Background Cigarette smoking and physical inactivity are two critical risk factors for noncommunicable diseases and all-cause mortality. However, few studies have compared the long-term trajectories of both behaviors, as well as multilevel factors associated with trajectory patterns. Using the National Longitudinal Study of Adolescent to Adult Health (Add Health) Wave I through V survey data, this study characterized distinct subgroups of the population sharing similar behavioral patterns from adolescence to adulthood, as well as predictors of subgroup membership for physical activity (PA) and cigarette smoking behavior respectively. Methods Using the Add Health Wave I through V survey data, we identified the optimal number of latent classes and class-specific trajectories of PA and cigarette smoking from early adolescence to adulthood, fitting latent growth mixture models with standardized PA score and past 30-day cigarette smoking intensity as outcome measures and age as a continuous time variable. Associations of baseline sociodemographic factors, neighborhood characteristics, and sociopsychological factors with trajectory class membership were assessed using multinomial logistic regression. Results We identified three distinct subgroups of non-linear PA trajectories in the study population: moderately active group (N = 1067, 5%), persistently inactive group (N = 14,257, 69%) and worsening activity group (N = 5410, 26%). Foror cigarette smoking, we identified three distinct non-linear trajectory subgroups: persistent non-smoker (N = 14,939, 72%), gradual quitter (N = 2357, 11%), and progressing smoker (N = 3393, 16%). Sex, race/ethnicity, neighborhood environment and perceived peer support during adolescence were significant predictors of both physical activity and cigarette smoking trajectory subgroup membership from early adolescence to adulthood. Conclusions There are three distinct subgroups of individuals sharing similar PA and cigarette smoking behavioral profile respectively from adolescence to adulthood in the Add Health study population. Behavioral interventions that focus on neighborhood environment (e.g. establish community-based activity center) and relationship to peers during adolescence (e.g. peer counseling) could be key to long-term PA promotion and cigarette smoking cessation.

Atrial fibrillation (AF) has been associated with cognitive impairment. Whether subclinical abnormalities in atrial function and substrate predisposing to AF impact cognitive function has received limited attention. We tested associations of echocardiographic markers of atrial structure and function with cognitive functioning and decline among 510 participants with overweight/obesity and metabolic syndrome (mean age [standard deviation] of 64.4 [5.2] years in men and 66.5 [3.9] in women). Left atrial (LA) markers (volume index, emptying fraction, strain, function index, and stiffness index) were estimated based on transthoracic echocardiography. General cognitive functioning (Mini-mental examination), verbal ability (verbal fluency test), memory and attention (Digit Span Tests), and processing speed and executive function (Trail-Making Tests A and B) were assessed at baseline and at the 2-year follow-up. Multiple linear regression was used to test associations of atrial markers (modeled in standard deviation units) with baseline and 2-year changes in cognitive scores adjusting for demographic and health covariates. LA structure and function were not associated with cognitive function at baseline. Larger LA volume index (standardized β [95% confidence interval] = −0.13 [−0.22, −0.03]), lower peak longitudinal strain (−0.11 [−0.20, −0.01]), and higher stiffness index (−0.18 [−0.28, −0.08) were associated with 2-year worsening in Trail-Making Test A. Strain measurements were also associated with 2-year change in the Controlled Oral Word Association Test. In conclusion, overall, adverse markers of LA structure and function were associated with 2-year detrimental executive function-related cognitive changes in a sample of participants at high risk for cardiovascular disease, highlighting LA substrate as a potential risk factor for cognitive decline and dementia.

Introduction This study investigates whether plasma biomarkers (Aβ42/40 and p‐tau 181), APS, as well as apolipoprotein E (APOE) proteotype predict cognitive deficits in elderly adults from the Democratic Republic of Congo. Methods Forty‐four with possible AD (pAD) and 41 healthy control (HC) subjects were screened using CSID and AQ, underwent cognitive assessment with the African Neuropsychology Battery (ANB), and provided blood samples for plasma Aβ42, Aβ40, Aβ42/40, and APOE proteotype. Linear and logistic regression were used to evaluate the associations of plasma biomarkers with ANB tests and the ability of biomarkers to predict cognitive status. Results Patients with pAD had significantly lower plasma Aβ42/40 levels, higher APS, and higher prevalence of APOE E4 allele compared to HC. Groups did not differ in levels of Aβ40, Aβ42, or P‐tau 181. Results showed that Aβ42/40 ratio and APS were significantly associated with African Naming Test (ANT), African List Memory Test (ALMT), and African Visuospatial Memory Test (AVMT) scores, while the presence of APOE E4 allele was associated with ANT, ALMT, AVMT, and APT scores. P‐tau 181 did not show any significant associations while adjusting for age, education, and gender. APS showed the highest area under the curve (AUC) value (AUC = 0.78, 95% confidence interval [CI]: 0.68–0.88) followed by Aβ42/40 (AUC = 0.75, 95% CI: 0.66–0.86) and APOE E4 (AUC = 0.69 (CI 0.57–0.81) in discriminating pAD from HC. Discussion These results demonstrate associations between select plasma biomarker of AD pathology (Aβ42/40), APS, and APOE E4 allele) and ANB test scores and the ability of these biomarkers to differentiate pAD from cognitively normal SSA individuals, consistent with findings reported in other settings.

Mitochondria carry their own circular genome and disruption of the mitochondrial genome is associated with various aging-related diseases. Unlike the nuclear genome, mitochondrial DNA (mtDNA) can be present at 1000 s to 10,000 s copies in somatic cells and variants may exist in a state of heteroplasmy, where only a fraction of the DNA molecules harbors a particular variant. We quantify mtDNA heteroplasmy in 194,871 participants in the UK Biobank and find that heteroplasmy is associated with a 1.5-fold increased risk of all-cause mortality. Additionally, we functionally characterize mtDNA single nucleotide variants (SNVs) using a constraint-based score, mitochondrial local constraint score sum (MSS) and find it associated with all-cause mortality, and with the prevalence and incidence of cancer and cancer-related mortality, particularly leukemia. These results indicate that mitochondria may have a functional role in certain cancers, and mitochondrial heteroplasmic SNVs may serve as a prognostic marker for cancer, especially for leukemia. Mitochondrial DNA is known to exhibit heterogeneity of variants, even within a single cell. Here, the authors assessed this heteroplasmy of mitochondrial DNA within the UK Biobank cohort and showed that the presence of heteroplasmy and a functional score generated from heteroplasmic SNVs were associated with all-cause mortality and certain cancers.

Background: No previous study has examined racial differences in recurrent acute myocardial infarction (AMI) in a community population. We aimed to examine racial differences in recurrent AMI risk, along with first AMI risk in a community population. Methods: The community surveillance of the Atherosclerosis Risk in Communities Study (2005–2014) included 470000 people 35–84 years old in 4 U.S. communities. Hospitalizations for recurrent and first AMI were identified from ICD-9-CM discharge codes. Poisson regression models were used to compare recurrent and first AMI risk ratios between Black and White residents. Results: Recurrent and first AMI risk per 1000 persons were 8.8 (95% CI, 8.3–9.2) and 20.7 (95 % CI, 20.0–21.4) in Black men, 6.8 (95% CI, 6.5–7.0) and 14.1 (95 % CI, 13.8–14.5) in White men, 5.3 (95% CI, 5.0–5.7) and 16.2 (95 % CI, 15.6–16.8) in Black women, and 3.1 (95% CI, 3.0–3.3) and 8.8 (95 % CI, 8.6–9.0) in White women, respectively. The age-adjusted risk ratios (RR) of recurrent AMI were higher in Black men vs. White men (RR, 1.58 95 % CI, 1.30–1.92) and Black women vs. White women (RR, 2.09 95 % CI, 1.64–2.66). The corresponding RRs were slightly lower for first AMI: Black men vs. White men, RR, 1.49 (95 % CI, 1.30–1.71) and Black women vs. White women, RR, 1.65 (95 % CI, 1.42–1.92) Conclusions: Large disparities exist by race for recurrent AMI risk in the community. The magnitude of disparities is stronger for recurrent events than for first events, and particularly among women.

Objective: To evaluate utilization of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor neprilysin inhibitors (ARNi) in patients with atrial fibrillation (AF) and heart failure (HF). Methods: We analyzed the MarketScan databases for the period 1/1/2021 to 6/30/2022. Validated algorithms were used to identify patients with AF and HF, and to classify patients into HF with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). We assessed the prevalence of SGLT2i and ARNi use overall and by HF type. Additionally, we explored correlates of lower utilization, including demographics and comorbidities. Results: The study population included 60,927 patients (mean age 75, 43% female) diagnosed with AF and HF (85% with HFpEF, 15% with HFrEF). Prevalence of ARNi use was 11% overall (30% in HFrEF, 8% in HFpEF), while the corresponding figure was 6% for SGLT2i (13% in HFrEF, 5% in HFpEF). Use of both medications increased over the study period: ARNi from 9% to 12% (from 22% to 29% in HFrEF, from 6% to 8% in HFpEF), and SGLT2i from 3% to 9% (from 6% to 16% in HFrEF, from 2% to 7% in HFpEF). Female sex, older age, and specific comorbidities were associated with lower utilization of these two medication types overall and by HF type. Conclusion: Use of ARNi and SGLT2i in patients with AF and HF is suboptimal, particularly among females and older individuals, though utilization is increasing. These results underscore the need for understanding reasons for these disparities and developing interventions to improve adoption of evidence-based therapies among patients with comorbid AF and HF.

Background: Alzheimer’s Disease (AD), the most common cause of dementia, poses a significant global burden. Diagnosis typically involves invasive and costly methods like neuroimaging or cerebrospinal fluid (CSF) biomarker testing of phosphorylated tau (p-tau) and amyloid-β42/40 (Aβ42/40). Such procedures are especially impractical in resource-constrained regions, such as the Democratic Republic of Congo (DRC). Blood-based biomarker testing may provide a more accessible screening opportunity. Objective: This study aims to examine if AD-related blood-based biomarkers are associated with cognitive test performance in the Congolese population, where limited research has been conducted. Methods: In this cross-sectional study of 81 Congolese individuals, cognitive assessments (Alzheimer’s Questionnaire (AQ) and Community Screening Interview for Dementia (CSID)) distinguished dementia cases from controls. Blood draws were taken to assess p-tau 181 and Aβ42/40 biomarkers. Relationships between the biomarkers and cognitive performance were analyzed using multiple linear regression models. Results: Lower plasma Aβ42/40 was significantly associated with lower CSID scores and higher AQ scores, indicative of AD (p<0.001). These relationships were observed in healthy controls (CSID p=0.01, AQ p=0.03), but not in dementia cases. However, p-tau 181 did not exhibit significant associations with either measure. Factors such as age, sex, education, presence of APOE e4 allele, did not alter these relationships. Conclusion: Understanding relationships between AD-related screening tests and blood-biomarkers is a step towards utilization of blood-based biomarker tests as a screening tool for AD, especially in resource-limited regions. Further research should be conducted to evaluate blood biomarker test efficacy in larger samples and other populations.

Evidence supports associations of lifestyle (including diet and physical activity) and weight with cognitive functioning, but the pathways responsible for these associations have not been fully elucidated. Because healthier lifestyles have been associated with better left atrial structure and function, which in turn is associated with better cognitive functioning, we tested the hypothesis that left atrial structure and function is a potential mediator of the association between lifestyle and cognition. We included 476 participants classed as overweight or obese with metabolic syndrome from three centers in Spain. These participants underwent lifestyle assessments and transthoracic echocardiography at baseline and repeated measurements of the Trail Making A test, a measure of executive function, taken at baseline and at the two-year follow-up. We conducted mediation analyses to test if measures of left atrial structure and function mediated associations between adherence to the Mediterranean diet scores, physical activity, and weight at baseline, as well as a two-year change in Trail Making A scores. The analysis did not find an association between these factors and Trail Making A scores, and no indirect effects appeared to be mediated by echocardiographic measurements. The modest sample size in this analysis is a limitation, and larger studies should be conducted to determine potential cardiovascular factors mediating the association between lifestyle and cognition.

BACKGROUND: The search for risk factors of hypertension requires the study of large populations. Sometimes, the only feasible way of studying these populations is to rely on self-reported data of the outcome. The objective of this study was to evaluate validity of self-reported diagnosis of hypertension in a cohort of university graduates in Spain. METHODS: The Seguimiento Universidad de Navarra (SUN) Study is a cohort of more than 15,000 university graduates in Spain. We selected a random sample of 79 cohort participants who reported a diagnosis of hypertension and 48 participants who did not report such diagnosis (76% participation proportion). Then, we compared information on the self-reported diagnosis of hypertension and hypertension status as assessed through two personal blood pressure measurements and an interview. Additionally, we compared self-reported and measured blood pressure levels with intraclass correlation coefficients and the survival-agreement plot. RESULTS: From those 79 reporting a diagnosis of hypertension, 65 (82.3%, 95% CI 72.8-92.8) were confirmed through conventional measurement of blood pressure and the interview. From those 48 that did not report a diagnosis of hypertension, 41 (85.4%, 95% CI 72.4-89.1) were confirmed as non hypertensives. Results were similar among men and women, but were worse for overweight and obese individuals, and for those with a family history of hypertension. The agreement between self-reported and measured blood pressure levels (as a continuous variable), as estimated by the intraclass correlation coefficient, was 0.35 for both systolic and diastolic blood pressure. CONCLUSION: Self-reported hypertension among highly educated participants in a cohort study is a relatively valid tool to assess the hypertensive status of participants. However, the investigators should be cautious when using self-reported blood pressure values.

Higher serum magnesium is associated with lower risk of multiple morbidities, including diabetes, stroke, and atrial fibrillation, but its potential neuroprotective properties have also been gaining traction in cognitive function and decline research. We studied 12,040 participants presumed free of dementia in the Atherosclerosis Risk in Communities (ARIC) study. Serum magnesium was measured in fasting blood samples collected in 1990–1992. Dementia status was ascertained through cognitive examinations in 2011–2013, 2016–2017, and 2018–2019, along with informant interviews and indicators of dementia-related hospitalization events and death. Participants’ cognitive functioning capabilities were assessed up to five times between 1990–1992 and 2018–2019. The cognitive function of participants who did not attend follow-up study visits was imputed to account for attrition. We identified 2519 cases of dementia over a median follow-up period of 24.2 years. The lowest quintile of serum magnesium was associated with a 24% higher rate of incident dementia compared to those in the highest quintile of magnesium (HR, 1.24; 95% CI, 1.07, 1.44). No relationship was found between serum magnesium and cognitive decline in any cognitive domain. Low midlife serum magnesium is associated with increased risk of incident dementia, but does not appear to impact rates of cognitive decline.