%0 Journal Article %J Housing and Society %D 2022 %T Mortgage delinquency, foreclosure, and cognition in later life %A Gillian L Marshall %A Sarah L. Canham %A Eva Kahana %A Eric B Larson %K Cognition %K Foreclosure %K mortgage delinquency %K Stress %X The rapid growth in housing insecurity among older adults is a major public health concern. While there is evidence that stress contributes to poor health, the relationship between housing-related financial stressors and cognitive functioning is relatively unknown. We investigated the association between the personal experiences of mortgage delinquency and foreclosure and cognition and its sub-components of episodic memory and mental status among Americans age 65 years and older. Using the data from two concatenated waves (2010, 2012) of the Health and Retirement Study, we analyzed data for respondents (N = 6,612) across both waves using generalized linear regressions. Our findings suggest that there is a negative association between mortgage delinquency/foreclosure and cognitive scores. Further, we found a negative association between mortgage delinquency and mental status among women, specifically. These results highlight the importance of financial well-being vis-à-vis housing stability and its significance to mental well-being and cognition of adults in later life. Future research is needed to identify macro-level stressors such as mortgage delinquency and/or foreclosure. Such information would improve strategies for prevention and intervention particularly for older adults living on fixed incomes who have little opportunity to earn pre-retirement levels of income. %B Housing and Society %V 49 %P 113-127 %G eng %N 2 %R https://doi.org/10.1080/08882746.2021.2006548 %0 Journal Article %J Journal of General Internal Medicine %D 2022 %T Observational study of patient characteristics associated with a timely diagnosis of dementia and mild cognitive impairment without dementia. %A White, Lindsay %A Ingraham, Bailey %A Eric B Larson %A Fishman, Paul %A Park, Sungchul %A Norma B Coe %K cognitive impairment %K Dementia %K Diagnosis %K Disparities %X

BACKGROUND: Timely diagnosis of cognitive impairment is a key goal of the National Plan to Address Alzheimer's Disease, but studies of factors associated with a timely diagnosis are limited.

OBJECTIVE: To identify patient characteristics associated with a timely diagnosis of dementia and mild cognitive impairment (MCI).

DESIGN: Retrospective observational study using survey data from the Health and Retirement Study (HRS) from 1995-2016 (interview waves 3-13).

PARTICIPANTS: 4,760 respondents with incident dementia and 1,864 with incident MCI identified using longitudinal measures of cognitive functioning.

MAIN MEASURES: Timely or delayed diagnosis based on the timing of a self or proxy report of a healthcare provider diagnosis in relation to respondents first dementia or MCI-qualifying cognitive score, sociodemographic characteristics, health status, health care utilization, insurance provider, and year of first qualifying score.

KEY RESULTS: Only 26.0% of the 4,760 respondents with incident dementia and 11.4% of the 1,864 respondents with incident MCI received a timely diagnosis. Non-Hispanic Black respondents and respondents with less than a college degree were significantly less likely to receive a timely diagnosis of either dementia or MCI than Non-Hispanic White respondents (dementia odds ratio (OR): 0.61, 95% CI: 0.50, 0.75; MCI OR: 0.40, 95% CI: 0.23, 0.70) and those with a college degree (dementia OR for less than high school degree: 0.30, 95% CI: 0.23, 0.38; MCI OR: 0.36, 95% CI: 0.22, 0.60). Respondents that lived alone were also less likely to receive a timely diagnosis of dementia (OR: 0.69, 95% CI: 0.59, 0.81), though not MCI. Timely diagnosis of both conditions increased over time.

CONCLUSIONS: Targeting resources for timely diagnosis of cognitive impairment to individuals from racial and ethnic minorities, lower educational attainment, and living alone may improve detection and reduce disparities around timely diagnosis of dementia and MCI.

%B Journal of General Internal Medicine %V 37 %P 2957-2965 %G eng %N 12 %R https://doi.org/10.1007/s11606-021-07169-7 %0 Journal Article %J Gerontology and Geriatric Medicine %D 2020 %T Dementia Is Associated With Earlier Mortality for Men and Women in the United States. %A White, Lindsay %A Fishman, Paul %A Basu, Anirban %A Paul K Crane %A Eric B Larson %A Norma B Coe %K Dementia %K gender %K Medicare %K Medicare administrative data %X

Sociodemographic trends in the United States may influence future dementia-associated mortality, yet there is little evidence about their potential impact. Our study objective was to estimate the effect of dementia on survival in adults stratified by sex, education, and marital status. Using survey data from the Health and Retirement Study (HRS) linked to Medicare claims from 1991 to 2012, we identified a retrospective cohort of adults with at least one International Classification of Diseases-ninth revision-Clinical Modification (ICD-9-CM) dementia diagnosis code ( = 3,714). For each case, we randomly selected up to five comparators, matching on sex, birth year, education, and HRS entry year ( = 9,531), and assigned comparators the diagnosis date of their matched case. Participants were followed for up to 60 months following diagnosis. We estimated a survival function for the entire study population and then within successive strata defined by sex, education, and marital status. On average, dementia cases were 80.5 years old at diagnosis. Most were female, had less than college-level education, and approximately 40% were married at diagnosis. In multivariate analyses, dementia diagnosis was associated with earlier mortality for women (predicted median survival of 54.5 months vs. 62.5 months; dementia coefficient = -0.13; 95% confidence interval [CI] = [-0.22, -0.04]; = .003), but even more so among men (predicted median survival of 35.5 months vs. 54.5 months; dementia coefficient = -0.42; 95% CI = [-0.52, -0.31]; < .001). We found substantial heterogeneity in the relationship between dementia and survival, associated with both education and marital status. Both sex and level of education moderate the relationship between dementia diagnosis and length of survival.

%B Gerontology and Geriatric Medicine %V 6 %P 2333721420945922 %G eng %R 10.1177/2333721420945922 %0 Journal Article %J Health Services Research %D 2019 %T Medicare expenditures attributable to dementia. %A Lindsay L Waite %A Fishman, Paul %A Basu, Anirban %A Paul K Crane %A Eric B Larson %A Norma B Coe %K Cognition & Reasoning %K Dementia %K Medicare linkage %K Medicare/Medicaid/Health Insurance %X

OBJECTIVE: To estimate dementia's incremental cost to the traditional Medicare program.

DATA SOURCES: Health and Retirement Study (HRS) survey-linked Medicare part A and B claims from 1991 to 2012.

STUDY DESIGN: We compared Medicare expenditures for 60 months following a claims-based dementia diagnosis to those for a randomly selected, matched comparison group.

DATA COLLECTION/EXTRACTION METHODS: We used a cost estimator that accounts for differential survival between individuals with and without dementia and decomposes incremental costs into survival and cost intensity components.

PRINCIPAL FINDINGS: Dementia's five-year incremental cost to the traditional Medicare program is approximately $15 700 per patient, nearly half of which is incurred in the first year after diagnosis. Shorter survival with dementia mitigates the incremental cost by about $2650. Increased costs for individuals with dementia were driven by more intensive use of Medicare part A covered services. The incremental cost of dementia was about $7850 higher for females than for males because of sex-specific differential mortality associated with dementia.

CONCLUSIONS: Dementia's cost to the traditional Medicare program is significant. Interventions that target early identification of dementia and preventable inpatient and post-acute care services could produce substantial savings.

%B Health Services Research %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/30868557?dopt=Abstract %R 10.1111/1475-6773.13134 %0 Journal Article %J Journal of the American Geriatrics Society %D 2018 %T A Comprehensive Measure of the Costs of Caring for a Parent: Differences According to Functional Status %A Norma B Coe %A Meghan M. Skira %A Eric B Larson %K Caregiving %K Informal care %K Well-being %X Approximately 34 million family and friends provided unpaid care to individuals aged 50 and older in 2015. It is difficult to place a value on that time, because no payment is made to the caregiver, and multiplying caregiving hours by a wage does not account for the value of lost leisure time, implications for future employability and wages, or any intrinsic benefits accrued to the care provider. This study used a dynamic discrete choice model to estimate the costs of informal care provided by a daughter to her mother, including these other costs and benefits not typically accounted for, and compared these cost estimates for 4 categories of the mother's functional status: doctor-diagnosed memory-related disease, limitations in activities of daily living (ADLs), combination of both, cannot be left alone for 1 hour or more. We studied women aged 40 to 70 with a living mother at the start of the sample period (N=3,427 adult daughters) using data from the Health and Retirement Study (1998–2012). The primary outcome was the monetized change in well-being due to caregiving, what economists call “welfare costs.” We estimate that the median cost to the daughter's well-being of providing care to an elderly mother ranged from $144,302 to $201,896 over 2 years, depending on the mother's functional status. These estimates suggest that informal care cost $277 billion in 2011, 20% more than estimates that account only for current foregone wages. © 2018, Copyright the Author Journal compilation © 2018, The American Geriatrics Society %B Journal of the American Geriatrics Society %V 66 %P 2003 - 2008 %8 Jan-10-2018 %G eng %U https://pubmed.ncbi.nlm.nih.gov/30222183/ %N 10 %! J Am Geriatr Soc %R 10.1111/jgs.15552 %0 Journal Article %J Nat Genet %D 2018 %T Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. %A Turcot, Valérie %A Lu, Yingchang %A Highland, Heather M %A Schurmann, Claudia %A Justice, Anne E %A Fine, Rebecca S %A Bradfield, Jonathan P %A Tõnu Esko %A Giri, Ayush %A Graff, Mariaelisa %A Guo, Xiuqing %A Hendricks, Audrey E %A Karaderi, Tugce %A Lempradl, Adelheid %A Locke, Adam E %A Mahajan, Anubha %A Marouli, Eirini %A Sivapalaratnam, Suthesh %A Young, Kristin L %A Alfred, Tamuno %A Feitosa, Mary F %A Masca, Nicholas G D %A Alisa Manning %A Medina-Gomez, Carolina %A Mudgal, Poorva %A Ng, Maggie C Y %A Reiner, Alex P %A Vedantam, Sailaja %A Willems, Sara M %A Thomas W Winkler %A Gonçalo R Abecasis %A Aben, Katja K %A Alam, Dewan S %A Alharthi, Sameer E %A Matthew A. Allison %A Amouyel, Philippe %A Asselbergs, Folkert W %A Auer, Paul L %A Balkau, Beverley %A Bang, Lia E %A Barroso, Inês %A Bastarache, Lisa %A Benn, Marianne %A Bergmann, Sven %A Bielak, Lawrence F %A Blüher, Matthias %A Boehnke, Michael %A Boeing, Heiner %A Boerwinkle, Eric %A Böger, Carsten A %A Bork-Jensen, Jette %A Bots, Michiel L %A Erwin P Bottinger %A Bowden, Donald W %A Brandslund, Ivan %A Breen, Gerome %A Brilliant, Murray H %A Broer, Linda %A Brumat, Marco %A Burt, Amber A %A Adam S Butterworth %A Campbell, Peter T %A Cappellani, Stefania %A Carey, David J %A Catamo, Eulalia %A Caulfield, Mark J %A Chambers, John C %A Daniel I Chasman %A Yii-Der I Chen %A Chowdhury, Rajiv %A Cramer Christensen %A Chu, Audrey Y %A Cocca, Massimiliano %A Collins, Francis S %A Cook, James P %A Corley, Janie %A Jordi Corominas Galbany %A Cox, Amanda J %A Crosslin, David S %A Cuellar-Partida, Gabriel %A D'Eustacchio, Angela %A Danesh, John %A Gail Davies %A Bakker, Paul I W %A Groot, Mark C H %A Mutsert, Renée %A Ian J Deary %A George Dedoussis %A Ellen W Demerath %A Heijer, Martin %A Anneke I den Hollander %A Hester M den Ruijter %A Joe G Dennis %A Denny, Josh C %A Angelantonio, Emanuele %A Drenos, Fotios %A Du, Mengmeng %A Dubé, Marie-Pierre %A Dunning, Alison M %A Easton, Douglas F %A Edwards, Todd L %A Ellinghaus, David %A Ellinor, Patrick T %A Elliott, Paul %A Evangelou, Evangelos %A Farmaki, Aliki-Eleni %A Farooqi, I Sadaf %A Jessica Faul %A Fauser, Sascha %A Feng, Shuang %A Ferrannini, Ele %A Ferrières, Jean %A Florez, Jose C %A Ford, Ian %A Myriam Fornage %A Franco, Oscar H %A Franke, Andre %A Franks, Paul W %A Friedrich, Nele %A Frikke-Schmidt, Ruth %A Galesloot, Tessel E %A Gan, Wei %A Gandin, Ilaria %A Paolo P. Gasparini %A Gibson, Jane %A Giedraitis, Vilmantas %A Gjesing, Anette P %A Gordon-Larsen, Penny %A Gorski, Mathias %A Hans-Jörgen Grabe %A Grant, Struan F A %A Grarup, Niels %A Griffiths, Helen L %A Grove, Megan L %A Gudnason, Vilmundur %A Gustafsson, Stefan %A Jeffrey Haessler %A Hakonarson, Hakon %A Anke R Hammerschlag %A Hansen, Torben %A Tamara B Harris %A Andrew T Hattersley %A Have, Christian T %A Caroline Hayward %A He, Liang %A Heard-Costa, Nancy L %A Andrew C Heath %A Iris M Heid %A Helgeland, Øyvind %A Hernesniemi, Jussi %A Hewitt, Alex W %A Oddgeir L Holmen %A Hovingh, G Kees %A Howson, Joanna M M %A Hu, Yao %A Huang, Paul L %A Huffman, Jennifer E %A Mohammed Arfan Ikram %A Ingelsson, Erik %A Jackson, Anne U %A Jansson, Jan-Håkan %A Jarvik, Gail P %A Jensen, Gorm B %A Jia, Yucheng %A Johansson, Stefan %A Jørgensen, Marit E %A Jørgensen, Torben %A Jukema, J Wouter %A Kahali, Bratati %A Kahn, René S %A Kähönen, Mika %A Kamstrup, Pia R %A Kanoni, Stavroula %A Kaprio, Jaakko %A Karaleftheri, Maria %A Sharon L R Kardia %A Karpe, Fredrik %A Kathiresan, Sekar %A Kee, Frank %A Lambertus A Kiemeney %A Eric S Kim %A Kitajima, Hidetoshi %A Komulainen, Pirjo %A Kooner, Jaspal S %A Charles Kooperberg %A Korhonen, Tellervo %A Kovacs, Peter %A Kuivaniemi, Helena %A Kutalik, Zoltán %A Kuulasmaa, Kari %A Kuusisto, Johanna %A Laakso, Markku %A Lakka, Timo A %A Lamparter, David %A Lange, Ethan M %A Leslie A Lange %A Langenberg, Claudia %A Eric B Larson %A Lee, Nanette R %A Lehtimäki, Terho %A Lewis, Cora E %A Li, Huaixing %A Li, Jin %A Li-Gao, Ruifang %A Lin, Honghuang %A Lin, Keng-Hung %A Lin, Li-An %A Lin, Xu %A Lars Lind %A Lindström, Jaana %A Linneberg, Allan %A Liu, Ching-Ti %A Liu, Dajiang J %A Yongmei Liu %A Ken Sin Lo %A Lophatananon, Artitaya %A Lotery, Andrew J %A Loukola, Anu %A Luan, Jian'an %A Lubitz, Steven A %A Lyytikäinen, Leo-Pekka %A Männistö, Satu %A Marenne, Gaëlle %A Mazul, Angela L %A McCarthy, Mark I %A McKean-Cowdin, Roberta %A Sarah E Medland %A Meidtner, Karina %A Lili Milani %A Mistry, Vanisha %A Mitchell, Paul %A Mohlke, Karen L %A Moilanen, Leena %A Moitry, Marie %A Grant W Montgomery %A Dennis O Mook-Kanamori %A Moore, Carmel %A Mori, Trevor A %A Morris, Andrew D %A Morris, Andrew P %A Müller-Nurasyid, Martina %A Munroe, Patricia B %A Michael A Nalls %A Narisu, Narisu %A Nelson, Christopher P %A Neville, Matt %A Sune Fallgaard Nielsen %A Nikus, Kjell %A Njølstad, Pål R %A Børge G Nordestgaard %A Nyholt, Dale R %A Jeff O'Connell %A O'Donoghue, Michelle L %A Ophoff, Roel A %A Owen, Katharine R %A Packard, Chris J %A Padmanabhan, Sandosh %A Palmer, Colin N A %A Palmer, Nicholette D %A Pasterkamp, Gerard %A Patel, Aniruddh P %A Pattie, Alison %A Pedersen, Oluf %A Peissig, Peggy L %A Peloso, Gina M %A Pennell, Craig E %A Markus Perola %A Perry, James A %A Perry, John R B %A Pers, Tune H %A Person, Thomas N %A Peters, Annette %A Petersen, Eva R B %A Peyser, Patricia A %A Pirie, Ailith %A Polasek, Ozren %A Tinca J Polderman %A Puolijoki, Hannu %A Olli T Raitakari %A Rasheed, Asif %A Rauramaa, Rainer %A Reilly, Dermot F %A Renstrom, Frida %A Rheinberger, Myriam %A Ridker, Paul M %A Rioux, John D %A Rivas, Manuel A %A Roberts, David J %A Neil R Robertson %A Robino, Antonietta %A Rolandsson, Olov %A Rudan, Igor %A Ruth, Katherine S %A Saleheen, Danish %A Veikko Salomaa %A Nilesh J Samani %A Sapkota, Yadav %A Sattar, Naveed %A Schoen, Robert E %A Schreiner, Pamela J %A Schulze, Matthias B %A Scott, Robert A %A Segura-Lepe, Marcelo P %A Svati H Shah %A Sheu, Wayne H-H %A Sim, Xueling %A Slater, Andrew J %A Small, Kerrin S %A Albert Vernon Smith %A Southam, Lorraine %A Timothy Spector %A Elizabeth K Speliotes %A John M Starr %A Stefansson, Kari %A Steinthorsdottir, Valgerdur %A Kathleen E Stirrups %A Strauch, Konstantin %A Heather M Stringham %A Stumvoll, Michael %A Sun, Liang %A Surendran, Praveen %A Swift, Amy J %A Tada, Hayato %A Tansey, Katherine E %A Tardif, Jean-Claude %A Kent D Taylor %A Teumer, Alexander %A Thompson, Deborah J %A Thorleifsson, Gudmar %A Thorsteinsdottir, Unnur %A Thuesen, Betina H %A Tönjes, Anke %A Tromp, Gerard %A Trompet, Stella %A Tsafantakis, Emmanouil %A Tuomilehto, Jaakko %A Tybjaerg-Hansen, Anne %A Tyrer, Jonathan P %A Uher, Rudolf %A André G Uitterlinden %A Uusitupa, Matti %A Laan, Sander W %A Duijn, Cornelia M %A Leeuwen, Nienke %A van Setten, Jessica %A Vanhala, Mauno %A Varbo, Anette %A Varga, Tibor V %A Varma, Rohit %A Digna R Velez Edwards %A Vermeulen, Sita H %A Veronesi, Giovanni %A Vestergaard, Henrik %A Vitart, Veronique %A Vogt, Thomas F %A Völker, Uwe %A Vuckovic, Dragana %A Wagenknecht, Lynne E %A Walker, Mark %A Wallentin, Lars %A Wang, Feijie %A Wang, Carol A %A Wang, Shuai %A Wang, Yiqin %A Erin B Ware %A Wareham, Nicholas J %A Warren, Helen R %A Dawn M Waterworth %A Wessel, Jennifer %A White, Harvey D %A Willer, Cristen J %A Wilson, James G %A Daniel Witte %A Andrew R Wood %A Wu, Ying %A Yaghootkar, Hanieh %A Yao, Jie %A Yao, Pang %A Laura M Yerges-Armstrong %A Young, Robin %A Zeggini, Eleftheria %A Zhan, Xiaowei %A Zhang, Weihua %A Wei Zhao %A Zhou, Wei %A Krina T Zondervan %A Rotter, Jerome I %A Pospisilik, John A %A Fernando Rivadeneira %A Ingrid B Borecki %A Deloukas, Panos %A Timothy M Frayling %A Lettre, Guillaume %A Kari E North %A Lindgren, Cecilia M %A Joel N Hirschhron %A Ruth J F Loos %X

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

%B Nat Genet %V 50 %P 26-41 %8 2018 Jan %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/29273807?dopt=Abstract %R 10.1038/s41588-017-0011-x %0 Journal Article %J Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring %D 2017 %T Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality %A Mez, Jesse %A Jessica R Marden %A Mukherjee, Shubhabrata %A Stefan Walter %A Laura E Gibbons %A Alden L Gross %A Laura B Zahodne %A Paola Gilsanz %A Brewster, Paul %A Nho, Kwangsik %A Paul K Crane %A Eric B Larson %A M. Maria Glymour %K Alzheimer's disease %K APoE4 %K Cognitive Ability %K Genetics %K Mortality %K Risk Factors %X We hypothesized that, like apolipoprotein E (APOE), other late-onset Alzheimer'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: 1.00–1.10, 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: 0.41–1.00, P =.05). Discussion Non-APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence. %B Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring %V 8 %P 188-195 %G eng %U 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 %! Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring %R 10.1016/j.dadm.2017.07.002 %0 Journal Article %J JAMA Intern Med %D 2017 %T A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012. %A Kenneth M. Langa %A Eric B Larson %A Eileen M. Crimmins %A Jessica Faul %A Deborah A Levine %A Mohammed U Kabeto %A David R Weir %K Aged %K Dementia %K Female %K Humans %K Male %K Prevalence %K Risk Factors %K United States %X

Importance: The aging of the US population is expected to lead to a large increase in the number of adults with dementia, but some recent studies in the United States and other high-income countries suggest that the age-specific risk of dementia may have declined over the past 25 years. Clarifying current and future population trends in dementia prevalence and risk has important implications for patients, families, and government programs.

Objective: To compare the prevalence of dementia in the United States in 2000 and 2012.

Design, Setting, and Participants: We used data from the Health and Retirement Study (HRS), a nationally representative, population-based longitudinal survey of individuals in the United States 65 years or older from the 2000 (n = 10 546) and 2012 (n = 10 511) waves of the HRS.

Main Outcomes and Measures: Dementia was identified in each year using HRS cognitive measures and validated methods for classifying self-respondents, as well as those represented by a proxy. Logistic regression was used to identify socioeconomic and health variables associated with change in dementia prevalence between 2000 and 2012.

Results: The study cohorts had an average age of 75.0 years (95% CI, 74.8-75.2 years) in 2000 and 74.8 years (95% CI, 74.5-75.1 years) in 2012 (P = .24); 58.4% (95% CI, 57.3%-59.4%) of the 2000 cohort was female compared with 56.3% (95% CI, 55.5%-57.0%) of the 2012 cohort (P < .001). Dementia prevalence among those 65 years or older decreased from 11.6% (95% CI, 10.7%-12.7%) in 2000 to 8.8% (95% CI, 8.2%-9.4%) (8.6% with age- and sex-standardization) in 2012 (P < .001). More years of education was associated with a lower risk for dementia, and average years of education increased significantly (from 11.8 years [95% CI, 11.6-11.9 years] to 12.7 years [95% CI, 12.6-12.9 years]; P < .001) between 2000 and 2012. The decline in dementia prevalence occurred even though there was a significant age- and sex-adjusted increase between years in the cardiovascular risk profile (eg, prevalence of hypertension, diabetes, and obesity) among older US adults.

Conclusions and Relevance: The prevalence of dementia in the United States declined significantly between 2000 and 2012. An increase in educational attainment was associated with some of the decline in dementia prevalence, but the full set of social, behavioral, and medical factors contributing to the decline is still uncertain. Continued monitoring of trends in dementia incidence and prevalence will be important for better gauging the full future societal impact of dementia as the number of older adults increases in the decades ahead.

%B JAMA Intern Med %V 177 %P 51-58 %8 2017 01 01 %G eng %U http://archinte.jamanetwork.com/article.aspx?doi=10.1001/jamainternmed.2016.6807http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2587084 %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/27893041?dopt=Abstract %! JAMA Intern Med %R 10.1001/jamainternmed.2016.6807 %0 Journal Article %J Nature %D 2017 %T Rare and low-frequency coding variants alter human adult height. %A Marouli, Eirini %A Graff, Mariaelisa %A Medina-Gomez, Carolina %A Ken Sin Lo %A Andrew R Wood %A Kjaer, Troels R %A Fine, Rebecca S %A Lu, Yingchang %A Schurmann, Claudia %A Highland, Heather M %A Rüeger, Sina %A Thorleifsson, Gudmar %A Justice, Anne E %A Lamparter, David %A Kathleen E Stirrups %A Turcot, Valérie %A Young, Kristin L %A Thomas W Winkler %A Tõnu Esko %A Karaderi, Tugce %A Locke, Adam E %A Masca, Nicholas G D %A Ng, Maggie C Y %A Mudgal, Poorva %A Rivas, Manuel A %A Vedantam, Sailaja %A Mahajan, Anubha %A Guo, Xiuqing %A Gonçalo R Abecasis %A Aben, Katja K %A Adair, Linda S %A Alam, Dewan S %A Albrecht, Eva %A Allin, Kristine H %A Matthew A. Allison %A Amouyel, Philippe %A Appel, Emil V %A Arveiler, Dominique %A Asselbergs, Folkert W %A Auer, Paul L %A Balkau, Beverley %A Banas, Bernhard %A Bang, Lia E %A Benn, Marianne %A Bergmann, Sven %A Bielak, Lawrence F %A Blüher, Matthias %A Boeing, Heiner %A Boerwinkle, Eric %A Böger, Carsten A %A Bonnycastle, Lori L %A Bork-Jensen, Jette %A Bots, Michiel L %A Erwin P Bottinger %A Bowden, Donald W %A Brandslund, Ivan %A Breen, Gerome %A Brilliant, Murray H %A Broer, Linda %A Burt, Amber A %A Adam S Butterworth %A Carey, David J %A Caulfield, Mark J %A Chambers, John C %A Daniel I Chasman %A Yii-Der I Chen %A Chowdhury, Rajiv %A Cramer Christensen %A Chu, Audrey Y %A Cocca, Massimiliano %A Collins, Francis S %A Cook, James P %A Corley, Janie %A Jordi Corominas Galbany %A Cox, Amanda J %A Cuellar-Partida, Gabriel %A Danesh, John %A Gail Davies %A de Bakker, Paul I W %A de Borst, Gert J %A de Denus, Simon %A de Groot, Mark C H %A de Mutsert, Renée %A Ian J Deary %A George Dedoussis %A Ellen W Demerath %A Anneke I den Hollander %A Joe G Dennis %A Di Angelantonio, Emanuele %A Drenos, Fotios %A Du, Mengmeng %A Dunning, Alison M %A Easton, Douglas F %A Ebeling, Tapani %A Edwards, Todd L %A Ellinor, Patrick T %A Elliott, Paul %A Evangelou, Evangelos %A Farmaki, Aliki-Eleni %A Jessica Faul %A Feitosa, Mary F %A Feng, Shuang %A Ferrannini, Ele %A Marco M Ferrario %A Ferrières, Jean %A Florez, Jose C %A Ford, Ian %A Myriam Fornage %A Franks, Paul W %A Frikke-Schmidt, Ruth %A Galesloot, Tessel E %A Gan, Wei %A Gandin, Ilaria %A Paolo P. 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R Kardia %A Karpe, Fredrik %A Kee, Frank %A Keeman, Renske %A Lambertus A Kiemeney %A Kitajima, Hidetoshi %A Kluivers, Kirsten B %A Kocher, Thomas %A Komulainen, Pirjo %A Kontto, Jukka %A Kooner, Jaspal S %A Charles Kooperberg %A Kovacs, Peter %A Kriebel, Jennifer %A Kuivaniemi, Helena %A Küry, Sébastien %A Kuusisto, Johanna %A La Bianca, Martina %A Laakso, Markku %A Lakka, Timo A %A Lange, Ethan M %A Leslie A Lange %A Langefeld, Carl D %A Langenberg, Claudia %A Eric B Larson %A Lee, I-Te %A Lehtimäki, Terho %A Lewis, Cora E %A Li, Huaixing %A Li, Jin %A Li-Gao, Ruifang %A Lin, Honghuang %A Lin, Li-An %A Lin, Xu %A Lars Lind %A Lindström, Jaana %A Linneberg, Allan %A Liu, Yeheng %A Yongmei Liu %A Lophatananon, Artitaya %A Luan, Jian'an %A Lubitz, Steven A %A Lyytikäinen, Leo-Pekka %A Mackey, David A %A Pamela A F Madden %A Alisa Manning %A Männistö, Satu %A Marenne, Gaëlle %A Marten, Jonathan %A Nicholas G Martin %A Mazul, Angela L %A Meidtner, Karina %A Andres Metspalu %A Mitchell, Paul %A Mohlke, Karen L %A Dennis O Mook-Kanamori %A Morgan, Anna %A Morris, Andrew D %A Morris, Andrew P %A Müller-Nurasyid, Martina %A Munroe, Patricia B %A Michael A Nalls %A Nauck, Matthias %A Nelson, Christopher P %A Neville, Matt %A Sune Fallgaard Nielsen %A Nikus, Kjell %A Njølstad, Pål R %A Børge G Nordestgaard %A Ntalla, Ioanna %A Jeff O'Connell %A Oksa, Heikki %A Loes M Olde Loohuis %A Ophoff, Roel A %A Owen, Katharine R %A Packard, Chris J %A Padmanabhan, Sandosh %A Palmer, Colin N A %A Pasterkamp, Gerard %A Patel, Aniruddh P %A Pattie, Alison %A Pedersen, Oluf %A Peissig, Peggy L %A Peloso, Gina M %A Pennell, Craig E %A Markus Perola %A Perry, James A %A Perry, John R B %A Person, Thomas N %A Pirie, Ailith %A Polasek, Ozren %A Posthuma, Danielle %A Olli T Raitakari %A Rasheed, Asif %A Rauramaa, Rainer %A Reilly, Dermot F %A Reiner, Alex P %A Renstrom, Frida %A Ridker, Paul M %A Rioux, John D %A Neil R Robertson %A Robino, Antonietta %A Rolandsson, Olov %A Rudan, Igor %A 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%A Joel N Hirschhron %A Deloukas, Panos %A Lettre, Guillaume %X

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

%B Nature %V 542 %P 186-190 %8 2017 Feb 09 %G eng %N 7640 %1 http://www.ncbi.nlm.nih.gov/pubmed/28146470?dopt=Abstract %R 10.1038/nature21039 %0 Journal Article %J PLOS Medicine %D 2017 %T What’s the “Take Home” from Research on Dementia Trends? %A Eric B Larson %A Kenneth M. Langa %K Cognitive Ability %K Dementia %B PLOS Medicine %V 14 %P e1002236 %8 Jul-03-2017 %G eng %U http://dx.plos.org/10.1371/journal.pmed.1002236http://dx.plos.org/10.1371/journal.pmed.1002236 %N 3 %! PLoS Med %R 10.1371/journal.pmed.1002236 %0 Journal Article %J Alzheimers Dement %D 2015 %T Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses. %A Mukherjee, Shubhabrata %A Stefan Walter %A Kauwe, John S K %A Andrew J Saykin %A David A Bennett %A Eric B Larson %A Paul K Crane %A M. Maria Glymour %K Aged %K Aged, 80 and over %K Alzheimer disease %K Body Mass Index %K Female %K Genotype %K Humans %K Linear Models %K Male %K Mendelian Randomization Analysis %K Obesity %K Phenotype %K Polymorphism, Single Nucleotide %K Risk Factors %X

Observational research shows that higher body mass index (BMI) increases Alzheimer'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.

%B Alzheimers Dement %V 11 %P 1439-1451 %8 2015 Dec %G eng %N 12 %1 http://www.ncbi.nlm.nih.gov/pubmed/26079416?dopt=Abstract %R 10.1016/j.jalz.2015.05.015 %0 Journal Article %J The Journal of the Economics of Ageing %D 2014 %T Education, brain health, and improving life opportunities for women %A Kenneth M. Langa %A Eric B Larson %K Education %K Gender Differences %K Life opportunities %K Older Adults %K Women and Minorities %X The paper by Lei et al. in this issue adds to the growing body of empirical evidence that education and cognitive stimulation, both in early-life and in later-life, seem especially important for cognitive health and the prevention of cognitive decline with aging. The expanding educational opportunities for girls and women in developing countries such as China over the last few decades appear to have played an important role in improving their cognitive health and, in turn, have likely expanded their opportunities to participate more fully and successfully in both work and social roles. While “curing” dementia in the coming decades seems unlikely, decreasing the risk of cognitive impairment and disability in both developed and developing countries through increasing education, life-long cognitive stimulation, and improved control of cardiovascular risk appears achievable. Success would benefit people of all ages by keeping older adults more independent and productive, and minimizing the burden of support on younger generations. %B The Journal of the Economics of Ageing %V 4 %P 56 - 58 %8 Jan-12-2014 %G eng %U http://linkinghub.elsevier.com/retrieve/pii/S2212828X14000176http://api.elsevier.com/content/article/PII:S2212828X14000176?httpAccept=text/xmlhttp://api.elsevier.com/content/article/PII:S2212828X14000176?httpAccept=text/plain %! The Journal of the Economics of Ageing %R 10.1016/j.jeoa.2014.08.001 %0 Journal Article %J New England Journal of Medicine %D 2013 %T New insights into the dementia epidemic. %A Eric B Larson %A Kristine Yaffe %A Kenneth M. Langa %K Aging %K Cognitive Ability %K Dementia %K Health Conditions and Status %K Older Adults %B New England Journal of Medicine %V 369 %P 2275-7 %8 2013 Dec 12 %G eng %N 24 %R 10.1056/NEJMp1311405 %0 Journal Article %J Alzheimers Dement %D 2011 %T Trends in the incidence and prevalence of Alzheimer's disease, dementia, and cognitive impairment in the United States. %A Walter A Rocca %A Ronald C Petersen %A David S Knopman %A Liesi Hebert %A Denis A Evans %A Kathleen S Hall %A Gao, Sujuan %A Frederick W Unverzagt %A Kenneth M. Langa %A Eric B Larson %A Lon R White %K Age Factors %K Alzheimer disease %K Cognition Disorders %K Cohort Studies %K Community Health Planning %K Dementia %K Humans %K Incidence %K Prevalence %K Residence Characteristics %K Retrospective Studies %K Time Factors %K United States %X

Declines in heart disease and stroke mortality rates are conventionally attributed to reductions in cigarette smoking, recognition and treatment of hypertension and diabetes, effective medications to improve serum lipid levels and to reduce clot formation, and general lifestyle improvements. Recent evidence implicates these and other cerebrovascular factors in the development of a substantial proportion of dementia cases. Analyses were undertaken to determine whether corresponding declines in age-specific prevalence and incidence rates for dementia and cognitive impairment have occurred in recent years. Data spanning 1 or 2 decades were examined from community-based epidemiological studies in Minnesota, Illinois, and Indiana, and from the Health and Retirement Study, which is a national survey. Although some decline was observed in the Minnesota cohort, no statistically significant trends were apparent in the community studies. A significant reduction in cognitive impairment measured by neuropsychological testing was identified in the national survey. Cautious optimism appears justified.

%B Alzheimers Dement %I 7 %V 7 %P 80-93 %8 2011 Jan %G eng %N 1 %L newpubs20110328_Rocca.pdf %1 http://www.ncbi.nlm.nih.gov/pubmed/21255746?dopt=Abstract %2 PMC3026476 %4 Alzheimers disease/Dementia/Cognitive impairment/Prevalence/Incidence/Time trends %$ 24610 %R 10.1016/j.jalz.2010.11.002 %0 Journal Article %J Alzheimers Dement %D 2008 %T Trends in the prevalence and mortality of cognitive impairment in the United States: is there evidence of a compression of cognitive morbidity? %A Kenneth M. Langa %A Eric B Larson %A Jason H. Karlawish %A David M Cutler %A Mohammed U Kabeto %A Scott Y H Kim %A Allison B Rosen %K Aged %K Aged, 80 and over %K Cognition Disorders %K Female %K Humans %K Male %K Neurology %K Prevalence %K Quality of Life %K Socioeconomic factors %K United States %X

BACKGROUND: Recent medical, demographic, and social trends might have had an important impact on the cognitive health of older adults. To assess the impact of these multiple trends, we compared the prevalence and 2-year mortality of cognitive impairment (CI) consistent with dementia in the United States in 1993 to 1995 and 2002 to 2004.

METHODS: We used data from the Health and Retirement Study (HRS), a nationally representative population-based longitudinal survey of U.S. adults. Individuals aged 70 years or older from the 1993 (N = 7,406) and 2002 (N = 7,104) waves of the HRS were included. CI was determined by using a 35-point cognitive scale for self-respondents and assessments of memory and judgment for respondents represented by a proxy. Mortality was ascertained with HRS data verified by the National Death Index.

RESULTS: In 1993, 12.2% of those aged 70 or older had CI compared with 8.7% in 2002 (P < .001). CI was associated with a significantly higher risk of 2-year mortality in both years. The risk of death for those with moderate/severe CI was greater in 2002 compared with 1993 (unadjusted hazard ratio, 4.12 in 2002 vs 3.36 in 1993; P = .08; age- and sex-adjusted hazard ratio, 3.11 in 2002 vs 2.53 in 1993; P = .09). Education was protective against CI, but among those with CI, more education was associated with higher 2-year mortality.

CONCLUSIONS: These findings support the hypothesis of a compression of cognitive morbidity between 1993 and 2004, with fewer older Americans reaching a threshold of significant CI and a more rapid decline to death among those who did. Societal investment in building and maintaining cognitive reserve through formal education in childhood and continued cognitive stimulation during work and leisure in adulthood might help limit the burden of dementia among the growing number of older adults worldwide.

%B Alzheimers Dement %I 4 %V 4 %P 134-44 %8 2008 Mar %G eng %N 2 %L newpubs20090908/Langa_etal_AD.pdf %1 http://www.ncbi.nlm.nih.gov/pubmed/18631957?dopt=Abstract %2 PMC2390845 %4 Dementia/Epidemiology/heart disease/Education %$ 20300 %R 10.1016/j.jalz.2008.01.001 %0 Journal Article %J Alzheimer Dis Assoc Disord %D 2004 %T Out-of-pocket health care expenditures among older Americans with dementia. %A Kenneth M. Langa %A Eric B Larson %A Robert B Wallace %A A. Mark Fendrick %A Norman L Foster %A Mohammed U Kabeto %A David R Weir %A Robert J. Willis %A A. Regula Herzog %K Aged %K Aged, 80 and over %K Alzheimer disease %K Costs and Cost Analysis %K Data Interpretation, Statistical %K Female %K Financing, Personal %K Health Care Costs %K Health Expenditures %K Health Surveys %K Humans %K Insurance Coverage %K Longitudinal Studies %K Male %X

The number of older individuals with dementia will likely increase significantly in the next decades, but there is currently limited information regarding the out-of-pocket expenditures (OOPE) for medical care made by cognitively impaired individuals and their families. We used data from the 1993 and 1995 Asset and Health Dynamics Study, a nationally representative longitudinal survey of older Americans, to determine the OOPE for individuals with and without dementia. Dementia was identified in 1993 using a modified version of the Telephone Interview for Cognitive Status for self-respondents, and proxy assessment of memory and judgment for proxy respondents. In 1995, respondents reported OOPE over the prior 2 years for: 1) hospital and nursing home stays, 2) outpatient services, 3) home care, and 4) prescription medications. The adjusted mean annual OOPE was 1,350 US dollars for those without dementia, 2,150 US dollars for those with mild/moderate dementia, and 3,010 US dollars for those with severe dementia (p < 0.01). Expenditures for hospital/nursing home care (1,770 per year US dollars) and prescription medications (800 per year US dollars) were the largest OOPE components for those with severe dementia. We conclude that dementia is independently associated with significantly higher OOPE for medical care compared with those with normal cognitive function. Severe dementia is associated with a doubling of OOPE, mainly due to higher payments for long-term care. Given that the number of older Americans with dementia will likely increase significantly in the coming decades, changes in public funding aimed at reducing OOPE for both long-term care and prescription medications would have considerable impact on individuals with dementia and their families.

%B Alzheimer Dis Assoc Disord %I 18 %V 18 %P 90-8 %8 2004 Apr-Jun %G eng %N 2 %L pubs_2004_Langa_etal_dementia_ADAD.pdf %1 http://www.ncbi.nlm.nih.gov/pubmed/15249853?dopt=Abstract %4 Dementia/Health Expenditures %$ 12282 %R 10.1097/01.wad.0000126620.73791.3e