Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.

Long-term multivitamin supplementation and cognitive function in men: a randomized trial.

BACKGROUND: Despite widespread use of multivitamin supplements, their effect on cognitive health-a critical issue with aging-remains inconclusive. To date, no long-term clinical trials have studied multivitamin use and cognitive decline in older persons. OBJECTIVE: To evaluate whether long-term multivitamin supplementation affects cognitive health in later life. DESIGN: Randomized, double-blind, placebo-controlled trial of a multivitamin from 1997 to 1 June 2011. The cognitive function substudy began in 1998. Up to 4 repeated cognitive assessments by telephone interview were completed over 12 years. (ClinicalTrials.gov: NCT00270647) SETTING: The Physicians' Health Study II. PATIENTS: 5947 male physicians aged 65 years or older. INTERVENTION: Daily multivitamin or placebo. MEASUREMENTS: A global composite score averaging 5 tests of global cognition, verbal memory, and category fluency. The secondary end point was a verbal memory score combining 4 tests of verbal memory, which is a strong predictor of Alzheimer disease. RESULTS: No difference was found in mean cognitive change over time between the multivitamin and placebo groups or in the mean level of cognition at any of the 4 assessments. Specifically, for the global composite score, the mean difference in cognitive change over follow-up was -0.01 SU (95% CI, -0.04 to 0.02 SU) when treatment was compared with placebo. Similarly, cognitive performance did not differ between the multivitamin and placebo groups on the secondary outcome, verbal memory (mean difference in cognitive change over follow-up, -0.005 SU [CI, -0.04 to 0.03 SU]). LIMITATION: Doses of vitamins may be too low or the population may be too well-nourished to benefit from a multivitamin. CONCLUSION: In male physicians aged 65 years or older, long-term use of a daily multivitamin did not provide cognitive benefits. PRIMARY FUNDING SOURCE: National Institutes of Health, BASF, Pfizer, and DSM Nutritional Products.

Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA.

Primary open-angle glaucoma (POAG) is a genetically complex common disease characterized by progressive optic nerve degeneration that results in irreversible blindness. Recently, a genome-wide association study (GWAS) for POAG in an Icelandic population identified significant associations with single nucleotide polymorphisms (SNPs) between the CAV1 and CAV2 genes on chromosome 7q31. In this study, we confirm that the identified SNPs are associated with POAG in our Caucasian US population and that specific haplotypes located in the CAV1/CAV2 intergenic region are associated with the disease. We also present data suggesting that associations with several CAV1/CAV2 SNPs are significant mostly in women.

Dietary intakes of berries and flavonoids in relation to cognitive decline.

OBJECTIVE: Berries are high in flavonoids, especially anthocyanidins, and improve cognition in experimental studies. We prospectively evaluated whether greater long-term intakes of berries and flavonoids are associated with slower rates of cognitive decline in older women. METHODS: Beginning in 1980, a semiquantitative food frequency questionnaire was administered every 4 years to Nurses' Health Study participants. In 1995-2001, we began measuring cognitive function in 16,010 participants, aged ≥70 years; follow-up assessments were conducted twice, at 2-year intervals. To ascertain long-term diet, we averaged dietary variables from 1980 through the initial cognitive interview. Using multivariate-adjusted, mixed linear regression, we estimated mean differences in slopes of cognitive decline by long-term berry and flavonoid intakes. RESULTS: Greater intakes of blueberries and strawberries were associated with slower rates of cognitive decline (eg, for a global score averaging all 6 cognitive tests, for blueberries: p-trend = 0.014 and mean difference = 0.04, 95% confidence interval [CI] = 0.01-0.07, comparing extreme categories of intake; for strawberries: p-trend = 0.022 and mean difference = 0.03, 95% CI = 0.00-0.06, comparing extreme categories of intake), after adjusting for multiple potential confounders. These effect estimates were equivalent to those we found for approximately 1.5 to 2.5 years of age in our cohort, indicating that berry intake appears to delay cognitive aging by up to 2.5 years. Additionally, in further supporting evidence, greater intakes of anthocyanidins and total flavonoids were associated with slower rates of cognitive decline (p-trends = 0.015 and 0.053, respectively, for the global score). INTERPRETATION: Higher intake of flavonoids, particularly from berries, appears to reduce rates of cognitive decline in older adults.

Adherence to Healthy Lifestyle Prior to Infection and Risk of Post-COVID-19 Condition.

Importance: Few modifiable risk factors for post-COVID-19 condition (PCC) have been identified. Objective: To investigate the association between healthy lifestyle factors prior to SARS-CoV-2 infection and risk of PCC. Design, Setting, and Participants: In this prospective cohort study, 32 249 women in the Nurses' Health Study II cohort reported preinfection lifestyle habits in 2015 and 2017. Healthy lifestyle factors included healthy body mass index (BMI, 18.5-24.9; calculated as weight in kilograms divided by height in meters squared), never smoking, at least 150 minutes per week of moderate to vigorous physical activity, moderate alcohol intake (5 to 15 g/d), high diet quality (upper 40% of Alternate Healthy Eating Index-2010 score), and adequate sleep (7 to 9 h/d). Main Outcomes and Measures: SARS-CoV-2 infection (confirmed by test) and PCC (at least 4 weeks of symptoms) were self-reported on 7 periodic surveys administered from April 2020 to November 2021. Among participants with SARS-CoV-2 infection, the relative risk (RR) of PCC in association with the number of healthy lifestyle factors (0 to 6) was estimated using Poisson regression and adjusting for demographic factors and comorbidities. Results: A total of 1981 women with a positive SARS-CoV-2 test over 19 months of follow-up were documented. Among those participants, mean age was 64.7 years (SD, 4.6; range, 55-75); 97.4% (n = 1929) were White; and 42.8% (n = 848) were active health care workers. Among these, 871 (44.0%) developed PCC. Healthy lifestyle was associated with lower risk of PCC in a dose-dependent manner. Compared with women without any healthy lifestyle factors, those with 5 to 6 had 49% lower risk (RR, 0.51; 95% CI, 0.33-0.78) of PCC. In a model mutually adjusted for all lifestyle factors, BMI and sleep were independently associated with risk of PCC (BMI, 18.5-24.9 vs others, RR, 0.85; 95% CI, 0.73-1.00, P = .046; sleep, 7-9 h/d vs others, RR, 0.83; 95% CI, 0.72-0.95, P = .008). If these associations were causal, 36.0% of PCC cases would have been prevented if all participants had 5 to 6 healthy lifestyle factors (population attributable risk percentage, 36.0%; 95% CI, 14.1%-52.7%). Results were comparable when PCC was defined as symptoms of at least 2-month duration or having ongoing symptoms at the time of PCC assessment. Conclusions and Relevance: In this prospective cohort study, pre-infection healthy lifestyle was associated with a substantially lower risk of PCC. Future research should investigate whether lifestyle interventions may reduce risk of developing PCC or mitigate symptoms among individuals with PCC or possibly other postinfection syndromes.

Phenotype harmonization and cross-study collaboration in GWAS consortia: the GENEVA experience.

Genome-wide association study (GWAS) consortia and collaborations formed to detect genetic loci for common phenotypes or investigate gene-environment (G*E) interactions are increasingly common. While these consortia effectively increase sample size, phenotype heterogeneity across studies represents a major obstacle that limits successful identification of these associations. Investigators are faced with the challenge of how to harmonize previously collected phenotype data obtained using different data collection instruments which cover topics in varying degrees of detail and over diverse time frames. This process has not been described in detail. We describe here some of the strategies and pitfalls associated with combining phenotype data from varying studies. Using the Gene Environment Association Studies (GENEVA) multi-site GWAS consortium as an example, this paper provides an illustration to guide GWAS consortia through the process of phenotype harmonization and describes key issues that arise when sharing data across disparate studies. GENEVA is unusual in the diversity of disease endpoints and so the issues it faces as its participating studies share data will be informative for many collaborations. Phenotype harmonization requires identifying common phenotypes, determining the feasibility of cross-study analysis for each, preparing common definitions, and applying appropriate algorithms. Other issues to be considered include genotyping timeframes, coordination of parallel efforts by other collaborative groups, analytic approaches, and imputation of genotype data. GENEVA's harmonization efforts and policy of promoting data sharing and collaboration, not only within GENEVA but also with outside collaborations, can provide important guidance to ongoing and new consortia.

Demographic and geographic features of exfoliation glaucoma in 2 United States-based prospective cohorts.

PURPOSE: To examine prospectively the association between demographic and geographic factors in relation to exfoliation glaucoma (EG) or exfoliation glaucoma suspect (EGS). DESIGN: Prospective cohort study. PARTICIPANTS: Seventy-eight thousand nine hundred fifty-five women in the Nurses' Health Study and 41 191 men in the Health Professionals Follow-up Study. METHODS: Female and male health professionals were followed prospectively from 1980 through 2008 and from 1986 through 2008, respectively. Eligible participants were 40 years of age or older, did not have EG or EGS at baseline, and reported undergoing eye examinations during follow-up. Information regarding demographic features, lifetime geographic residence, and potential confounders was collected. During follow-up, 348 EG or EGS cases were confirmed with medical record review. The relative risk of EG or EGS in each cohort was estimated separately and the results were pooled with meta-analysis. MAIN OUTCOME MEASURES: Multivariate rate ratios (MVRRs) of EG or EGS and their 95% confidence intervals (CIs). RESULTS: Exfoliation glaucoma or EGS was strongly age related with subjects 75 years of age or older at 46.22-fold (95% CI, 22.77-93.80) increased risk compared with those between 40 and 55 years of age. Although men were 68% less likely to develop EG or EGS than women (MVRR, 0.32; 95% CI, 0.23-0.46), no predisposition to EG or EGS by ancestry, particularly Scandinavian ancestry, emerged. Compared with a lifetime of living in the northern tier of the continental United States, lifetime residence in the middle geographic tier (MVRR, 0.53; 95% CI, 0.40-0.71) and in the southern geographic tier (MVRR, 0.25; 95% CI, 0.09-0.71) was associated with markedly reduced risks of EG or EGS. CONCLUSIONS: In this mainly white cohort from the United States, increasing age and female gender were significant risk factors for EG or EGS; however, Scandinavian heritage was not. Living in the middle or southern regions of the United States relative to living in the northern region was associated with a reduced risk of EG or EGS. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Vigorous Physical Activity and Cognitive Trajectory Later in Life: Prospective Association and Interaction by Apolipoprotein E e4 in the Nurses' Health Study.

BACKGROUND: The apolipoprotein E (APOE) e4 allele is a well-established genetic risk factor of brain aging. Vigorous physical activity may be particularly important in APOE-e4 carriers, but data have been inconsistent, likely due to differences in the timing of the physical activity assessment, definition of cognitive decline, and/or sample size. METHODS: We prospectively evaluated the association between vigorous physical activity and cognition assessed at least 9 years later, according to APOE-e4 carrier status. Biennially from 1986, Nurses' Health Study participants reported their leisure-time physical activities. Starting in 1995-2001 and through 2008, participants (aged 70+ years) underwent up to 4 repeated cognitive telephone assessments (6 tasks averaged together using z-scores). RESULTS: Among 7252 women, latent process mixed models identified 3 major patterns of cognitive change over 6 years: high-stable, medium-stable, and decline. Taking the high-stable cognitive trajectory as the outcome reference in multinomial logistic regressions, highest tertile of vigorous physical activity (≥5.9 metabolic-equivalent [MET]-hours/wk) compared to lowest tertile (≤0.9 MET-hours/wk) was significantly associated with subsequent lower likelihood of the medium-stable trajectory in the global score (odds ratio [OR] [95% CI] = 0.72 [0.63, 0.82]), verbal memory (OR [95% CI] = 0.78 [0.68-0.89]), and telephone interview of cognitive status score (OR [95% CI] = 0.81 [0.70-0.94]). Vigorous physical activity was also associated with lower likelihood of decline in category fluency (OR [95% CI] = 0.72 [0.56, 0.92]). We observed some evidence (p-interaction = .07 for the global score) that the association was stronger among APOE-e4 carriers than noncarriers (OR [95% CI] = 0.60 [0.39, 0.92] vs 0.82 [0.59, 1.16]). CONCLUSION: Midlife vigorous physical activity was associated with better cognitive trajectories in women in their seventies, with suggestions of stronger associations among APOE-e4 carriers.

Associations of Depression, Anxiety, Worry, Perceived Stress, and Loneliness Prior to Infection With Risk of Post-COVID-19 Conditions.

Importance: Few risk factors for long-lasting (≥4 weeks) COVID-19 symptoms have been identified. Objective: To determine whether high levels of psychological distress before SARS-CoV-2 infection, characterized by depression, anxiety, worry, perceived stress, and loneliness, are prospectively associated with increased risk of developing post-COVID-19 conditions (sometimes called long COVID). Design, Setting, and Participants: This prospective cohort study used data from 3 large ongoing, predominantly female cohorts: Nurses' Health Study II, Nurses' Health Study 3, and the Growing Up Today Study. Between April 2020 and November 2021, participants were followed up with periodic surveys. Participants were included if they reported no current or prior SARS-CoV-2 infection at the April 2020 baseline survey when distress was assessed and returned 1 or more follow-up questionnaires. Exposures: Depression, anxiety, worry about COVID-19, perceived stress, and loneliness were measured at study baseline early in the pandemic, before SARS-CoV-2 infection, using validated questionnaires. Main Outcomes and Measures: SARS-CoV-2 infection was self-reported during each of 6 monthly and then quarterly follow-up questionnaires. COVID-19-related symptoms lasting 4 weeks or longer and daily life impairment due to these symptoms were self-reported on the final questionnaire, 1 year after baseline. Results: Of 54 960 participants, 38.0% (n = 20 902) were active health care workers, and 96.6% (n = 53 107) were female; the mean (SD) age was 57.5 (13.8) years. Six percent (3193 participants) reported a positive SARS-CoV-2 test result during follow-up (1-47 weeks after baseline). Among these, probable depression (risk ratio [RR], 1.32; 95% CI = 1.12-1.55), probable anxiety (RR = 1.42; 95% CI, 1.23-1.65), worry about COVID-19 (RR, 1.37; 95% CI, 1.17-1.61), perceived stress (highest vs lowest quartile: RR, 1.46; 95% CI, 1.18-1.81), and loneliness (RR, 1.32; 95% CI, 1.08-1.61) were each associated with post-COVID-19 conditions (1403 cases) in generalized estimating equation models adjusted for sociodemographic factors, health behaviors, and comorbidities. Participants with 2 or more types of distress prior to infection were at nearly 50% increased risk for post-COVID-19 conditions (RR, 1.49; 95% CI, 1.23-1.80). All types of distress were associated with increased risk of daily life impairment (783 cases) among individuals with post-COVID-19 conditions (RR range, 1.15-1.51). Conclusions and Relevance: The findings of this study suggest that preinfection psychological distress may be a risk factor for post-COVID-19 conditions in individuals with SARS-CoV-2 infection. Future work should examine the biobehavioral mechanism linking psychological distress with persistent postinfection symptoms.

Reproductive factors and NOS3 variant interactions in primary open-angle glaucoma.

PURPOSE: To investigate whether associations with the nitric oxide synthase gene (NOS3) variants and risk of primary open-angle glaucoma (POAG) depend on female reproductive factors. METHODS: Two functional and two tagging single nucleotide polymorphisms (SNPs; T-786C: rs2070744, Glu298Asp: rs1799983, rs7830, and rs3918188) were evaluated in a nested case-control study from the Nurses' Health Study (women followed 1980 - 2002). Participants were aged ≥40 years and Caucasian, who were followed biennially with update information on reproductive factors. We included 374 Nurses' Health Study (NHS) cases and 1,085 controls, matched on age and eye exam at the matched cases' diagnosis dates. Relative risks (RRs) were estimated using multivariable conditional logistic regression. RESULTS: Among women with age at menarche <13 years, compared with the CC homozygotes of the rs3918188 tagging SNP, the wild-type AA homozygotes were at significantly reduced risk of POAG (RR=0.31, 95% CI=0.16, 0.59); however, for women with age at menarche ≥13 years, the SNP was not associated with POAG (p-interaction=0.0007). Among parous women with 3+ children, carriers of the minor variant (T) allele of the functional Glu298Asp SNP were at increased risk, while among parous women with 1-2 children, they were not (p-interaction=0.003). No significant interactions between NOS3 SNPs and oral contraceptive use in POAG were detected. CONCLUSIONS: These data provide further support for the notion that NOS3 genotype - female reproductive health interactions are important in POAG pathogenesis.

Vitamin E, vitamin C, beta carotene, and cognitive function among women with or at risk of cardiovascular disease: The Women's Antioxidant and Cardiovascular Study.

BACKGROUND: Cardiovascular factors are associated with cognitive decline. Antioxidants may be beneficial. METHODS AND RESULTS: The Women's Antioxidant Cardiovascular Study was a trial of vitamin E (402 mg every other day), beta carotene (50 mg every other day), and vitamin C (500 mg daily) for the secondary prevention of cardiovascular disease. From 1995 to 1996, women > or =40 years of age with cardiovascular disease or > or =3 coronary risk factors were randomized. From 1998 to 1999, a cognitive function substudy was initiated among 2824 participants > or =65 years of age. With 5 cognitive tests, cognition was assessed by telephone 4 times over 5.4 years. The primary outcome was a global composite score averaging all scores; repeated-measures analyses were used to examine cognitive change over time. Vitamin E supplementation and beta carotene supplementation were not associated with slower rates of cognitive change (mean difference in change for vitamin E versus placebo, -0.01; 95% confidence interval, -0.05 to 0.04; P=0.78; for beta carotene, 0.03; 95% confidence interval, -0.02 to 0.07; P=0.28). Although vitamin C supplementation was associated with better performance at the last assessment (mean difference, 0.13; 95% confidence interval, 0.06 to 0.20; P=0.0005), it was not associated with cognitive change over time (mean difference in change, 0.02; 95% confidence interval, -0.03 to 0.07; P=0.39). Vitamin C was more protective against cognitive change among those with new cardiovascular events during the trial (P for interaction=0.009). CONCLUSIONS: Antioxidant supplementation did not slow cognitive change among women with preexisting cardiovascular disease or cardiovascular disease risk factors. A possible late effect of vitamin C or beta carotene among those with low dietary intake on cognition warrants further study.

Antioxidant intake and risks of rheumatoid arthritis and systemic lupus erythematosus in women.

Antioxidants may protect against development of rheumatoid arthritis or systemic lupus erythematosus by combating oxidative stress. The authors identified and confirmed incident cases of rheumatoid arthritis and systemic lupus erythematosus among 184,643 US women followed in the Nurses' Health Study and Nurses' Health Study II cohorts in 1980-2004. Semiquantitative food frequency questionnaires assessed intakes of vitamins A, C, and E and alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin from foods and supplements. The authors examined total antioxidant intake by calculating a "ferric-reducing ability of plasma" score, a new method for quantifying the total antioxidant effect of a food based on the reduction of ferric to ferrous iron by antioxidants. Cumulative updated total energy-adjusted dietary intakes were used. Associations between intake of each nutrient and incident rheumatoid arthritis and systemic lupus erythematosus were examined in age-adjusted and Cox proportional hazards models, adjusted for confounders. Results from the cohorts were pooled meta-analytically by using random-effects models. The authors identified 787 incident rheumatoid arthritis cases and 192 systemic lupus erythematosus cases for whom prospective dietary information was available. In these large, prospective cohorts of women, antioxidant intake was not associated with the risk of developing either rheumatoid arthritis or systemic lupus erythematosus.

Anthropometric measures and their relation to incident primary open-angle glaucoma.

PURPOSE: To assess the relation between anthropometric measures and incident primary open-angle glaucoma (POAG). DESIGN: Prospective cohort study. PARTICIPANTS: Included were 78,777 women in the Nurses' Health Study and 41,352 men in the Health Professionals Follow-up Study. METHODS: Females and male health professionals were followed prospectively from 1980 through 2004 and 1986 through 2004, respectively. Eligible participants were 40 years of age or older, did not have POAG at baseline, and reported undergoing eye examinations during follow-up. Information regarding anthropometric measures, potential confounders, and ophthalmic status was updated using biennial questionnaires. During follow-up, 980 POAG cases were identified. MAIN OUTCOME MEASURES: Multivariate rate ratios (MVRR) of POAG and their 95% confidence intervals (CIs). RESULTS: There was no significant relation between cumulatively averaged body mass index (BMI) in kilograms per meter squared and POAG overall (P = 0.06, for trend). However, in relation to POAG with intraocular pressure (IOP) of 22 mmHg or less at diagnosis, each unit increase in BMI was associated with a 6% reduced risk in women (MVRR, 0.94; 95% CI, 0.91-0.98; P = 0.01), but not for men (MVRR, 1.02; 95% CI, 0.96-1.09; P = 0.57); this gender difference was significant (P = 0.03, for heterogeneity). In multivariate analyses to explore the independent effects of height and weight, weight (as height-adjusted weight residuals; P = 0.002, for trend), but not height (P = 0.10, for trend) seemed to account for most of the inverse association between BMI and POAG with IOP of 21 mmHg or less at diagnosis in women. There was no association between BMI and POAG with IOP of more than 21 mmHg at diagnosis for either gender (P> or =0.26, for trend). Among women, analyses found that the relations between anthropometric parameters and both POAG subtypes (POAG with IOP< or =21 mmHg vs. POAG with IOP >21 mmHg when diagnosed) were significantly different (P< or =0.0001). CONCLUSIONS: Among women, higher BMI was associated with a lower risk of POAG with IOP of 21 mmHg or less at diagnosis. The factors contributing to this tendency may yield insight into the pathogenesis of POAG.

The COronavirus Pandemic Epidemiology (COPE) Consortium: A Call to Action.

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.

Physical activity levels and cognition in women with type 2 diabetes.

Persons with type 2 diabetes have a high risk of late-life cognitive impairment, and physical activity might be a potential target for modifying this risk. Therefore, the authors evaluated the association between physical activity level and cognition in women with type 2 diabetes. Beginning in 1995-2000, cognitive function was assessed in 1,550 Nurses' Health Study participants aged > or =70 years with type 2 diabetes. Follow-up assessments were completed twice thereafter, at 2-year intervals. Multivariate-adjusted linear regression models were used to obtain mean differences in baseline cognitive scores and cognitive decline across tertiles of long-term physical activity. Initial results from age- and education-adjusted models indicated that greater physical activity levels were associated with better baseline cognition (for a global score averaging scores from 6 cognitive tests, P-trend = 0.02). However, results were substantially attenuated after adjustment for multiple potential confounders, largely because of physical disability indicators (global score: P-trend = 0.06); for example, the mean difference for the global score was 0.07 standard units (95% confidence interval: -0.01, 0.15) when comparing extreme tertiles. Results were similar for cognitive decline. These findings indicate little overall association between physical activity and cognition after adjustment for disability factors in older women with type 2 diabetes.

Effects of moderate alcohol consumption on cognitive function in women.

BACKGROUND: The adverse effects of excess alcohol intake on cognitive function are well established, but the effect of moderate consumption is uncertain. METHODS: Between 1995 and 2001, we evaluated cognitive function in 12,480 participants in the Nurses' Health Study who were 70 to 81 years old, with follow-up assessments in 11,102 two years later. The level of alcohol consumption was ascertained regularly beginning in 1980. We calculated multivariate-adjusted mean cognitive scores and multivariate-adjusted risks of cognitive impairment (defined as the lowest 10 percent of the scores) and a substantial decline in cognitive function over time (defined as a change that was in the worst 10 percent of the distribution of the decline). We also stratified analyses according to the apolipoprotein E genotype in a subgroup of women. RESULTS: After multivariate adjustment, moderate drinkers (those who consumed less than 15.0 g of alcohol per day [about one drink]) had better mean cognitive scores than nondrinkers. Among moderate drinkers, as compared with nondrinkers, the relative risk of impairment was 0.77 on our test of general cognition (95 percent confidence interval, 0.67 to 0.88) and 0.81 on the basis of a global cognitive score combining the results of all tests (95 percent confidence interval, 0.70 to 0.93). The results for cognitive decline were similar; for example, on our test of general cognition, the relative risk of a substantial decline in performance over a two-year period was 0.85 (95 percent confidence interval, 0.74 to 0.98) among moderate drinkers, as compared with nondrinkers. There were no significant associations between higher levels of drinking (15.0 to 30.0 g per day) and the risk of cognitive impairment or decline. There were no significant differences in risks according to the beverage (e.g., wine or beer) and no interaction with the apolipoprotein E genotype. CONCLUSIONS: Our data suggest that in women, up to one drink per day does not impair cognitive function and may actually decrease the risk of cognitive decline.

Caffeine consumption and the risk of primary open-angle glaucoma: a prospective cohort study.

PURPOSE: To investigate whether caffeine, which transiently increases intraocular pressure (IOP) is associated with the risk of primary open-angle glaucoma (POAG). METHODS: A total of 79,120 women from 1980 to 2004 and 42,052 men from 1986 to 2004, who were 40+ years of age, did not have POAG, and reported undergoing eye examinations, were observed. Information on caffeine consumption, potential confounders, and POAG diagnoses were repeatedly updated in validated follow-up questionnaires. One thousand eleven incident POAG cases were confirmed with medical record review. Cohort-specific and pooled analyses across cohorts were conducted to calculate multivariate rate ratios (RRs). RESULTS: Compared with daily intake of less than 150 mg, the pooled multivariate RRs were 1.05 (95% confidence interval [CI], 0.89-1.25) for consumption of 150 to 299 mg/d, 1.19 (95% CI, 0.99-1.43) for 300 to 449 mg/d, 1.13 (95% CI, 0.89-1.43) for 450 to 559 mg/d, and 1.17 (95% CI, 0.90-1.53) for 600+ mg/d (P for trend = 0.11). However, for consumption of five or more cups of caffeinated coffee daily, the RR was 1.61 (95% CI, 1.00-2.59; P for trend = 0.02); tea or caffeinated cola intake were not associated with risk. Greater caffeine intake was more adversely associated with POAG among those reporting a family history of glaucoma, particularly in relation to POAG with elevated IOP (P for trend = 0.0009; P interaction = 0.04). CONCLUSIONS: Overall caffeine intake was not associated with increased risk of POAG. However, in secondary analyses, caffeine appeared to elevate risk of high-tension POAG among those with a family history of glaucoma. This result may be due to chance, but warrants further study.

Fasting insulin levels and cognitive decline in older women without diabetes.

BACKGROUND: Type 2 diabetes has been associated with an increased risk of dementia. To assess possible independent effects of insulin, we investigated the relation of insulin levels to cognitive decline in nondiabetic women. METHODS: Fasting plasma insulin levels were measured in mid-life in 1,416 nondiabetic Nurses' Health Study participants, who also completed cognitive testing that began 10 years later (current age: 70-75 years). Over 4 years, 3 assessments of general cognition, verbal memory, category fluency and attention were administered. Primary outcomes were the Telephone Interview for Cognitive Status (TICS) performance, the global score (average of all tests) and verbal memory (average of verbal recall tests). Linear mixed-effects models were used to calculate the association between insulin and cognitive decline. RESULTS: Higher insulin levels were associated with a faster decline on the TICS and verbal memory. For analysis, batch-specific quartiles of insulin levels were constructed. Compared to the lowest quartile, adjusted differences in the annual rates of decline (with 95% CI values in parentheses) for the second, third and fourth quartiles were: TICS, -0.06 (-0.16, 0.03), -0.14 (-0.24, -0.04), and -0.09 (-0.19, 0.01) points (p trend = 0.04); verbal memory, -0.01 (-0.04, 0.02), -0.05 (-0.08, -0.02), and -0.02 (-0.05, 0.01) units (p trend = 0.02). These associations remained after multivariable adjustment. CONCLUSIONS: Our study provides evidence for a potential role of higher fasting insulin levels in cognitive decline, possibly independent of diabetes.