Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption.

Dietary flavanols are food constituents found in certain fruits and vegetables that have been linked to cognitive aging. Previous studies suggested that consumption of dietary flavanols might specifically be associated with the hippocampal-dependent memory component of cognitive aging and that memory benefits of a flavanol intervention might depend on habitual diet quality. Here, we tested these hypotheses in the context of a large-scale study of 3,562 older adults, who were randomly assigned to a 3-y intervention of cocoa extract (500 mg of cocoa flavanols per day) or a placebo [(COcoa Supplement and Multivitamin Outcomes Study) COSMOS-Web, NCT04582617]. Using the alternative Healthy Eating Index in all participants and a urine-based biomarker of flavanol intake in a subset of participants [n = 1,361], we show that habitual flavanol consumption and diet quality at baseline are positively and selectively correlated with hippocampal-dependent memory. While the prespecified primary end point testing for an intervention-related improvement in memory in all participants after 1 y was not statistically significant, the flavanol intervention restored memory among participants in lower tertiles of habitual diet quality or habitual flavanol consumption. Increases in the flavanol biomarker over the course of the trial were associated with improving memory. Collectively, our results allow dietary flavanols to be considered in the context of a depletion-repletion paradigm and suggest that low flavanol consumption can act as a driver of the hippocampal-dependent component of cognitive aging.

Sociopolitical stress and acute cardiovascular disease hospitalizations around the 2016 presidential election.

Previous research suggests that stressors may trigger the onset of acute cardiovascular disease (CVD) events within hours to days, but there has been limited research around sociopolitical events such as presidential elections. Among adults ≥18 y of age in Kaiser Permanente Southern California, hospitalization rates for acute CVD were compared in the time period immediately prior to and following the 2016 presidential election date. Hospitalization for CVD was defined as an inpatient or emergency department discharge diagnosis of acute myocardial infarction (AMI) or stroke using International Classification of Diseases, 10th revision codes. Rate ratios (RR) and 95% confidence intervals (CIs) were calculated comparing CVD rates in the 2 d following the 2016 election to rates in the same 2 d of the prior week. In a secondary analysis, AMI and stroke were analyzed separately. The rate of CVD events in the 2 d after the 2016 presidential election (573.14 per 100,000 person-years [PY]) compared to the rate in the window prior to the 2016 election (353.75 per 100,000 PY) was 1.62 times higher (95% CI 1.17, 2.25). Results were similar across sex, age, and race/ethnicity groups. The RRs were similar for AMI (RR 1.67, 95% CI 1.00, 2.76) and stroke (RR 1.59, 95% CI 1.03, 2.44) separately. Transiently heightened cardiovascular risk around the 2016 election may be attributable to sociopolitical stress. Further research is needed to understand the intersection between major sociopolitical events, perceived stress, and acute CVD events.

Association of Depressive Symptoms with Sleep Disturbance: A Co-twin Control Study.

BACKGROUND: Few studies have comprehensively evaluated the association of depression with sleep disturbance using a controlled twin study design. PURPOSE: To cross-sectionally evaluate the association of depression with both objective and subjective sleep disturbance. METHODS: We studied 246 members of the Vietnam Era Twin Registry. We measured depressive symptoms using the Beck Depression Inventory-II (BDI) and assessed major depression using structured clinical interviews. Twins underwent one-night polysomnography and 7-day actigraphy to derive measures of objective sleep and completed the Pittsburgh Sleep Quality Index for subjective sleep. Multivariable mixed-effects models were used to examine the association. RESULTS: Twins were all male, mostly white (97%), with a mean (SD) age of 68 (2). The mean (SD) BDI was 5.9 (6.3), and 49 (20%) met the criteria for major depression. For polysomnography, each 5-unit higher BDI, within-pair, was significantly associated with 19.7 min longer rapid eye movement (REM) sleep latency, and 1.1% shorter REM sleep after multivariable adjustment. BDI was not associated with sleep architecture or sleep-disordered breathing. For actigraphy, a higher BDI, within-pair, was significantly associated with lower sleep efficiency, more fragmentation and higher variability in sleep duration. BDI was associated with almost all dimensions of self-reported sleep disturbance. Results did not differ by zygosity, and remained consistent using major depression instead of BDI and were independent of the presence of comorbid posttraumatic stress disorder and antidepressant use. CONCLUSIONS: Depression is associated with REM sleep disruption in lab and sleep fragmentation and sleep variability at home, but not with sleep architecture or sleep-disordered breathing.

The Impact of Aerobic Training on Cardiovascular Reactivity to and Recovery From Psychological and Orthostatic Challenge.

OBJECTIVE: Elevated cardiovascular reactivity to, and reduced recovery from, challenging events may increase the risk of cardiovascular disease, and exercise training may reduce this reactivity. However, in a randomized controlled trial of aerobic versus strength training in sedentary, healthy young adults, we found no training group differences in reactivity or recovery. Because strength training also may have a reactivity-reducing effect, we conducted a secondary analysis of data from another trial, this time with a wait-list control condition. METHODS: One hundred nineteen healthy, young, sedentary adults were randomized to a 12-week aerobic training program or wait-list control. Before (T1) and after (T2) training and after 4 weeks of sedentary deconditioning (T3), we measured heart rate (HR), heart rate variability, and blood pressure at rest and in response to and recovery from psychological and orthostatic challenge. Data were analyzed using a group (aerobic versus wait-list) by session (T1, T2, and deconditioning) and by period (baseline, psychological challenge, recovery, standing) three-way analysis of variance with prespecified contrasts. RESULTS: Aerobic capacity significantly increased at T2 and decreased at T3 only in the aerobic training group. The groups did not differ on HR, heart rate variability, or blood pressure reactivity to or recovery from challenge. Without baseline adjustment, there were no significant treatment differences in response to challenges. With baseline adjustment, there were significant treatment by session effects for HR (Cohen d = 0.54, p = .002), systolic blood pressure (d = 0.44, p = .014), diastolic blood pressure (d = 0.74, p = .002), and root mean squared successive difference (d = 0.48, p = .006) reactivity from T1 to T2 only for orthostatic challenge: at T2, reactivity in the aerobic group was nonsignificantly reduced, compared with T1. In the wait-list group, reactivity significantly increased after T1. CONCLUSIONS: This study raises further doubt about attenuation of cardiovascular reactivity or enhancement of recovery as a cardioprotective mechanism of aerobic exercise training.Clinical Trial Registration:ClinicalTrials.gov Unique identifier: NCT01335737.

Parasympathetic neural activity and the reciprocal regulation of innate antiviral and inflammatory genes in the human immune system.

The vagus nerve mediates parasympathetic nervous system control of peripheral physiological processes including cardiovascular activity and immune response. In mice, tonic vagal activation down-regulates inflammation via nicotinic acetylcholine receptor-mediated inhibition of the pro-inflammatory transcription factor NF-κB in monocyte/macrophages. Because Type I interferon and pro-inflammatory genes are regulated reciprocally at the level of transcription factor activation and cell differentiation, we hypothesized that vagal activity would up-regulate Type I interferon response genes concurrently with inflammatory downregulation in human immune cells. We mapped empirical individual differences in the circulating leukocyte transcriptome and vagal activity indexed by high frequency (0.15-0.40 Hz) heart rate variability (HF-HRV) in 380 participants in the Midlife in the US study. Here we show that promoter-based bioinformatics analyses linked greater HF-HRV to reduced NF-κB activity and increased activity of IRF transcription factors involved in Type I interferon response (independent of ß-antagonists, BMI, smoking, heavy alcohol consumption, and demographic factors). Transcript origin analyses implicated myeloid lineage immune cells as targets, representing per-cell alterations in gene transcription as HF-HRV was not associated with differential prevalence of leukocyte subsets. These findings support the concept of parasympathetic inhibition of pro-inflammatory gene expression in humans and up-regulation of Type I interferons that could augment host defense against viral infections.

Child and Adult Socioeconomic Status and the Cortisol Response to Acute Stress: Evidence From the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: A long-hypothesized pathway through which low socioeconomic status (SES) harms health is through dysregulation of the physiologic stress response systems. No previous studies have tested this hypothesis by investigating cortisol reactivity and recovery to acute stress in relation to SES at different times in the life course in adults. Alteration of the cortisol response to an acute stressor could signal dysregulation of the hypothalamic-pituitary-adrenal axis and has been associated with chronic illness. METHODS: We used data on 997 adults 54 years or older from a multiethnic, multisite United States study to examine associations between life course SES and cortisol response to a laboratory stress challenge. Informed by life course theory, we hypothesized that lower child and adult SES would be associated with lower reactivity (i.e., smaller increase in cortisol) and a slower recovery rate (i.e., slower rate of decline in cortisol after the challenge). RESULTS: In demographics-adjusted multilevel piecewise linear regression models, low child and adult SES were associated with a 19% (95% CI = 4%-50%) and 27% (7%-55%) slower recovery rate compared with high child and adult SES, respectively. Compared with participants with stable high SES, those with stable low SES had a 48% (16%-70%) slower recovery rate. Differences in reactivity by SES were small. CONCLUSIONS: Our results support the hypothesis that low SES throughout life affects the hypothalamic-pituitary-adrenal axis and in turn the ability to recover from exposure to acute stressors. This mechanism can help explain how socioeconomic disparities contribute to disparities in chronic disease.

The Association of Cigarette Smoking With High-Frequency Heart Rate Variability: An Ecological Momentary Assessment Study.

OBJECTIVE: Evidence from both laboratory and observational studies suggests that acute and chronic smoking leads to reduced high-frequency heart rate variability (HF-HRV), a measure of cardiac vagal regulation. We used ecological momentary assessment (EMA) to study the effect of smoking on concurrent HF-HRV in a trial measuring the effects of hostility reduction and compared 24-hour HF-HRV in smokers and nonsmokers. METHOD: Ambulatory electrocardiogram data were collected before randomization from 149 healthy individuals with high hostility levels (20-45 years, body mass index ≤ 32 kg/m) and paired with concurrent EMA ratings of smoking and physical position during waking hours. A multilevel mixed model was estimated associating ln(HF-HRV) from smoking status (between-person factor) and person-centered momentary smoking (within-person factor, treated as a random effect), adjusting for momentary physical position, medication use, and consumption of alcohol and caffeine. RESULTS: Thirty-five smokers and 114 nonsmokers provided both EMA and HF-HRV data. Within smokers, ln HF-HRV was reduced by 0.31 millisecond (p = .04) when participants reported having recently smoked cigarettes, compared with when they had not. The 24-hour HF-HRV was significantly lower in smokers (M [SD] = 5.24 [0.14] milliseconds) than nonsmokers (5.63 ± 0.07 milliseconds, p = .01). CONCLUSIONS: In healthy smokers with high hostility levels used as their own controls during daily living, smoking acutely reduced HF-HRV. HF-HRV was also reduced in smokers as compared with nonsmokers. Although limited by a small sample of individuals with high hostility levels, these findings nonetheless provide additional evidence that cardiac vagal regulation is lowered by cigarette smoking, which may be one of the numerous pathophysiological effects of smoking.

Linking Daily Stress Processes and Laboratory-Based Heart Rate Variability in a National Sample of Midlife and Older Adults.

OBJECTIVE: This study evaluates the associations between people's trait-like patterns of stress in daily life (stressor frequency, perceived stressor severity, affective reactivity to stressors, and negative affect) and laboratory-assessed heart rate variability (HRV). METHODS: Data were collected from 909 participants aged 35 to 85 years in the Midlife in the United States Study. Participants reported negative affect and minor stressful events during telephone interviews on 8 consecutive evenings. On a separate occasion, HRV was measured from electrocardiograph recordings taken at rest during a laboratory-based psychophysiology protocol. Regression models were used to evaluate the associations between daily stress processes and three log-transformed HRV indices: standard deviation of R-R intervals (SDRR), root mean square of successive differences (RMSSD), and high-frequency power (high-frequency HRV [HF-HRV]). Analyses were adjusted for demographics, body mass index, comorbid conditions, medications, physical activity, and smoking. RESULTS: Stressor frequency was unrelated to HRV (r values ranging from -0.04 to -0.01, p values >.20). However, people with greater perceived stressor severity had lower resting SDRR (fully adjusted B [standard error {SE}] = -0.05 [0.02]), RMSSD (-0.08 [0.03]), and HF-HRV (-0.16 [0.07]). Individuals with more pronounced affective reactivity to stressors also had lower levels of all three HRV indices (SDRR: B [SE] = -0.28 [0.14]; RMSSD: -0.44 [0.19]; HF-HRV: -0.96 [0.37]). Furthermore, aggregated daily negative affect was linked to reduced RMSSD (B [SE] = -0.16 [0.08]) and HF-HRV (-0.35 [0.15]). CONCLUSIONS: In a national sample, individual differences in daily negative affect and responses to daily stressors were more strongly related to cardiovascular autonomic regulation than the frequency of such stressors.

The Effect of Hostility Reduction on Autonomic Control of the Heart and Vasculature: A Randomized Controlled Trial.

OBJECTIVE: Hostility is associated with coronary artery disease. One candidate mechanism may be autonomic nervous system (ANS) dysregulation. In this study, we report the effect of cognitive behavioral treatment on ANS regulation. METHODS: Participants were 158 healthy young adults, high in hostility measured by the Cook-Medley Hostility and Spielberger Trait Anger scales. Participants were also interviewed using the Interpersonal Hostility Assessment Technique. They were randomized to a 12-week cognitive behavioral treatment program for reducing hostility or a wait-list control group. The outcome measures were preejection period, low-frequency blood pressure variability, and high-frequency heart rate variability measured at rest and in response to and recovery from cognitive and orthostatic challenge. Linear-mixed models were used to examine group by session and group by session by period interactions while controlling for sex and age. Contrasts of differential group and session effects were used to examine reactivity and recovery from challenge. RESULTS: After Bonferroni correction, two-way and three-way interactions failed to achieve significance for preejection period, low-frequency blood pressure variability, or high-frequency heart rate variability (p > .002), indicating that hostility reduction treatment failed to influence ANS indices. CONCLUSIONS: Reduction in anger and hostility failed to alter ANS activity at rest or in response to or recovery from challenge. These findings raise questions about whether autonomic dysregulation represents a pathophysiological link between hostility and heart disease.

Heart rate variability predicts levels of inflammatory markers: Evidence for the vagal anti-inflammatory pathway.

Evidence from numerous animal models shows that vagal activity regulates inflammatory responses by decreasing cytokine release. Heart rate variability (HRV) is a reliable index of cardiac vagal regulation and should be inversely related to levels of inflammatory markers. Inflammation is also regulated by sympathetic inputs, but only one previous paper controlled for this. In a larger and more representative sample, we sought to replicate those results and examine potential sex differences in the relationship between HRV and inflammatory markers. Using data from the MIDUS II study, we analyzed the relationship between 6 inflammatory markers and both HF-HRV and LF-HRV. After controlling for sympathetic effects measured by urinary norepinephrine as well as a host of other factors, LF-HRV was found to be inversely associated with fibrinogen, CRP and IL-6, while HF-HRV was inversely associated with fibrinogen and CRP. We did not observe consistent sex differences. These results support the existence of the vagal anti-inflammatory pathway and suggest that it has similar effects in men and women.

Beat-to-beat heart rate and blood pressure variability and hypertensive disease in pregnancy.

OBJECTIVE: The aim of this study is to determine the relationship between heart rate and/or blood pressure variability, measured at 28 weeks' gestation, and the incidence of pregnancy-induced hypertension or preeclampsia. STUDY DESIGN: Secondary analysis of data from a prospectively enrolled cohort of 385 active military women in whom spectral analysis of continuous heart rate and variability was measured at 28 weeks' gestation. The primary outcome was the predictive value of spectral analysis of heart rate and blood pressure for hypertensive diseases of pregnancy. RESULTS: High-frequency heart rate variability was reduced and low-frequency variability of systolic and diastolic blood pressure increased in women who would develop pregnancy-induced hypertension but not preeclampsia. Low-frequency variability of diastolic blood pressure remained a significant predictor of pregnancy-induced hypertension but not preeclampsia after adjustment for age, weight, and blood pressure in a multivariate model. CONCLUSION: Early identification of pregnancy-induced hypertension can facilitate treatment to avoid maternal morbidity. Understanding the physiological underpinnings of the two very different diseases may lead to improved treatment and prevention. If proven effective in a broader population, the ability to differentiate pregnancy-induced hypertension from preeclampsia may reduce unnecessary iatrogenic interventions or inappropriate preterm delivery.

Quantifying serotonin transporters by PET with [11C]-DASB before and after interferon-α treatment.

BACKGROUND: Interferon-α (IFN-α) therapy is frequently associated with disabling depression, fatigue, and related neuropsychiatric effects. Although depression in major depressive disorder is associated with low serotonin transporter binding, animal models suggest that IFN-associated mood effects are linked to increased presynaptic serotonin transporter binding. This study tested the hypotheses that IFN administration to human subjects increases presynaptic serotonin binding activity, and that this effect correlates with incident depression symptoms. METHODS: Positron emission tomography (PET) scans using [11C]-DASB were obtained for nine hepatitis C patients before and after IFN-α treatment for 8 weeks. Serotonin transporter binding was estimated using the likelihood estimation in graphical analysis (LEGA) model and measured as the volume of distribution (VT) divided by the free fraction of ligand (fP). Depression was measured with the Structured Clinical Interview for DSM-IV Diagnosis (SCID) and the Hamilton Rating Scale for Depression (HAM-D). RESULTS: Compared to pre-IFN treatment values, changes in serotonin transporter binding and depression symptoms were not significant. There was no correlation between changes in serotonin transporter binding and depression symptoms. LIMITATIONS: The study is limited by small sample size, minimal effect on observed mood symptoms within the sample, and brief duration of follow-up. CONCLUSION: These findings do not support the hypothesis of an IFN-induced change in serotonin transporter function as the cause of incident depressive symptoms in patients treated with IFN-α. Additional study of these possible relationships should be of longer duration and include more subjects with more pronounced changes in mood.

A platform to map the mind-mitochondria connection and the hallmarks of psychobiology: the MiSBIE study.

Health emerges from coordinated psychobiological processes powered by mitochondrial energy transformation. But how do mitochondria regulate the multisystem responses that shape resilience and disease risk across the lifespan? The Mitochondrial Stress, Brain Imaging, and Epigenetics (MiSBIE) study was established to address this question and determine how mitochondria influence the interconnected neuroendocrine, immune, metabolic, cardiovascular, cognitive, and emotional systems among individuals spanning the spectrum of mitochondrial energy transformation capacity, including participants with rare mitochondrial DNA (mtDNA) lesions causing mitochondrial diseases (MitoDs). This interdisciplinary effort is expected to generate new insights into the pathophysiology of MitoDs, provide a foundation to develop novel biomarkers of human health, and integrate our fragmented knowledge of bioenergetic, brain-body, and mind-mitochondria processes relevant to medicine and public health.

Aerobic exercise and strength training effects on cardiovascular sympathetic function in healthy adults: a randomized controlled trial.

OBJECTIVE: Exercise has widely documented cardioprotective effects, but the mechanisms underlying these effects are not entirely known. Previously, we demonstrated that aerobic but not strength training lowered resting heart rate and increased cardiac vagal regulation, changes that were reversed by sedentary deconditioning. Here, we focus on the sympathetic nervous system and test whether aerobic training lowers levels of cardiovascular sympathetic activity in rest and that deconditioning would reverse this effect. METHODS: We conducted a randomized controlled trial contrasting the effects of aerobic (A) versus strength (S) training on indices of cardiac (preejection period, or PEP) and vascular (low-frequency blood pressure variability, or LF BPV) sympathetic regulation in 149 young, healthy, and sedentary adults. Participants were studied before and after conditioning, as well as after 4 weeks of sedentary deconditioning. RESULTS: As previously reported, aerobic capacity increased in response to conditioning and decreased after deconditioning in the aerobic, but not the strength, training group. Contrary to prediction, there was no differential effect of training on either PEP (A: mean [SD] -0.83 [7.8] milliseconds versus S: 1.47 [6.69] milliseconds) or LF BPV (A: mean [SD] -0.09 [0.93] ln mm Hg(2) versus S: 0.06 [0.79] ln mm Hg(2)) (both p values > .05). CONCLUSIONS: These findings, from a large randomized controlled trial using an intent-to-treat design, show that moderate aerobic exercise training has no effect on resting state cardiovascular indices of PEP and LF BPV. These results indicate that in healthy, young adults, the cardioprotective effects of exercise training are unlikely to be mediated by changes in resting sympathetic activity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00358137.

Anatomical biology guides a search for nutrients for the aging brain.

Considerable evidence has established the importance of specific nutrients that have been found vital for the developing brain. We hypothesize that in a similar manner there should be nutrients vital to the aging brain and that based on aging's distinct pathophysiology they should be different than those essential to development. Specific brain networks that govern cognition are particularly vulnerable to the aging process, resulting in what is referred to as 'cognitive aging'. Common late-life disorders, however, such as Alzheimer's disease also target these same brain networks. Studies have disambiguated cognitive aging from late-life disease by isolating regions and biological pathways within each network differentially linked to one or the other. This anatomical biology anchors a framework to identify nutrients and/or dietary bioactives relevant to cognitive aging whose utility is illustrated via a decades-long research program into how dietary bioactive flavanols benefit the brain. As we are living longer in cognitively more demanding lives, the framework's ultimate goal is to generate specific dietary recommendations that will fortify our mind for its golden years.

Cardiovascular variability, sociodemographics, and biomarkers of disease: the MIDUS study.

Introduction: Like heart rate, blood pressure (BP) is not steady but varies over intervals as long as months to as short as consecutive cardiac cycles. This blood pressure variability (BPV) consists of regularly occurring oscillations as well as less well-organized changes and typically is computed as the standard deviation of multiple clinic visit-to-visit (VVV-BP) measures or from 24-h ambulatory BP recordings (ABPV). BP also varies on a beat-to-beat basis, quantified by methods that parse variation into discrete bins, e.g., low frequency (0.04-0.15 Hz, LF). However, beat-to-beat BPV requires continuous recordings that are not easily acquired. As a result, we know little about the relationship between LF-BPV and basic sociodemographic characteristics such as age, sex, and race and clinical conditions. Methods: We computed LF-BPV during an 11-min resting period in 2,118 participants in the Midlife in the US (MIDUS) study. Results: LF-BPV was negatively associated with age, greater in men than women, and unrelated to race or socioeconomic status. It was greater in participants with hypertension but unrelated to hyperlipidemia, hypertriglyceridemia, diabetes, elevated CRP, or obesity. LF-diastolic BPV (DBPV), but not-systolic BPV (SBPV), was negatively correlated with IL-6 and s-ICAM and positively correlated with urinary epinephrine and cortisol. Finally, LF-DBPV was negatively associated with mortality, an effect was rendered nonsignificant by adjustment by age but not other sociodemographic characteristics. Discussion: These findings, the first from a large, national sample, suggest that LF-BPV differs significantly from VVV-BP and ABPV. Confirming its relationship to sociodemographic risk factors and clinical outcomes requires further study with large and representative samples.

Multivitamin Supplementation Improves Memory in Older Adults: A Randomized Clinical Trial.

BACKGROUND: Maintenance of cognitive abilities is of critical importance to older adults, yet few effective strategies to slow cognitive decline currently exist. Multivitamin supplementation is used to promote general health; it is unclear whether it favorably affects cognition in older age. OBJECTIVES: To examine the effect of daily multivitamin/multimineral supplementation on memory in older adults. METHODS: The COcoa Supplement and Multivitamin Outcomes Study Web (COSMOS-Web) ancillary study (NCT04582617) included 3562 older adults. Participants were randomly assigned to a daily multivitamin supplement (Centrum Silver) or placebo and evaluated annually with an Internet-based battery of neuropsychological tests for 3 y. The prespecified primary outcome measure was change in episodic memory, operationally defined as immediate recall performance on the ModRey test, after 1 y of intervention. Secondary outcome measures included changes in episodic memory over 3 y of follow-up and changes in performance on neuropsychological tasks of novel object recognition and executive function over 3 y. RESULTS: Compared with placebo, participants randomly assigned to multivitamin supplementation had significantly better ModRey immediate recall at 1 y, the primary endpoint (t(5889) = 2.25, P = 0.025), as well as across the 3 y of follow-up on average (t(5889) = 2.54, P = 0.011). Multivitamin supplementation had no significant effects on secondary outcomes. Based on cross-sectional analysis of the association between age and performance on the ModRey, we estimated that the effect of the multivitamin intervention improved memory performance above placebo by the equivalent of 3.1 y of age-related memory change. CONCLUSIONS: Daily multivitamin supplementation, compared with placebo, improves memory in older adults. Multivitamin supplementation holds promise as a safe and accessible approach to maintaining cognitive health in older age. This trial was registered at clinicaltrials.gov as NCT04582617.

Association of the 2020 US Presidential Election With Hospitalizations for Acute Cardiovascular Conditions.

Importance: Prior studies found a higher risk of acute cardiovascular disease (CVD) around population-wide psychosocial or environmental stressors. Less is known about acute CVD risk in relation to political events. Objective: To examine acute CVD hospitalizations following the 2020 presidential election. Design, Setting, and Participants: This retrospective cohort study examined acute CVD hospitalizations following the 2020 presidential election. Participants were adult members aged 18 years or older at Kaiser Permanente Southern California and Kaiser Permanente Northern California, 2 large, integrated health care delivery systems. Statistical analysis was performed from March to July 2021. Exposure: 2020 US presidential election. Main Outcomes and Measures: Hospitalizations for acute CVD around the 2020 presidential election were examined. CVD was defined as hospitalizations for acute myocardial infarction (AMI), heart failure (HF), or stroke. Rate ratios (RR) and 95% CIs were calculated comparing rates of CVD hospitalization in the 5 days following the 2020 election with the same 5-day period 2 weeks prior. Results: Among 6 396 830 adults (3 970 077 [62.1%] aged 18 to 54 years; 3 422 479 [53.5%] female; 1 083 128 [16.9%] Asian/Pacific Islander, 2 101 367 [32.9%] Hispanic, and 2 641 897 [41.3%] White), rates of hospitalization for CVD following the election (666 hospitalizations; rate = 760.5 per 100 000 person-years [PY]) were 1.17 times higher (95% CI, 1.05-1.31) compared with the same 5-day period 2 weeks prior (569 hospitalizations; rate = 648.0 per 100 000 PY). Rates of AMI were significantly higher following the election (RR, 1.42; 95% CI, 1.13-1.79). No significant difference was found for stroke (RR, 1.02; 95% CI, 0.86-1.21) or HF (RR, 1.18; 95% CI, 0.98-1.42). Conclusions and Relevance: Higher rates of acute CVD hospitalization were observed following the 2020 presidential election. Awareness of the heightened risk of CVD and strategies to mitigate risk during notable political events are needed.