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1دورية أكاديمية
المؤلفون: Wang, Jingxuan, Hill‐Jarrett, Tanisha, Buto, Peter, Pederson, Annie, Sims, Kendra D, Zimmerman, Scott C, DeVost, Michelle A, Ferguson, Erin, Lacar, Benjamin, Yang, Yulin, Choi, Minhyuk, Caunca, Michelle R, La Joie, Renaud, Chen, Ruijia, Glymour, M Maria, Ackley, Sarah F
المصدر: Human Brain Mapping. 45(4)
مصطلحات موضوعية: Biological Psychology, Cognitive and Computational Psychology, Psychology, Brain Disorders, Neurosciences, Behavioral and Social Science, Basic Behavioral and Social Science, Neurological, Humans, Middle Aged, Brain, Cognition, Hippocampus, Intelligence, Neuroimaging, brain-wide association studies, cognitive aging, intracranial volume correction, reproducibility, structural magnetic resonance imaging, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
الوصف: Most neuroimaging studies linking regional brain volumes with cognition correct for total intracranial volume (ICV), but methods used for this correction differ across studies. It is unknown whether different ICV correction methods yield consistent results. Using a brain-wide association approach in the MRI substudy of UK Biobank (N = 41,964; mean age = 64.5 years), we used regression models to estimate the associations of 58 regional brain volumetric measures with eight cognitive outcomes, comparing no correction and four ICV correction approaches. Approaches evaluated included: no correction; dividing regional volumes by ICV (proportional approach); including ICV as a covariate in the regression (adjustment approach); and regressing the regional volumes against ICV in different normative samples and using calculated residuals to determine associations (residual approach). We used Spearman-rank correlations and two consistency measures to quantify the extent to which associations were inconsistent across ICV correction approaches for each possible brain region and cognitive outcome pair across 2320 regression models. When the association between brain volume and cognitive performance was close to null, all approaches produced similar estimates close to the null. When associations between a regional volume and cognitive test were not null, the adjustment and residual approaches typically produced similar estimates, but these estimates were inconsistent with results from the crude and proportional approaches. For example, when using the crude approach, an increase of 0.114 (95% confidence interval [CI]: 0.103-0.125) in fluid intelligence was associated with each unit increase in hippocampal volume. However, when using the adjustment approach, the increase was 0.055 (95% CI: 0.043-0.068), while the proportional approach showed a decrease of -0.025 (95% CI: -0.035 to -0.014). Different commonly used methods to correct for ICV yielded inconsistent results. The proportional method diverges notably from other methods and results were sometimes biologically implausible. A simple regression adjustment for ICV produced biologically plausible associations.
وصف الملف: application/pdf
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2دورية أكاديمية
المؤلفون: Shaw, Crystal, Wu, Yingyan, Zimmerman, Scott C, Hayes-Larson, Eleanor, Belin, Thomas R, Power, Melinda C, Glymour, M Maria, Mayeda, Elizabeth Rose
المصدر: American Journal of Epidemiology. 192(12)
مصطلحات موضوعية: Epidemiology, Public Health, Health Sciences, Mental Health, Aging, Depression, Health Disparities, Minority Health, Mental Illness, Brain Disorders, Generic health relevance, Good Health and Well Being, Humans, Data Interpretation, Statistical, Proportional Hazards Models, Research Design, Linear Models, Bias, Computer Simulation, fully conditional specification, Health and Retirement Study, joint modeling, longitudinal data, missing not at random, multiple imputation, multiple imputation by chained equations, predictive mean matching, Mathematical Sciences, Medical and Health Sciences
الوصف: Incomplete longitudinal data are common in life-course epidemiology and may induce bias leading to incorrect inference. Multiple imputation (MI) is increasingly preferred for handling missing data, but few studies explore MI-method performance and feasibility in real-data settings. We compared 3 MI methods using real data under 9 missing-data scenarios, representing combinations of 10%, 20%, and 30% missingness and missing completely at random, at random, and not at random. Using data from Health and Retirement Study (HRS) participants, we introduced record-level missingness to a sample of participants with complete data on depressive symptoms (1998-2008), mortality (2008-2018), and relevant covariates. We then imputed missing data using 3 MI methods (normal linear regression, predictive mean matching, variable-tailored specification), and fitted Cox proportional hazards models to estimate effects of 4 operationalizations of longitudinal depressive symptoms on mortality. We compared bias in hazard ratios, root mean square error, and computation time for each method. Bias was similar across MI methods, and results were consistent across operationalizations of the longitudinal exposure variable. However, our results suggest that predictive mean matching may be an appealing strategy for imputing life-course exposure data, given consistently low root mean square error, competitive computation times, and few implementation challenges.
وصف الملف: application/pdf
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3دورية أكاديمية
المؤلفون: Ackley, Sarah F, Zimmerman, Scott C, Flatt, Jason D, Riley, Alicia R, Sevelius, Jae, Duchowny, Kate A
المصدر: Proceedings of the National Academy of Sciences of the United States of America. 120(18)
مصطلحات موضوعية: Gender Studies, Human Society, Sexual and Gender Minorities (SGM/LGBT*), Behavioral and Social Science, Male, Female, Infant, Newborn, Humans, Transgender Persons, Self Report, Biological Specimen Banks, Disorders of Sex Development, Data Collection, United Kingdom, Gender Identity, transgender research, inclusive research methods, health surveys
الوصف: There is growing need to distinguish between sex and gender. While sex is assigned at birth, gender is socially constructed and may not correspond to one's assigned sex. However, in most research studies, sex or gender is assessed in isolation or the terms are used interchangeably, which has implications for research accuracy and inclusivity. We used data from the UK Biobank to quantify the prevalence of disagreement between chromosomal and self-reported sex and identify potential reasons for discordance. Among approximately 200 individuals with sex discordance, 71% of discordances were potentially explained by the presence of intersex traits or transgender identity. The findings indicate that when describing sex- and/or gender-specific differences in health, researchers may be limited in their ability to draw conclusions regarding specific sex and/or gender health information.
وصف الملف: application/pdf
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4دورية أكاديمية
المؤلفون: Calmasini, Camilla, Swinnerton, Kaitlin N, Zimmerman, Scott C, Peterson, Rachel L, George, Kristen M, Gilsanz, Paola, Hayes-Larson, Eleanor, Mayeda, Elizabeth Rose, Mungas, Dan M, Whitmer, Rachel A, Glymour, Medellena Maria
المصدر: Journal of Geriatric Psychiatry and Neurology. 35(6)
مصطلحات موضوعية: Biological Psychology, Psychology, Dementia, Neurosciences, Basic Behavioral and Social Science, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Aging, Minority Health, Brain Disorders, Health Disparities, Acquired Cognitive Impairment, Behavioral and Social Science, Alzheimer's Disease, Mental Health, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Aged, Humans, Cognition, Ethnicity, Healthy Aging, Life Change Events, California, Social Integration, social integration, cognition, racial/ethnic disparities, Clinical Sciences, Geriatrics, Clinical sciences, Biological psychology
الوصف: We evaluated overall and race-specific relationships between social integration and cognition in older adults. Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort participants included 1343 Asian, Black, Latino, or non-Latino White Kaiser Permanente Northern California members. We estimated the effect of social integration on verbal episodic memory, semantic memory, and executive function derived from the Spanish and English Neuropsychological Assessment (SENAS) Scales. Social integration scores included marital status; volunteer activity; and contact with children, relatives, friends, and confidants. We estimated covariate-adjusted linear mixed-effects models for baseline and 17-month follow-up cognition. Social integration was associated with higher baseline cognitive scores (average β = 0.066 (95% confidence interval: 0.040, 0.092)) overall and in each racial/ethnic group. The association did not vary by race/ethnicity. Social integration was not associated with the estimated rate of cognitive change. In this cohort, more social integration was similarly associated with better late-life cognition across racial/ethnic groups.
وصف الملف: application/pdf
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5دورية أكاديمية
المؤلفون: Hayes-Larson, Eleanor, Shaw, Crystal, Ackley, Sarah F, Zimmerman, Scott C, Glymour, M Maria, Graff, Rebecca E, Witte, John S, Kobayashi, Lindsay C, Mayeda, Elizabeth Rose
المصدر: The Journals of Gerontology Series A. 77(6)
مصطلحات موضوعية: Dementia, Breast Cancer, Prostate Cancer, Aging, Acquired Cognitive Impairment, Prevention, Cancer, Brain Disorders, Lung Cancer, Lung, Neurological, Good Health and Well Being, Cohort Studies, Delayed Diagnosis, Humans, Incidence, Lung Neoplasms, Male, Alzheimer's disease, Bias, Markov model, Neoplasm, Simulation study, Alzheimer’s disease, Clinical Sciences, Gerontology
الوصف: BackgroundCancer is inversely associated with dementia. Using simulations, we examined whether this inverse association may be explained by dementia diagnosis timing, including death before dementia diagnosis and differential diagnosis patterns by cancer history.MethodsWe used multistate Markov simulation models to generate cohorts 65 years of age and free of cancer and dementia at baseline; follow-up for incident cancer (all cancers, breast, prostate, and lung cancer), dementia, dementia diagnosis among those with dementia, and death occurred monthly over 30 years. Models specified no true effect of cancer on dementia, and used age-specific transition rates calibrated to U.S. population and cohort data. We varied the average lapse between dementia onset and diagnosis, including nondifferential and differential delays by cancer history, and examined observed incidence rate ratios (IRRs) for the effect of cancer on dementia diagnosis.ResultsNondifferential dementia diagnosis delay introduced minimal bias (IRRs = 0.98-1.02) for all cancer, breast, and prostate models and substantial bias (IRR = 0.78) in lung cancer models. For the differential dementia diagnosis delay model of all cancer types combined, simulation scenarios with ≥20% lower dementia diagnosis rate (additional 4.5-month delay) in those with cancer history versus without yielded results consistent with literature estimates. Longer dementia diagnosis delays in those with cancer and higher mortality in those with cancer and dementia yielded more bias.ConclusionsDelays in dementia diagnosis may play a role in the inverse cancer-dementia relationship, especially for more fatal cancers, but moderate differential delays in those with cancer were needed to fully explain the literature-reported IRRs.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/7cd5f4m3Test
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6دورية أكاديمية
المؤلفون: Buto, Peter T., Wang, Jingxuan, La Joie, Renaud, Zimmerman, Scott C., Glymour, M. Maria, Ackley, Sarah F., Hoffmann, Thomas J., Yaffe, Kristine, Zeki Al Hazzouri, Adina, Brenowitz, Willa D.
المصدر: Alzheimer's & Dementia ; volume 20, issue 3, page 1978-1987 ; ISSN 1552-5260 1552-5279
الوصف: INTRODUCTION We estimated the ages when associations between Alzheimer's disease (AD) genes and brain volumes begin among middle‐aged and older adults. METHODS Among 45,616 dementia‐free participants aged 45–80, linear regressions tested whether genetic risk score for AD (AD‐GRS) had age‐dependent associations with 38 regional brain magnetic resonance imaging volumes. Models were adjusted for sex, assessment center, genetic ancestry, and intracranial volume. RESULTS AD‐GRS modified the estimated effect of age (per decade) on the amygdala (−0.41 mm 3 [−0.42, −0.40]); hippocampus (−0.45 mm 3 [−0.45, −0.44]), nucleus accumbens (−0.55 mm 3 [−0.56, −0.54]), thalamus (−0.38 mm 3 [−0.39, −0.37]), and medial orbitofrontal cortex (−0.23 mm 3 [−0.24, −0.22]). Trends began by age 45 for the nucleus accumbens and thalamus, 48 for the hippocampus, 51 for the amygdala, and 53 for the medial orbitofrontal cortex. An AD‐GRS excluding apolipoprotein E ( APOE ) was additionally associated with entorhinal and middle temporal cortices. DISCUSSION APOE and other genes that increase AD risk predict lower hippocampal and other brain volumes by middle age.
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7دورية أكاديمية
المؤلفون: Brenowitz, Willa D, Zimmerman, Scott C, Filshtein, Teresa J, Yaffe, Kristine, Walter, Stefan, Hoffmann, Thomas J, Jorgenson, Eric, Whitmer, Rachel A, Glymour, M Maria
المصدر: American Journal of Epidemiology. 190(10)
مصطلحات موضوعية: Epidemiology, Health Services and Systems, Health Sciences, Prevention, Dementia, Nutrition, Aging, Acquired Cognitive Impairment, Brain Disorders, Neurosciences, Alzheimer's Disease, Genetics, Obesity, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aetiology, 2.1 Biological and endogenous factors, Neurological, Adult, Aged, Alzheimer Disease, Body Mass Index, Causality, Female, Genetic Predisposition to Disease, Humans, Linear Models, Male, Mendelian Randomization Analysis, Middle Aged, Risk Factors, United Kingdom, Weight Loss, White People, Alzheimer disease, body mass index, disease natural history, Mendelian randomization, Mathematical Sciences, Medical and Health Sciences
الوصف: Weight loss or lower body mass index (BMI) could be an early symptom of Alzheimer disease (AD), but when this begins to emerge is difficult to estimate with traditional observational data. In an extension of Mendelian randomization, we leveraged variation in genetic risk for late-onset AD risk to estimate the causal effect of AD on BMI and the earliest ages at which AD-related weight loss (or lower BMI as a proxy) occurs. We studied UK Biobank participants enrolled in 2006-2010, who were without dementia, aged 39-73, with European genetic ancestry. BMI was calculated with measured height/weight (weight (kg)/height (m)2). An AD genetic risk score (AD-GRS) was calculated based on 23 genetic variants. Using linear regressions, we tested the association of AD-GRS with BMI, stratified by decade, and calculated the age of divergence in BMI trends between low and high AD-GRS. AD-GRS was not associated with BMI in 39- to 49-year-olds (β = 0.00, 95% confidence interval (CI): -0.03, 0.03). AD-GRS was associated with lower BMI in 50- to 59-year-olds (β = -0.03, 95% CI: -0.06, -0.01) and 60- to 73-year-olds (β = -0.09, 95% CI:-0.12, -0.07). Model-based BMI age curves for high versus low AD-GRS began to diverge after age 47 years. Sensitivity analyses found no evidence for pleiotropy or survival bias. Longitudinal replication is needed; however, our findings suggest that AD genes might begin to reduce BMI decades prior to dementia diagnosis.
وصف الملف: application/pdf
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8دورية أكاديمية
المؤلفون: Hayes‐Larson, Eleanor, Ackley, Sarah F, Zimmerman, Scott C, Ospina‐Romero, Monica, Glymour, M Maria, Graff, Rebecca E, Witte, John S, Kobayashi, Lindsay C, Mayeda, Elizabeth Rose
المصدر: Alzheimer's & Dementia. 16(12)
مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Clinical Research, Brain Disorders, Acquired Cognitive Impairment, Aging, Cancer, Dementia, Prevention, Good Health and Well Being, Aged, Bias, Cohort Studies, Computer Simulation, Female, Humans, Incidence, Male, Neoplasms, Prevalence, Risk Factors, Alzheimer's disease, cancer, competing risks, dementia, selection bias, simulation, Clinical Sciences, Neurosciences, Geriatrics, Clinical sciences, Biological psychology
الوصف: IntroductionWe evaluated whether competing risk of death or selective survival could explain the reported inverse association between cancer history and dementia incidence (incidence rate ratio [IRR] ≈ 0.62-0.85).MethodsA multistate simulation model of a cancer- and dementia-free cohort of 65-year-olds was parameterized with real-world data (cancer and dementia incidence, mortality), assuming no effect of cancer on dementia (true IRR = 1.00). To introduce competing risk of death, cancer history increased mortality. To introduce selective survival, we included a factor (prevalence ranging from 10% to 50%) that reduced cancer mortality and dementia incidence (IRRs ranged from 0.30 to 0.90). We calculated IRRs for cancer history on dementia incidence in the simulated cohorts.ResultsCompeting risk of death yielded unbiased cancer-dementia IRRs. With selective survival, bias was small (IRRs = 0.89 to 0.99), even under extreme scenarios.DiscussionThe bias induced by selective survival in simulations was too small to explain the observed inverse cancer-dementia link, suggesting other mechanisms drive this association.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/0887q3r7Test
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9دورية أكاديمية
المؤلفون: Goin, Dana E, M Gomez, Anu, Farkas, Kriszta, Zimmerman, Scott C, Matthay, Ellicott C, Ahern, Jennifer
المصدر: Epidemiology. 30(5)
مصطلحات موضوعية: Epidemiology, Public Health, Health Sciences, Clinical Research, Infant Mortality, Mental Health, Prevention, Perinatal Period - Conditions Originating in Perinatal Period, Pediatric, Preterm, Low Birth Weight and Health of the Newborn, Reproductive health and childbirth, Peace, Justice and Strong Institutions, Adult, California, Case-Control Studies, Female, Fetal Growth Retardation, Homicide, Humans, Infant, Newborn, Infant, Small for Gestational Age, Male, Maternal Exposure, Pregnancy, Pregnancy Outcome, Premature Birth, Regression Analysis, Risk Factors, Stress, Psychological, Premature birth, Small for gestational age, Violence, Statistics, Public Health and Health Services, Public health
الوصف: BackgroundCommunity violence is an understudied aspect of social context that may affect risk of preterm birth and small-for-gestational age (SGA).MethodsWe matched California mothers with live singleton births who were exposed to a homicide in their Census tract of residence in 2007-2011 to unexposed mothers within the same tract. We estimated risk differences with a weighted linear probability model, with weights corresponding to the matched data structure. We estimated the average treatment effect on the treated of homicide exposure on the risk of preterm birth and SGA during the preconception period and first and second trimester.ResultsWe found a small increase in risk of SGA associated with homicide exposure in the first trimester (0.14% [95% confidence interval (CI) = -0.01%, 0.30%]), but not for exposure during the preconception period (-0.01% [95% CI = -0.17%, 0.15%]) or the second trimester (-0.06% [95% CI = -0.23%, 0.11%]). Risk of preterm birth was not affected by homicide exposure. When women were exposed to homicides during all three exposure windows, there was a larger increase in risk of SGA (1.09% [95% CI = 0.15%, 2.03%]) but not preterm birth (0.14% [95% CI = -0.74%, 1.01%]). Exposure to three or more homicides was also associated with greater risk of SGA (0.78% [95% CI = 0.15%, 1.40%]). Negative controls indicated that residual confounding by temporal patterning was unlikely.ConclusionsHomicide exposure during early pregnancy is associated with a small increased risk of SGA.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/6w94j22tTest
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10دورية أكاديمية
المؤلفون: Wang, Jingxuan, Sims, Kendra D., Ackley, Sarah F., Chen, Ruijia, Kobayashi, Lindsay C., Hayes‐Larson, Eleanor, Mayeda, Elizabeth Rose, Buto, Peter, Zimmerman, Scott C., Graff, Rebecca E., Glymour, M. Maria
المساهمون: National Institute on Aging
المصدر: Alzheimer's & Dementia ; volume 20, issue 2, page 880-889 ; ISSN 1552-5260 1552-5279
الوصف: INTRODUCTION Cancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD). METHODS In the UK Biobank, we investigated associations between cancer history and five structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed‐effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution of MRI markers. RESULTS Cancer history was associated with smaller mean hippocampal volume ( b = ‐19 mm 3 , 95% CI = ‐36, ‐1) and lower mean cortical thickness in the Alzheimer's disease signature region ( b = ‐0.004 mm, 95% CI = ‐0.007, ‐0.000). Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history. DISCUSSION Some brain MRI markers associated with ADRD risk were elevated in adults with a history of cancer. The magnitude of the adverse associations varied across quantiles of neuroimaging markers, and the pattern suggests possible harmful associations for individuals already at high ADRD risk. Highlights We found no evidence of an inverse association between cancer history and ADRD‐related neurodegeneration. Cancer history was associated with smaller mean hippocampal volume and lower mean cortical thickness in the Alzheimer's disease signature region. Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.
