@article {12159, title = {Does a Cancer Diagnosis in Mid-to-Later Life Modify Racial Disparities in Memory Aging?}, journal = {Alzheimer Disease \& Associated Disorders}, volume = {36}, year = {2022}, pages = {140-147}, abstract = {

BACKGROUND: It is unknown whether an incident cancer diagnosis differentially impacts acute and long-term memory aging between older White and Black Americans.

METHODS: Incident cancer diagnoses and memory (immediate and delayed recall, combined with proxy-reported memory) were assessed at biennial study interviews in the US Health and Retirement Study (N=14,235, 1998-2016). We used multivariable segmented linear mixed-effects models to evaluate the rate of change in standardized memory score (SD/decade) in the years before, acutely at the time of, and in the years following an incident cancer diagnosis, compared to cancer-free adults, by race.

RESULTS: Black participants experienced faster memory decline than White participants (cancer-free group: -1.211 vs. -1.077; P<0.0001). An incident cancer diagnosis was associated with an acute memory drop in White, but not Black participants (-0.065 vs. 0.024; P<0.0001). However, White cancer survivors experienced slower memory decline than cancer-free White adults before and after diagnosis, but this memory advantage was not observed among Black cancer survivors.

CONCLUSIONS: Racial disparities in memory aging are not modified by an incident cancer diagnosis. The acute cancer-related memory decline and long-term memory advantage experienced by White, but not Black, cancer survivors relative to cancer-free older adults, requires further investigation.

}, keywords = {cancer diagnosis, Memory, Racial Disparities}, issn = {1546-4156}, doi = {10.1097/WAD.0000000000000493}, author = {Eastman, Marisa R and Ospina-Romero, Monica and Westrick, Ashly C and Jasdeep S Kler and M. Maria Glymour and Abdiwahab, Ekland and Lindsay C Kobayashi} } @article {12004, title = {Explaining the variance in cardiovascular disease risk factors: A comparison of demographic, socioeconomic, and genetic predictors.}, journal = {Epidemiology}, volume = {33}, year = {2022}, pages = {25-33}, abstract = {

BACKGROUND: Efforts to explain the burden of cardiovascular disease (CVD) often focus on genetic factors or social determinants of health. There is little evidence on the comparative predictive value of each, which could guide clinical and public health investments in measuring genetic versus social information. We compared the variance in CVD-related outcomes explained by genetic versus socioeconomic predictors.

METHODS: Data were drawn from the Health and Retirement Study (N=8,720). We examined self-reported diabetes, heart disease, depression, smoking, and body mass index, and objectively measured total and high-density lipoprotein cholesterol. For each outcome, we compared the variance explained by demographic characteristics, socioeconomic position (SEP), and genetic characteristics including a polygenic score for each outcome and principal components (PCs) for genetic ancestry. We used R-squared values derived from race-stratified multivariable linear regressions to evaluate the variance explained.

RESULTS: The variance explained by models including all predictors ranged from 3.7\% to 14.3\%. Demographic characteristics explained more than half this variance for most outcomes. SEP explained comparable or greater variance relative to the combination of the polygenic score and PCs for most conditions among both white and Black participants. The combination of SEP, polygenic score, and PCs performed substantially better, suggesting that each set of characteristics may independently contribute to prediction of CVD related outcomes.

CONCLUSIONS: Focusing on genetic inputs into personalized medicine predictive models, without considering measures of social context that have clear predictive value, needlessly ignores relevant information that is more feasible and affordable to collect on patients in clinical settings.

}, keywords = {Cardiovascular disease, Demographics, Genetics, Risk Factors, socioeconomics}, issn = {1531-5487}, doi = {10.1097/EDE.0000000000001425}, author = {Hamad, Rita and M. Maria Glymour and Calmasini, Camilla and Thu T Nguyen and Stefan Walter and David Rehkopf} } @article {11186, title = {The Association Between Cancer and Spousal Rate of Memory Decline: A Negative Control Study to Evaluate (Unmeasured) Social Confounding of the Cancer-memory Relationship.}, journal = {Alzheimer Disease \& Associated Disorders}, volume = {35}, year = {2021}, pages = {271-274}, abstract = {

Cancer diagnoses are associated with better long-term memory in older adults, possibly reflecting a range of social confounders that increase cancer risk but improve memory. We used spouse{\textquoteright}s memory as a negative control outcome to evaluate this possible confounding, since spouses share social characteristics and environments, and individuals{\textquoteright} cancers are unlikely to cause better memory among their spouses. We estimated the association of an individual{\textquoteright}s incident cancer diagnosis (exposure) with their own (primary outcome) and their spouse{\textquoteright}s (negative control outcome) memory decline in 3601 couples from 1998 to 2014 in the Health and Retirement Study, using linear mixed-effects models. Incident cancer predicted better long-term memory for the diagnosed individual. We observed no association between an individual{\textquoteright}s cancer diagnosis and rate of spousal memory decline. This negative control study suggests that the inverse association between incident cancer and rate of memory decline is unlikely to be attributable to social/behavioral factors shared between spouses.

}, keywords = {Cancer, Cognition, Spouses}, issn = {1546-4156}, doi = {10.1097/WAD.0000000000000398}, author = {Ospina-Romero, Monica and Willa D Brenowitz and M. Maria Glymour and Elizabeth R Mayeda and Graff, Rebecca E and Witte, John S and Ackley, Sarah F and Lu, Kun Ping and Lindsay C Kobayashi} } @article {11622, title = {Association of Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention With Memory Decline in Older Adults Undergoing Coronary Revascularization}, journal = {JAMA}, volume = {325}, year = {2021}, pages = {1955-1964}, abstract = {It is uncertain whether coronary artery bypass grafting (CABG) is associated with cognitive decline in older adults compared with a nonsurgical method of coronary revascularization (percutaneous coronary intervention [PCI]).To compare the change in the rate of memory decline after CABG vs PCI.Retrospective cohort study of community-dwelling participants in the Health and Retirement Study, who underwent CABG or PCI between 1998 and 2015 at age 65 years or older. Data were modeled for up to 5 years preceding and 10 years following revascularization or until death, drop out, or the 2016-2017 interview wave. The date of final follow-up was November 2017.CABG (including on and off pump) or PCI, ascertained from Medicare fee-for-service billing records.The primary outcome was a summary measure of cognitive test scores and proxy cognition reports that were performed biennially in the Health and Retirement Study, referred to as memory score, normalized as a z score (ie, mean of 0, SD of 1 in a reference population of adults aged >=72 years). Memory score was analyzed using multivariable linear mixed-effects models, with a prespecified subgroup analysis of on-pump and off-pump CABG. The minimum clinically important difference was a change of 1 SD of the population-level rate of memory decline (0.048 memory units/y).Of 1680 participants (mean age at procedure, 75 years; 41\% female), 665 underwent CABG (168 off pump) and 1015 underwent PCI. In the PCI group, the mean rate of memory decline was 0.064 memory units/y (95\% CI, 0.052 to 0.078) before the procedure and 0.060 memory units/y (95\% CI, 0.048 to 0.071) after the procedure (within-group change, 0.004 memory units/y [95\% CI, -0.010 to 0.018]). In the CABG group, the mean rate of memory decline was 0.049 memory units/y (95\% CI, 0.033 to 0.065) before the procedure and 0.059 memory units/y (95\% CI, 0.047 to 0.072) after the procedure (within-group change, -0.011 memory units/y [95\% CI, -0.029 to 0.008]). The between-group difference-in-differences estimate for memory decline for PCI vs CABG was 0.015 memory units/y (95\% CI, -0.008 to 0.038; P = .21). There was statistically significant increase in the rate of memory decline after off-pump CABG compared with after PCI (difference-in-differences: mean increase in the rate of decline of 0.046 memory units/y [95\% CI, 0.008 to 0.084] after off-pump CABG), but not after on-pump CABG compared with PCI (difference-in-differences: mean slowing of decline of 0.003 memory units/y [95\% CI, -0.024 to 0.031] after on-pump CABG).Among older adults undergoing coronary revascularization with CABG or PCI, the type of revascularization procedure was not significantly associated with differences in the change of rate of memory decline.}, keywords = {cardiology, cardiothoracic surgery, ischemic heart disease}, isbn = {0098-7484}, doi = {10.1001/jama.2021.5150}, author = {Elizabeth L Whitlock and L Grisell Diaz-Ramirez and Alexander K Smith and W John Boscardin and Kenneth E Covinsky and Michael S. Avidan and M. Maria Glymour} } @article {11824, title = {Estimating the effects of Mexico to U.S. migration on elevated depressive symptoms: evidence from pooled cross-national cohorts.}, journal = {Annals of Epidemiology}, volume = {64}, year = {2021}, pages = {53-66}, abstract = {

BACKGROUND: Migrating from Mexico to the U.S. is a major, stressful life event with potentially profound influences on mental health. However, estimating the health effects of migration is challenging because of differential selection into migration and time-varying confounder mediators of migration effects on health.

METHODS: We pooled data from the Mexican Health and Aging Study (N=17,771) and Mexican-born U.S. Health and Retirement Study (N=898) participants to evaluate the effects of migration to the U.S. (at any age and in models for migration in childhood or adulthood) on depressive symptom-count, measured with a modified Centers for Epidemiologic Studies-Depression scale. We modeled probability of migrating in each year of life from birth to either age at initial migration to the U.S. or enrollment and used these models to calculate inverse probability of migration weights. We applied the weights to covariate-adjusted negative binomial GEE models, estimating the ratio of average symptom-count associated with migration.

RESULTS: Mexico to U.S. migration was unrelated to depressive symptoms among men (ratio of average symptom-count= 0.98 [95\% CI: 0.89, 1.08]) and women (ratio of average symptom-count=1.00 [95\% CI: 0.92, 1.09]). Results were similar for migration in childhood, early adulthood, or later adulthood.

CONCLUSIONS: In this sample of older Mexican-born adults, migration to the U.S. was unrelated to depressive symptoms.

}, keywords = {depression, Immigration, Mental Health, MHAS, Selection}, issn = {1873-2585}, doi = {10.1016/j.annepidem.2021.08.014}, author = {Audrey R Murchland and Adina Zeki Al Hazzouri and Zhang, Lanyu and Elfassy, Tali and Grasset, Leslie and Riley, Alicia and Wong, Rebecca and Mary Haan and Richard N Jones and Jacqueline M Torres and M. Maria Glymour} } @article {11268, title = {Quantifying Lifecourse Drivers of International Migration: A Cross-national Analysis of Mexico and the United States.}, journal = {Epidemiology}, volume = {32}, year = {2021}, pages = {50-60}, abstract = {

BACKGROUND: Evaluating the long-term health consequences of migration requires longitudinal data on migrants and non-migrants to facilitate adjustment for time-varying confounder-mediators of the effect of migration on health.

METHODS: We merged harmonized data on subjects aged 50+ from the US-based Health and Retirement Study (HRS) and the Mexican Health and Aging Study (MHAS). Our exposed group includes MHAS-return migrants (n = 1555) and HRS Mexican-born migrants (n = 924). Our unexposed group includes MHAS-never migrants (n = 16,954). We constructed a lifecourse data set from birth (age 0) until either age at migration to the United States or age at study entry. To account for confounding via inverse probability of treatment weights (IPTW), we modeled the probability of migration at each year of life using time-varying pre-migration characteristics. We then evaluated the effect of migration on mortality hazard estimated with and without IPTW.

RESULTS: Mexico to the United States migration was predicted by time-varying factors that occurred before migration. Using measured covariates at time of enrollment to account for selective migration, we estimated that, for women, migrating reduces mortality risk by 13\%, although this estimate was imprecise and results were compatible with either large protective or deleterious associations (hazard ratio [HR] =0.87, 95\% confidence interval [CI]: 0.60, 1.27). When instead using IPTWs, the estimated effect on mortality was similarly imprecise (HR = 0.98, 95\% CI: 0.77, 1.25). The relationship among men was similarly uncertain in both models.

CONCLUSIONS: Although time-varying social factors predicted migration, IPTW weighting did not affect our estimates. Larger samples are needed to precisely estimate the health effects of migration.

}, keywords = {long-term health consequences, MHAS, migrants}, issn = {1531-5487}, doi = {10.1097/EDE.0000000000001266}, author = {Adina Zeki Al Hazzouri and Zhang, Lanyu and Audrey R Murchland and Grasset, Leslie and Jacqueline M Torres and Richard N Jones and Rebeca Wong and M. Maria Glymour} } @article {11518, title = {Temporal Trends in Stroke-Related Memory Change: Results From a US National Cohort 1998-2016.}, journal = {Stroke}, volume = {52}, year = {2021}, pages = {1702-1711}, abstract = {

BACKGROUND AND PURPOSE: Findings from the Framingham Heart Study suggest that declines in dementia incidence rates over recent decades are partially due to decreases in stroke incidence and mortality; however, whether trends of declining dementia rates extend to survivors of incident stroke remains unclear. We investigated evidence for temporal trends in memory change related to incident stroke in a nationally representative cohort.

METHODS: Adults age 50+ in the HRS (Health and Retirement Study) were followed across three successive 6-year epochs (epoch 1: 1998-2004, n=16 781; epoch 2: 2004-2010, n=15 345; and epoch 3: 2010-2016; n=15 949). Participants were included in an epoch if they were stroke-free at the start of that epoch. Annual rates of change in a composite z-standardized memory score were compared using demographic-adjusted linear regression models for stroke-free participants, those who survived after stroke, and those who died after stroke, considering memory change before stroke, at the time of stroke, and for years following stroke.

RESULTS: Crude stroke incidence rates decreased from 8.5 per 1000 person-years in epoch 1 to 6.8 per 1000 person-years in epoch 3. Rates of memory change before and following stroke onset were similar across epochs. Memory decrement immediately after stroke onset attenuated from -0.37 points (95\% CI, -0.44 to -0.29) in epoch 1 to -0.26 (95\% CI, -0.33 to -0.18) points in epoch 2 and -0.25 (95\% CI, -0.33 to -0.17) points in epoch 3 ( value for linear trend=0.02).

CONCLUSIONS: Decreases in stroke-related dementia in recent years may be partially attributable to smaller memory decrements immediately after stroke onset. Findings suggest reductions in stroke incidence and improvements in stroke care may also reduce population burden of dementia. Further investigations into whether temporal trends are attributable to improvements in stroke care are needed.

}, keywords = {Dementia, Incidence, Memory, Survivors}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.120.031063}, author = {Chloe W Eng and Elizabeth R Mayeda and Paola Gilsanz and Rachel A Whitmer and Kim, Anthony S and M. Maria Glymour} } @article {9916, title = {Cognitive Change After Cardiac Surgery Versus Cardiac Catheterization: A Population-Based Study.}, journal = {The Annals of Thoracic Surgergy}, volume = {107}, year = {2019}, pages = {1119-1125}, abstract = {

BACKGROUND: Despite concern that cardiac surgery may adversely affect cognition, little evidence is available from population-based studies using presurgery data. With the use of the Health and Retirement Study, we compared memory change after participant-reported cardiac catheterization or cardiac surgery.

METHODS: Participants were community-dwelling adults aged 65 years and older who self-reported cardiac catheterization or "heart surgery" at any biennial Health and Retirement Study interview between 2000 and 2014. Participants may have undergone the index procedure any time in the preceding 2 years. We modeled preprocedure to postprocedure change in composite memory score, derived from objective memory testing, using linear mixed effects models. We modeled postprocedure subjective memory decline with logistic regression. To quantify clinical relevance, we used the predicted memory change to estimate impact on ability to manage medications and finances independently.

RESULTS: Of 3,105 participants, 1,921 (62\%) underwent catheterization and 1,184 (38\%) underwent operation. In adjusted analyses, surgery participants had little difference in preprocedure to postprocedure memory change compared with participants undergoing cardiac catheterization (-0.021 memory units; 95\% confidence interval:~-0.046 to 0.005 memory units, p~= 0.12). If the relationship were causal, the point estimate for memory decline would confer an absolute 0.26\% or 0.19\% decrease in ability to manage finances or medications, respectively, corresponding to 4.6 additional months of cognitive aging. Cardiac surgery was not associated with subjective memory decline (adjusted odds ratio 0.93, 95\% confidence interval: 0.74 to 1.18).

CONCLUSIONS: In this large, population-based cohort, memory declines after heart surgery and cardiac catheterization were similar. These findings suggest intermediate-term population-level adverse cognitive effects of cardiac surgery, if any, are likely subtle.

}, keywords = {Cardiac surgery, Cardiovascular disease, Cognition \& Reasoning, Memory}, issn = {1552-6259}, doi = {10.1016/j.athoracsur.2018.10.021}, author = {Elizabeth L Whitlock and L Grisell Diaz-Ramirez and Alexander K Smith and W John Boscardin and Michael S. Avidan and M. Maria Glymour} } @article {9926, title = {Comparison of methods for algorithmic classification of dementia status in the Health and Retirement Study.}, journal = {Epidemiology}, volume = {30}, year = {2019}, pages = {291-302}, abstract = {

BACKGROUND: Dementia ascertainment is time-consuming and costly. Several algorithms use existing data from the U.S.-representative Health and Retirement Study (HRS) to algorithmically identify dementia. However, relative performance of these algorithms remains unknown.

METHODS: We compared performance across five algorithms (Herzog-Wallace, Langa-Kabeto-Weir, Crimmins, Hurd, Wu) overall and within sociodemographic subgroups in participants in HRS and Wave A of the Aging, Demographics, and Memory Study (ADAMS, 2000-2002), an HRS sub-study including in-person dementia ascertainment. We then compared algorithmic performance in an internal (time-split) validation dataset including participants of HRS and ADAMS Waves B, C, and/or D (2002-2009).

RESULTS: In the unweighted training data, sensitivity ranged from 53\% to 90\%, specificity ranged from 79\% to 97\%, and overall accuracy ranged from 81\% to 87\%. Though sensitivity was lower in the unweighted validation data (range: 18\% to 62\%), overall accuracy was similar (range: 79\% to 88\%) due to higher specificities (range: 82\% to 98\%). In analyses weighted to represent the age-eligible US population, accuracy ranged from 91\% to 94\% in the training data and 87\% to 94\% in the validation data. Using a 0.5 probability cutoff, Crimmins maximized sensitivity, Herzog-Wallace maximized specificity, and Wu and Hurd maximized accuracy. Accuracy was higher among younger, highly-educated, and non-Hispanic white participants versus their complements in both weighted and unweighted analyses.

CONCLUSIONS: Algorithmic diagnoses provide a cost-effective way to conduct dementia research. However, na{\"\i}ve use of existing algorithms in disparities or risk-factor research may induce non-conservative bias. Algorithms with more comparable performance across relevant subgroups are needed.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

}, keywords = {Cognition \& Reasoning, Dementia, Meta-analyses, Survey Methodology}, issn = {1531-5487}, doi = {10.1097/EDE.0000000000000945}, author = {Kan Z Gianattasio and Bei Wu and M. Maria Glymour and Melinda C Power} } @article {9337, title = {Alzheimer{\textquoteright}s disease genetic risk variants beyond APOE ε4 predict mortality}, journal = {Alzheimer{\textquoteright}s \& Dementia: Diagnosis, Assessment \& Disease Monitoring}, volume = {8}, year = {2017}, pages = {188-195}, abstract = {We hypothesized that, like apolipoprotein E (APOE), other late-onset Alzheimer{\textquoteright}s disease (LOAD) genetic susceptibility loci predict mortality. Methods We used a weighted genetic risk score (GRS) from 21 non-APOE LOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age >=90 years with controls who died between ages 55 and 80 years. Results Higher GRS predicted mortality (hazard ratio = 1.05; 95\% confidence interval: 1.00{\textendash}1.10, P =.04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case-control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95\% confidence interval: 0.41{\textendash}1.00, P =.05). Discussion Non-APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence.}, keywords = {Alzheimer{\textquoteright}s disease, APoE4, Cognitive Ability, Genetics, Mortality, Risk Factors}, issn = {23528729}, doi = {10.1016/j.dadm.2017.07.002}, url = {http://linkinghub.elsevier.com/retrieve/pii/S2352872917300416http://api.elsevier.com/content/article/PII:S2352872917300416?httpAccept=text/xmlhttp://api.elsevier.com/content/article/PII:S2352872917300416?httpAccept=text/plain}, author = {Mez, Jesse and Jessica R Marden and Mukherjee, Shubhabrata and Stefan Walter and Laura E Gibbons and Alden L Gross and Laura B Zahodne and Paola Gilsanz and Brewster, Paul and Nho, Kwangsik and Paul K Crane and Eric B Larson and M. Maria Glymour} } @article {9116, title = {Association between persistent pain and memory decline and dementia in a longitudinal cohort of elders}, journal = {JAMA Internal Medicine}, volume = {177}, year = {2017}, chapter = {1146-1153}, abstract = {Importance: Chronic pain is common among the elderly and is associated with cognitive deficits in cross-sectional studies; the population-level association between chronic pain and longitudinal cognition is unknown. Objective: To determine the population-level association between persistent pain, which may reflect chronic pain, and subsequent cognitive decline. Design, Setting, and Participants: Cohort study with biennial interviews of 10 065 community-dwelling older adults in the nationally representative Health and Retirement Study who were 62 years or older in 2000 and answered pain and cognition questions in both 1998 and 2000. Data analysis was conducted between June 24 and October 31, 2016. Exposures: {\textquotedblleft}Persistent pain,{\textquotedblright} defined as a participant reporting that he or she was often troubled with moderate or severe pain in both the 1998 and 2000 interviews. Main Outcomes and Measures: Coprimary outcomes were composite memory score and dementia probability, estimated by combining neuropsychological test results and informant and proxy interviews, which were tracked from 2000 through 2012. Linear mixed-effects models, with random slope and intercept for each participant, were used to estimate the association of persistent pain with slope of the subsequent cognitive trajectory, adjusting for demographic characteristics and comorbidities measures in 2000 and applying sampling weights to represent the 2000 US population. We hypothesized that persistent pain would predict accelerated memory decline and increased probability of dementia. To quantify the impact of persistent pain on functional independence, we combined our primary results with information on the association between memory and ability to manage medications and finances independently. Results: Of the 10,065 eligible HRS sample members, 60\% were female, and median baseline age was 73 years (interquartile range, 67-78 years). At baseline, persistent pain affected 10.9\% of participants and was associated with worse depressive symptoms and more limitations in activities of daily living. After covariate adjustment, persistent pain was associated with 9.2\% (95\% CI, 2.8\%-15.0\%) more rapid memory decline compared with those without persistent pain. After 10 years, this accelerated memory decline implied a 15.9\% higher relative risk of inability to manage medications and an 11.8\% higher relative risk of inability to manage finances independently. Adjusted dementia probability increased 7.7\% faster (95\% CI, 0.55\%-14.2\%); after 10 years, this translates to an absolute 2.2\% increase in dementia probability for those with persistent pain. Conclusions and Relevance: Persistent pain was associated with accelerated memory decline and increased probability of dementia.}, keywords = {Chronic pain, Cognitive Ability, Memory}, doi = {10.1001/jamainternmed.2017.1622}, url = {https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2629448}, author = {Elizabeth L Whitlock and L Grisell Diaz-Ramirez and M. Maria Glymour and W John Boscardin and Kenneth E Covinsky} } @article {6502, title = {Loneliness, depression and cognitive function in older U.S. adults.}, journal = {Int J Geriatr Psychiatry}, volume = {32}, year = {2017}, month = {2017 May}, pages = {564-573}, abstract = {

OBJECTIVE: To examine reciprocal relations of loneliness and cognitive function in older adults.

METHODS: Data were analyzed from 8382 men and women, age 65 and older, participating in the US Health and Retirement Study from 1998 to 2010. Participants underwent biennial assessments of loneliness and depression (classified as no, low or high depression) determined by the Center for Epidemiologic Studies Depression scale (8-item version), cognition (a derived memory score based on a word list memory task and proxy-rated memory and global cognitive function), health status and social and demographic characteristics from 1998 to 2010. We used repeated measures analysis to examine the reciprocal relations of loneliness and cognitive function in separate models controlling sequentially and cumulatively for socio-demographic factors, social network, health conditions and depression.

RESULTS: Loneliness at baseline predicted accelerated cognitive decline over 12 years independent of baseline socio-demographic factors, social network, health conditions and depression (β = -0.2, p = 0.002). After adjustment for depression interacting with time, both low and high depression categories were related to faster cognitive decline and the estimated effect of loneliness became marginally significant. Reciprocally, poorer cognition at baseline was associated with greater odds of loneliness over time in adjusted analyses (OR 1.3, 95\% CI (1.1-1.5) p = 0.005), but not when controlling for baseline depression. Furthermore, cognition did not predict change in loneliness over time.

CONCLUSION: Examining longitudinal data across a broad range of cognitive abilities, loneliness and depressive symptoms appear to be related risk factors for worsening cognition but low cognitive function does not lead to worsening loneliness over time. Copyright {\textcopyright} 2016 John Wiley \& Sons, Ltd.

}, keywords = {Aged, Aged, 80 and over, Cognitive Dysfunction, Demography, Depressive Disorder, Female, Humans, Loneliness, Longitudinal Studies, Male, Middle Aged, Risk Factors}, issn = {1099-1166}, doi = {10.1002/gps.4495}, url = {http://dx.doi.org/10.1002/gps.4495}, author = {Nancy J. Donovan and Bei Wu and Dorene M. Rentz and Reisa A. Sperling and Gad A. Marshall and M. Maria Glymour} } @article {9237, title = {The role of literacy in the association between educational attainment and depressive symptoms}, journal = {SSM - Population Health}, volume = {3}, year = {2017}, pages = {586-593}, abstract = {There is a consistent association between education and depressive symptoms, but research on the mechanisms to explain this association remains limited. No study has formally evaluated the extent to which the association between education and depressive symptoms is mediated through a foundational skill such as literacy. Inverse odds ratio weighting (IORW) was used to estimate total, natural direct, and natural indirect effects in examining literacy as a mediator of the association between education and depressive symptoms. Health and Retirement Study participants born in the U.S. between 1900 and 1947 were interviewed biennially for up to 12 years (N = 16,718). Literacy was assessed with a brief vocabulary measure. Depressive symptoms were measured using the 8-item Centers for Epidemiologic Studies-Depression (CES-D) scale. Decomposition estimates were derived using regression analyses of repeated measures of depressive symptoms. Standard errors were obtained using a nonparametric bootstrap with the individual as the independent unit to account for dependence of observations within an individual. In a large cohort of older Americans, a one standard deviation difference in educational attainment (~ 3 years) was associated with a 0.35-point decrement in CES-D score (95\% CI: -0.38, -0.32). This decrement represents a 0.22 standard deviation difference in depressive symptoms. Using IORW, the estimated effect of education on depressive symptoms mediated through literacy was -0.10 (95\% CI: -0.18, -0.01), which represents 28\% of the total effect. Education confers many benefits; as demonstrated by this study for depressive symptoms, one important benefit is literacy.}, keywords = {Depressive symptoms, Education, Literacy}, issn = {23528273}, doi = {10.1016/j.ssmph.2017.07.002}, url = {http://linkinghub.elsevier.com/retrieve/pii/S2352827316301197http://api.elsevier.com/content/article/PII:S2352827316301197?httpAccept=text/xmlhttp://api.elsevier.com/content/article/PII:S2352827316301197?httpAccept=text/plain}, author = {Thu T Nguyen and Eric J. Tchetgen Tchetgen and Ichiro Kawachi and Stephen E. Gilman and Stefan Walter and M. Maria Glymour} } @article {8350, title = {African Ancestry, Social Factors, and Hypertension Among Non-Hispanic Blacks in the Health and Retirement Study.}, journal = {Biodemography Soc Biol}, volume = {62}, year = {2016}, month = {2016}, pages = {19-35}, publisher = {62}, abstract = {

The biomedical literature contains much speculation about possible genetic explanations for the large and persistent black-white disparities in hypertension, but profound social inequalities are also hypothesized to contribute to this outcome. Our goal is to evaluate whether socioeconomic status (SES) differences provide a plausible mechanism for associations between African ancestry and hypertension in a U.S. cohort of older non-Hispanic blacks. We included only non-Hispanic black participants (N~=~998) from the Health and Retirement Study who provided genetic data. We estimated percent African ancestry based on 84,075 independent single nucleotide polymorphisms using ADMIXTURE V1.23, imposing K~=~4 ancestral populations, and categorized into quartiles. Hypertension status was self-reported in the year 2000. We used linear probability models (adjusted for age, sex, and southern birth) to predict prevalent hypertension with African ancestry quartile, before and after accounting for a small set of SES measures. Respondents with the highest quartile of African ancestry had 8 percentage points{\textquoteright} (RD~=~0.081; 95\% CI: -0.001, 0.164) higher prevalence of hypertension compared to the lowest quartile. Adjustment for childhood disadvantage, education, income, and wealth explained over one-third (RD~=~0.050; 95\% CI: -0.034, 0.135) of the disparity. Explanations for the residual disparity remain unspecified and may include other indicators of SES or diet, lifestyle, and psychosocial mechanisms.

}, keywords = {African Americans, Aged, Female, Health Status Disparities, Humans, Hypertension, Life Style, Male, Middle Aged, Prevalence, Risk Factors, Socioeconomic factors, United States}, issn = {1948-5573}, doi = {10.1080/19485565.2015.1108836}, url = {http://www.tandfonline.com/doi/full/10.1080/19485565.2015.1108836}, author = {Jessica R Marden and Stefan Walter and Jay S Kaufman and M. Maria Glymour} } @article {8512, title = {Association of a Genetic Risk Score With Body Mass Index Across Different Birth Cohorts.}, journal = {JAMA}, volume = {316}, year = {2016}, month = {2016 Jul 05}, pages = {63-9}, chapter = {63}, abstract = {

IMPORTANCE: Many genetic variants are associated with body mass index (BMI). Associations may have changed with the 20th century obesity epidemic and may differ for black vs white individuals.

OBJECTIVE: Using birth cohort as an indicator for exposure to obesogenic environment, to evaluate whether genetic predisposition to higher BMI has a larger magnitude of association among adults from more recent birth cohorts, who were exposed to the obesity epidemic at younger ages.

DESIGN, SETTING, AND PARTICIPANTS: Observational study of 8788 adults in the US national Health and Retirement Study who were aged 50 years and older, born between 1900 and 1958, with as many as 12 BMI assessments from 1992 to 2014.

EXPOSURES: A multilocus genetic risk score for BMI (GRS-BMI), calculated as the weighted sum of alleles of 29 single nucleotide polymorphisms associated with BMI, with weights equal to the published per-allele effects. The GRS-BMI represents how much each person{\textquoteright}s BMI is expected to differ, based on genetic background (with respect to these 29 loci), from the BMI of a sample member with median genetic risk. The median-centered GRS-BMI ranged from -1.68 to 2.01.

MAIN OUTCOMES AND MEASURES: BMI based on self-reported height and weight.

RESULTS: GRS-BMI was significantly associated with BMI among white participants (n = 7482; mean age at first assessment, 59 years; 3373 [45\%] were men; P <.001) and among black participants (n = 1306; mean age at first assessment, 57 years; 505 [39\%] were men; P <.001) but accounted for 0.99\% of variation in BMI among white participants and 1.37\% among black participants. In multilevel models accounting for age, the magnitude of associations of GRS-BMI with BMI were larger for more recent birth cohorts. For example, among white participants, each unit higher GRS-BMI was associated with a difference in BMI of 1.37 (95\% CI, 0.93 to 1.80) if born after 1943, and 0.17 (95\% CI, -0.55 to 0.89) if born before 1924 (P = .006). For black participants, each unit higher GRS-BMI was associated with a difference in BMI of 3.70 (95\% CI, 2.42 to 4.97) if born after 1943, and 1.44 (95\% CI, -1.40 to 4.29) if born before 1924.

CONCLUSIONS AND RELEVANCE: For participants born between 1900 and 1958, the magnitude of association between BMI and a genetic risk score for BMI was larger among persons born in later cohorts. This suggests that associations of known genetic variants with BMI may be modified by obesogenic environments.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Aged, 80 and over, Alleles, Body Mass Index, Cohort Studies, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Multilocus Sequence Typing, Obesity, Polymorphism, Single Nucleotide, Risk Factors, United States}, issn = {1538-3598}, doi = {10.1001/jama.2016.8729}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27380344}, author = {Stefan Walter and Mej{\'\i}a-Guevara, Iv{\'a}n and Estrada, Karol and Sze Y Liu and M. Maria Glymour} } @article {8498, title = {Comparing Alternative Effect Decomposition Methods: The Role of Literacy in Mediating Educational Effects on Mortality.}, journal = {Epidemiology}, volume = {27}, year = {2016}, month = {2016 09}, pages = {670-6}, abstract = {

BACKGROUND: Inverse odds ratio weighting, a newly proposed tool to evaluate mediation in exposure-disease associations, may be valuable for a host of research questions, but little is known about its performance in real data. We compare this approach to a more conventional Baron and Kenny type of decomposition on an additive hazards scale to estimate total, direct, and indirect effects using the example of the role of literacy in mediating the effects of education on mortality.

METHODS: Health and Retirement Study participants born in the United States between 1900 and 1947 were interviewed biennially for up to 12 years (N = 17,054). Literacy was measured with a brief vocabulary assessment. Decomposition estimates were derived based on Aalen additive hazards models.

RESULTS: A 1 standard deviation difference in educational attainment (3 years) was associated with 6.7 fewer deaths per 1000 person-years (β = -6.7, 95\% confidence interval [CI]: -7.9, -5.4). Of this decrease, 1.3 fewer deaths (β = -1.3, 95\% CI: -4.0, 1.2) were attributed to the literacy pathway (natural indirect), representing 19\% of the total effect. Baron and Kenny estimates were consistent with inverse odds ratio weighting estimates but were less variable (natural indirect effect: -1.2 [95\% CI: -1.7, -0.69], representing 18\% of total effect).

CONCLUSION: In a cohort of older Americans, literacy partially mediated the effect of education on mortality. See Video Abstract at http://links.lww.com/EDE/B78.

}, keywords = {Aged, Aged, 80 and over, Educational Status, Female, Humans, Literacy, Longitudinal Studies, Male, Middle Aged, Mortality, Odds Ratio, Proportional Hazards Models, United States}, issn = {1531-5487}, doi = {10.1097/EDE.0000000000000517}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27280331}, author = {Thu T Nguyen and Eric J. Tchetgen Tchetgen and Ichiro Kawachi and Stephen E. Gilman and Stefan Walter and M. Maria Glymour} } @article {8401, title = {Diabetic Phenotypes and Late-Life Dementia Risk: A Mechanism-specific Mendelian Randomization Study.}, journal = {Alzheimer Dis Assoc Disord}, volume = {30}, year = {2016}, month = {2016 Jan-Mar}, pages = {15-20}, publisher = {30}, abstract = {

BACKGROUND: Mendelian Randomization (MR) studies have reported that type 2 diabetes (T2D) was not associated with Alzheimer disease (AD). We adopted a modified, mechanism-specific MR design to explore this surprising result.

METHODS: Using inverse-variance weighted MR analysis, we evaluated the association between T2D and AD using data from 39 single nucleotide polymorphisms (SNPs) significantly associated with T2D in DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) and the corresponding associations of each SNP with AD risk obtained from the International Genomics of Alzheimer{\textquoteright}s Project (IGAP, n=17,008 AD cases and n=37,154 controls). We evaluated mechanism-specific genetic subscores, including β-cell function, insulin sensitivity, and adiposity, and repeated analyses in 8501 Health and Retirement Study participants for replication and model validation.

RESULTS: In IGAP, the overall T2D polygenic score did not predict AD [odds ratio (OR) for the T2D polygenic score=1.01; 95\% confidence interval (CI), 0.96, 1.06] but the insulin sensitivity polygenic score predicted higher AD risk (OR=1.17; 95\% CI, 1.02, 1.34). In the Health and Retirement Study, polygenic scores were associated with T2D risk; the associations between insulin sensitivity genetic polygenic score and cognitive phenotypes were not statistically significant.

CONCLUSIONS: Evidence from polygenic scores suggests that insulin sensitivity specifically may affect AD risk, more than T2D overall.

}, keywords = {Alzheimer disease, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Humans, Insulin, Mendelian Randomization Analysis, Phenotype, Polymorphism, Single Nucleotide, Risk Factors}, issn = {1546-4156}, doi = {10.1097/WAD.0000000000000128}, url = {http://europepmc.org/abstract/MED/26650880}, author = {Stefan Walter and Jessica R Marden and Laura D Kubzansky and Elizabeth R Mayeda and Paul K Crane and Chang, Shun-Chiao and Marilyn C Cornelis and David Rehkopf and Mukherjee, Shubhabrata and M. Maria Glymour} } @article {8342, title = {Instrumental variable approaches to identifying the causal effect of educational attainment on dementia risk.}, journal = {Ann Epidemiol}, volume = {26}, year = {2016}, note = {Times Cited: 0 0}, month = {2016 Jan}, pages = {71-6.e1-3}, publisher = {26}, abstract = {

PURPOSE: Education is an established correlate of cognitive status in older adulthood, but whether expanding educational opportunities would improve cognitive functioning remains unclear given limitations of prior studies for causal inference. Therefore, we conducted instrumental variable (IV) analyses of the association between education and dementia risk, using for the first time in this area, genetic variants as instruments as well as state-level school policies.

METHODS: IV analyses in the Health and Retirement Study cohort (1998-2010) used two sets of instruments: (1) a genetic risk score constructed from three single-nucleotide polymorphisms (SNPs; n = 7981); and (2) compulsory schooling laws (CSLs) and state school characteristics (term length, student teacher ratios, and expenditures; n = 10,955).

RESULTS: Using the genetic risk score as an IV, there was a 1.1\% reduction in dementia risk per year of schooling (95\% confidence interval, -2.4 to 0.02). Leveraging compulsory schooling laws and state school characteristics as IVs, there was a substantially larger protective effect (-9.5\%; 95\% confidence interval, -14.8 to -4.2). Analyses evaluating the plausibility of the IV assumptions indicated estimates derived from analyses relying on CSLs provide the best estimates of the causal effect of education.

CONCLUSIONS: IV analyses suggest education is protective against risk of dementia in older adulthood.

}, keywords = {Aged, Aged, 80 and over, Dementia, Education, Nonprofessional, Educational Status, Female, Genetic Predisposition to Disease, Health Surveys, Humans, Longitudinal Studies, Male, Middle Aged, Polymorphism, Single Nucleotide, Protective factors, Risk Factors, Schools, United States}, issn = {1873-2585}, doi = {10.1016/j.annepidem.2015.10.006}, author = {Thu T Nguyen and Eric J. Tchetgen Tchetgen and Ichiro Kawachi and Stephen E. Gilman and Stefan Walter and Sze Y Liu and Jennifer J Manly and M. Maria Glymour} } @article {8378, title = {Modifiable risk factors for nursing home admission among individuals with high and low dementia risk}, journal = {Archives of Gerontology and Geriatrics}, volume = {65}, year = {2016}, pages = {140-145}, publisher = {65}, abstract = {AbstractBackground Strategies to prevent or delay nursing home admission in individuals with cognitive impairment are urgently needed. We hypothesized that physical inactivity, not consuming alcohol (as opposed to moderate alcohol use), and having a history of smoking predict nursing home admission among individuals with normal cognitive function, but these behavioral factors would have attenuated associations with nursing home admission among individuals with impaired cognition. Methods We performed a prospective cohort study among 7631 Health and Retirement Study participants aged 65 at baseline. Baseline dementia risk (high versus low, based on brief psychometric assessments and proxy reports) and modifiable risk factors (physical inactivity, ever smoking, and not consuming alcohol) were used to predict nursing home admission in pooled logistic regression models. We evaluated whether estimated effects of modifiable factors varied by dementia risk, comparing both relative and absolute effects using interaction terms between dementia risk and each modifiable risk factor. Results Low dementia probability was associated with lower nursing home admission risk (RR = 0.49; 95 CI: 0.41, 0.59). Physical inactivity (RR = 1.27; 95 CI: 1.15, 1.41), ever smoking (RR = 1.12; 95 CI: 1.01, 1.25), and not consuming alcohol (RR = 1.28; 95 CI: 1.13, 1.45) predicted increased relative risk of nursing home admission regardless of cognitive status. The relative effects of modifiable risk factors were similar for those with low and high dementia risk. Conclusion Although cognitive impairment associated with incipient dementia strongly predicts nursing home admission, this risk can be partially ameliorated with modifiable risk factors such as physical activity.}, keywords = {Health Conditions and Status, Healthcare, Risk Taking}, doi = {10.1016/j.archger.2016.03.016}, url = {http://www.sciencedirect.com/science/article/pii/S0167494316300565}, author = {Pamela M. Rist and Thu T Nguyen and Rachel A Whitmer and M. Maria Glymour} } @article {6498, title = {Using an Alzheimer Disease Polygenic Risk Score to Predict Memory Decline in Black and White Americans Over 14 Years of Follow-up.}, journal = {Alzheimer Dis Assoc Disord}, volume = {30}, year = {2016}, month = {2016 Jul-Sep}, pages = {195-202}, abstract = {

Evidence on whether genetic predictors of Alzheimer disease (AD) also predict memory decline is inconsistent, and limited data are available for African ancestry populations. For 8253 non-Hispanic white (NHW) and non-Hispanic black (NHB) Health and Retirement Study participants with memory scores measured 1 to 8 times between 1998 and 2012 (average baseline age=62), we calculated weighted polygenic risk scores [AD Genetic Risk Score (AD-GRS)] using the top 22 AD-associated loci, and an alternative score excluding apolipoprotein E (APOE) (AD-GRSexAPOE). We used generalized linear models with AD-GRS-by-age and AD-GRS-by-age interactions (age centered at 70) to predict memory decline. Average NHB decline was 26\% faster than NHW decline (P<0.001). Among NHW, 10\% higher AD-GRS predicted faster memory decline (linear β=-0.058 unit decrease over 10 y; 95\% confidence interval,-0.074 to -0.043). AD-GRSexAPOE also predicted faster decline for NHW, although less strongly. Among NHB, AD-GRS predicted faster memory decline (linear β=-0.050; 95\% confidence interval, -0.106 to 0.006), but AD-GRSexAPOE did not. Our nonsignificant estimate among NHB may reflect insufficient statistical power or a misspecified AD-GRS among NHB as an overwhelming majority of genome-wide association studies are conducted in NHW. A polygenic score based on previously identified AD loci predicts memory loss in US blacks and whites.

}, keywords = {Alzheimer disease, Black or African American, ethnicity, Female, Follow-Up Studies, Genome-Wide Association Study, Humans, Male, Memory Disorders, Middle Aged, Risk Factors, United States, White People}, issn = {1546-4156}, doi = {10.1097/WAD.0000000000000137}, author = {Jessica R Marden and Elizabeth R Mayeda and Stefan Walter and Vivot, Alexandre and Tchetgen Tchetgen, Eric J and Ichiro Kawachi and M. Maria Glymour} } @article {8330, title = {Changes in Depressive Symptoms and Incidence of First Stroke Among Middle-Aged and Older US Adults.}, journal = {J Am Heart Assoc}, volume = {4}, year = {2015}, month = {2015 May 13}, publisher = {4}, abstract = {

BACKGROUND: Although research has demonstrated that depressive symptoms predict stroke incidence, depressive symptoms are dynamic. It is unclear whether stroke risk persists if depressive symptoms remit.

METHODS AND RESULTS: Health and Retirement Study participants (n=16 178, stroke free and noninstitutionalized at baseline) were interviewed biennially from 1998 to 2010. Stroke and depressive symptoms were assessed through self-report of doctors{\textquoteright} diagnoses and a modified Center for Epidemiologic Studies - Depression scale (high was >=3 symptoms), respectively. We examined whether depressive symptom patterns, characterized across 2 successive interviews (stable low/no, onset, remitted, or stable high depressive symptoms) predicted incident stroke (1192 events) during the subsequent 2 years. We used marginal structural Cox proportional hazards models adjusted for demographics, health behaviors, chronic conditions, and attrition. We also estimated effects stratified by age (>=65 years), race or ethnicity (non-Hispanic white, non-Hispanic black, Hispanic), and sex. Stroke hazard was elevated among participants with stable high (adjusted hazard ratio 2.14, 95\% CI 1.69 to 2.71) or remitted (adjusted hazard ratio 1.66, 95\% CI 1.22 to 2.26) depressive symptoms compared with participants with stable low/no depressive symptoms. Stable high depressive symptom predicted stroke among all subgroups. Remitted depressive symptoms predicted increased stroke hazard among women (adjusted hazard ratio 1.86, 95\% CI 1.30 to 2.66) and non-Hispanic white participants (adjusted hazard ratio 1.66, 95\% CI 1.18 to 2.33) and was marginally associated among Hispanics (adjusted hazard ratio 2.36, 95\% CI 0.98 to 5.67).

CONCLUSIONS: In this cohort, persistently high depressive symptoms were associated with increased stroke risk. Risk remained elevated even if depressive symptoms remitted over a 2-year period, suggesting cumulative etiologic mechanisms linking depression and stroke.

}, keywords = {Adult, Aged, Aged, 80 and over, Aging, depression, Female, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Proportional Hazards Models, Risk Factors, Sex Factors, Stroke, Time Factors}, issn = {2047-9980}, doi = {10.1161/JAHA.115.001923}, author = {Stefan Walter and Eric J. Tchetgen Tchetgen and Kristen K Patton and J Robin Moon and Benjamin D Capistrant and Jessica R Marden and Laura D Kubzansky and Paola Gilsanz and Ichiro Kawachi and M. Maria Glymour} } @article {6483, title = {Do Physical Activity, Smoking, Drinking, or Depression Modify Transitions from Cognitive Impairment to Functional Disability?}, journal = {Journal of Alzheimer{\textquoteright}s Disease}, volume = {44}, year = {2015}, pages = {1171-1180}, chapter = {1171}, abstract = {Background: Individual-level modifiers can delay onset of limitations in basic activities of daily living (ADLs) among cognitively impaired individuals. We assessed whether these modifiers also delayed onset of limitations in instrumental ADLs (IADLs) among individuals at elevated dementia risk. Objectives: To determine whether modifiable individual-level factors delay incident IADL limitations among adults stratified by dementia risk. Methods: Health and Retirement Study participants aged 65 without activity limitations in 1998 or 2000 (n = 5,219) were interviewed biennially through 2010. Dementia probability, categorized in quartiles, was used to predict incident IADL limitations with Poisson regression. We estimated relative (risk ratio) and absolute (number of limitations) effects from models including dementia, individual-level modifiers (physical inactivity, smoking, no alcohol consumption, and depression) and interaction terms between dementia and individual-level modifiers. Results: Dementia probability quartile predicted incident IADL limitations (relative risk for highest versus lowest quartile = 0.44; 95 CI: 0.28 0.70). Most modifiers did not significantly increase risk of IADL limitations among the cognitively impaired. Physical inactivity (RR = 1.60; 95 CI: 1.16, 2.19) increased the risk of IADL limitations among the cognitively impaired. The interaction between physical inactivity and low dementia probability was statistically significant (p = 0.009) indicating that physical inactivity had significantly larger effects on incident IADLs among cognitively normal than among those with high dementia probability. Conclusion: Physical activity may protect against IADL limitations while smoking, alcohol consumption, and depression do not afford substantial protection among the cognitively impaired. Results highlight the need for extra support for IADLs among individuals with cognitive losses.}, keywords = {Disabilities, Health Conditions and Status, Healthcare}, doi = {10.3233/JAD-141866}, url = {http://dx.doi.org/10.3233/JAD-141866}, author = {Pamela M. Rist and Jessica R Marden and Benjamin D Capistrant and Bei Wu and M. Maria Glymour} } @article {8187, title = {Estimating the Cognitive Effects of Prevalent Diabetes, Recent Onset Diabetes, and the Duration of Diabetes among Older Adults}, journal = {Dementia and Geriatric Cognitive Disorders}, volume = {39}, year = {2015}, note = {Times Cited: 0 0}, pages = {239-249}, publisher = {39}, abstract = {Background: Little evidence is available on the effects of incident diabetes or diabetes duration on cognitive aging. Methods: We evaluated the effects of prevalent and incident diabetes on deteriorations in cognitive function, based on participants (n = 8,671) aged 65 in the Health and Retirement Study in 2000. Inverse probability weighting was used to account for selective attrition and time-varying confounding of incident diabetes. Results: Prevalent diabetes predicted higher odds of dementia odds ratio 1.27; 95 confidence interval (CI) 1.03-1.58 and worse memory (-0.06 in z-score units; 95 CI -0.10 to -0.02), but incident diabetes or diabetes duration up to 8 years of follow-up was not predictive. Conclusion: Prevalent diabetes predicted lower cognition but not recent onset diabetes. (C) 2015 S. Karger AG, Basel}, keywords = {Health Conditions and Status}, doi = {10.1159/000368654}, author = {Bei Wu and Eric J. Tchetgen Tchetgen and Theresa L Osypuk and Weuve, Jennifer and White, Kellee and Mujahid, Mahasin and M. Maria Glymour} } @article {8612, title = {Genetic vulnerability to diabetes and obesity: does education offset the risk?}, journal = {Soc Sci Med}, volume = {127}, year = {2015}, month = {2015 Feb}, pages = {150-8}, abstract = {

The prevalence of type 2 diabetes (T2D) and obesity has recently increased dramatically. These common diseases are likely to arise from the interaction of multiple genetic, socio-demographic and environmental risk factors. While previous research has found genetic risk and education to be strong predictors of these diseases, few studies to date have examined their joint effects. This study investigates whether education modifies the association between genetic background and risk for type 2 diabetes (T2D) and obesity. Using data from non-Hispanic Whites in the Health and Retirement Study (HRS, n~=~8398), we tested whether education modifies genetic risk for obesity and T2D, offsetting genetic effects; whether this effect is larger for individuals who have high risk for other (unobserved) reasons, i.e., at higher quantiles of HbA1c and BMI; and whether effects differ by gender. We measured T2D risk using Hemoglobin A1c (HbA1c) level, and obesity risk using body-mass index (BMI). We constructed separate genetic risk scores (GRS) for obesity and diabetes respectively based on the most current available information on the single nucleotide polymorphism (SNPs) confirmed as genome-wide significant predictors for BMI (29 SNPs) and diabetes risk (39 SNPs). Linear regression models with years of schooling indicate that the effect of genetic risk on HbA1c is smaller among people with more years of schooling and larger among those with less than a high school (HS) degree compared to HS degree-holders. Quantile regression models show that the GRS~{\texttimes}~education effect systematically increased along the HbA1c outcome distribution; for example the GRS~{\texttimes}~years of education interaction coefficient was~-0.01 (95\% CI~=~-0.03, 0.00) at the 10th percentile compared to~-0.03 (95\% CI~=~-0.07, 0.00) at the 90th percentile. These results suggest that education may be an important socioeconomic source of heterogeneity in responses to genetic vulnerability to T2D.

}, keywords = {Aged, Body Mass Index, Diabetes Mellitus, Type 2, Educational Status, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genotype, Glycated Hemoglobin A, Health Status Disparities, Humans, Male, Middle Aged, Obesity, Risk Factors, Social determinants of health}, issn = {1873-5347}, doi = {10.1016/j.socscimed.2014.09.009}, url = {http://www.sciencedirect.com/science/article/pii/S0277953614005760}, author = {Sze Y Liu and Stefan Walter and Jessica R Marden and David Rehkopf and Laura D Kubzansky and Thu T Nguyen and M. Maria Glymour} } @article {10640, title = {Genetically predicted body mass index and Alzheimer{\textquoteright}s disease-related phenotypes in three large samples: Mendelian randomization analyses.}, journal = {Alzheimers Dement}, volume = {11}, year = {2015}, month = {2015 Dec}, pages = {1439-1451}, abstract = {

Observational research shows that higher body mass index (BMI) increases Alzheimer{\textquoteright}s disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95\% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90-1.01); HRS, OR = 1.00 (0.75-1.32); GERAD1, OR = 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk.

}, keywords = {Aged, Aged, 80 and over, Alzheimer disease, Body Mass Index, Female, Genotype, Humans, Linear Models, Male, Mendelian Randomization Analysis, Obesity, Phenotype, Polymorphism, Single Nucleotide, Risk Factors}, issn = {1552-5279}, doi = {10.1016/j.jalz.2015.05.015}, author = {Mukherjee, Shubhabrata and Stefan Walter and Kauwe, John S K and Andrew J Saykin and David A Bennett and Eric B Larson and Paul K Crane and M. Maria Glymour} } @article {8318, title = {Instrumental variable estimation in a survival context}, journal = {Epidemiology}, volume = {26}, year = {2015}, note = {Times Cited: 1 0 1}, pages = {402-410}, publisher = {26}, abstract = {Bias due to unobserved confounding can seldom be ruled out with certainty when estimating the causal effect of a nonrandomized treatment. The instrumental variable (IV) design offers, under certain assumptions, the opportunity to tame confounding bias, without directly observing all confounders. The IV approach is very well developed in the context of linear regression and also for certain generalized linear models with a nonlinear link function. However, IV methods are not as well developed for regression analysis with a censored survival outcome. In this article, we develop the IV approach for regression analysis in a survival context, primarily under an additive hazards model, for which we describe 2 simple methods for estimating causal effects. The first method is a straightforward 2-stage regression approach analogous to 2-stage least squares commonly used for IV analysis in linear regression. In this approach, the fitted value from a first-stage regression of the exposure on the IV is entered in place of the exposure in the second-stage hazard model to recover a valid estimate of the treatment effect of interest. The second method is a so-called control function approach, which entails adding to the additive hazards outcome model, the residual from a first-stage regression of the exposure on the IV. Formal conditions are given justifying each strategy, and the methods are illustrated in a novel application to a Mendelian randomization study to evaluate the effect of diabetes on mortality using data from the Health and Retirement Study. We also establish that analogous strategies can also be used under a proportional hazards model specification, provided the outcome is rare over the entire follow-up.}, keywords = {Health Conditions and Status, Methodology}, doi = {10.1097/ede.0000000000000262}, author = {Eric J. Tchetgen Tchetgen and Stefan Walter and Vansteelandt, Stijn and Martinussen, Torben and M. Maria Glymour} } @article {9524, title = {Reciprocal relations of loneliness and cognitive function in older U.S. adults}, year = {2015}, abstract = {In older adults, loneliness has been associated with functional decline and increased progression to dementia. The objective of this study was to examine the reciprocal relations of loneliness and cognitive function in older adults, adjusting for sociodemographic and health-related factors, social network and depression.}, keywords = {Cognitive Ability, Lone, Relationships}, doi = {10.1016/j.jalz.2015.07.194}, url = {http://www.alzheimersanddementia.com/article/S1552-5260(15)02344-4/fulltext}, author = {Nancy J. Donovan and Bei Wu and Dorene M. Rentz and Reisa A. Sperling and Gad A. Marshall and M. Maria Glymour} } @article {8230, title = {Role of Place in Explaining Racial Heterogeneity in Cognitive Outcomes among Older Adults}, journal = {Journal of the International Neuropsychological Society}, volume = {21}, year = {2015}, note = {Times Cited: 0 Si 0}, pages = {677-687}, publisher = {21}, abstract = {Racially patterned disadvantage in Southern states, especially during the formative years of primary school, may contribute to enduring disparities in adult cognitive outcomes. Drawing on a lifecourse perspective, we examine whether state of school attendance affects cognitive outcomes in older adults and partially contributes to persistent racial disparities. Using data from older African American and white participants in the national Health and Retirement Study (HRS) and the New York based Washington Heights Inwood Cognitive Aging Project (WHICAP), we estimated age-and gender-adjusted multilevel models with random effects for states predicting years of education and cognitive outcomes (e.g., memory and vocabulary). We summarized the proportion of variation in outcomes attributable to state of school attendance and compared the magnitude of racial disparities across states. Among WHICAP African Americans, state of school attendance accounted for 9 of the variance in years of schooling, 6 of memory, and 12 of language. Among HRS African Americans, state of school attendance accounted for 13 of the variance in years of schooling and also contributed to variance in cognitive function (7 ), memory (2 ), and vocabulary (12 ). Random slope models indicated state-level African American and white disparities in every Census region, with the largest racial differences in the South. State of school attendance may contribute to racial disparities in cognitive outcomes among older Americans. Despite tremendous within-state heterogeneity, state of school attendance also accounted for some variability in cognitive outcomes. Racial disparities in older Americans may reflect historical patterns of segregation and differential access to resources such as education.}, keywords = {Health Conditions and Status, Healthcare, Women and Minorities}, doi = {10.1017/s1355617715000806}, author = {Sze Y Liu and M. Maria Glymour and Laura B Zahodne and Weiss, Christopher and Jennifer J Manly} } @article {8052, title = {Changes in Memory before and after Stroke Differ by Age and Sex, but Not by Race}, journal = {Cerebrovascular Diseases}, volume = {37}, year = {2014}, note = {Export Date: 21 April 2014 Source: Scopus Article in Press}, pages = {235-243}, publisher = {37}, abstract = {Background: Post-stroke memory impairment is more common among older adults, women and blacks. It is unclear whether post-stroke differences reflect differential effects of stroke per se or differences in prestroke functioning. We compare memory trajectories before and after stroke by age, sex and race. Methods: Health and Retirement Study participants aged 50 years (n = 17,341), with no stroke history at baseline, were interviewed biennially up to 10 years for first self- or proxy-reported stroke (n = 1,574). Segmented linear regression models were used to compare annual rates of memory change before and after stroke among 1,169 stroke survivors, 405 stroke decedents and 15,767 stroke-free participants. Effect modification was evaluated with analyses stratified by baseline age ( 70 vs. 70), sex and race (white vs. nonwhite), and using interaction terms between age/sex/race indicators and annual memory change. Results: Older ( 70 years) adults experienced a faster memory decline before stroke (-0.19 vs. -0.10 points/year for survivors, -0.24 vs. -0.13 points/year for decedents, p 0.001 for both interactions), and among stroke survivors, larger memory decrements (-0.64 vs. -0.26 points, p 0.001) at stroke and faster memory decline (-0.15 vs. -0.07 points/year, p = 0.003) after stroke onset, compared to younger adults. Female stroke survivors experienced a faster prestroke memory decline than male stroke survivors (-0.14 vs. -0.10 points/year, p 0.001). However, no sex differences were seen for other contrasts. Although whites had higher post-stroke memory scores than nonwhites, race was not associated with rate of memory decline during any period of time; i.e. race did not significantly modify the rate of decline before or after stroke or the immediate effect of stroke on memory. Conclusions: Older age predicted worse memory change before, at and after stroke onset. Sex and race differences in post-stroke memory outcomes might be attributable to prestroke disparities, which may be unrelated to cerebrovascular disease. 2014 S. Karger AG, Basel.}, keywords = {Health Conditions and Status, Methodology}, url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84897121425andpartnerID=40andmd5=22785f81bf8b09c85697670c6a2e2382}, author = {Qianyi Wang and Mej{\'\i}a-Guevara, Iv{\'a}n and Pamela M. Rist and Stefan Walter and Benjamin D Capistrant and M. Maria Glymour} } @article {6475, title = {Dementia and dependence: Do Modifiable Risk Factors Delay Disability?}, journal = {Neurology}, volume = {82}, year = {2014}, month = {04/2014}, pages = {1543-1550}, chapter = {1543}, abstract = {Objective: To identify modifying factors that preserve functional independence among individuals at high dementia risk. Methods: Health and Retirement Study participants aged 65 years or older without baseline activities of daily living (ADL) limitations (n = 4,922) were interviewed biennially for up to 12 years. Dementia probability, estimated from direct and proxy cognitive assessments, was categorized as low (i.e., normal cognitive function), mild, moderate, or high risk (i.e., very impaired) and used to predict incident ADL limitations (censoring after limitation onset). We assessed multiplicative and additive interactions of dementia category with modifiers (previously self-reported physical activity, smoking, alcohol consumption, depression, and income) in predicting incident limitations. Results: Smoking, not drinking, and income predicted incident ADL limitations and had larger absolute effects on ADL onset among individuals with high dementia probability than among cognitively normal individuals. Smoking increased the 2-year risk of ADL limitations onset from 9.9 to 14.9 among the lowest dementia probability category and from 32.6 to 42.7 among the highest dementia probability category. Not drinking increased the 2-year risk of ADL limitations onset by 2.1 percentage points among the lowest dementia probability category and 13.2 percentage points among the highest dementia probability category. Low income increased the 2-year risk of ADL limitations onset by 0.4 among the lowest dementia probability category and 12.9 among the highest dementia probability category. Conclusions: Smoking, not drinking, and low income predict incident dependence even in the context of cognitive impairment. Regardless of cognitive status, reducing these risk factors may improve functional outcomes and delay institutionalization.}, keywords = {Health Conditions and Status, Income}, doi = {10.1212/WNL.0000000000000357}, author = {Pamela M. Rist and Benjamin D Capistrant and Bei Wu and Jessica R Marden and M. Maria Glymour} } @article {8020, title = {Diabetes risk, diagnosis, and control: Do psychosocial factors predict hemoglobin A1C defined outcomes or accuracy of self-reports?}, journal = {Ethnicity and Disease}, volume = {24}, year = {2014}, note = {Times Cited: 0}, pages = {19-27}, publisher = {24}, abstract = {Objective: To evaluate the accuracy of self-reported diabetes among multi-ethnic older adults by psychosocial factors and assess predictors of diabetes risk, diagnosis, and control. Design and Methods: The 2006 Health and Retirement Study (N=5,594) was used to determine agreement between self-reported diabetes and measured diabetes (HbA1c = 6.5 ) by age, sex, race/ethnicity, nativity, education, health insurance coverage, body mass index, depressive symptoms, and prior report of racial discrimination. We also examined associations between these factors and pre-diabetes (HbA1c = 6.0- 6.5 ) among individuals without diabetes, and those with undiagnosed and poorly controlled (HbA1c = 8.0 ) diabetes. Results: Accuracy of self-reported diabetes was good (ie, sensitivity = 80 and specificity = 95 ) among all demographic subgroups and across most social strata. Among those who reported racial discrimination, sensitivity of self-reported diabetes was lower among Blacks who reported racial discrimination in comparison to Blacks who did not report racial discrimination (82.7 vs 89.0 ) an association that was marginally statistically significant (P=.05). Blacks and Hispanics had higher odds of pre-diabetes, undiagnosed diabetes, and poor glycemic control. Conclusions: Self-reported diabetes corresponded well with HbA1c assessed disease for all social strata examined in this sample of multi-ethnic older adults. Blacks with a history of racial discrimination may be less likely to know diabetes status.}, keywords = {Demographics, Health Conditions and Status, Other}, author = {White, Kellee and Mondesir, Favel L. and Lisa M. Bates and M. Maria Glymour} } @article {7995, title = {The disability burden associated with stroke emerges before stroke onset and differentially affects blacks: results from the health and retirement study cohort.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Jul}, pages = {860-70}, publisher = {69}, abstract = {

BACKGROUND: Few longitudinal studies compare changes in instrumental activities of daily living (IADLs) among stroke-free adults to prospectively document IADL changes among adults who experience stroke. We contrast annual declines in IADL independence for older individuals who remain stroke free to those for individuals who experienced stroke. We also assess whether these patterns differ by sex, race, or Southern birthplace.

METHODS: Health and Retirement Study participants who were stroke free in 1998 (n = 17,741) were followed through 2010 (average follow-up = 8.9 years) for self- or proxy-reported stroke. We used logistic regressions to compare annual changes in odds of self-reported independence in six IADLs among those who remained stroke free throughout follow-up (n = 15,888), those who survived a stroke (n = 1,412), and those who had a stroke and did not survive to participate in another interview (n = 442). We present models adjusted for demographic and socioeconomic covariates and also stratified on sex, race, and Southern birthplace.

RESULTS: Compared with similar cohort members who remained stroke free, participants who developed stroke had faster declines in IADL independence and lower probability of IADL independence prior to stroke. After stroke, independence declined at an annual rate similar to those who did not have stroke. The black-white disparity in IADL independence narrowed poststroke.

CONCLUSION: Racial differences in IADL independence are apparent long before stroke onset. Poststroke differences in IADL independence largely reflect prestroke disparities.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Aging, Black or African American, Cohort Studies, Disabled Persons, Female, Humans, Male, Prospective Studies, Stroke, United States, White People}, issn = {1758-535X}, doi = {10.1093/gerona/glt191}, url = {http://biomedgerontology.oxfordjournals.org/content/early/2014/01/19/gerona.glt191.abstract}, author = {Benjamin D Capistrant and Nicte I Mejia and Sze Y Liu and Qianyi Wang and M. Maria Glymour} } @article {8101, title = {The health effects of US unemployment insurance policy: does income from unemployment benefits prevent cardiovascular disease?}, journal = {PLoS One}, volume = {9}, year = {2014}, note = {Times Cited: 0}, month = {2014}, pages = {e101193}, publisher = {9}, abstract = {

OBJECTIVE: Previous studies suggest that unemployment predicts increased cardiovascular disease (CVD) risk, but whether unemployment insurance programs mitigate this risk has not been assessed. Exploiting US state variations in unemployment insurance benefit programs, we tested the hypothesis that more generous benefits reduce CVD risk.

METHODS: Cohort data came from 16,108 participants in the Health and Retirement Study (HRS) aged 50-65 at baseline interviewed from 1992 to 2010. Data on first and recurrent CVD diagnosis assessed through biennial interviews were linked to the generosity of unemployment benefit programmes in each state and year. Using state fixed-effect models, we assessed whether state changes in the generosity of unemployment benefits predicted CVD risk.

RESULTS: States with higher unemployment benefits had lower incidence of CVD, so that a 1\% increase in benefits was associated with 18\% lower odds of CVD (OR:0.82, 95\%-CI:0.71-0.94). This association remained after introducing US census regional division fixed effects, but disappeared after introducing state fixed effects (OR:1.02, 95\%-CI:0.79-1.31).This was consistent with the fact that unemployment was not associated with CVD risk in state-fixed effect models.

CONCLUSION: Although states with more generous unemployment benefits had lower CVD incidence, this appeared to be due to confounding by state-level characteristics. Possible explanations are the lack of short-term effects of unemployment on CVD risk. Future studies should assess whether benefits at earlier stages of the life-course influence long-term risk of CVD.

}, keywords = {Aged, Cardiovascular Diseases, Female, Geography, Humans, Incidence, Insurance Benefits, Insurance, Health, Longitudinal Studies, Male, Middle Aged, Risk Factors, Unemployment, United States}, issn = {1932-6203}, doi = {10.1371/journal.pone.0101193}, author = {Stefan Walter and M. Maria Glymour and Mauricio Avendano} } @article {8613, title = {Validation of a polygenic risk score for dementia in black and white individuals.}, journal = {Brain Behav}, volume = {4}, year = {2014}, month = {2014 Sep}, pages = {687-97}, abstract = {

OBJECTIVE: To determine whether a polygenic risk score for Alzheimer{\textquoteright}s disease (AD) predicts dementia probability and memory functioning in non-Hispanic black (NHB) and non-Hispanic white (NHW) participants from a sample not used in previous genome-wide association studies.

METHODS: Non-Hispanic white and NHB Health and Retirement Study (HRS) participants provided genetic information and either a composite memory score (n = 10,401) or a dementia probability score (n = 7690). Dementia probability score was estimated for participants{\textquoteright} age 65+ from 2006 to 2010, while memory score was available for participants age 50+. We calculated AD genetic risk scores (AD-GRS) based on 10 polymorphisms confirmed to predict AD, weighting alleles by beta coefficients reported in AlzGene meta-analyses. We used pooled logistic regression to estimate the association of the AD-GRS with dementia probability and generalized linear models to estimate its effect on memory score.

RESULTS: Each 0.10 unit change in the AD-GRS was associated with larger relative effects on dementia among NHW aged 65+ (OR = 2.22; 95\% CI: 1.79, 2.74; P < 0.001) than NHB (OR=1.33; 95\% CI: 1.00, 1.77; P = 0.047), although additive effect estimates were similar. Each 0.10 unit change in the AD-GRS was associated with a -0.07 (95\% CI: -0.09, -0.05; P < 0.001) SD difference in memory score among NHW aged 50+, but no significant differences among NHB (β = -0.01; 95\% CI: -0.04, 0.01; P = 0.546). [Correction added on 29 July 2014, after first online publication: confidence intervalshave been amended.] The estimated effect of the GRS was significantly smaller among NHB than NHW (P < 0.05) for both outcomes.

CONCLUSION: This analysis provides evidence for differential relative effects of the GRS on dementia probability and memory score among NHW and NHB in a new, national data set.

}, keywords = {African Americans, Aged, Aged, 80 and over, Dementia, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Genetic, Reproducibility of Results, Risk Assessment, Risk Factors, Surveys and Questionnaires, United States}, issn = {2162-3279}, doi = {10.1002/brb3.248}, author = {Jessica R Marden and Stefan Walter and Eric J. Tchetgen Tchetgen and Ichiro Kawachi and M. Maria Glymour} } @article {7881, title = {Combining direct and proxy assessments to reduce attrition bias in a longitudinal study.}, journal = {Alzheimer Dis Assoc Disord}, volume = {27}, year = {2013}, note = {Times Cited: 0}, month = {2013 Jul-Sep}, pages = {207-12}, publisher = {27}, abstract = {

Retaining severely impaired individuals poses a major challenge in longitudinal studies of determinants of dementia or memory decline. In the Health and Retirement Study (HRS), participants complete direct memory assessments biennially until they are too impaired to complete the interview. Thereafter, proxy informants, typically spouses, assess the subject{\textquoteright}s memory and cognitive function using standardized instruments. Because there is no common scale for direct memory assessments and proxy assessments, proxy reports are often excluded from longitudinal analyses. The Aging, Demographics, and Memory Study (ADAMS) implemented full neuropsychological examinations on a subsample (n=856) of HRS participants, including respondents with direct or proxy cognitive assessments in the prior HRS core interview. Using data from the ADAMS, we developed an approach to estimating a dementia probability and a composite memory score on the basis of either proxy or direct assessments in HRS core interviews. The prediction model achieved a c-statistic of 94.3\% for DSM diagnosed dementia in the ADAMS sample. We applied these scoring rules to HRS core sample respondents born 1923 or earlier (n=5483) for biennial assessments from 1995 to 2008. Compared with estimates excluding proxy respondents in the full cohort, incorporating information from proxy respondents increased estimated prevalence of dementia by 12 percentage points in 2008 (average age=89) and suggested accelerated rates of memory decline over time.

}, keywords = {Aged, Bias, Caregivers, Dementia, Female, Humans, Longitudinal Studies, Male, Neuropsychological tests, Prevalence, Proxy}, issn = {1546-4156}, doi = {10.1097/WAD.0b013e31826cfe90}, author = {Bei Wu and Tchetgen Tchetgen, Eric J and Theresa L Osypuk and White, Kellee and Mujahid, Mahasin and M. Maria Glymour} } @article {7900, title = {A Genetic IV Analysis to Assess the Effect of Body Mass Index on Depression in the Health And Retirement Study}, journal = {Am J Epidemiol}, volume = {177}, year = {2013}, pages = {S12}, publisher = {177}, abstract = {Background: The relationship between adiposity and mental health remains controversial despite extensive prior observational research. We use a genetic risk score (GRS) as an instrumental variable (IV) to estimate effects of increases in body mass index (BMI) on depressive symptoms. Methods: Data are from 11842 (whites = 10322, blacks = 1520) individuals from the nationally representative Health and Retirement Study with data on a 10-item Center for Epidemiologic Studies Depression (CESD) scale and genetics collected in 2006 or 2008. Based on 32 Single Nucleotide Polymorphisms (SNPs) known to predict BMI, we calculated a GRS as the sum of the number of risk alleles multiplied by the per allele effect size on BMI (based on prior publica- tions). We conducted over-identification tests with 4 IVs using subsets of the SNPs organized based on biological pathways (adiposity, appetite, and cardio-pulmonary factors) by which the genes might influence adiposity. Self-reported BMI prior to the assessment of CESD was used for validation of the external instrument. The CESD score was regressed on each genetic IV plus population stratification eigenvectors to derive the IV effect estimate. We compared these to conventional effect estimates derived from regressing CESD on self-reported BMI. Results: The GRS significantly predicted BMI in blacks (r2=0.016, p 0.001) and whites (r2=0.010, p 0.001). Self-reported BMI significantly predicted CESD, more strongly in whites (0.043, 95 -CI: 0.036, 0.05) than blacks (0.021, CI: 0.004, 0.038). IV effect estimates were large and statistically significant for whites (0.0 96, CI: 0.026, 0.167) but had very wide CIs for blacks (0.016, CI: -0.224, 0.256) . Over-identification tests showed no evidence of possible pleiotropy in the genetic risk score. Conclusions: Our IV analysis reveals that genotypes associated with BMI are also associated with depressive symptoms in whites, supporting a causal effect of BMI on depression.}, keywords = {Genetics, Health Conditions and Status, Public Policy}, author = {Stefan Walter and Mej{\'\i}a-Guevara, Iv{\'a}n and Eric J. Tchetgen Tchetgen and Karestan C Koenen and Ichiro Kawachi and Laura D Kubzansky and M. Maria Glymour} } @article {7814, title = {Stroke-associated differences in rates of activity of daily living loss emerge years before stroke onset.}, journal = {J Am Geriatr Soc}, volume = {61}, year = {2013}, month = {2013 Jun}, pages = {931-938}, publisher = {61}, abstract = {

OBJECTIVES: To compare typical age-related changes in activities of daily living (ADLs) independence in stroke-free adults with long-term ADL trajectories before and after stroke.

DESIGN: Prospective, observational study.

SETTING: Community-dwelling Health and Retirement Study (HRS) cohort.

PARTICIPANTS: HRS participants who were stroke free in 1998 and were followed through 2008 (average follow-up 7.9 years) (N = 18,441).

MEASUREMENTS: Strokes were assessed using self- or proxy-report of a doctor{\textquoteright}s diagnosis and month and year of event. Logistic regression was used to compare within-person changes in odds of self-reported independence in five ADLs in those who remained stroke free throughout follow-up (n = 16,816), those who survived a stroke (n = 1,208), and those who had a stroke and did not survive to participate in another interview (n = 417). Models were adjusted for demographic and socioeconomic covariates.

RESULTS: Even before stroke, those who later developed stroke had significantly lower ADL independence and were experiencing faster independence losses than similar-aged individuals who remained stroke free. Of those who developed a stroke, survivors experienced slower pre-stroke loss of ADL independence than those who died. ADL independence declined at the time of stroke and decline continued afterwards.

CONCLUSION: In adults at risk of stroke, disproportionate ADL limitations emerge well before stroke onset. Excess disability in stroke survivors should not be entirely attributed to effects of acute stroke or quality of acute stroke care. Although there are many possible causal pathways between ADL and stroke, the association may be noncausal. For example, ADL limitations may be a consequence of stroke risk factors (e.g., diabetes mellitus) or early cerebrovascular ischemia.

}, keywords = {Activities of Daily Living, Age of Onset, Aged, Aged, 80 and over, Bayes Theorem, Disability Evaluation, Disabled Persons, Female, Follow-Up Studies, Geriatric Assessment, Humans, Male, Middle Aged, Morbidity, Prospective Studies, Risk Assessment, Risk Factors, Socioeconomic factors, Stroke, Stroke Rehabilitation, Survival Rate, Survivors, Time Factors, United States}, issn = {1532-5415}, doi = {10.1111/jgs.12270}, author = {Benjamin D Capistrant and Qianyi Wang and Sze Y Liu and M. Maria Glymour} } @article {7759, title = {Long-term rate of change in memory functioning before and after stroke onset.}, journal = {Stroke}, volume = {43}, year = {2012}, month = {2012 Oct}, pages = {2561-6}, abstract = {

BACKGROUND AND PURPOSE: Memory impairment is a predictor and a consequence of stroke, but memory decline is common even in healthy elderly individuals. We compared the long-term trajectory of memory functioning before and after stroke with memory change in stroke-free elderly individuals.

METHODS: Health and Retirement Study participants aged 50 years and older (n=17 340) with no stroke history at baseline were interviewed biennially up to 10 years for first self-reported or proxy-reported stroke (n=1574). Age-, sex-, and race-adjusted segmented linear regression models were used to compare annual rates of change in a composite memory score before and after stroke among 3 groups: 1189 stroke survivors; 385 stroke decedents; and 15 766 cohort members who remained stroke-free.

RESULTS: Before stroke onset, individuals who later survived stroke had significantly (P<0.001) faster average annual rates of memory decline (-0.143 points per year) than those who remained stroke-free throughout follow-up (-0.101 points per year). Stroke decedents had even faster prestroke memory decline (-0.212 points per year). At stroke onset, memory declined an average of -0.369 points among stroke survivors, comparable with 3.7 years of age-related decline in stroke-free cohort members. After stroke, memory in stroke survivors continued to decline at -0.142 points per year, similar to their prestroke rates (P=0.93). Approximately 50\% of the memory difference between stroke survivors soon after stroke and age-matched stroke-free individuals was attributable to prestroke memory.

CONCLUSIONS: Although stroke onset induced large decrements in memory, memory differences were apparent years before stroke. Memory declines before stroke, especially among those who did not survive the stroke, were faster than declines among stroke-free adults.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, disease progression, Female, Follow-Up Studies, Humans, Linear Models, Longitudinal Studies, Male, Memory, Memory Disorders, Middle Aged, Stroke, Survivors, Time Factors}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.112.661587}, author = {Qianyi Wang and Benjamin D Capistrant and Amy Ehntholt and M. Maria Glymour} } @article {7725, title = {Self-reported and measured hypertension among older US- and foreign-born adults.}, journal = {J Immigr Minor Health}, volume = {14}, year = {2012}, note = {Copyright - Springer Science Business Media, LLC 2012 Language of summary - English Location - United States--US Pages - 721-6 ProQuest ID - 1022672464 Document feature - References SubjectsTermNotLitGenreText - United States--US Last updated - 2012-07-11 Place of publication - New York Corporate institution author - White, Kellee; Avenda o, Mauricio; Capistrant, Benjamin D; Robin Moon, J; Liu, Sze Y; Maria Glymour, M DOI - 2699707771; 70149852; 53471; JIMH; 22109587; SPVLJIMH109031449549}, month = {2012 Aug}, pages = {721-6}, publisher = {14}, abstract = {

Self-reported hypertension is frequently used for health surveillance. However, little is known about the validity of self-reported hypertension among older Americans by nativity status. This study compared self-reported and measured hypertension among older black, white, and Hispanic Americans by nativity using the 2006 and 2008 Health and Retirement Study (n~=~13,451). Sensitivity and specificity of self-reported hypertension were calculated using the Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure definition. Sensitivity was high among older blacks (88.9\%), whites (82.8\%), and Hispanics (84.0\%), and both foreign-born (83.2\%) and US-born (84.0\%). Specificity was above 90\% for both US-born and foreign-born, but higher for whites (92.8\%) than blacks (86.0\%). Despite the potential vulnerability of older foreign-born Americans, self-reported hypertension may be considered a reasonable estimate of hypertension status. Future research should confirm these findings in samples with a larger and more ethnically diverse foreign-born population.

}, keywords = {Aged, Black or African American, Blood Pressure Determination, Emigrants and Immigrants, Female, Hispanic or Latino, Humans, Hypertension, Male, Middle Aged, Nutrition Surveys, Reproducibility of Results, Self Report, United States, White People}, issn = {1557-1920}, doi = {10.1007/s10903-011-9549-3}, url = {http://search.proquest.com.proxy.lib.umich.edu/docview/1022672464?accountid=14667http://mgetit.lib.umich.edu/?ctx_ver=Z39.88-2004andctx_enc=info:ofi/enc:UTF-8andrfr_id=info:sid/ProQ 3Aabiglobalandrft_val_fmt=info:ofi/fmt:kev:mtx:journalandrft.genre=articl}, author = {White, Kellee and Mauricio Avendano and Benjamin D Capistrant and J Robin Moon and Sze Y Liu and M. Maria Glymour} } @article {12659, title = {Neighborhood disadvantage and self-assessed health, disability, and depressive symptoms: longitudinal results from the health and retirement study.}, journal = {Ann Epidemiol}, volume = {20}, year = {2010}, month = {2010 Nov}, pages = {856-61}, abstract = {

PURPOSE: By using a longitudinal cohort, we assessed the association between neighborhood disadvantage and incidence of poor health and function in three domains.

METHODS: More than 4,000 enrollees aged 55 to 65 years in the national Health and Retirement Study were assessed biennially from 1998 through 2006 for incidence of fair/poor self-rated health, elevated depressive symptoms, and limitations in six basic activities of daily living (disability). Each analysis was restricted to subjects without that condition in 1994 or 1996. Neighborhoods (census tracts, time-updated for moves), were considered disadvantaged if they fell below the 25th percentile in an index comprising six socioeconomic status indicators. Repeated measures logistic regressions, inverse probability weighted to account for individual confounders, selective survival, and loss to follow-up were used to estimate odds ratios (ORs) for incidence of each outcome in the wave after exposure to disadvantaged neighborhood.

RESULTS: After covariate adjustment, neighborhood disadvantage predicted onset of fair/poor SRH (OR, 1.36; 95\% confidence interval, 1.15-1.59) but not disability (OR, 0.97; 0.81-1.16) or elevated depressive symptoms (OR, 0.97; 0.81-1.16).

CONCLUSIONS: Results confirmed previous findings that neighborhood disadvantage predicts self-rated health in a longitudinal context but did not support an association between neighborhood disadvantage and onset of disability or elevated depressive symptoms.

}, keywords = {Activities of Daily Living, Age Factors, Aged, Confidence Intervals, depression, Disabled Persons, Female, Health Status Disparities, Humans, Incidence, Logistic Models, Longitudinal Studies, Male, Middle Aged, Odds Ratio, Poverty, Residence Characteristics, Risk, Self-Assessment, Socioeconomic factors, Time Factors}, issn = {1873-2585}, doi = {10.1016/j.annepidem.2010.08.003}, author = {M. Maria Glymour and Mujahid, Mahasin and Wu, Qiong and White, Kellee and Tchetgen Tchetgen, Eric J} } @article {7055, title = {When is baseline adjustment useful in analyses of change? An example with education and cognitive change.}, journal = {Am J Epidemiol}, volume = {162}, year = {2005}, month = {2005 Aug 01}, pages = {267-78}, publisher = {162}, abstract = {

In research on the determinants of change in health status, a crucial analytic decision is whether to adjust for baseline health status. In this paper, the authors examine the consequences of baseline adjustment, using for illustration the question of the effect of educational attainment on change in cognitive function in old age. With data from the US-based Assets and Health Dynamics Among the Oldest Old survey (n = 5,726; born before 1924), they show that adjustment for baseline cognitive test score substantially inflates regression coefficient estimates for the effect of schooling on change in cognitive test scores compared with models without baseline adjustment. To explain this finding, they consider various plausible assumptions about relations among variables. Each set of assumptions is represented by a causal diagram. The authors apply simple rules for assessing causal diagrams to demonstrate that, in many plausible situations, baseline adjustment induces a spurious statistical association between education and change in cognitive score. More generally, when exposures are associated with baseline health status, this bias can arise if change in health status preceded baseline assessment or if the dependent variable measurement is unreliable or unstable. In some cases, change-score analyses without baseline adjustment provide unbiased causal effect estimates when baseline-adjusted estimates are biased.

}, keywords = {Age Factors, Aged, Bias, Cognition Disorders, Educational Status, Epidemiologic Methods, Female, Health Status, Humans, Longitudinal Studies, Male, Models, Statistical, Neuropsychological tests, Regression Analysis, United States}, issn = {0002-9262}, doi = {10.1093/aje/kwi187}, author = {M. Maria Glymour and Weuve, Jennifer and Lisa F Berkman and Ichiro Kawachi and Robins, James M.} }