Excessive Alcohol Use Research Articles

In vitro and In vivo Study of Gastroprotective effect of Purified Extract Andrographis paniculata

Gastric ulcers are caused by excessive gastric acid secretion, alcohol, and long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin is one of the NSAIDS that can induce peptic ulcers. Traditional medicines that have been proven to have gastroprotective activity is Andrographis paniculata (APAC). The purpose of this study is to assess the antioxidant activity and gastroprotective effect of purified extract of APAC. The herbal treatment was given for 7 days, and on the eighth day, all groups except the negative control (Na CMC 0.5%) were given 1000mg/kgBW of aspirin. Six hours later, the rats were sacrificed and opened for macroscopic examination, pH gastric juice value, the volume of gastric value, ulcer index, and inhibition percentage. Antioxidant studies using 2,2-diphenyl-1-picrylhydrazyl (DPPH) showed that APAC has strong antioxidant activity with IC50 value = 64.54. APAC could reduce the occurrence of gastric ulcers by decreasing gastric pH, ulcer index, and increasing inhibition percentage (P=0.000<0.05). Andrographis paniculata has gastroprotective properties associated with antioxidant activity.

Epidemic within pandemic: Alcohol-associated hepatitis and COVID-19.

An increase in alcoholic beverage sales was observed during the peak of the COVID pandemic in the US. Little is known about the impact of SARS-CoV-2 infection among hospitalized alcohol-associated hepatitis (AH) patients. In this study we analyzed the available National Inpatient Data (NIS) data from 2020 to determine mortality and healthcare utilization among hospitalized AH patients with and without COVID-19 in the United States. We observed an ~15.6% increase in cases of hospitalized AH patients from 136,620 in 2019 to 157,885 in 2020, a significant increase from an average of 5.5% per annum despite an 8.7% decline in US hospital admissions over the same time span. Men younger than 40 was the fastest growing AH group, representing a 23% increase in 2020. Approximately 1.8% of hospitalized AH patients had a SARS-CoV-2 infection. An infection with SARS-CoV-2 significantly worsened the mortality among patients with AH (11.4% vs. 4.1%, p<0.0001), especially among older AH patients with concomitant comorbidities such as clinically apparent cirrhosis, acute renal failure, upper gastrointestinal bleeding, and sepsis. AH patients with COVID-19 also had a longer length of stay (8.6 vs. 6.1 days, p <0.0001) and higher hospital charges during the stay ($93,670 vs. $66,283, p <0.0001). Our study highlighted the rise in AH cases during the COVID-19 pandemic. Screening and appropriate management of excessive alcohol use and the preventive measure such as the recommendation of COVID-19 vaccination should be considered to prevent the morbidity and mortality among patients with ALD.

Adverse Childhood Experiences and Alcohol Use among Black College Students: Examining the Mediating Roles of Depression and Coping Drinking Motives

Background: Over the past two decades, research has linked adverse childhood experiences (ACEs) to adult health-risk behaviors such as excessive alcohol use. Yet, few have investigated health-risk behaviors among Black college students. Research suggests that Black college students are at lower risk for hazardous drinking patterns, yet ACEs appear to alter the drinking patterns of Black students. Other studies have also shown depressive symptoms and coping-motivated drinking to predict greater alcohol consumption for this ethnic group. Objective: The current study investigated the relationship between ACEs and hazardous patterns of drinking, including frequency of alcohol use, binge, and heavy drinking episodes, using a sample of 282 Black students attending a historically black college/university (HBCU). Results: Depressive symptoms and coping drinking motives were tested as serial mediators between ACEs and the three drinking patterns. Results revealed a significant indirect effect of ACEs on the frequency of alcohol use, binge, and heavy drinking episodes, through depressive symptoms and coping drinking motives. Depressive symptoms also independently mediated the relationship between ACEs and heavy drinking episodes. Conclusion: The finding suggested that drinking perhaps serves as a maladaptive coping strategy to address underlying early life stress and depression for Black students.

Sex-dependent factors of alcohol and neuroimmune mechanisms

Excessive alcohol use disrupts neuroimmune signaling across various cell types, including neurons, microglia, and astrocytes. The present review focuses on recent, albeit limited, evidence of sex differences in biological factors that mediate neuroimmune responses to alcohol and underlying neuroimmune systems that may influence alcohol drinking behaviors. Females are more vulnerable than males to the neurotoxic and negative consequences of chronic alcohol drinking, reflected by elevations of pro-inflammatory cytokines and inflammatory mediators. Differences in cytokine, microglial, astrocytic, genomic, and transcriptomic evidence suggest females are more reactive than males to neuroinflammatory changes after chronic alcohol exposure. The growing body of evidence supports that innate immune factors modulate synaptic transmission, providing a mechanistic framework to examine sex differences across neurocircuitry. Targeting neuroimmune signaling may be a viable strategy for treating AUD, but more research is needed to understand sex-specific differences in alcohol drinking and neuroimmune mechanisms.

Shifts in the Australian public's opinions towards alcohol policies: 2004-2019.

After a period of stagnation, alcohol policy in Australia has received increased attention in the past decade, with Sydney's lockout laws and Queensland's restrictions on trading hours garnering media attention. This study will investigate any changing trends in support towards alcohol policy and identify any demographic-specific shifts. Respondents from the National Drug Strategy Household Survey (conducted every 3 years from 2004 to 2019) were asked to gauge their level of support for 16 alcohol policy items proposed to reduce the problems associated with excessive alcohol use. Mean levels of support for various policy options, as well as demographic predictors of support, were assessed. After an increase from 2004 to 2013, support for more evidence-based policies on alcohol (e.g., restricting the availability of alcohol) has decreased since 2013. Support for policy items that focus less on the restriction of the availability of alcohol and more on education remained relatively stable in comparison. While demographic groups continue to vary in their extent of support, shifts appear to be occurring fairly uniformly across sex, age, states and drinking groups. Support for public health-oriented alcohol policies has been decreasing since 2013. The introduction of high-profile policies and less of a media focus on alcohol may be contributing to decreases in support.

A Qualitative Exploration on Perceived Socio-Cultural Factors Contributing to Undernutrition Among Under-Fives in the Southern Highlands of Tanzania.

Objective: Under nutrition especially among under-fives is a major public health challenge in Tanzania. However, the contribution of cultural practices to child under nutrition is often overlooked. This study aimed to explore the perceived socio-cultural factors contributing to the persisting under nutrition among under-fives in Tanzania. Methods: The study applied focus group discussion (FDGs) with forty practitioners to examine the sociocultural factors contributing to under nutrition during early childhood. The study participants were purposively selected and thematic analysis was used to identify themes within the data. Results: This study revealed that, under nutrition for under-fives is caused by a number of socio-cultural factors including existence of gender inequality related to dietary practices and qualities, women's excessive workload, patriarchy social-norm, excessive alcohol use and cultural taboos prohibiting women and girls from eating certain types of nutrient dense foods. Conclusion: The study highlights the multiplicity of factors including socio-cultural perspectives contributing to under nutrition among under-fives, and calls for a concerted efforts in developing and implementing issue-specific and culturally sensitive strategies towards elimination of child under nutrition.

Alcohol dependence syndrome in patients with alcoholic liver disease: A cross sectional observational study.

Excessive alcohol use leads to a spectrum of liver disease. While physicians treat liver disease, the cause, i.e. alcohol, often remains untreated. This portends a poor overall outcome as such patients may continue to consume alcohol for the want of appropriate treatment directed at alcohol dependence or abuse. To assess the prevalence and severity of alcohol dependence among patients with Alcoholic Liver Disease (ALD). A cross-sectional observational study was conducted among patients with varying severity of ALD (steatosis, hepatitis, and cirrhosis) where 75 were included. They were evaluated for alcohol dependence using clinical interview and M.I.N.I 6.0. The severity of dependence was rated using the SADQ (Severity of Alcohol Dependence Questionnaire). Appropriate statistical tests were applied to identify correlations. All the patients of ALD met the criteria of Alcohol Dependence Syndrome (Clinical interview and ICD 10 criteria). Among them, 40% were severely dependent (SADQ >30). Among those with ALD, 57.3% had alcoholic hepatitis, 18.7% had steatosis, and 24% suffered cirrhosis. Patients with cirrhosis had higher median SADQ scores compared to those with steatosis or hepatitis. All the patients with ALD suffered from Alcohol Dependence Syndrome. Those with the most severe ALD had a higher severity of dependence. To ensure effective treatment and lasting outcomes, there is a need for greater awareness of this fact among physicians. Psychiatric referral of those suffering from ALD will ensure concurrent treatment of Alcohol Dependence Syndrome.

Diagnostic stigmas of alcoholic liver disease

Alcohol is a toxic substance that is associated with a spectrum of liver damage, including simple steatosis or fatty- degeneration of liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is the general term used for this spectrum of alcohol-related liver damage. Excessive or harmful alcohol use is among the top five risk factors for death and disability worldwide, causing 2.5 million deaths and 69.4 million annual disability-adjusted life years. The diagnosis of ABP can usually be made on the basis of anamnesis, clinical and laboratory findings. However, the diagnosis of ABP can be clinically challenging because there is no a single diagnostic test to confirm the diagnosis, and patients may not report the extent of their alcohol use.

The Impact of Universal Screening for Substance Use Disorders During Emergency Services Within an Integrated Health Care System.

Each day, across America, people come to emergency service providers in need of care and support. Although not ideal, emergency departments have become the de facto outpatient treatment center in many communities. This positions emergency department providers to be ideal partners in the treatment of substance use disorders. Substance use and deaths by overdose have been of great concern for many years, and since the start of the pandemic, the trends have caused further concern. Drug overdoses have claimed the lives of more than 932 000 Americans over the past 21 years. Excessive alcohol use is a leading cause of premature death in the United States. In 2020, of people identified as needing substance use treatment in the past year, only 1.4% received any treatment. As we watch the death tolls and cost of care continue to trend upward, emergency service providers have the unique opportunity to quickly screen, intervene, and refer to help get these complex and sometimes challenging patients better care, while also avoiding the worsening of the crisis in which we find ourselves.

Trends in major non-communicable diseases and related risk factors in China 2002–2019: an analysis of nationally representative survey data

Prevention and control of non-communicable diseases (NCDs) are prioritized in both the Sustainable Development Goal and the Healthy China 2030 Initiatives. Efforts have been devoted to combating NCDs in China. This study examined changes in NCD trajectory. We described and analyzed the trends in prevalence and control of major NCDs including obesity, hypertension, diabetes, and dyslipidemia and examined selected main behavioral risk factors in China by sex, age group, and residence using nationally representative CDC survey data. Data included were from the China Chronic Disease Risk Factor Surveillance (CCDRFS, 2013 and 2018) and China National Nutrition Survey (CNNS, 2002, 2010-2013, 2015, and 2020). Annual and relative changes in rates were used. Rural-urban ratio of related indicators was assessed. NCD-attributed deaths increased from 80.0% in 2002 to 86.6% in 2012, and 88.5% in 2019, with cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes accounted for 47.1%, 24.1%, 8.8%, and 2.5% of deaths in 2019, respectively. Prevalence of obesity (7.1%-16.4%), overweight/obesity (29.9%-50.7%), hypertension (18.8%-27.5%), diabetes (2.6%-11.9%), and dyslipidemia (18.6%-35.6%) all increased from 2002 to 2018. These rates increased faster in rural areas than in urban areas. Rates of awareness, treatment and control of hypertension and diabetes increased very slowly from 2012 to 2018. Most rates were between 30 and 40% with the lowest rate of 11% for hypertension control even in 2018. The rates were worse for rural residents compared to urban residents. Furthermore, many modifiable behavioral risk factors showed little improvement and some became worse over time, including smoking, excessive alcohol use, inadequate vegetable/fruit intake, excessive red meat intake, and physical inactivity. NCD burden in China increased during 2002-2019 despite of the intervention efforts. To reach the global and national targets, China must strengthen its actions, especially in rural areas, including improvement of NCD screening and management and reduction of behavioral risk factors. The study was supported in part by research grants of National Key R&D Program of China (2017YFC0907200, 2017YFC0907201), International Collaboration Project from the Chinese Ministry of Science and Technology-Prevention and control of chronic diseases and health promotion (G2021170007L), Natural Scientific Foundation of China (82103846), Key R&D and Transformation Program of Qinghai (2023-QY-204).

Non-Alcoholic Fatty Liver Disease: Translating Disease Mechanisms into Therapeutics Using Animal Models.

Nonalcoholic fatty liver disease (NAFLD) is a range of pathologies arising from fat accumulation in the liver in the absence of excess alcohol use or other causes of liver disease. Its complications include cirrhosis and liver failure, hepatocellular carcinoma, and eventual death. NAFLD is the most common cause of liver disease globally and is estimated to affect nearly one-third of individuals in the United States. Despite knowledge that the incidence and prevalence of NAFLD are increasing, the pathophysiology of the disease and its progression to cirrhosis remain insufficiently understood. The molecular pathogenesis of NAFLD involves insulin resistance, inflammation, oxidative stress, and endoplasmic reticulum stress. Better insight into these molecular pathways would allow for therapies that target specific stages of NAFLD. Preclinical animal models have aided in defining these mechanisms and have served as platforms for screening and testing of potential therapeutic approaches. In this review, we will discuss the cellular and molecular mechanisms thought to contribute to NAFLD, with a focus on the role of animal models in elucidating these mechanisms and in developing therapies.

Alcohol-Induced Mortality in the USA: Trends from 1999 to 2020.

The online version contains supplementary material available at 10.1007/s11469-023-01083-1.

Black sexual minority women’s Internalized stigma and coping motivated alcohol use: the role of emotional suppression

Black sexual minority women have an increased risk for excessive alcohol use, which has been attributed to their use of alcohol to cope with oppression. Internalized stigma is suggested to be one of the most insidious byproducts of systemic oppression whereby people internalize ideologies of self-hatred. Still, research has yet to examine the association between internalized stigma and alcohol use among sexual minorities of color. This survey-based study investigated the associations between internalized homonegativity and internalized racism with coping motivated alcohol use among 330 Black sexual minority women. Additionally, we explored the role of emotional suppression within these associations. Internalized homonegativity was significantly positively associated with coping motivated alcohol use. The significant positive association between internalized racism and coping motivated alcohol use was strongest at higher levels of emotional suppression. Given the majority of our sample identified as having a masculine gender expression, we recommend research exploring whether the identity-based experiences of masculine Black sexual minority women impact their substance use behaviors. Implications for culturally sensitive and emotion-centered practice with Black sexual minority women are discussed.

Prevalence of alcohol consumption among clients of opioid agonist treatment (OAT) centers in Golestan province, Iran.

Opioid agonist treatments (OATs) with methadone and buprenorphine are known to be effective treatments for people with opioid use disorder (OUD). However, concomitant use of other substances such as alcohol can negatively affect OAT outcomes. This study aimed to determine the prevalence of alcohol use among clients of OAT centers in the Golestan province in the northern part of Iran. This is a secondary analysis of a sample of 706 clients who were receiving OATs from certified OAT centers in Golestan province in 2015. They had been on OATs for at least 1 month and were randomly selected for the study. Data were collected via interviews with selected OAT clients. The main indicators studied in the present study were lifetime history of alcohol consumption, alcohol consumption during last month, lifetime history of excessive alcohol use on one occasion, and years of regular alcohol consumption. The prevalence of lifetime history of alcohol consumption was estimated at 39.2%. Prevalence of alcohol consumption during last month and lifetime history of excessive alcohol use on one occasion was 6.9 and 18.8%, respectively. Despite a total ban on alcohol consumption in Iran, a sub-sample of participants admitted past-month alcohol use concurrent with their OATs. The estimated past-month prevalence of alcohol use was lower than the reported prevalence in countries where the production, distribution, and consumption of alcohol are legal.

Association Between Alcohol Consumption and Cardiovascular Risk Based on Data from the Three Generations for Health Program in Hungary.

BACKGROUND Alcohol consumption has a significant effect on cardiovascular health, and risk factors, such as excessive alcohol use, should be avoided. Although alcohol consumption has decreased over the last decade in Hungary, it is still significantly higher than the average across the European Union. The objective of this study was to describe the patterns of alcohol use based on the Alcohol Use Disorders Identification Test (AUDIT), with a special focus on cardiovascular risk status (low, moderate, high, or very high). MATERIAL AND METHODS The Three Generations for Health program focuses on the development of primary health care in Hungary. One of the key elements of the program is the identification of risk factors of cardiovascular diseases. An ordinal multiple logistic regression analysis was performed with 10 categorical explanatory variables and the outcome was the categorical cardiovascular risk. RESULTS The database consisted of patients aged 40-65 years with a sample size of 11 348. A significant relationship was found between alcohol consumption and cardiovascular risk status; people with high-risk drinking patterns had higher a value of odds ratio (OR=1.306 [1.003-1.701]) for having a more serious cardiovascular status. According to multiple regression analysis, alcohol dependence was associated with cardiovascular risk. CONCLUSIONS From a public health perspective, the results highlight the importance of reducing alcohol consumption with the help of primary care and preventive services in countries with a high cardiovascular risk profile to reduce the cardiovascular disease-related burden.

Insula Dynorphin and Kappa Opioid Receptor Systems Regulate Alcohol Drinking in a Sex-Specific Manner in Mice.

Alcohol use disorder is complex and multifaceted, involving the coordination of multiple signaling systems across numerous brain regions. Previous work has indicated that both the insular cortex and dynorphin (DYN)/kappa opioid receptor (KOR) systems contribute to excessive alcohol use. More recently, we identified a microcircuit in the medial aspect of the insular cortex that signals through DYN/KOR. Here, we explored the role of insula DYN/KOR circuit components on alcohol intake in a long-term intermittent access (IA) procedure. Using a combination of conditional knock-out strategies and site-directed pharmacology, we discovered distinct and sex-specific roles for insula DYN and KOR in alcohol drinking and related behavior. Our findings show that insula DYN deletion blocked escalated consumption and decreased the overall intake of and preference for alcohol in male and female mice. This effect was specific to alcohol in male mice, as DYN deletion did not impact sucrose intake. Further, insula KOR antagonism reduced alcohol intake and preference during the early phase of IA in male mice only. Alcohol consumption was not affected by insula KOR knockout in either sex. In addition, we found that long-term IA decreased the intrinsic excitability of DYN and deep layer pyramidal neurons (DLPNs) in the insula of male mice. Excitatory synaptic transmission was also impacted by IA, as it drove an increase in excitatory synaptic drive in both DYN neurons and DLPNs. Combined, our findings suggest there is a dynamic interplay between excessive alcohol consumption and insula DYN/KOR microcircuitry.SIGNIFICANCE STATEMENT The insular cortex is a complex region that serves as an integratory hub for sensory inputs. In our previous work, we identified a microcircuit in the insula that signals through the kappa opioid receptor (KOR) and its endogenous ligand dynorphin (DYN). Both the insula and DYN/KOR systems have been implicated in excessive alcohol use and alcohol use disorder (AUD). Here, we use converging approaches to determine how insula DYN/KOR microcircuit components contribute to escalated alcohol consumption. Our findings show that insula DYN/KOR systems regulate distinct phases of alcohol consumption in a sex-specific manner, which may contribute to the progression to AUD.

Validation of scores of PRO-C3 to predict liver-related events in alcohol-related liver disease.

Risk prediction in alcohol-related liver disease (ArLD) is an unmet need. We aimed to assess PRO-C3 models to predict liver-related events (LRE) in patients with a history of excessive alcohol use without an established diagnosis of chronic liver disease. A prospective cohort study of 462 patients with ArLD, split into a derivation cohort of 221 secondary care patients and a validation cohort of 241 primary care patients. Baseline variables, including fibrogenesis marker PRO-C3, were used to develop a prediction model. Prognostic accuracy was compared to enhanced liver fibrosis (ELF), fibrosis-4-index (FIB-4), transient elastography (TE) and ADAPT. In the derivation and validation cohorts, 67 (30%) and 19 (8%) experienced an LRE during a median follow-up of 5.2 years (IQR: 3.2-6.8) and 4.0 years (IQR: 2.7-5.6). On top of PRO-C3 and ADAPT score, we generated a model (ALPACA) of independent predictors of LREs (PRO-C3, AST/ALT, platelets). ALPACA had high prognostic accuracy with a C-statistic of 0.85 in the derivation cohort, comparable to ELF (0.83) and TE (0.84) and significantly higher than FIB-4 (0.78), PRO-C3 (0.80) and ADAPT (0.81). In the validation cohort, all tests had comparable C-statistics. Compared to low-risk patients (ALPACA ≤11), high-risk patients (>11) had a subhazard ratio for LREs of 12.6 (95% CI 5.9-26.8, p < .001) and higher cumulative incidence (57% vs. 7%, p < .001; derivation cohort). We observed similar subhazard ratio in the validation cohort. PRO-C3-based scores are reliable tools to predict LREs in ArLD patients and are suitable for risk stratification in primary and secondary care.

Using urinary metabolomics to identify metabolic pathways linked to cardiac structural alterations in young adults: The African-PREDICT study

Background and aimsRisk factor exposure from young ages was shown to contribute to cardiovascular events - cardiac hypertrophy, which may be accompanied by an altered metabolism. To determine how early metabolic alterations associate with myocardial structural changes, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and a control group without CVD risk factors. Methods and resultsWe included healthy adults (N = 1202), aged 20–30 years, stratified based on risk factors, i.e., obesity, physical inactivity, elevated blood pressure (BP), hyperglycemia, dyslipidemia, low socio-economic status, smoking and excessive alcohol use - forming the CVD risk group (N = 1036) and the control group (N = 166). Relative wall thickness (RWT) and left ventricular mass index (LVMi) were measured using echocardiography. Targeted metabolomics data were obtained using a liquid chromatography-tandem mass spectrometry method. Clinic systolic BP, 24 h BP and RWT were higher in the CVD risk group compared to the control group (all P ≤ 0.031). Exclusively in the CVD risk group, RWT associated with creatine and dodecanoylcarnitine; while LVMi associated with glycine, serine, glutamine, threonine, alanine, citrulline, creatine, proline, pyroglutamic acid and glutamic acid (all P ≤ 0.040). Exclusively in the control group, LVMi associated with propionylcarnitine and butyrylcarnitine (all P ≤ 0.009). ConclusionIn young adults without CVD, but with CVD risk factors, LVMi and RWT associated with metabolites linked energy metabolism (shifting from solely fatty acid oxidation to glycolysis, with impaired creatine kinase activity) and oxidative stress. Our findings support early onset metabolic changes accompanying cardiac structural alterations due to lifestyle and behavioural risk factors.

Liver Disease Prediction Using Machine Learning

Due to the rapid rise in liver illness caused by excessive alcohol use, drug use, tainted food, and pickled food packaging, a doctor can make an automatic forecast with the aid of a medical expert system. Early liver disease prediction is now attainable because to the consistent advancements in machine learning technology, allowing for simple early identification of the fatal condition. This will make healthcare more beneficial, and a medical expert system can be employed in a remote location. The liver is vital to life and promotes the body's ability to rid itself of poisons. Early detection of the condition is therefore crucial for recovery. many machine learning techniques, including supervised, unsupervised, and supervised, Reinforcement SVM, KNN, K- Mean clustering, neural networks, decision trees, and other learning techniques for diagnosing liver disease and providing varying accuracy, precision, and sensitivity.

Cardiometabolic multimorbidity, lifestyle behaviours, and cognitive function: a multicohort study

Little is known about the effect of lifestyle factors on cognitive decline related to cardiometabolic multimorbidity. We aimed to examine the association between cardiometabolic multimorbidity and cognitive decline, and the role of lifestyle factors in this association. We did a pooled multi-cohort study using pooled data from four cohort studies (the Health and Retirement Study; the English Longitudinal Study of Ageing; the Survey of Health, Ageing and Retirement in Europe; and the China Health and Retirement Longitudinal Study) across 14 countries. Eligible participants were age 50 years and older, and those who were missing information on exposure and outcomes, or who had been diagnosed with dementia or Parkinson's disease, were excluded. Cardiometabolic multimorbidity was defined as the co-occurrence of two or three cardiometabolic diseases, including diabetes, heart disease, and stroke. The primary outcome of cognitive function was measured in three domains, on the basis of the mean and SD of the corresponding tests: memory, numeracy, and orientation, in all participants with available data. A global cognitive score was created by summing the individual scores. The final sample consisted of 160 147 individuals across all four studies (73 846 [46·1%] men and 86 301 [53·9%] women) and participants had a mean age of 67·49 years (SD 10·43). An increasing number of cardiometabolic diseases was dose-dependently associated with the decline in cognitive function score (one disease, β=-0·15 [95% CI -0·17 to -0·13]; two diseases, β=-0·37 [-0·40 to -0·34]; three diseases, β=-0·57 [-0·64 to -0·50]), with comorbid diabetes and stroke (β=-0·23 [-0·29 to -0·17]) contributing most strongly to cardiometabolic disease-associated cognitive decline. Cognitive decline associated with cardiometabolic disease was accelerated with physical inactivity (one cardiometablic disease, p=0·020; two cardiometablic diseases, p=0·42; and three cardiometablic diseases, p=0·24), excessive alcohol use (one cardiometablic disease, p=0·016; two cardiometablic diseases, p=0·65; and three cardiometablic diseases, p=0·50), and the higher number of unhealthy lifestyle factors (one cardiometablic disease, p=0·79; two cardiometablic diseases, p=0·0050; and three cardiometablic diseases, p=0·888). These findings indicated a targeted approach for simultaneously developing preventative interventions on lifestyles and integrated treatment for cardiometabolic comorbidities to delay cognitive decline in older people. Major Project of the National Social Science Fund of China, National Natural Science Foundation of China, China Medical Board, and Young Elite Scientists Sponsorship Program by CAST.