfunction, ERC should be considered in this population.

The impact of sodium-glucose co-transporter-2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation.

The effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase-4 inhibitors (DPP4i). We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. After up to 5years of follow-up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51-0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24-0.82). SGLT2i was related to reduced risks of AF-related hospitalisation (HR: 0.72, 95% CI: 0.56-0.93), stroke (HR: 0.75, 95% CI: 0.60-0.94), and all-cause death (HR: 0.33, 95% CI: 0.24-0.44). The protective effects were consistent irrespective of the concurrent use of non-vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF-related hospitalisation, stroke, and all-cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i.

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.

New Prediction Model for Incidence of Dementia in Patients with Type 2 Diabetes.

New Prediction Model for Incidence of Dementia in Patients with Type 2 Diabetes.

Glycemic control and dementia risk in patients aged above and below 75 years.

There is a lack of data about the treatment effect of glycemic control on incident dementia in patients with advanced age. In a nationwide Korean cohort of 79,076 diabetic patients 75years or older and a representative cohort of 74,672 diabetics aged 50 to 74years, multivariable-adjusted incidence of overt dementia was estimated across yearly-averaged on-treatment fasting blood glucose (FBG) levels. During 9-year follow-up, overt dementia was noted in 24,710 (31.2%) patients 75years or older and in 5237 (7.0%) patients aged 50 to 74years. For dementia risk, J-shaped associations were observed across on-treatment FBG levels (80-99, 100-109, 110-125, 126-139, 140-159, 160-179, and 180-900mg/dl) in patients 75years or older (respective incidence: 49.3, 45.7, 45.9, 45.7, 48.5, 51.5, and 57.9 per 1000 person-years) and in those aged 50 to 74years (respective incidence: 8.9, 8.3, 7.7, 7.6, 8.0, 8.6, and 10.6 per 1000 person-years) with a significant interaction of FBG level and age group (P = 0.001). For all-cause mortality, the J-shaped association curve was left-shifted in patients 75years or older (respective incidence: 64.9, 59.1, 57.6, 60.4, 64.0, 70.9, and 90.4 per 1000 person-years) relative to that in patients aged 50 to 74years (respective incidence: 15.7, 13.4, 12.3, 12.2, 13.4, 15.7, and 21.8 per 1000 person-years; P < 0.001 for interaction). The achieved glycemic level with the lowest risk for dementia and mortality was lower in older patients, and absolute risk increase related to poorly controlled glucose was greater in the elderly compared with younger patients. The online version contains supplementary material available at 10.1007/s13340-023-00684-4.

Brachial-Ankle Pulse Wave Velocity is Associated with Incident Dementia in Patients with Cerebral Small-Vessel Disease.

Increased arterial stiffness is associated with the severity of cerebral small-vessel disease (SVD) and may predict incident dementia. This study investigated the predictive value of brachial-ankle pulse wave velocity (ba-PWV) for dementia and cognitive decline. Data were obtained from a Japanese cohort of 478 patients who underwent ba-PWV measurement. Magnetic resonance imaging (MRI) was used to evaluate SVD severity. The Mini-Mental State Examination (MMSE) and the Japanese version of the Montreal Cognitive Assessment (MoCA-J) were used to assess the cognitive function. The primary outcome was the incidence of dementia. The secondary outcome was cognitive change during three years of follow-up. The median age was 71 years old, 61% were men, and the median ba-PWV was 1787 cm/s. Dementia was diagnosed in 23 patients during a mean follow-up of 4.8 years. A Cox proportional hazard regression analysis revealed that the highest quartile (ba-PWV ≥ 2102 cm/s) was associated with a significantly higher risk of dementia than the first to third quartiles (ba-PWV ≤ 2099 cm/s) after adjusting for risk factors, the mean blood pressure, the MoCA-J score, and SVD severity (adjusted HR, 3.40; 95% CI, 1.24-9.34; P=0.018). Longitudinal cognitive changes in 192 patients indicated that ba-PWV was negatively related to changes in the MoCA-J score (r=-0.184, P=0.011). The decline in the MoCA-J score in the highest quartile was greater than that in the first to third quartiles after adjusting for risk factors, SVD severity, and baseline MoCA-J score (P=0.017). ba-PWV was associated with incident dementia and cognitive decline, independent of age, risk factors, the baseline cognitive function, and the SVD severity.

Anti-diabetics and the Prevention of Dementia: A Systematic Review.

Type 2 diabetes mellitus (T2DM) is a worldwide epidemic that is only increasing as the years progress, and as of 2019, affecting over 37 million. T2DM is a chronic condition caused by reduced insulin secretion and increased insulin resistance. Due to insulin not operating at optimal conditions, blood glucose rises and remains high, thus disturbing metabolic hemostasis. Many complications can arise from T2DM, such as coronary vascular disease, kidney damage, eye damage, and, quite significantly, dementia. It is theorized that dementia from T2DM stems from the fact that the brain is susceptible to hyperglycemic conditions, which are promoted by the increase in insulin resistance of target cells in the central nervous system. This directly affects cognitive processes and memory, which correlates to decreased temporal and front lobes volume. The risk of diabetic complications can be minimized with therapeutic interventions such as oral-antidiabetic (OAD) agents and insulin. Several OADs are on the market, but the first-line agent is metformin, a biguanide that decreases glucose production and increases insulin sensitivity. This paper aims to determine if currently prescribed OADs can help slow cognitive decline and reduce the risk and incidence of dementia as a complication of T2DM. Studies found that, for the most part, all OADs except sulfonylureas (SU) significantly slowed the decline of cognitive function and reduced the risk and incidence of dementia. SU's were shown to increase the risk of dementia in most studies. Of all the OADs, thiazolidinediones may be the most beneficial drug class for reducing the risk of dementia in T2DM patients. Future research should focus on whether early intervention with specific classes of OADs can not only improve glycemic control, leading to decreased hyperglycemia but also prevent the build-up of damaged brain tissue and help to reduce the risk and incidence of dementia in patients with T2DM.

Post-stroke dysphagia and ambient air pollution are associated with dementia.

This cohort study aimed to explore the potential association between ambient air pollution and dementia incidence in adults who have experienced a stroke. Additionally, the study aimed to determine dysphagia as a predictive factor for the subsequent development of dementia in patients with stroke. This retrospective nested case-control study used data from the Kaohsiung Medical University Hospital Database in Taiwan. Data collected include average ambient air pollution concentrations within 3 months and 1 year after the index dysphagia date. The primary outcome includes incident dementia in patients with or without dysphagia. Logistic regression analysis was performed to examine the association between significant air pollution exposure and the risk of dementia while controlling for baseline demographic characteristics (age and sex), and comorbidities. The univariable regression models revealed a higher likelihood of dementia diagnosis in patients with dysphagia (odds ratio = 1.493, 95% confidence interval = 1.000-2.228). The raw odds ratios indicated a potential link between air pollution exposure and elevated dementia risks in the overall study population and patients with stroke without dysphagia, except for O3. Particulate matter (PM)2.5 and nitrogen oxides (NOx) exhibited significant effects on the risk of dementia in the stepwise logistic regression models. The presence of dysphagia following a stroke may pose a risk of developing dementia. Additionally, PM2.5 and NOx exposure appears to elevate the risk of dementia in patients with stroke.

A comparison of the effects of NOAC and VKA therapy on the incidence of dementia in patients with atrial fibrillation: A systematic review and meta-analysis.

Atrial fibrillation (AF) patients are more susceptible to dementia, but the results about the effect of oral anticoagulants (OACs) on the risk of dementia are not consistent. We hypothesize that OAC is associated with a reduced risk of dementia with AF and that nonvitamin K antagonist oral anticoagulants (NOAC) are superior to vitamin K antagonists (VKA). Four databases were systematically searched until July 1, 2022. Two reviewers independently selected literature, evaluated quality, and extracted data. Data were examined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Fourteen research studies involving 910 patients were enrolled. The findings indicated that OACs were associated with a decreased risk of dementia (pooled HR: 0.68, 95% CI: 0.55-0.82, I2 = 87.7%), and NOACs had a stronger effect than VKAs (pooled HR: 0.87, 95% CI: 0.79-0.95, I2 = 72%), especially in participants with a CHA2DS2VASc score ≥ 2 (pooled HR: 0.85, 95% CI: 0.72-0.99). Subgroup analysis demonstrated no statistical significance among patients aged <65 years old (pooled HR: 0.83, 95% CI: 0.64-1.07), patients in "based on treatment" studies (pooled HR: 0.89, 95% CI: 0.75-1.06), or people with no stroke background (pooled HR: 0.90, 95% CI: 0.71-1.15). This analysis revealed that OACs were related to the reduction of dementia incidence in AF individuals, and NOACs were better than VKAs, remarkably in people with a CHA2DS2VASc score ≥ 2. The results should be confirmed by further prospective studies, particularly in patients in "based on treatment" studies aged <65 years old with a CHA2DS2VASc score < 2 or without a stroke background.

Anticoagulants and Dementia: A Systematic Review.

Many patients diagnosed with atrial fibrillation (AF) develop dementia. Most AF patients are also prescribed some antithrombotic medication to reduce the incidence of stroke, as clots can form within the left atrium. Some research has found that, excluding patients who have experienced strokes, anticoagulants mayserve as protective agents against dementia in AF. This systematic review aims to analyze the incidence of dementia in patients who were prescribed anticoagulants. A comprehensive literature review was conducted using the databases PubMed, ProQuest, and ScienceDirect. Only experimental studies and meta-analyses were chosen. The search included the keywords "dementia and anticoagulant" and "cognitive decline and anticoagulants". Our initial search generated 53,306 articles, which were narrowed down to 29 by applying strict inclusion and exclusion algorithms. There was a decreased risk of dementia in patients who had been prescribed oral anticoagulants (OACs) in general, but only studies investigating direct oral anticoagulants OACs (DOACs) suggested that they were protective against dementia. Vitamin K antagonist(VKA) anticoagulants showed conflicting results, with some studies indicating they might increase the risk for dementia, while others suggested that they are protective against it. Warfarin, a specific VKA, was mainly shown to reduce the risk of dementia but was not as effective as DOACs or other OACs. Lastly, it was found that antiplatelet therapy mayincrease the risk of dementia in AF patients.

Acupuncture is associated with reduced dementia risk in patients with insomnia: A propensity-score-matched cohort study of real-world data.

Insomnia is a subjective illness that has been identified as a risk factor for dementia. In this study, we investigated the association of acupuncture treatment for insomnia with the risk of dementia. We collected data from the National Health Insurance Research Database (NHIRD) of Taiwan to analyze the incidence of dementia in patients with insomnia who received acupuncture treatment. This retrospective matched-cohort study included 152,585 patients, selected from the NHIRD, who were newly diagnosed with insomnia between 2000 and 2010. The follow-up period ranged from the index date to the date of dementia diagnosis, date of withdrawal from the insurance program, or December 31, 2013. A 1:1 propensity score method was used to match an equal number of patients (N=18,782) in the acupuncture and non-acupuncture cohorts. We employed Cox proportional hazards models to evaluate the risk of dementia. The cumulative incidence of dementia in both cohorts was estimated using the Kaplan-Meier method, and the difference between them was assessed through a log-rank test. Patients with insomnia who received acupuncture treatment were observed to have a lower risk of dementia (adjusted hazard ratio=0.54, 95% confidence interval=0.50-0.60) than those who did not undergo acupuncture treatment. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the non-acupuncture cohort (log-rank test, p<0.001). The results suggest that acupuncture treatment significantly reduced or slowed the development of dementia in patients with insomnia.

Abstract #1406426: Association of Combined Healthy Lifestyle Factors with Incident Dementia in Patients with Type 2 Diabetes

Abstract #1406426: Association of Combined Healthy Lifestyle Factors with Incident Dementia in Patients with Type 2 Diabetes

The Correlation between Metformin Use and Incident Dementia in Patients with New-Onset Diabetes Mellitus: A Population-Based Study.

The evidence of metformin's effect on dementia is conflicting. This study investigates the association between metformin use and the risk of dementia among patients with diabetes mellitus (DM). This study included patients with new-onset DM between 2002 and 2013. We divided the patients into patients who used metformin and patients who did not. Two models were used to assess metformin use: the cumulative defined daily dose (cDDD) of metformin use and the intensity of metformin use. This study with 3-year and 5-year follow-ups investigated the risk of dementia among patients with DM who used metformin. At the 3-year follow-up, patients who received cDDD < 300 had an odds ratio (OR) of developing dementia of 0.92 (95% confidence interval [CI] = 0.89-0.96); patients who used metformin at intensities <10 and 10-25 DDD/month had ORs of 0.92 (95% CI: 0.87-0.97) and 0.92 (95% CI: 0.85-1.00), respectively. Metformin use at cDDD 300-500 (OR = 0.80, 95% CI = 0.56-1.15) or >500 (OR = 1.48, 95% CI = 0.48-4.60) or at an intensity >25 DDD/month (OR = 0.84, 95% CI = 0.60-1.18) were not associated with an incident of dementia. There were similar results at the 5-year follow-up. Patients with a low intensity of metformin use had a lower risk of dementia. However, higher doses of metformin with higher intensity exhibited no protective role in dementia. Prospective clinical trials are warranted to evaluate the actual underlying mechanisms between metformin dosage and the risk of dementia.

Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke.

Previous studies have reported the protective effect of pioglitazone on dementia in patients with type 2 diabetes mellitus (DM). Recent studies have shown that pioglitazone also lowers the risk of primary and recurrent stroke. Understanding the characteristics of patients particularly associated with the benefits of pioglitazone would facilitate its personalized use by specifying subpopulations during routine clinical care. The aim of this study was to examine the effects of pioglitazone use on dementia in consideration of stroke occurrence. Using nationwide longitudinal data of patients with DM from the Korean National Health Insurance Service DM cohort (2002-2017), we investigated the association of pioglitazone use with incident dementia in patients with new-onset type 2 DM. The heterogeneity of the treatment effect was examined using exploratory analyses. Using a multistate model, we assessed the extent to which incident stroke affects the association between pioglitazone use and dementia. Pioglitazone use was associated with a reduced risk of dementia, compared with nonuse (adjusted hazard ratio [aHR] = 0.84, 95% CI 0.75-0.95); the risk reduction in dementia was greater among patients with a history of ischemic heart disease or stroke before DM onset (aHR = 0.46, 95% CI 0.24-0.90; aHR = 0.57, 95% CI 0.38-0.86, respectively). The incidence of stroke was also reduced by pioglitazone use (aHR = 0.81, 95% CI 0.66-1.00). However, when the stroke developed during the observation period of pioglitazone use, such lowered risk of dementia was not observed (aHR = 1.27, 95% CI 0.80-2.04). Pioglitazone use is associated with a lower risk of dementia in patients with DM, particularly in those with a history of stroke or ischemic heart disease, suggesting the possibility of applying a personalized approach when choosing pioglitazone to suppress dementia in patients with DM.

Association between severe hypoglycaemia and risk of dementia in patients with type 2 diabetes mellitus: Asystematic review and meta-analysis.

The aim of this systematic review was to analyse whether there is an association between severe hypoglycaemia and the incidence of dementia in patients with type 2 diabetes mellitus. We systematically searched the MEDLINE, Scopus, and Cochrane databases from their inception until September 2022 for observational studies on the association between hypoglycaemia and the risk of dementia. The DerSimonian and Laird method was used to compute a pooled estimate of the risk for such association. Risk ratio (RR) and its respective 95% confidence interval (95% CI). Two analyses were performed to estimate the risk of dementia: (i) any hypoglycaemia versus no hypoglycaemia and (ii) a dose-response analysis for one, two, or more than three hypoglycemic events versus no hypoglycaemia. PROSPERO registration number CRD42020219200. Seven studies were included. The pooled RR for the association of severe hypoglycaemia and risk of dementia was 1.47 (95% CI: 1.24-1.74). When the dose-response trend was analysed, the pooled RR for the risk of dementia was increased according to the hypoglycaemia events as follows: 1.29 (95% CI: 1.15-1.44) for one hypoglycemic event; 1.68 (95% CI: 1.38-2.04) for two hypoglycemic events; and 1.99 (95% CI: 1.48-2.68) for three or more hypoglycemic events. Our study demonstrates a 54% higher risk of dementiaamong people who suffer a hypoglycaemia event compared to nonhypoglycaemia. Considering our results and the prevalence of people suffering from diabetes mellitus, health education for both newly diagnosed and already diagnosed people could be a useful tool for glycaemic control, thus avoiding hypoglycaemic events.