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ObjectiveTo examine whether late-life exposure to PM2.5 (particulate matter with aerodynamic diameters MethodsAD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the Alzheimer’s Disease Neuroimaging Initiative, were used to capture high-dimensional gray matter atrophy in brain areas vulnerable to AD (e.g., amygdala, hippocampus, parahippocampal gyrus, thalamus, inferior temporal lobe areas, and midbrain). Using participants' addresses and air monitoring data, we implemented a spatiotemporal model to estimate 3-year average exposure to PM2.5 preceding MRI-1. General linear models were used to examine the association between PM2.5 and AD-PS scores (baseline and 5-year standardized change), accounting for potential confounders and white matter lesion volumes.ResultsFor 1,365 women 77.9 ± 3.7 years of age in 2005 to 2006, there was no association between PM2.5 and baseline AD-PS score in cross-sectional analyses (β = −0.004; 95% confidence interval [CI] −0.019 to 0.011). Longitudinally, each interquartile range increase of PM2.5 (2.82 µg/m3) was associated with increased AD-PS scores during the follow-up, equivalent to a 24% (hazard ratio 1.24, 95% CI 1.14–1.34) increase in AD risk over 5 years (n = 712, age 77.4 ± 3.5 years). This association remained after adjustment for sociodemographics, intracranial volume, lifestyle, clinical characteristics, and white matter lesions and was present with levels below US regulatory standards (3).ConclusionsLate-life exposure to PM2.5 is associated with increased neuroanatomic risk of AD, which may not be explained by available indicators of cerebrovascular damage.

Background While sex differences in incidence of Alzheimer's disease (AD) and potential explanations have received considerable attention, less attention has been paid to possible sex differences in genetic risk for AD. Objective We examined sex differences in genetic and environmental influences on disease risk and age at onset for All Dementia, AD Only, and Non-AD Dementia. Methods Twin pairs were drawn from the Swedish Twin Registry. All Dementia analysis included 9,467 pairs; AD only, 8,696 pairs; and non-AD dementia, 8,195 pairs. APOE analyses included 1,923 individual twins with measured ɛ4 alleles. Dementia diagnoses were based on clinical workup and national health registry linkage. Results Although within-pair correlations for All Dementia and AD Only were higher for women than for men, sex differences did not statistically differ for genetic or environmental etiology of All Dementia, AD Only, and Non-AD dementia. Similar results were observed when looking at specific genetic effects (APOEɛ4). Co-twin control analyses indicated that among twin pairs discordant for dementia, female twins without dementia had approximately 40% greater risk of developing dementia, compared with their male counterparts, in the 2-5 years following the first twin's diagnosis. Conclusion For All Dementia, AD Only, and Non-AD Dementia, genetic influences could be equated across sex. Co-twin analyses, however, suggest greater risk to female than to male co-twins of dementia cases even though sex differences in either genetic or shared environmental influences on the risk of dementia could not be differentiated.

Brain atrophy is correlated with risk of cognitive impairment, functional decline, and dementia. Despite a high infectious disease burden, Tsimane forager-horticulturists of Bolivia have the lowest prevalence of coronary atherosclerosis of any studied population and present few cardiovascular disease (CVD) risk factors despite a high burden of infections and therefore inflammation. This study (a) examines the statistical association between brain volume (BV) and age for Tsimane and (b) compares this association to that of 3 industrialized populations in the United States and Europe. This cohort-based panel study enrolled 746 participants aged 40–94 (396 males), from whom computed tomography (CT) head scans were acquired. BV and intracranial volume (ICV) were calculated from automatic head CT segmentations. The linear regression coefficient estimate β^T of the Tsimane (T), describing the relationship between age (predictor) and BV (response, as a percentage of ICV), was calculated for the pooled sample (including both sexes) and for each sex. β^T was compared to the corresponding regression coefficient estimate β^R of samples from the industrialized reference (R) countries. For all comparisons, the null hypothesis β T = β R was rejected both for the combined samples of males and females, as well as separately for each sex. Our results indicate that the Tsimane exhibit a significantly slower decrease in BV with age than populations in the United States and Europe. Such reduced rates of BV decrease, together with a subsistence lifestyle and low CVD risk, may protect brain health despite considerable chronic inflammation related to infectious burden.

The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the USA. It comprises 15,924 White male twin pairs born in the years 1917–1927 (N = 31.848), both of whom served in the armed forces, chiefly during World War II. This article updates activities in this registry since the most recent report in Twin Research and Human Genetics (Page, 2006). Records-based data include information from enlistment charts and Veterans Administration data linkages. There have been three major epidemiologic questionnaires and an education and earnings survey. Separate data collection efforts with the NAS-NRC registry include the National Heart, Lung, and Blood Institute (NHLBI) subsample, the Duke Twins Study of Memory in Aging and a clinically based study of Parkinson’s disease. Progress has been made on consolidating the various data holdings of the NAS-NRC Twin Registry. Data that had been available through the National Academy of Sciences are now freely available through National Archive of Computerized Data on Aging (NACDA).

Background Medicare claims record linkage has been used to identify diagnosed dementia cases in order to estimate dementia prevalence and cost of care. Claims records in the 1990 s and early 2000 s have been found to provide 85% - ∼90% sensitivity and specificity. Objective Considering that dementia awareness has improved over time, we sought to examine sensitivity and specificity of more recent Medicare claims records against a standard criterion, clinical diagnosis of dementia. Methods For a sample of patients evaluated at the University of Southern California Alzheimer Disease Research Center (ADRC), we performed database linkage with Medicare claims files for a six-year period, 2007-2012. We used clinical diagnosis at the ADRC as the criterion diagnosis in order to calculate sensitivity and specificity. Results Medicare claims correctly identified 85% of dementia patients and 77% of individuals with normal cognition. About half of patients clinically diagnosed with mild cognitive impairment had dementia diagnoses in Medicare claims. Misclassified dementia patients (i.e., missed diagnosis by Medicare claims) had more favorable Mini-Mental State Examination and Clinical Dementia Rating scores and were less likely to present behavioral symptoms than correctly-classified dementia patients. Conclusions Database linkage to Medicare claims records is an efficient and reasonably accurate tool to identify dementia cases in a population-based cohort. However, possibilities of obtaining biased results due to misclassification of dementia status need to be carefully considered to use Medicare claims diagnosis for etiologic research studies. Additional confirmation of dementia diagnosis may also be considered. A larger study is warranted to confirm our findings.

Despite the relevance of semantic fluency measures to risk for dementia and psychiatric disorders, little is known about their genetic and environmental architecture in mid-to-late life. Participants represent 21,684 middle-aged and older adult twins (M = 60.84 years, SD = 11.21; Range 40-89) from six studies from three countries participating in the Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium. All completed the same measure of semantic fluency (naming animals in 60 seconds). Results revealed small-to-moderate phenotypic associations with age and education, with education more strongly and positively associated with fluency performance in females than males. Heritability and environmental influences did not vary by age. Environmental variance was smaller with higher levels of education, but this effect was observed only in males. This is the largest study to examine the genetic and environmental architecture of semantic fluency, and the first to demonstrate that environmental influences vary based on levels of education.

Introduction: To study if declining cognition drives weight loss in preclinical dementia, we examined the longitudinal association between body mass index (BMI) and cognitive abilities in individuals who did or did not later develop dementia. Methods: Using data from individuals spanning age 50 to 89, we applied dual change score models separately in individuals who remained cognitively intact (n = 1498) and those who were diagnosed with dementia within 5 years of last assessment (n = 459). Results: Among the cognitively intact, there was a bidirectional association: Stable BMI predicted stable cognition and vice versa. Among individuals who were subsequently diagnosed with dementia, the association was unidirectional: Higher BMI predicted declining cognition but cognition did not predict change in BMI. Discussion: Although BMI and cognition stabilized each other when cognitive functioning was intact, this buffering effect was missing in the preclinical dementia phase. This finding indicates that weight loss in preclinical dementia is not driven by declining cognition. CC BY-NC-ND 4.0Correspondence Ida K. Karlsson, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-1177 Stockholm, Sweden. Email: ida.karlsson@ki.se

Evidence suggests exposure to particulate matter with aerodynamic diameter

Introduction Hormones may be one possible mechanism underlying sex differences in dementia incidence. We examined whether presumed differential prenatal hormone milieu is related to dementia risk by comparing dementia rates in same‐ and opposite‐sex dizygotic twin pairs in male and female twins. Methods The sample comprised 43,254 individuals from dizygotic twin pairs aged 60 and older from the Swedish Twin Registry. Survival analyses were conducted separately for females and males. Results Female twins from opposite‐sex pairs had significantly lower dementia risk than female twins from same‐sex pairs, but the differences emerged only after age 70 (hazard ratio = 0.64, P = 0.004). Results were not explained by postnatal risk factors for dementia, and no interaction between twin type and apolipoprotein E (APOE) ε4 was found. Male twins from same‐sex versus opposite‐sex pairs did not differ significantly. Discussion The results suggest that relatively masculine prenatal hormone milieus correlate with lower dementia risk in females.

Background While a high body mass index (BMI) in midlife is associated with higher risk of dementia, high BMI in late-life may be associated with lower risk. This study combined genetic designs with longitudinal data to achieve a better understanding of this paradox. Methods We used longitudinal data from 22,156 individuals in the Swedish Twin Registry (STR) and 25,698 from the Health and Retirement Study (HRS). The STR sample had information about BMI from early adulthood through late-life, and the HRS sample from age 50 through late-life. Survival analysis was applied to investigate age-specific associations between BMI and dementia risk. To examine if the associations are influenced by genetic susceptibility to higher BMI, an interaction between BMI and a polygenic score for BMI (PGSBMI) was included in the models and results stratified into those with genetic predisposition to low, medium, and higher BMI. In the STR, co-twin control models were applied to adjust for familial factors beyond those captured by the PGSBMI. Results At age 35–49, 5 units higher BMI was associated with 15% (95% CI 7–24%) higher risk of dementia in the STR. There was a significant interaction (p = 0.04) between BMI and the PGSBMI, and the association present only among those with genetic predisposition to low BMI (HR 1.38, 95% CI 1.08–1.78). Co-twin control analyses indicated genetic influences. After age 80, 5 units higher BMI was associated with 10–11% lower risk of dementia in both samples. There was a significant interaction between late-life BMI and the PGSBMI in the STR (p = 0.01), but not the HRS, with the inverse association present only among those with a high PGSBMI (HR 0.70, 95% CI 0.52–0.94). No genetic influences were evident from co-twin control models of late-life BMI. Conclusions Not only does the association between BMI and dementia differ depending on age at BMI measurement, but also the effect of genetic influences. In STR, the associations were only present among those with a BMI in opposite direction of their genetic predisposition, indicating that the association between BMI and dementia across the life course might be driven by environmental factors and hence likely modifiable.

By 2050, Spain is projected to be home to the largest amount of elders in the world, due to a combination of high life expectancy, low birth rates, and the baby boomer generation entering their elder years. Consequently, in the next decades, Spain will have one of the highest dependency rates in the world. The country has nearly 800,000 people with dementia, with more than half in a situation of dependency. A conservative estimate suggests that the cost of each dependent is approximately 30,000 euros per year. When extended to all Spaniards with dementia, the cost reaches 24,000 million euros a year between direct costs for medical and professional care and indirect costs to caregivers and relatives who must alter their working life. Meanwhile, the dependency subsidy suffers from administrative blockages and budget cuts. The situation brings enormous challenge, affecting the patient, the caregiver, and the nature of care. Effective intervention for patients with Alzheimer’s disease and other dementias increasingly includes the presence of psychologists specialized in the care of older adults. Psychologists work in both public and private settings including hospital units (memory units, dementia units, psychiatric units, etc.), day centers, residential centers, and universities and research centers. There is increasing use and evidence of the effectiveness of psychosocial, or non-pharmacological, interventions to address cognitive symptoms, such as altered memory or language, and especially psychological and behavioral symptoms associated with dementia, such as depression, anxiety, delusional disorders, altered behavior, etc., with advantages over psychotropic drugs with respect to greater effectiveness and fewer side effects.

Loos, Ruth J F/0000-0002-8532-5087; Huibregtse, Brooke M./0000-0003-0977-7249; Kandler, Christian/0000-0002-9175-235X; Hjelmborg, Jacob/0000-0001-9630-9149; mangino, massimo/0000-0002-2167-7470; Siribaddana, Sisira/0000-0001-5821-2557; Plomin, Robert/0000-0002-0756-3629; Latvala, Antti/0000-0001-5695-117X; Kaprio, Jaakko/0000-0002-3716-2455; Willemsen, Gonneke/0000-0003-3755-0236; Tan, Qihua/0000-0003-3194-0030; Pahlen, Shandell/0000-0003-0753-4155; Pedersen, Nancy/0000-0001-8057-3543; Haworth, Claire/0000-0002-8608-289X; Nistico, Lorenza/0000-0003-1805-6240; Skytthe, Axel/0000-0002-8629-4913; van Beijsterveldt, Toos/0000-0002-6617-4201; Rebato, Esther/0000-0003-1221-8501; Li, Lintao/0000-0002-0604-9660; Bartels, Meike/0000-0002-9667-7555; Silventoinen, Karri/0000-0003-1759-3079; Cunha Oliveira, Vinicius/0000-0002-8658-3774; Sund, Reijo/0000-0002-6268-8117; Sodemann, Morten/0000-0001-8992-2500; Rasmussen, Finn/0000-0001-7915-7809; Harden, Kathryn/0000-0002-1557-6737; Medda, Emanuela/0000-0003-4837-4549; Kyvik, Kirsten Ohm/0000-0003-2981-0245; Colodro Conde, Lucia/0000-0002-9004-364X WOS: 000517442200060 PubMed: 31364586 The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m(2)) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status. Academy of FinlandAcademy of Finland [266592, 100499, 205585, 118555, 141054, 265240, 263278, 264146]; Osaka University's International Joint Research Promotion Program; Centre of Research Excellence Grant from the National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1079102]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HD068435, R01 MH062375, 1R01ESO15150-01, R21 AG039572]; National Medical Research Council Research Fellowship; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [1RO1-AG13662-01A2]; Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Swedish Asthma and Allergy Association's Research Foundation; Special Fund for Health Scientific Research in the Public Welfare, China [201502006]; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015, HD10333]; National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation; Research Council for Health and Disease; Velux Foundation; US National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 AG08761]; Fund of Scientific Research, FlandersFWO; ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007 [201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Cancer Research UKCancer Research UK [C1418/A7974]; W T Grant Foundation; University of London Central Research fund; Medical Research CouncilMedical Research Council UK (MRC) [G81/343, G120/635]; Economic and Social Research CouncilEconomic & Social Research Council (ESRC) [RES-000-22-2206]; Institute of Social Psychiatry [06/07-11]; Leverhulme Research FellowshipLeverhulme Trust [RF/2/RFG/2008/0145]; Goldsmiths, University of London; UK Medical Research CouncilMedical Research Council UK (MRC) [MR/M021475/1, G0901245]; National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AG053217, RC2 HL103416]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81125007]; Global Research Network Program of the National Research Foundation [NRF 2011-220-E00006]; European Research Council (ERC)European Research Council (ERC) [240994]; Michigan State University; National Institute of Mental Health (NIMH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01, 1R01-MH118848-01]; Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) [R01-HD066040]; MSU Foundation [11-SPG-2518]; Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain [08633/PHCS/08, 15302/PHCS/10, 19479/PI/14]; Ministry of Science and Innovation, SpainSpanish Government [PSI2009-11560, PSI2014-56680-R]; MagW/ZonMW [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192]; European Research CouncilEuropean Research Council (ERC) [ERC-230374]; JSPS KAKENHI JP [23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261]; Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [437015, 607358]; Bonnie Babes Foundation [BBF20704]; Financial Markets Foundation for Children [032-2007]; Victorian Government; Portuguese agency for research (The Foundation for Science and Technology [FCT]) [POCI/DES/56834/2004]; Wellcome TrustWellcome Trust; Medical Research CouncilMedical Research Council UK (MRC); European UnionEuropean Union (EU); National Institute for Health Research (NIHR)National Institute for Health Research (NIHR); King's College London; Fonds Quebecois de la Recherche sur la Societe et la CultureFQRNT; Fonds de la Recherche en Sante du QuebecFonds de la Recherche en Sante du Quebec; Social Science and Humanities Research Council of Canada; National Health Research Development Program; Canadian Institutes for Health ResearchCanadian Institutes of Health Research (CIHR); Sainte-Justine Hospital's Research Center; Canada Research Chair ProgramCanada Research Chairs; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1 B00047]; Swedish Research CouncilSwedish Research Council [2017-00641]; UK Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [31/D19086]; MRCMedical Research Council UK (MRC) [MR/M021475/1]; Krkkale University [2009/43]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH58354]; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIA R01 AG018384, R01 AG018386, R01 AG022381, R01 AG022982]; VA San Diego Center of Excellence for Stress and Mental Health; Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15H05105]; Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; Stockholm County Council (ALF-projects)Stockholm County Council; Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium); [5T32DA017637]; [5T32AG052371] This study was conducted within the CODATwins project (Academy of Finland #266592). K Silventoinen is supported by Osaka University's International Joint Research Promotion Program. This research was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (ID: 1079102), from the National Health and Medical Research Council. The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. Paulo Ferreira is funded by a National Medical Research Council Research Fellowship. California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01).; The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. The CATSS-Study is supported by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867, grants provided by the Stockholm County Council (ALF-projects), the Swedish Heart-Lung Foundation and the Swedish Asthma and Allergy Association's Research Foundation.; Chinese National Twin Registry is funded by Special Fund for Health Scientific Research in the Public Welfare (Project No: 201502006), China. Colorado Twin Registry is funded by NIDA-funded center grant DA011015, & Longitudinal Twin Study HD10333; Author Huibregtse is supported by 5T32DA017637 and 5T32AG052371. Danish Twin Registry is supported by the National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation, The Research Council for Health and Disease, the Velux Foundation and the US National Institute of Health (P01 AG08761). Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145 and AA-09203 to R J Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J Kaprio). Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Waves 1-3 of Genesis 12-19 were funded by the W T Grant Foundation, the University of London Central Research fund and a Medical Research Council Training Fellowship (G81/343) and Career Development Award (G120/635) to Thalia C. Eley. Wave 4 was supported by grants from the Economic and Social Research Council (RES-000-22-2206) and the Institute of Social Psychiatry (06/07-11) to Alice M. Gregory, who was also supported at that time by a Leverhulme Research Fellowship (RF/2/RFG/2008/0145). Wave 5 was supported by funding to Alice M. Gregory from Goldsmiths, University of London. T. C. Eley is partly funded by a program grant from the UK Medical Research Council (MR/M021475/1).; This study presents independent research [partly] funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Minnesota Twin Registry (MTR) acknowledges support from NIH grant R01AG053217. Guangzhou Twin Eye Study is supported by National Natural Science Foundation of China (grant #81125007). Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 and 1R01-MH118848-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) and 11-SPG-2518 from the MSU Foundation. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD or the National Institutes of Health. The Murcia Twin Registry is supported by Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08, 15302/PHCS/10 & 19479/PI/14) and Ministry of Science and Innovation, Spain (PSI2009-11560 & PSI2014-56680-R). The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572. Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; VU University's Institute for Health and Care Research (EMGO+); the European Research Council (ERC-230374), the Avera Institute, Sioux Falls, South Dakota (USA). Osaka University Aged Twin Registry is supported by grants from JSPS KAKENHI JP (23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261). PETS was supported by grants from the Australian National Health and Medical Research Council (grant numbers 437015 and 607358 to JC, and RS), the Bonnie Babes Foundation (grant number BBF20704 to JMC), the Financial Markets Foundation for Children (grant no. 032-2007 to JMC), and by the Victorian Government's Operational Infrastructure Support Program.; Madeira data comes from the following project: Genetic and environmental influences on physical activity, fitness and health: the Madeira family study Project reference: POCI/DES/56834/2004 Founded by the Portuguese agency for research (The Foundation for Science and Technology [FCT]). TwinsUK receives funding from the Wellcome Trust, Medical Research Council and European Union.; TwinsUK and M. Mangino are supported by the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The Quebec Newborn Twin Study acknowledges financial support from the Fonds Quebecois de la Recherche sur la Societe et la Culture, the Fonds de la Recherche en Sante du Quebec, the Social Science and Humanities Research Council of Canada, the National Health Research Development Program, the Canadian Institutes for Health Research, Sainte-Justine Hospital's Research Center, and the Canada Research Chair Program (Michel Boivin). South Korea Twin Registry is supported by National Research Foundation of Korea (NRF-371-2011-1 B00047). We acknowledge The Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no. 2017-00641.; The Twins Early Development Study (TEDS) is supported by a program grant (G0901245) from the UK Medical Research Council and the work on obesity in TEDS is supported in part by a grant from the UK Biotechnology and Biological Sciences Research Council (31/D19086). Currently TEDS is supported by MRC grant 'MR/M021475/1'. The Texas Twin Project is currently funded by grant R01HD083613 from the National Institutes of Health. S. Y. oncel and F. Aliev are supported by Krkkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117. The University of Southern California Twin Study is funded by a grant from the National Institute of Mental Health (R01 MH58354). Washington State Twin Registry (formerly the University of Washington Twin Registry) was supported in part by grant NIH RC2 HL103416 (D. Buchwald, PI). Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381 and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 15H05105) from the Japan Society for the Promotion of Science.

In the following brief report, we examined gender differences in incidence rates of any dementia, Alzheimer's disease (AD) alone, and non-Alzheimer's dementia alone in 16,926 women and men in the Swedish Twin Registry aged 65+. Dementia diagnoses were based on clinical workup and national health registry linkage. Incidence rates of any dementia and AD were greater in women than men, with any dementia rates diverging after age 85 and AD rates diverging around 80. This pattern is consistent with women's survival to older ages compared to men. These findings are similar to incidence rates reported in other Swedish samples.

Background This study aims to investigate if DNA methylation of the apolipoprotein E (APOE) locus affects the risks of dementia, Alzheimeŕs disease (AD) or cardiovascular disease (CVD). Methods DNA methylation across theAPOE gene has previously been categorized into three distinct regions: a hypermethylated region in the promoter, a hypomethylated region in the first two introns and exons and a hypermethylated region in the 3′exon that also harbours theAPOE ε2 and ε4 alleles. DNA methylation levels in leukocytes were measured using the Illumina 450K array in 447 Swedish twins (mean age 78.1 years). We used logistic regression to investigate whether methylation levels in those regions affect the odds of disease. Results We found that methylation levels in the promoter region were associated with dementia and AD after adjusting for sex, age at blood draw, education, smoking and relatedness among twins [odds ratio (OR) 1.32 per standard deviation increase in methylation levels, 95% confidence interval (CI) 1.08–1.62 for dementia; OR 1.38, 95% CI 1.07–1.78 for AD). We did not detect any difference in methylation levels between CVD cases and controls. Results were similar when comparing within discordant twin pairs, and did not differ as a function ofAPOE genotype. Conclusions We found that higher DNA methylation levels in the promoter region ofAPOE increase the odds of dementia and AD, but not CVD. The effect was independent ofAPOE genotype, indicating that allelic variation and methylation variation inAPOE may act independently to increase the risk of dementia.

Less supportive social relationships are linked to greater risk of cognitive decline in older adulthood. Few studies have examined if declines in social support predict risk of developing Mild Cognitive Impairment (MCI) or dementia and the neurobiological factors that may contribute to these associations. We analyzed data from 926 women in the Women’s Health Initiative Memory Study-MRI (WHIMS-MRI) to examine whether low social support at baseline and declines over an 8-year period predicted subsequent risk of developing MCI/dementia. Social support (Medical Outcomes Study Social Support Scale) was self-reported at the baseline (1994-1998) and closeout (2004-2005) of the parent WHI hormone therapy clinical trial. Annual neuropsychological assessments were conducted in WHIMS (through 2018) to ascertain incident MCI/dementia; structural brain scans were performed in 2005-2006. Structural equation models assessed the association between level and change in social support and risk of incident MCI/dementia and putative mediation of these associations by structural brain variables in women free of MCI/dementia as of the trial closeout, adjusting for demographic, lifestyle, depression, and biomedical covariates. Both low baseline social support (HR=1.24 per 1-SD; p

Objectives Body fat, measured with body mass index (BMI), and obesity are associated with depressive symptoms. Among younger adults there is stronger evidence of obesity leading to depressive symptoms than of depressive symptoms leading to obesity, but the temporal relationship is unknown among older adults. This study utilized dual-change-score models (DCSMs) to determine the directional relationship between body mass and depressive symptoms among older adults. Method Participants (n = 1,743) from the Swedish Twin Registry (baseline age range 50–96 years) completed at least one assessment of BMI (nurse measurement of height and weight) and the Center for Epidemiologic Studies-Depression scale (CESD). More than half the sample completed 3 or more assessments, scheduled at intervals of 2–4 years. DCSMs modeled the relationship of BMI and CESD across age, both independently and as part of bivariate relationships. Results Depressive symptoms contributed to subsequent changes in BMI after age 70, while BMI contributed to subsequent changes in depressive symptoms after age 82. Thus, there is a reciprocal relationship that may change with age. The effect was more pronounced for women. Discussion The association of BMI and depressive symptoms is bidirectional among older adults, and it appears to be affected by both age and sex.

Introduction In a geographically diverse sample of women, we asked whether cognitive reserve (CR) is best viewed as a general or cognitive domain-specific construct and whether some cognitive reserve domains but not others exert protective effects on risk of developing mild cognitive impairment (MCI) or dementia. Methods Estimates of general and domain-specific CR were derived via variance decomposition in 972 cognitively intact women from the Women's Health Initiative Study of Cognitive Aging and Women's Health Memory Study Magnetic Resonance Imaging. Women were then followed up for 13 years. Results General CR was the strongest predictor of reduced risk for both MCI and dementia, compared to domain-specific CR measures. Verbal memory, figural memory, and spatial CR were independently protective of MCI, but only verbal memory was independently associated with reduced risk for dementia. Discussion Cognitive reserve is a heterogenous construct with valid quantitative measures identifiable across different neuropsychological processes associated with MCI and dementia.

The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene–environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14–103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.

More supportive social relationships are protective of cognitive decline in older adulthood. Although supportive social relationships are hypothesized to promote cognitive reserve (CR; the cognitive adaption to neuropathology), it is unknown whether CR mediates associations between social support and risk of developing mild cognitive impairment or dementia (MCI/dementia). Data from 815 women (aged 73-87 years) participating in the Women’s Health Initiative Memory Study-MRI cohort (WHIMS-MRI) and Women’s Health Initiative Study of Cognitive Aging (WHISCA) were analyzed to examine whether domain-specific estimates of CR mediate associations between social support and incident MCI/dementia risk. Women completed the Medical Outcomes Study Social Support Scale (MOS-SS) in 2004-2005, a structural MRI (sMRI) of the brain in 2005-06, and annual extensive neuropsychological examinations till 2018. CR (6-months after completing the MOS-SS) was estimated across different domains (e.g. verbal memory, figural memory, language, visuospatial, and attention) as the residual variance after regressing out effects of sMRI variables, sociodemographic factors, and measurement error. Structural equation models were constructed to examine whether CR mediate associations between social support and MCI/dementia risk while adjusting for covariates. Higher social support was associated with lower MCI/dementia risk (hazard ratio=0.85 per 1-SD;p=0.037), higher language reserve (standardized β=0.09;p=0.008) and verbal memory reserve (standardized β=0.08;p=0.025). Language and verbal memory reserve each significantly explained approximately 14% of the protective effect of social support. Findings illustrate the heterogeneous effect of social support on CR, highlighting the importance of language and verbal memory reserve as mediators of the association between social support and MCI/dementia risk.

Background: While research has shown that sleep disorders are prevalent among people with dementia, the temporal relationship is unclear. We investigated whether atypical sleep characteristics were associated with incident dementia while accounting for baseline cognitive functioning. Methods: Screening Across the Lifespan Twin Study (SALT) participants were 11,247 individuals from the Swedish Twin Registry who were at least 65 years at baseline (1998-2002). Sleep and baseline cognitive functioning were assessed via the SALT telephone screening interview. Data on dementia diagnoses came from national health registers. Cox regression was performed to estimate hazard ratios (HR) for dementia. Results: After 17 years of follow-up, 1,850 dementia cases were identified. Short (≤ 6 hours) and extended (> 9 hours) time-in-bed (TIB) compared to the middle reference group (HR=1.40, 95% CI=1.06-1.85, HR=1.11, 95% CI=1.00-1.24, respectively) and rising at 8:00AM or later compared to earlier rising (HR=1.12, 95% CI=1.01-1.24) were associated with higher dementia incidence. Bedtime, sleep quality, restorative sleep, and heavy snoring were not significant predictors. Findings stratified by baseline cognitive status indicated that the association between short TIB and dementia remained in those cognitively intact at the start. Conclusions: Short and extended TIB as well as delayed rising among older adults predicted increased dementia incidence in the following 17 years. The pattern of findings suggests that extended TIB and late rising represent prodromal features whereas short TIB appeared to be a risk factor for dementia. This work was supported by grants from the National Institute on Aging (R01-AG08724) and the Swedish Research Council for Health, Working Life and Welfare (FORTE).

Kandler, Christian/0000-0002-9175-235X; Bartels, Meike/0000-0002-9667-7555; Medland, Sarah E/0000-0003-1382-380X; Kaprio, Jaakko/0000-0002-3716-2455; Fagnani, Corrado/0000-0001-5771-7772; de Freitas, Duarte Luis/0000-0001-6642-3370; Hjelmborg, Jacob/0000-0001-9630-9149; mangino, massimo/0000-0002-2167-7470; Busjahn, Andreas/0000-0001-9650-6919; Montgomery, Grant W/0000-0002-4140-8139; Moller, Soren/0000-0003-0858-4269; Heikkila, Kauko/0000-0002-9256-8028; Skytthe, Axel E/0000-0002-8629-4913; Christensen, Kaare/0000-0002-5429-5292; Knafo-Noam, Ariel/0000-0003-0613-1960; ONCEL, Sevgi YURT/0000-0002-0990-292X; Sund, Reijo/0000-0002-6268-8117; Aliev, Fazil/0000-0001-8357-4699; Magnusson, Patrik/0000-0002-7315-7899; Huibregtse, Brooke M./0000-0003-0977-7249; Loos, Ruth J F/0000-0002-8532-5087; Boivin, Michel/0000-0001-8621-9844; Kyvik, Kirsten Ohm/0000-0003-2981-0245; Pahlen, Shandell/0000-0003-0753-4155; van Beijsterveldt, Toos/0000-0002-6617-4201; McAdams, Tom/0000-0002-6825-3499; Sodemann, Morten/0000-0001-8992-2500; Pedersen, Nancy/0000-0001-8057-3543; Derom, Catherine/0000-0001-5574-796X; Plomin, Robert/0000-0002-0756-3629; Rebato, Esther/0000-0003-1221-8501; Saffery, Richard/0000-0002-9510-4181; Harden, Kathryn/0000-0002-1557-6737; Willemsen, Gonneke/0000-0003-3755-0236; Aaltonen, Sari/0000-0002-2873-4263; Silventoinen, Karri/0000-0003-1759-3079; Rasmussen, Finn/0000-0001-7915-7809; Haworth, Claire/0000-0002-8608-289X; Llewellyn, Clare/0000-0002-0066-2827 WOS: 000381870200017 PubMed: 27413137 Background: Both genetic and environmental factors are known to affect body mass index (BMI), but detailed understanding of how their effects differ during childhood and adolescence is lacking. Objectives: We analyzed the genetic and environmental contributions to BMI variation from infancy to early adulthood and the ways they differ by sex and geographic regions representing high (North America and Australia), moderate (Europe), and low levels (East Asia) of obesogenic environments. Design: Data were available for 87,782 complete twin pairs from 0.5 to 19.5 y of age from 45 cohorts. Analyses were based on 383,092 BMI measurements. Variation in BMI was decomposed into genetic and environmental components through genetic structural equation modeling. Results: The variance of BMI increased from 5 y of age along with increasing mean BMI. The proportion of BMI variation explained by additive genetic factors was lowest at 4 y of age in boys (a(2) = 0.42) and girls (a(2) = 0.41) and then generally increased to 0.75 in both sexes at 19 y of age. This was because of a stronger influence of environmental factors shared by co-twins in midchildhood. After 15 y of age, the effect of shared environment was not observed. The sex-specific expression of genetic factors was seen in infancy but was most prominent at 13 y of age and older. The variance of BMI was highest in North America and Australia and lowest in East Asia, but the relative proportion of genetic variation to total variation remained roughly similar across different regions. Conclusions: Environmental factors shared by co-twins affect BMI in childhood, but little evidence for their contribution was found in late adolescence. Our results suggest that genetic factors play a major role in the variation of BMI in adolescence among populations of different ethnicities exposed to different environmental factors related to obesity. CODATwins project (Academy of Finland) [266592]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HD068435, R01 MH062375, 1R01ESO15150-01, HD081437, AA023322, RC2 HL103416]; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; Special Fund for Health Scientific Research in the Public Welfare, China [201502006]; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015, HD10333]; National Program for Research Infrastructure from the Danish Agency for Science, Technology and Innovation, The Research Council for Health and Disease; Velux Foundation; US NIH grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 AG08761]; Fund of Scientific Research, Flanders and Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium); ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4 [201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease Genetics grantAcademy of Finland [213506, 129680]; Academy of Finland grantAcademy of Finland [100499, 205585, 118555, 141054, 265240, 263278, 264146]; Osaka University's International Joint Research Promotion Program; Cancer Research UKCancer Research UK [C1418/A7974]; W T Grant Foundation; University of London Central Research fund; Medical Research CouncilMedical Research Council UK (MRC) [G81/343, G120/635]; Economic and Social Research CouncilEconomic & Social Research Council (ESRC) [RES-000-22-2206]; Institute of Social Psychiatry [06/07-11]; Leverhulme Research Fellowship grant [RF/2/RFG/2008/0145]; Goldsmiths, University of London, United Kingdom; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81125007]; Medexpert Ltd., Budapest, Hungary; European Research CouncilEuropean Research Council (ERC) [240994, 230374]; Michigan State University; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01]; Eunice Kennedy Shriver National Institute for Child Health and Human DevelopmentUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [R01-HD066040]; MSU Foundation [11-SPG-2518]; NIH grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21 AG039572]; MagW/ZonMW grant [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464- 14192]; VU University's Institute for Health and Care Research; Avera Institute, Sioux Falls, SD; Australian National Health and Medical Research Council grantNational Health and Medical Research Council of Australia [437015, 607358]; Bonnie Babes Foundation [BBF20704]; Financial Markets Foundation for Children grant [032-2007]; Victorian Government's Operational Infrastructure Support Program; Portuguese agency for research (The Foundation for Science and Technology) [POCI/DES/56834/2004]; Fonds Quebecois de la Recherche sur la Societe et la CultureFQRNT; Fonds de la Recherche en Sante du QuebecFonds de la Recherche en Sante du Quebec; Social Science and Humanities Research Council of Canada; National Health Research Development Program; Canadian Institutes for Health ResearchCanadian Institutes of Health Research (CIHR); Sainte-Justine Hospital's Research Center; Canada Research Chair ProgramCanada Research Chairs; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1 B00047]; UK Medical Research CouncilMedical Research Council UK (MRC) [G0901245]; UK Biotechnology and Biological Sciences Research Council grant [31/D19086]; Kirikkale University Research grantKirikkale University [KKU 2009/43]; TUBITAK grantTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; European CommunityEuropean Community (EC); National Institute for Health Research BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London, United Kingdom; National Institute of Mental Health grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH58354]; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15H05105]; [5T32DA017637-11]; Medical Research CouncilMedical Research Council UK (MRC) [G0901245]; NNF Center for Basic Metabolic ResearchNovo Nordisk Foundation [Metabolic Genetics]; Novo Nordisk FondenNovo NordiskNovo Nordisk Foundation [NNF10CC1016515] This study was conducted within the CODATwins project (Academy of Finland #266592). Support for participating twin projects: The Boston University Twin Project is funded by grants R01 HD068435 and R01 MH062375 from the NIH to KS. California Twin Program was supported by The California Tobacco-Related Disease Research Program grants 7RT-0134H, 8RT-0107H, and 6RT-0354H and by NIH grant 1R01ESO15150-01. Chinese National Twin Registry is funded by Special Fund for Health Scientific Research in the Public Welfare (Project No: 201502006), China. Colorado Twin Registry is funded by NIDA funded center grant DA011015, and Longitudinal Twin Study HD10333; BMH is supported by to 5T32DA017637-11. Danish Twin Registry is supported by the National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation, The Research Council for Health and Disease, the Velux Foundation and the US NIH grant P01 AG08761. Since its origin the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement 201413; National Institute of Alcohol Abuse and Alcoholism grants AA-12502, AA-00145, and AA-09203 to RJR; the Academy of Finland Center of Excellence in Complex Disease Genetics grants 213506 and 129680; and the Academy of Finland grants 100499, 205585, 118555, 141054, 265240, 263278, and 264146 to JK. KS is supported by Osaka University's International Joint Research Promotion Program. Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Waves 1-3 of Genesis 12-19 were funded by the W T Grant Foundation, the University of London Central Research fund and Medical Research Council Training Fellowship grant G81/343 and Career Development Award G120/635 to TCE. Wave 4 was supported by the Economic and Social Research Council grant RES-000-22-2206 and the Institute of Social Psychiatry (06/07-11) to AMG, who was also supported at that time by a Leverhulme Research Fellowship grant RF/2/RFG/2008/0145. Wave 5 was supported by funding to AMG from Goldsmiths, University of London, United Kingdom. Guangzhou Twin Eye Study is supported by National Natural Science Foundation of China grant 81125007. Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Longitudinal Israeli Study of Twins was funded by the Starting Grant 240994 from the European Research Council to AK. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, and R03-MH63851-01 from the National Institute of Mental Health, R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, and 11-SPG-2518 from the MSU Foundation. The NAS-NRC Twin Registry acknowledges financial support from NIH grant R21 AG039572. Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, and 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464- 14192; VU University's Institute for Health and Care Research; the European Research Council grant 230374; and the Avera Institute, Sioux Falls, SD.; PETS was supported by the Australian National Health and Medical Research Council grant 437015 and 607358 to JC and RS, the Bonnie Babes Foundation grant BBF20704 to JMC, the Financial Markets Foundation for Children grant 032-2007 to JMC, and by the Victorian Government's Operational Infrastructure Support Program. Madeira data comes from the following project: Genetic and environmental influences on physical activity, fitness and health: the Madeira family study Project reference: POCI/DES/56834/2004 Founded by the Portuguese agency for research (The Foundation for Science and Technology). The Quebec Newborn Twin Study acknowledges financial support from the Fonds Quebecois de la Recherche sur la Societe et la Culture, the Fonds de la Recherche en Sante du Quebec, the Social Science and Humanities Research Council of Canada, the National Health Research Development Program, the Canadian Institutes for Health Research, Sainte-Justine Hospital's Research Center, and the Canada Research Chair Program (MB). South Korea Twin Registry is supported by National Research Foundation of Korea grant NRF-371-2011-1 B00047. The Texas Twin Project is currently funded by grants AA023322 and HD081437 from the NIH. The Twins Early Development Study is supported by program grant G0901245 from the UK Medical Research Council and the work on obesity in the Twins Early Development Study is supported in part by the UK Biotechnology and Biological Sciences Research Council grant 31/D19086. SYO and FA are supported by Kirikkale University Research grant KKU 2009/43 and TUBITAK grant 114C117. TwinsUK was funded by European Community's Seventh Framework Programme grant FP7/2007-2013. The study also receives support from the National Institute for Health Research BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London, United Kingdom. The University of Southern California Twin Study is funded by the National Institute of Mental Health grant R01 MH58354. University of Washington Twin Registry was supported in part by grant NIH RC2 HL103416 (D and PI). The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) grant 15H05105 from the Japan Society for the Promotion of Science.

Previous studies reported the association of increased dementia risk with depressive symptoms assessed at one-time point, neglecting the inter-individual differences and intra-individual variability in the profiles of symptoms over time. We examined the association between longitudinal trajectories of depressive symptoms and cognitive impairment among participants from the Women’s Health Initiative Study of Cognitive Aging without prior depression (n=2,081; aged 73.4 ± 3.8 years), including a subsample (n=1,050) with 1.5-T brain MRI measures of small-vessel-ischemic-diseases (SVID) and spatial patterns of grey matter atrophy in Alzheimer’s disease (i.e., AD pattern similarity [AD-PS] score; Casanova 2013). Latent-class mixed models (LCMMs) were used to identify clusters with similar individual trajectories of symptoms assessed annually by the 15-item Geriatric Depression Scale (GDS). Using Cox-proportional hazard regression, we estimated the association between GDS-defined classes and global cognitive decline in the Modified Mini-Mental State [3MS] score;>10-point drop) and incident dementia. Multinomial logistic regressions estimated the associations between GDS classes and brain MRI measures. Compared to the resilient group with minimal symptoms (N=739;35.5%), the other two clusters with low-levels of depressive symptoms that either emerged (N=314;15.1%) in late life or sustained (N=1028;49.4%) during the follow-up were at increased risks for 3MS decline (HRemerging=1.93, p=0.02; HRsustained=2.51,p

Past research has identified an increased dementia risk with anxiety symptoms in older adulthood. Most of these previous studies examined cross-sectional anxiety symptoms measured at one time point in association with subsequent dementia incidence. This approach neglects longitudinal anxiety symptoms and intra-individual variability in symptoms over age. Here, we examined the association between longitudinal trajectories of anxiety symptoms and incident dementia among 2,066 participants of the Swedish Adoption Twin Study of Aging. Participants were twins over the age of 50 who completed upwards of 14 assessments of anxiety over a 30-year period (1984–2014). Participants were screened for dementia throughout the study period. Latent-class mixed models (LCMMs) were used to identify clusters of participants with similar trajectories of anxiety symptoms across age. Using Cox-proportional hazard regression, we estimated the association between anxiety symptom class and incident dementia, while adjusting for baseline depressive symptoms, age, sex, education, and physical illness. LCMMs identified three classes of anxiety-trajectories: minimal anxiety (n=1,127), mild anxiety (n=728), and elevated anxiety (n=211). Individuals in the mild anxiety class were more likely to develop dementia compared to those with minimal symptoms (HR=1.29, p=0.04). Dementia risk was greatest in the elevated anxiety class with participants being more likely to develop dementia compared to those in the minimal (HR=2.03, p

Objectives Although several environmental factors contribute to the etiology of late-life depressive symptoms, the role of ambient air pollution has been understudied. Experimental data support the neurotoxicity of airborne particulate matter with aerodynamic diameter of ≤2.5 μm (PM2.5), but it remains unclear whether long-term exposure is associated with late-life depressive symptoms. Our secondary aim was to explore whether the observed associations between exposure and depressive symptoms are explained by dementia risk. Design, Setting, and Participants Prospective community-dwelling cohort study from the Women's Health Initiative Study of Cognitive Aging (1999–2010). Our analyses included 1,989 older women (baseline age 73.3 ± 3.75) with no prior depression or cognitive impairment. Measurements Participants completed annual assessments of depressive symptoms (15-item Geriatric Depression Scale). Average ambient PM2.5 exposure at the residential location was estimated by spatiotemporal modeling for the 3-years preceding each neuropsychological assessment. Participants underwent separate annual examinations for incident dementia defined by DSM-IV. Latent-class mixture models examined the association between PM2.5 and identified trajectories of symptoms. Results Six trajectories of depressive symptoms were identified. Across all women, PM2.5 exposure was positively associated with depressive symptoms. The effect was especially strong in two clusters with sustained depressive symptoms (n = 625 sustained-mild [31%]; n = 125 sustained-moderate; [6%]). Among those with sustained-moderate symptoms, the estimated adverse effect of PM2.5 exposure was greater than that of hypertension. Among women without dementia, associations were modestly attenuated. Conclusion Long-term exposure to ambient fine particles was associated with increased depressive symptoms among older women without prior depression or cognitive impairment.

Background There is evidence for long-lasting effects of birth characteristics on cognitive ability in childhood and adulthood. Further, low cognitive ability throughout the lifetime has been linked to age-related cognitive decline and dementia risk. However, little is known about the effects of birth characteristics on cognitive dysfunction late in life. Here we explore potential associations between birth characteristics (weight, head circumference, length, and gestational age), adjusted and not adjusted for gestational age, and cognitive impairment and dementia late in life. Methods and findings Data from twins in the Swedish Twin Registry born 1926–1960 were merged with information from the Swedish birth, patient, and cause of death registries, resulting in a sample of 35,191 individuals. A subsample of 4,000 twins aged 65 years and older also participated in a telephone cognitive screening in 1998–2002. Associations of birth characteristics with registry-based dementia diagnoses and on telephone-assessed cognitive impairment were investigated in the full sample and subsample, respectively. The full sample contained 907 (2.6%) individuals with a dementia diagnosis (an incidence rate of 5.9% per 100,000 person-years), 803 (2.4%) individuals born small for gestational age, and 929 (2.8%) individuals born with a small head for gestational age. The subsample contained 569 (14.2%) individuals with cognitive impairment. Low birth weight for gestational age and being born with a small head for gestational age were significant risk factors for cognitive dysfunction late in life, with an up to 2-fold risk increase (p < 0.001) compared to infants with normal growth and head size, even after controlling for familial factors, childhood socioeconomic status, and education in adulthood. In line with this, each additional 100 g birth weight and each additional millimeter head circumference significantly reduced the risk for dementia (hazard ratio 0.98, 95% confidence interval 0.97 to 0.99, p = 0.004) and cognitive impairment (odds ratio 0.99, 95% confidence interval 0.99 to 1.00, p = 0.004), respectively. Within-pair analyses of identical twins, though hampered by small sample size, suggested that the observed associations between birth characteristics and dementia are likely not due to underlying shared genetic or environmental etiology. A limitation of the present study is that registry-based dementia diagnoses likely miss some of the true dementia cases in the population. Further, a more precise measure of cognitive reserve early in life as well as a date of onset for the cognitive impairment measure in the subsample would have been favorable. Conclusions In this study, we found that infants of smaller birth size (i.e., low birth weight or small head circumference adjusted and unadjusted for gestational age) have a significantly higher risk of age-related cognitive dysfunction compared to those with normal growth, highlighting the importance of closely monitoring the cognitive development of such infants and evaluating the potential of early life interventions targeted at enhancing cognitive reserve., Using data from the Swedish Birth Registry, Miriam Mosing and colleagues investigate associations between healthy prenatal growth and cognitive dysfunction in late-life., Author summary Why was this study done? There is evidence for associations between birth characteristics and cognitive ability in childhood and adulthood. Low cognitive ability throughout the lifetime has been linked to age-related cognitive decline and dementia risk. Little is known about associations between birth characteristics and cognitive dysfunction late in life, such as dementia and cognitive impairment. What did the researchers do and find? We conducted a registry-based cohort study of 35,191 individuals linking data from the Swedish birth registry to the Swedish patient, cause of death, and twin registries to explore potential associations between birth characteristics and age-related cognitive dysfunction as measured by all-cause dementia and cognitive impairment. Low birth weight and small head circumference pose a significant risk for late life cognitive dysfunction. What do these findings mean? The findings highlight the importance of healthy prenatal growth and closely monitoring the cognitive development of small infants and those with signs of poor fetal growth. Potential interventions to increase cognitive reserve could be considered for infants with low birth weight and small head circumference.

Loos, Ruth J F/0000-0002-8532-5087; Sund, Reijo/0000-0002-6268-8117; Busjahn, Andreas/0000-0001-9650-6919; Tan, Qihua/0000-0003-3194-0030; Aliev, Fazil/0000-0001-8357-4699; Kaprio, Jaakko/0000-0002-3716-2455; Magnusson, Patrik/0000-0002-7315-7899; Tan, Qihua/0000-0003-3194-0030; ONCEL, Sevgi YURT/0000-0002-0990-292X; Ordonana, Juan R./0000-0001-7779-6017; Colodro-Conde, Lucia/0000-0002-9004-364X; Huibregtse, Brooke M./0000-0003-0977-7249; ROMERA, JUAN FRANCISCO SANCHEZ/0000-0002-5405-6216; Rebato, Esther/0000-0003-1221-8501; Pedersen, Nancy/0000-0001-8057-3543; Latvala, Antti/0000-0001-5695-117X; Silventoinen, Karri/0000-0003-1759-3079; Rasmussen, Finn/0000-0001-7915-7809; Piirtola, Maarit/0000-0001-7270-6676 WOS: 000438457400025 PubMed: 30001359 Background Smokers tend to weigh less than never smokers, while successful quitting leads to an increase in body weight. Because smokers and non-smokers may differ in genetic and environmental family background, we analysed data from twin pairs in which the co-twins differed by their smoking behaviour to evaluate if the association between smoking and body mass index (BMI) remains after controlling for family background. Methods and findings The international CODATwins database includes information on smoking and BMI measured between 1960 and 2012 from 156,593 twin individuals 18-69 years of age. Individual-based data (230,378 measurements) and data of smoking discordant twin pairs (altogether 30,014 pairwise measurements, 36% from monozygotic [MZ] pairs) were analysed with linear fixed-effects regression models by 10-year periods. In MZ pairs, the smoking co-twin had, on average, 0.57 kg/m(2) lower BMI in men (95% confidence interval (CI): 0.49, 0.70) and 0.65 kg/m(2) lower BMI in women (95% CI: 0.52, 0.79) than the never smoking co-twin. Former smokers had 0.70 kg/m(2) higher BMI among men (95% CI: 0.63, 0.78) and 0.62 kg/m(2) higher BMI among women (95% CI: 0.51, 0.73) than their currently smoking MZ cotwins. Little difference in BMI was observed when comparing former smoking co-twins with their never smoking MZ co-twins (0.13 kg/m(2), 95% CI 0.04, 0.23 among men; -0.04 kg/m(2), 95% CI -0.16, 0.09 among women). The associations were similar within dizygotic pairs and when analysing twins as individuals. The observed series of cross-sectional associations were independent of sex, age, and measurement decade. Conclusions Smoking is associated with lower BMI and smoking cessation with higher BMI. However, the net effect of smoking and subsequent cessation on weight development appears to be minimal, i.e. never more than an average of 0.7 kg/m(2). Academy of FinlandAcademy of Finland [266592, 100499, 205585, 118555, 141054, 265240, 263278, 264146]; Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium); ENGAGE - European Network for Genetic and Genomic Epidemiology [FP7- HEALTH-F4-2007, 201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Sigrid Juselius FoundationSigrid Juselius Foundation; Osaka University's International Joint Research Promotion Program; Medexpert Ltd., Budapest, Hungary; European Union's Seventh Framework Programmes ENGAGE ConsortiumEuropean Union (EU) [HEALTH-F4- 2007-201413]; BioSHaRE EU [HEALTH-F4-2010-261433]; Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain [08633/PHCS/08, 15302/PHCS/10, 19479/PI/14]; Ministry of Science and Innovation, SpainSpanish Government [PSI2009-11560, PSI2014-56680-R]; Centre of Research Excellence grant from the National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1079102]; Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia; Australian Research CouncilAustralian Research Council; Australian National Health and Medical Research Council fellowshipNational Health and Medical Research Council of Australia [SRFB-1103623]; National Institutes of Health grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21 AG039572]; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIA R01 AG018384, R01 AG018386, R01 AG022381, R01 AG022982]; Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015]; Longitudinal Twin Study [HD10333]; JSPS KAKENHI JP [23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261]; Global Research Network Program of the National Research Foundation [NRF 2011-220- E00006]; Kirikkale University Research Grant: KKUKirikkale University [2009/43]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; [5T32DA017637]; [5T32AG052371] This study was conducted within the CODATwins project (Academy of Finland grant #266592 to KS). Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7- HEALTH-F4-2007 (grant agreement number 201413), National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to RJ Rose), the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to JK). JK also acknowledges support from the Sigrid Juselius Foundation. KS is supported by Osaka University's International Joint Research Promotion Program. Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Data collection and research stemming from the Norwegian Twin Registry is supported, in part, from the European Union's Seventh Framework Programmes ENGAGE Consortium (grant agreement HEALTH-F4- 2007-201413), and BioSHaRE EU (grant agreement HEALTH-F4-2010-261433). The Murcia Twin Registry is supported by Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08, 15302/PHCS/10 & 19479/PI/14) and Ministry of Science and Innovation, Spain (PSI2009-11560 & PSI2014-56680-R). The Australian Twin Registry is supported by a Centre of Research Excellence grant (ID 1079102) from the National Health and Medical Research Council administered by the University of Melbourne. The QIMR twin study acknowledges grants from the Australian National Health and Medical Research Council and the Australian Research Council. SM is supported by an Australian National Health and Medical Research Council fellowship (SRFB-1103623). The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572. The Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381, and R01 AG022982, and, in part, with resources from the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The Colorado Twin Registry is funded by NIDA-funded center grant DA011015 and Longitudinal Twin Study HD10333; BH was supported by 5T32DA017637 and 5T32AG052371. The Osaka University Aged Twin Registry is supported by grants from JSPS KAKENHI JP (23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261). The Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220- E00006). SO and FA are supported by Kirikkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117.; None of the funders including HealthTwiSt GmbH and Pfizer Inc played a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries, excluding HealthTwiSt GmbH and Pfizer Inc, and/or research materials. The funder HealthTwiSt GmbH did not provide support in the form of salaries for authors (AB). HealthTwiSt GmbH collects data on twin samples and makes these available to academic researchers for a service fee to cover the costs (technical staff salaries and material costs). The funder (Pfizer Inc) did provide support in the form of consultation fees for authors (JK and TK) outside of the submitted work.

BACKGROUND: Population-based health registers are potential assets in epidemiological research; however, the quality of case ascertainment is crucial. OBJECTIVE: To compare the case ascertainment of dementia, from the National Patient Register (NPR) and the Cause of Death Register (CDR) with dementia diagnoses from six Swedish population based studies. METHODS: Sensitivity, specificity, and positive predictive value (PPV) of dementia identification in NPR and CDR were estimated by individual record linkage with six Swedish population based studies (n = 19,035). Time to detection in NPR was estimated using data on dementia incidence from longitudinal studies with more than two decades of follow-up. RESULTS: Barely half of the dementia cases were ever detected by NPR or CDR. Using data from longitudinal studies we estimated that a record with a dementia diagnosis appears in the NPR on average 5.5 years after first diagnosis. Although the ability of the registers to detect dementia cases was moderate, the ability to detect non-dementia cases was almost perfect (99%). When registers indicate that there is a dementia diagnosis, there are very few instances in which the clinicians determined the person was not demented. Indeed, PPVs were close to 90%. However, misclassification between dementia subtype diagnoses is quite common, especially in NPR. CONCLUSIONS: Although the overall sensitivity is low, the specificity and the positive predictive value are very high. This suggests that hospital and death registers can be used to identify dementia cases in the community, but at the cost of missing a large proportion of the cases. CC BY-NC 4.0

Does Depression In Old Age Reflect Prodromal Dementia? : A Polygenic Risk Score Approach In Two Longitudinal Studies

Introduction We asked whether anxiety is associated with prospective risk of dementia, and the extent to which genetic influences mediate this association. Methods Nondemented twins (n = 1082) from the Swedish Adoption Twin Study of Aging completed an assessment of anxiety symptoms in 1984 and were followed for 28 years. Results Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up (hazard ratio [HR] = 1.04; 95% confidence interval [CI] = 1.01–1.06). There was 48% increased risk of becoming demented for those who had experienced high anxiety at any time compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic (HR = 1.11; 95% CI = 1.02–1.20) compared with monozygotic twins (HR = 1.06; 95% CI = 0.95–1.20), indicating genetic mediation. Discussion Anxiety symptoms were associated with increased risk of dementia. Genetic factors common to dementia and anxiety partially mediated this association.

Heritability estimates describe the proportion of variability in a trait attributed to genetic differences in a population in a given context. Secular improvements in environmental conditions across the 20th century may interact with genotype, thus leading to our hypothesis that genetic influences on dementia risk would be greater in recently born men and women versus earlier born men and women. We drew a sample of 5,970 complete sets of monozygotic (MZ) and dizygotic (DZ) twin pairs (MZ Male: 610; DZ Male: 971; MZ Female: 933; DZ 1,571, and DZ Opposite Sex: 1885) who met criteria for dementia or were cognitively intact in 4 aging studies of the Swedish Twin Registry. Dementia diagnosis was determined based on in-person workup and medical records (using DSM-IV criteria for dementia, and NINCDS-ADRDA criteria for AD) or individual-level data from the Swedish National Patient Register and Cause of Death Register. Twin correlations were calculated using a modified twin-correlation model that allowed birth year to moderate MZ, same-sex DZ and opposite-sex DZ twin correlations to explore sex differences in underlying genetic and environmental influences on dementia risk. In women, heritability estimates ranged from .52 to .79 from earliest to recent birth years. In men, heritability estimates ranged from essentially 0 to .72 from earlier to more recent birth years. Overall, twin correlations were lower at earlier than at more recent birth years. Genetic influences on dementia risk appeared to be greatest in recently born men compared to all women and earlier born men.

The objective of this study is to validate two abridged versions of the mini-mental state examination (MMSE): one intended for use in face-to-face interviews, and the other developed for telephonic interviews, using data from Sweden and the US to validate the abridged scales against dementia diagnoses as well as to compare their performance to that of the full MMSE scale. The abridged versions were based on eight domains from the original MMSE scale. The domains included in the MMSE-SF were registration, orientation, delayed recall, attention, and visual spatial ability. In the MMSE-SF-C, the visual spatial ability item was excluded, and instead, one additional orientation item was added. There were 794 participants from the Swedish HARMONY study [mean age 81.8 (4.8); the proportion of cognitively impaired was 51 %] and 576 participants from the US ADAMS study [mean age 83.2 (5.7); the proportion of cognitively impaired was 65 %] where it was possible to compare abridged MMSE scales to dementia diagnoses and to the full MMSE scale. We estimated the sensitivity and specificity levels of the abridged tests, using clinical diagnoses as reference. Analyses with both the HARMONY and the ADAMS data indicated comparable levels of sensitivity and specificity in detecting cognitive impairment for the two abridged scales relative to the full MMSE. Receiver operating characteristic curves indicated that the two abridged scales corresponded well to those of the full MMSE. The two abridged tests have adequate validity and correspond well with the full MMSE. The abridged versions could therefore be alternatives to consider in larger population studies where interview length is restricted, and the respondent burden is high. Electronic supplementary material The online version of this article (doi:10.1007/s10433-016-0394-z) contains supplementary material, which is available to authorized users.

Objective: The goal of this research was to evaluate nutrition education targeting Latinas, a group at particular risk of obesity and diabetes, which predict to later life cardiovascular disease and dementia. Method: Culturally tailored, theory-based nutrition education was provided to Mexican origin Latinas aged 48 to 84. The randomized design compared participants in workshops incorporating the connection between dietary fat and brain health, participants in workshops focusing only on dietary fat and heart health, a waitlist control group, and a posttest only control group. Results: Among those assigned to either intervention, there was statistically significant gain in health literacy, knowledge about dietary fat, and behaviors to reduce dietary fat compared with waitlist control. There was no difference in outcomes between those given the module about diet and brain health and those not provided that module. Discussion: A program to encourage dietary fat modification in Latinas proved feasible and modestly effective.

Twin studies are an incomparable source of investigation to shed light on genetic and non-genetic components of neurodegenerative diseases, as Alzheimer's disease (AD). Detailed clinicopathologic correlations using twin longitudinal data and post-mortem examinations are mostly missing. We describe clinical and pathologic findings of seven monozygotic (MZ) and dizygotic (DZ) twin pairs. Our findings show good agreement between clinical and pathologic diagnoses in the majority of the twin pairs, with greater neuropathologic concordance in MZ than DZ twins. Greater neuropathologic concordance was found for β-amyloid than tau pathology within the pairs. ApoE4 was associated with higher β-amyloid and earlier dementia onset, and importantly, higher frequency of other co-occurring brain pathologies, regardless of the zygosity. Dementia onset, dementia duration, difference between twins in age at dementia onset and at death, did not correlate with AD pathology. These clinicopathologic correlations of older identical and fraternal twins support the relevance of genetic factors in AD, but not their sufficiency to determine the pathology, and consequently the disease, even in monozygotic twins. It is the interaction among genetic and non-genetic risks which plays a major role in influencing, or probably determining, the degeneration of those brain circuits associated with pathology and cognitive deficits in AD.

We investigated the relation of subjective cognitive impairment (SCI) and cognitive impairment no dementia (CIND) to common chronic diseases of the elderly and multimorbidity, and assessed the contribution of genetic background and shared familial environment to these associations. Subjects were 11,379 dementia-free twin individuals aged ≥ 65 from the Swedish Twin Registry. SCI was defined as subjective complaint of cognitive change without objective cognitive impairment and CIND was defined according to current criteria. In unmatched, fully-adjusted regression models, mental, musculoskeletal, respiratory, and urological diseases were all significantly associated with increased odds ratios (ORs) of SCI and CIND. Circulatory and gastrointestinal diseases were related to SCI only, while endocrine diseases were associated with CIND. The adjusted ORs of multimorbidity were 2.1 [95% confidence intervals (95% CI): 1.8-2.3] for SCI and 1.5 for CIND (95% CI: 1.3-1.8). A dose-dependent relationship was observed between number of chronic diseases and ORs for SCI but not for CIND. In co-twin control analyses, the chronic diseases-SCI association was largely unchanged. On the other hand, the chronic diseases-CIND association was no longer statistically significant, except for cancer, where an increased OR was observed. In conclusion, chronic morbidity is associated with both SCI and CIND but disease profiles do not always overlap between the two cognitive syndromes. The association is stronger when diseases co-occur, especially for SCI. Genetic and early-life environmental factors may partially explain the association of CIND but not that of SCI with chronic diseases.

More than 5 million Americans are living with Alzheimer's disease (AD) today, and nearly two-thirds of Americans with AD are women. This sex difference may be due to the higher longevity women generally experience; however, increasing evidence suggests that longevity alone is not a sufficient explanation and there may be other factors at play. The Alzheimer's Association convened an expert think tank to focus on the state of the science and level of evidence around gender and biological sex differences for AD, including the knowledge gaps and areas of science that need to be more fully addressed. This article summarizes the think tank discussion, moving forward a research agenda and funding program to better understand the biological underpinnings of sex- and gender-related disparities of risk for AD.

Linkage studies have provided evidence that one or more loci on chromosome 9q influence Alzheimer disease (AD). The gene encoding the ATP-binding cassette A1 transporter (ABCA1) resides within proximity of previously identified linkage peaks and represents a plausible biological candidate for AD due to its central role in cellular lipid homeostasis. Several single nucleotide polymorphisms (SNPs) spanning ABCA1 have been genotyped and haplotype-based association analyses performed in four independent case-control samples, consisting of over 1,750 individuals from three European populations representing both early and late-onset AD. Prominent effects were observed for a common (H2) and rarer haplotype (H5) that were enriched in AD cases across studied populations (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.36-1.82; P

Objective The aim of the current study was to examine the effect of negative life events and widowhood on the incidence of dementia. Methods Data were from four Swedish longitudinal cohort studies with a total of nearly 2,000 participants and 8–25 years of follow-up. Seven stressful events were examined for which data were available in all cohorts. Clinical dementia diagnoses were made through medical and psychological examinations. Cox proportional hazards models were used to estimate the association between life events and dementia, adjusting for lifestyle and cardiovascular risk factors. Results The experience of one stressful life event was not associated with dementia incidence, but two or more negative life events at baseline predicted higher risk for dementia (pooled HR: 2.00). This was most apparent for the incidence of vascular dementia (pooled HR: 3.60) but not for Alzheimer disease (pooled HR: 1.29). Moreover, persons who were widowed and had experienced one or more negative life events were found to have a threefold risk for dementia. Conclusion Widowhood augments the effect of negative life events on dementia incidence and negative life events specifically increase the risk for vascular dementia.

The Study of Dementia in Swedish Twins is a study of dementia in a defined population of twins. The goals included estimating heritability of Alzheimer's disease and identifying risk and protective factors in twin pairs discordant for the disease. The data, including not only diagnoses and age of onset but also extensive information about potential environmental risk factors, are now archived as Study ICPSR 25963 at National Archive for Computerized Data on Aging, Inter-university Consortium for Political and Social Research, at the University of Michigan, and available for researchers to use. Up to the time of archiving, 215 cases of dementia have been identified from a base sample of 2,394 individuals.

We report the prevalence of subjective cognitive impairment (SCI) and cognitive impairment no dementia (CIND), their socio-demographic profile, and the contribution of genetic background and shared familial environment to SCI and CIND. Subjects were 11,926 dementia-free twin individuals aged ≥ 65 from the Swedish Twin Registry. SCI was defined as subjective complaint of cognitive change without objective cognitive impairment and CIND was defined according to current criteria. Overall prevalence of SCI and CIND was 39% (95% CI 38-39) and 25% (95% CI 24-25). Among those with CIND, 57% had subjective cognitive complaints; 43% did not. In multivariate GEE models, both SCI and CIND were older compared with people without any cognitive impairment. CIND were also less educated, more likely to be unmarried and to have lower socioeconomic status (SES). SCI individuals differed from persons with CIND as they were older, more educated, more likely to be married, and to have higher SES. Co-twin control analysis, which corrects for common genetic and shared environmental background, confirmed that low education was still associated with CIND. Probandwise concordance for SCI and CIND was 63% and 52% in monozygotic twins, 63% and 50% in dizygotic same-sex twins, and 42% and 29% in dizygotic unlike-sex twins. Tetrachoric correlations showed no significant differences between monozygotic and dizygotic same-sex twins. We conclude that subjective and objective cognitive impairment are both highly prevalent among nondemented elderly yet have distinct sociodemographic profiles. Shared environmental influences rather than genetic background play a role in the occurrence of SCI and CIND.

Background High midlife body mass index (BMI) has been linked to a greater risk of dementia in late life, but few have studied the effect of BMI across midlife on cognitive abilities and cognitive change in a dementia free sample. Methods We investigated the association between body mass index (BMI), measured twice across midlife (mean age 40 and 61 years, respectively), and cognitive change in four domains across two decades in the Swedish Adoption/Twin Study of Aging (SATSA). Results Latent growth curve models fitted to data from 657 non-demented participants showed that persons who were overweight/obese in early midlife had significantly lower cognitive performance across domains in late life and significantly steeper decline in perceptual speed, adjusting for cardio-metabolic factors. Both underweight and overweight/obesity in late midlife were associated with lower cognitive abilities in late life. However, the association between underweight and low cognitive abilities did not remain significant when weight decline between early and late midlife was controlled for. Conclusions There is a negative effect on cognitive abilities later in life related to being overweight/obese across midlife. Moreover, weight decline across midlife rather than low weight in late midlife per se was associated with low cognitive abilities. Weight patterns across midlife may be prodromal markers of late life cognitive health.

To examine job control, job demands, social support at work, and job strain (ratio of demands to control) in relation to risk of any dementia, Alzheimer's disease (AD), and vascular dementia (VaD).Cohort study.The population-based Study of Dementia in Swedish Twins.Two hundred fifty-seven people with dementia (167 AD, 46 VaD) and 9,849 without.Dementia diagnoses were based on telephone screening for cognitive impairment followed by in-person clinical examination. An established job exposure matrix was matched to main occupation categories to measure work characteristics.In generalized estimating equations (adjusted for the inclusion of complete twin pairs), lower job control was associated with greater risk of any dementia (odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.04-1.31) and VaD specifically (OR = 1.39, 95% CI = 1.07-1.81). Lower social support at work was associated with greater risk of dementia (OR = 1.15, 95% CI = 1.03-1.28), AD (OR = 1.14, 95% CI = 1.00-1.31), and VaD (OR = 1.28, 95% CI = 1.02-1.60). Greater job strain was associated with greater risk of VaD only (OR = 1.28, 95% CI = 1.02-1.60), especially in combination with low social support (OR = 1.35, 95% CI = 1.11-1.64). Age, sex, and education were controlled for. Work complexity, manual work, and vascular disease did not explain the results. No differences in work-related stress scores were observed in the 54 twin pairs discordant for dementia, although only two pairs included a twin with VaD.Work-related stress, including low job control and low social support at work, may increase the risk of dementia, particularly VaD. Modification to work environment, including attention to social context and provision of meaningful roles for employees, may contribute to efforts to promote cognitive health.

Background Several occupations and occupational exposures have been investigated for associations with Parkinson’s disease. Common findings are increased risk associated with pesticide exposure and no association between Parkinson’s disease and welding. Methods We explored the association between a broad range of possible occupational risk factors and Parkinson’s disease as well as Parkinson’s disease plus other forms of Parkinsonism (referred to as Parkinsonian disorders), using prospectively collected data in the population-based Swedish Twin Registry. A cohort of 14,169 Swedish men was followed for up to 43 years. We identified 234 Parkinsonian disorder cases including 204 Parkinson’s disease cases with complete data. We assessed exposure to 14 chemical and biological compounds through a job exposure matrix. Hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, smoking, and education were used to estimate the relative risk of disease associated with exposure. Results Exposure to inorganic dust was associated with increased risk of Parkinson’s disease and Parkinsonian disorders, HR 1.6 (95% CI 1.1–2.4) and 1.5 (1.0–2.2) respectively. There was no association between Parkinson’s disease or Parkinsonian disorders and occupational exposure to pesticides, welding smoke, metal dust, wood dust, animal handling, stone and concrete dust, chrome and nickel dust, quartz dust, organic dust, oil, asbestos, organic solvents and irritating gas. Conclusions Inorganic dust should be explored further as a potential risk factor for Parkinson’s disease. Occupational exposure to pesticides and twelve other compounds explored in this study may not be associated with risk of Parkinson’s disease in Swedish men.

Research has found that patients treated for cancer generally have an increased risk for cognitive problems. However, many studies have focused on cognitive performance of cancer patients under the age of 65 who received chemotherapy treatment. Less studied is the extent to which cancer diagnosis may be associated with cognitive impairment as a late effect for older adults.In this retrospective, co-twin design study, twin pairs 65 years of age and older discordant for cancer were identified from the Swedish Twin Registry. A pair was included if both twins participated in cognitive screening, and the twin with the cancer history was screened at least 3 years after cancer diagnosis and treatment.Female, but not male, survivors of cancer were significantly (odds ratio = 2.42, 95% confidence interval = 1.23-4.74) more likely to exhibit cognitive impairment 3 or more years after cancer diagnosis and treatment as their co-twin without a history of cancer. In particular, risk was higher among survivors of gynecologic cancers (odds ratio = 10.00, 95% confidence interval = 1.28-78.11) and those who had treatments directly or potentially affecting ovarian functioning (odds ratio = 13.00, 95% confidence interval = 1.70-99.36) compared with their respective co-twins.These findings suggest that localized treatments and other cancer-related factors should be explored as determinants that underlie the association between cancer diagnosis and long-term cognitive impairment.

Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) and dementia. We therefore sought to study DNA sequence variation and serum levels of the potent inflammatory mediators Interleukin-6 (IL6) and C-reactive protein (CRP) in relation to AD and dementia. Tagging single nucleotide polymorphisms (tagSNPs) were chosen to capture most variation in and around CRP and IL6 in 3937 elderly Swedish men and women (1,265 AD cases). A sub-set of the population (n = 723) with serum measurements of CRP and IL6 was included in 1) a nested case-control study of incident dementia cases, and 2) a case-control study of prevalent dementia cases. None of the SNPs or haplotypes was significantly associated with AD or dementia after correcting for multiple testing nor were elevated baseline levels of hsCRP or IL6 (measured on average 4.3 years before dementia onset) significantly associated with risk of future AD or dementia. However, prevalent AD cases had higher levels of IL6 (measured on average 5.5 years after dementia onset) than age- and gender-matched controls, OR 2.24 (95% CI 1.27-3.95), p-value 0.006. In summary, this data suggests that AD patients have an altered immune profile with higher circul- ating levels of IL6 than age- and gender-matched controls. However, neither variation in the CRP and IL6 genes nor circulating levels of their respective protein products were associated with an increased risk of developing late-life dementias.

Accurate knowledge about Alzheimer’s disease (AD) is essential to address the public health impact of dementia. This study examined AD knowledge in 794 people who completed the Alzheimer’s Disease Knowledge Scale and questions about their background and experience with AD. Whereas overall knowledge was fair, there was significant variability across groups. Knowledge was highest among professionals working in the dementia field, lower for dementia caregivers and older adults, and lowest for senior center staff and undergraduate students. Across groups, respondents knew the most about assessment, treatment, and management of AD and knew the least about risk factors and prevention. Greater knowledge was associated with working in the dementia field, having family members with AD, attending a related class or support group, and exposure to dementia-related information from multiple sources. Understanding where gaps in dementia knowledge exist can guide education initiatives to increase disease awareness and improve supportive services.

This study examined whether there were neuroanatomical differences evident on CT scans of individuals with dementia who differed on depression history. Neuroanatomical variables consisted of visual ratings of frontal lobe deep white matter, subcortical white matter, and subcortical gray matter hypodensities in the CT scans of 182 individuals from the Study of Dementia in Swedish Twins who were diagnosed with dementia and had information on depression history. Compared to individuals with Alzheimer's disease and no depression, individuals with Alzheimer's disease and late-onset depression (first depressive episode at age 60 or over) had a greater number of striatal hypodensities (gray matter hypodensities in the caudate nucleus and lentiform nucleus). There were no significant differences in frontal lobe deep white matter or subcortical white matter. These findings suggest that late-onset depression may be a process that is distinct from the neurodegenerative changes caused by Alzheimer's disease.