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Biomedical subjects

Nancy L Pedersen

Publications and source records attributed to Nancy L Pedersen.

At least 19 recordsLinked to original sources

Evaluating a Genome-Wide Polygenic Score for Handgrip Strength and Its Interplay with Leisure-Time Physical Activity Across the IGEMS Twin Cohorts.

PURPOSE: Polygenic scores (PGSs) may help assess genetic predisposition to multifactorial traits. We examined whether age, sex, and leisure-time physical activity (LTPA) modify the association between a PGS for handgrip strength (HGS) and measured HGS in older adults. METHODS: PGS for HGS (PGS hgs) , based on Pan-UK Biobank genome-wide association study data, was calculated for 5103 participants (aged 40-96; 44% women) from eight twin cohorts in Denmark, Sweden, Australia, the United States, and Finland within the IGEMS consortium. Sex-standardized HGS and self-reported LTPA were assessed cross-sectionally. Linear mixed models estimated associations between PGS hgs and HGS, including interactions with age, country, and LTPA, as well as an association between PGS hgs and LTPA. Fixed-effect within-pair models were conducted to assess environmental contributions. RESULTS: Higher PGS hgs was associated with greater HGS (&#x3b2; = 2.14, SE = 0.15, P < 0.001), explaining 4.6% of HGS variance overall, with modest variation across countries. In sex-stratified models, PGS hgs explained 5.2% of the variance in females and 4.3% in males. No statistically significant interaction with age was found. A significant PGS hgs &#xd7; LTPA interaction (&#x3b2; = -0.034, P = 0.013) indicated that the association between LTPA and HGS was more pronounced among individuals with lower PGS hgs . The within-pair models offered limited support for the independent environmental impact of LTPA. CONCLUSIONS: The PGS hgs was associated with measured HGS in the meta-analysis, highlighting the potential of PGSs to capture individual differences in strength-related traits across populations. The association of PGS hgs with HGS was moderated by LTPA, such that the beneficial impact of LTPA on HGS was greater among individuals with a lower genetic propensity for HGS.

Humans↗

Genome-wide association study of copy number variations in Parkinson's disease.

OBJECTIVE: To investigate the impact of copy number variations (CNVs) on Parkinson's disease (PD) pathogenesis using genome-wide data and explore their role in sporadic PD. METHODS: We analyzed CNV data from 11,035 PD patients (including 2,731 early-onset PD (EOPD)) and 8,901 controls from the COURAGE-PD consortium using a sliding window CNV-GWAS and genome-wide burden analysis. The independent dataset from the Global Parkinson Genetics Program (GP2) consisted of 23,089 cases and 18,824 controls were used to validate our initial findings. RESULTS: The exploratory dataset identifies multiple CNV regions associated with PD risk. The nominated CNV loci were not confirmed in an independent dataset, except that only a deletion in the PRKN gene, a well-established EOPD locus, remained genome-wide significant and robustly supported. CNV burden analysis showed a higher prevalence of CNVs in PD-related genes in patients compared to controls (OR=1.56 [1.18-2.09], p=0.0013), with PRKN showing the highest burden (OR=1.47 [1.10-1.98], p=0.026). Patients with CNVs in PRKN had an earlier disease onset. Burden analysis with controls and EOPD patients showed similar results. INTERPRETATION: The largest CNV-based GWAS on PD highlights both the promise and pitfalls of array-based CNV detection in PD and underscores the relevance of whole-genome sequencing approaches in resolving the role of CNV in PD. The array-based findings are prone towards false positive findings that might arise either from platform limitations and/or cohort biases. Future studies require improved genotyping resolution and rigorous cross-cohort validation to reliably assess CNV contributions to PD risk.

Journal Article↗

Genome-wide copy number variation association study in anorexia nervosa.

This study represents the first large-scale investigation of rare (<1% population frequency) copy number variants (CNVs) in anorexia nervosa (AN). Large, rare CNVs are reported to be causally associated with anthropometric traits, neurodevelopmental disorders, and schizophrenia, yet their role in the genetic basis of AN is unclear. Using genome-wide association study (GWAS) array data from the Anorexia Nervosa Genetics Initiative (ANGI), which included 7414 AN case and 5044 controls, we investigated the association of 67 well-established syndromic CNVs and 178 pleiotropic disease-risk dosage-sensitive CNVs with AN. To identify novel CNV regions (CNVRs) that increase the risk of AN, we conducted genome-wide association studies with a focus on rare CNV-breakpoints (CNV-GWAS). We found no net enrichment of rare CNVs, either deletions or duplications, in AN, and none of the well-established syndromic or pleiotropic CNVs had a significant association with AN status. However, the CNV-GWAS found 21 nominally associated CNVRs that contribute to AN risk, covering protein-coding genes implicated in synaptic function, metabolic/mitochondrial factors, and lipid characteristics, like the CD36 (7q21.11) gene, which transports long-chain fatty acids into cells. CNVRs intersecting genes previously related to neurodevelopmental traits include deletions of NRXN1 intron 5 (2p16.3), IMMP2L (7q31.1), and PTPRD (9p23). Overall, given that our study is well powered to detect the CNV burden level reported for schizophrenia, we can conclude that rare CNVs have a limited role in the etiology of AN, as reported for bipolar disorder. Our nominal associations for the 21 discovered CNVRs are consistent with AN being a metabo-psychiatric trait, as demonstrated by the common genetic architecture of AN, and we provide association results to allow for replication in future research.

Humans↗

Genetic influences on exercise participation in 37,051 twin pairs from seven countries.

BACKGROUND: A sedentary lifestyle remains a major threat to health in contemporary societies. To get more insight in the relative contribution of genetic and environmental influences on individual differences in exercise participation, twin samples from seven countries participating in the GenomEUtwin project were used. METHODOLOGY: Self-reported data on leisure time exercise behavior from Australia, Denmark, Finland, Norway, The Netherlands, Sweden and United Kingdom were used to create a comparable index of exercise participation in each country (60 minutes weekly at a minimum intensity of four metabolic equivalents). PRINCIPAL FINDINGS: Modest geographical variation in exercise participation was revealed in 85,198 subjects, aged 19-40 years. Modeling of monozygotic and dizygotic twin resemblance showed that genetic effects play an important role in explaining individual differences in exercise participation in each country. Shared environmental effects played no role except for Norwegian males. Heritability of exercise participation in males and females was similar and ranged from 48% to 71% (excluding Norwegian males). CONCLUSIONS: Genetic variation is important in individual exercise behavior and may involve genes influencing the acute mood effects of exercise, high exercise ability, high weight loss ability, and personality. This collaborative study suggests that attempts to find genes influencing exercise participation can pool exercise data across multiple countries and different instruments.

Adult↗

The sources of co-morbidity between major depression and generalized anxiety disorder in a Swedish national twin sample.

BACKGROUND: Prior studies report high levels of co-morbidity between major depression (MD) and generalized anxiety disorder (GAD) and suggest that these disorders are closely related genetically. The personality trait of neuroticism (N) is substantially correlated with risk for MD and GAD. METHOD: Bivariate twin models were applied to lifetime diagnoses of modified DSM-IV diagnosis of MD and GAD obtained at personal interview in 1998-2003 with 37296 twins from the population-based Swedish Twin Registry. A trivariate Cholesky model with N, MD and GAD was applied to a subset (23280 members of same-sex twin pairs) who completed a self-report questionnaire assessing N in 1972-1973. RESULTS: In the best-fit bivariate model, the genetic correlation between MD and GAD was estimated at +1.00 in females and +0.74 in males. Individual-specific environmental factors were also shared between the two disorders with an estimated correlation of +0.59 in males and +0.36 in females. In the best-fit trivariate Cholesky model, genetic factors indexed by N impacted equally on risk for MD and GAD in males and females. However, in both sexes, genetic risk factors indexed by N contributed only around 25% to the genetic correlation between MD and GAD. CONCLUSION: Genetic risk factors for lifetime MD and GAD are strongly correlated, with higher correlations in women than in men. Although genetic risk factors indexed by the personality trait of N contribute substantially to risk for both MD and GAD, the majority of genetic covariance between the two disorders results from factors not shared with N.

Adult↗

A prospective study of health, life-style and psychosocial predictors of self-rated health.

The aim of this study was to investigate what psychosocial predictors, life-style factors and health behaviors in early adulthood are of importance for self-ratings of health after the age of 45. Like-sexed adult twins born 1926-1950 (n = 16,080) from the Swedish Twin Registry that participated in a questionnaire in 1973 and in a telephone interview conducted between 1998 and 2002 were included. Exposure data was collected in 1973 and information on self-rated health and covariates was collected at the second contact 25 years later. Logistic regression using Generalized Estimating Equations was used to evaluate the associations. Conditional logistic regression was used to control for familial and genetic effects in the sample. Pain, lack of exercise, smoking, obesity, unemployment, perceived stress and personality are associated with future poor self-rated health, after controlling for age, sex, illness, education and socio-economic status. Familial and genetic effects influence the associations between recurrent headache, exercise, obesity, and poor self-rated health. Overall, these findings provide support for long-term effects of health behavior and psychosocial risk factors on poor self-ratings of health, beyond the influence of obvious health consequences such as disorders or illnesses. Genetic and familial factors are of importance only for some of these associations.

Aged↗

Lifetime prevalence and concordance risk of cluster headache in the Swedish twin population.

OBJECTIVE: To examine the lifetime prevalence and the concordance risk of cluster headache (CH) in a twin sample representative of the Swedish general population. METHODS: The authors assessed CH as defined by the second edition of the International Classification of Headache Disorders in 31,750 registered twins born from 1935 to 1958. Structured lay screening interviews were followed by neurologist interviews of possible cases. Co-twins of affected index twins were follow-up interviewed regardless of their screening outcome. RESULTS: A total of 250 screening-positives (0.8%) were found, of which 218 (88%) were follow-up interviewed. Forty-five (21%) had the CH diagnosis verified. Among screen-negatives, hospitalization records pointed at two more verified cases and index twins at one more verified case. A total of 48 CH cases provided a crude lifetime prevalence of 151 per 100,000 (95% CI: 108, 194). The male-to-female sex ratio corresponded to 4.8 (95% CI: 2.3, 9.9). The crude lifetime prevalence of CH was higher in the twins born from 1945 to 1958 than in the twins born from 1935 to 1944 (190 vs 90/100,000). CH recurred in 2 of 12 co-twins of monozygous index twins (including 1 nonparticipant twin), whereas all co-twins of 25 dizygous index twins proved to be unaffected. CONCLUSION: As many as 1 per 500 of the general population are affected by cluster headache. Twin concordance seems low, but genetic factors may play a role for familial clustering.

Adolescent↗

Likelihood ratio tests in behavioral genetics: problems and solutions.

The likelihood ratio test of nested models for family data plays an important role in the assessment of genetic and environmental influences on the variation in traits. The test is routinely based on the assumption that the test statistic follows a chi-square distribution under the null, with the number of restricted parameters as degrees of freedom. However, tests of variance components constrained to be non-negative correspond to tests of parameters on the boundary of the parameter space. In this situation the standard test procedure provides too large p-values and the use of the Akaike Information Criterion (AIC) or the Bayesian Information Criterion (BIC) for model selection is problematic. Focusing on the classical ACE twin model for univariate traits, we adapt existing theory to show that the asymptotic distribution for the likelihood ratio statistic is a mixture of chi-square distributions, and we derive the mixing probabilities. We conclude that when testing the AE or the CE model against the ACE model, the p-values obtained from using the chi(2)(1 df) as the reference distribution should be halved. When the E model is tested against the ACE model, a mixture of chi(2)(0 df), chi(2)(1 df) and chi(2)(2 df) should be used as the reference distribution, and we provide a simple formula to compute the mixing probabilities. Similar results for tests of the AE, DE and E models against the ADE model are also derived. Failing to use the appropriate reference distribution can lead to invalid conclusions.

Analysis of Variance↗

Genetic influence on human lifespan and longevity.

There is an intense search for longevity genes in both animal models and humans. Human family studies have indicated that a modest amount of the overall variation in adult lifespan (approximately 20-30%) is accounted for by genetic factors. But it is not known if genetic factors become increasingly important for survival at the oldest ages. We study the genetic influence on human lifespan and how it varies with age using the almost extinct cohorts of Danish, Finnish and Swedish twins born between 1870 and 1910 comprising 20,502 individuals followed until 2003-2004. We first estimate mean lifespan of twins by lifespan of co-twin and then turn to the relative recurrence risk of surviving to a given age. Mean lifespan for male monozygotic (MZ) twins increases 0.39 [95% CI (0.28, 0.50)] years for every year his co-twin survives past age 60 years. This rate is significantly greater than the rate of 0.21 (0.11, 0.30) for dizygotic (DZ) males. Females and males have similar rates and these are negligible before age 60 for both MZ and DZ pairs. We moreover find that having a co-twin surviving to old ages substantially and significantly increases the chance of reaching the same old age and this chance is higher for MZ than for DZ twins. The relative recurrence risk of reaching age 92 is 4.8 (2.2, 7.5) for MZ males, which is significantly greater than the 1.8 (0.10, 3.4) for DZ males. The patterns for females and males are very similar, but with a shift of the female pattern with age that corresponds to the better female survival. Similar results arise when considering only those Nordic twins that survived past 75 years of age. The present large population based study shows genetic influence on human lifespan. While the estimated overall strength of genetic influence is compatible with previous studies, we find that genetic influences on lifespan are minimal prior to age 60 but increase thereafter. These findings provide a support for the search for genes affecting longevity in humans, especially at advanced ages.

Adolescent↗

Alcohol, tobacco and caffeine use: spouse similarity processes.

Spouse similarity research has been largely descriptive yet is of theoretical and empirical importance to understanding individual differences in substance use. The present study considers phenotypic assortment versus social homogamy processes for alcohol, tobacco, and caffeine consumption traits using an extended twin-spouse design. Whereas both assortment processes were supported for quantity of alcohol consumed, phenotypic assortment was supported for quantity of tobacco and caffeine consumed, and social homogamy for tobacco use status. Moderate heritable influences were found for all traits though no shared environmental influences were found beyond those due to social background influences, i.e. those pertaining to social homogamy. Swedish government policies in effect at the time of marriage selection may explain the presence of social homogamy for quantity of alcohol versus quantity of tobacco and caffeine consumed. Social homogamy may be more important for some substance use traits such as alcohol consumption and tobacco use status but not others.

Adult↗

Longitudinal memory performance during normal aging: twin association models of APOE and other Alzheimer candidate genes.

The APOE gene (apolipoprotein E) is a major risk factor for Alzheimer's Disease (AD) but has been inconsistently associated with memory in nondemented adults. Two other genes with mixed support as genetic risk factors for AD, A2M (alpha-2-macroglobulin) and LRP (low-density lipoprotein receptor-related protein), have not been studied in relation to memory among nondemented adults. The present study examined these three genes and latent growth parameters estimated from memory performance spanning 13 years in 478 twins from the Swedish Adoption/Twin Study of Aging (SATSA). APOE was associated with working and recall memory ability levels and working memory rate of change, with e4 homozygotes exhibiting the worst performance at all ages. Homozygotes for the rare A2M insertion/deletion variant exhibited accelerating decline on delayed figural recognition. There were no significant findings for LRP. Dominance, often untested in previous studies, was important in the current study's findings.

Age Factors↗

Personality and major depression: a Swedish longitudinal, population-based twin study.

CONTEXT: Prior studies suggest that the personality traits of neuroticism and extroversion may be related to the liability to major depression (MD). OBJECTIVE: To clarify the magnitude and nature of the association between neuroticism and extroversion and the risk for MD. DESIGN: Longitudinal population-based twin cohort. SETTING: General community. PARTICIPANTS: A total of 20 692 members of same-sex twin pairs from the population-based Swedish Twin Registry who completed a self-report questionnaire assessing neuroticism and extroversion in 1972 and 1973 and were personally interviewed for lifetime history of MD more than 25 years later.Main Outcome Measure Lifetime history of modified DSM-IV MD. RESULTS: Levels of neuroticism strongly predicted the risks for both lifetime and new-onset MD. Twin modeling indicated that the association between neuroticism and MD resulted largely from shared genetic risk factors, with a genetic correlation of +0.46 to +0.47. Levels of extroversion were weakly and inversely related to the risks for lifetime and new-onset MD. This effect disappeared when we controlled for the level of neuroticism. Twin modeling produced similar results. CONCLUSIONS: Results from both longitudinal and genetic analyses support the hypothesis that neuroticism strongly reflects the liability to MD. This association arises largely because neuroticism indexes the genetic risk for depressive illness. However, substantial proportions of the genetic vulnerability to MD are not reflected in neuroticism. By contrast, extroversion is only weakly related to risk for MD.

Adult↗

Premorbid predictors of chronic fatigue.

CONTEXT: Chronic fatigue syndrome is a disabling problem characterized by persistent fatigue lasting at least 6 months with a number of ancillary symptoms. Although the etiology of chronic fatiguing illness is unknown, some evidence suggests that stress may confer increased risk for development of the disorder. Moreover, subjects with chronic fatiguing illness may have distinctive personality traits, although this finding could reflect confounding by other mechanisms. OBJECTIVE: To assess the prospective association of premorbid self-reported stress and personality with chronic fatigue-like illness. DESIGN: Prospective nested case-control study in a population-based sample. SETTING: General community. PARTICIPANTS: From the Swedish Twin Registry, 19,192 twins born between January 1, 1935, and December 31, 1958. MAIN OUTCOME MEASURES: Information about current chronic fatiguing illnesses was obtained from computer-assisted telephone interviews conducted between 1998 and 2002. Self-reported stress (based on a single question) and personality scales (emotional instability and extraversion in the Eysenck Personality Inventory) were measured from 1972 to 1973 by a mailed questionnaire. Relative risks were estimated with case-control analyses (matched for age and sex) and co-twin control analyses (comparing discordant pairs). RESULTS: Higher emotional instability and self-reported stress in the premorbid period were associated with higher risk for chronic fatigue-like illness in matched case-control analyses (odds ratios, 1.72 and 1.64, respectively). In co-twin control analyses, relative risk of emotional instability decreased to 1.02 whereas that of stress increased considerably to 5.81. There was no association between extraversion and fatigue. CONCLUSIONS: Elevated premorbid stress is a significant risk factor for chronic fatigue-like illness, the effect of which may be buffered by genetic influences. Emotional instability assessed 25 years earlier is associated with chronic fatigue through genetic mechanisms contributing to both personality style and expression of the disorder. These findings suggest plausible mechanisms for chronic fatiguing illness.

Affective Symptoms↗

Role of genes and environments for explaining Alzheimer disease.

CONTEXT: Twin studies using selected samples have shown high heritability for Alzheimer disease (AD). OBJECTIVE: To evaluate genetic and environmental influences on AD in a fully ascertained population of older twins, including like- and unlike-sex pairs. DESIGN: Five-group quantitative genetic model: male monozygotic twins, female monozygotic twins, male dizygotic twins, female dizygotic twins, and unlike-sex twins. SETTING AND PARTICIPANTS: All twins in the Swedish Twin Registry aged 65 years and older. The study included 11,884 twin pairs, among whom were 392 pairs in which 1 or both members had AD. MAIN OUTCOME MEASURES: All individuals were screened for cognitive dysfunction. Suspected cases of dementia and their co-twins received complete clinical diagnostic evaluations for AD. Estimates of heritability, shared environmental influences, and nonshared environmental influences, adjusting for age, were derived from the twin data. RESULTS: Heritability for AD was estimated to be 58% in the full model and 79% in the best-fitting model, with the balance of variation explained by nonshared environmental influences. There were no significant differences between men and women in prevalence or heritability after controlling for age. Within pairs concordant for AD, intrapair difference in age at onset was significantly greater in dizygotic than in monozygotic pairs, suggesting genetic influences on timing of the disease. CONCLUSIONS: In the largest twin study to date, we confirmed that heritability for AD is high and that the same genetic factors are influential for both men and women. However, nongenetic risk factors also play an important role and might be the focus for interventions to reduce disease risk or delay disease onset.

Age of Onset↗

Prevalence, heritability, and prospective risk factors for anorexia nervosa.

CONTEXT: Anorexia nervosa (AN) is a serious mental illness with marked morbidity and mortality. OBJECTIVE: To explore the prevalence, heritability, and prospectively assessed risk factors for AN in a large population-based cohort of Swedish twins. DESIGN: During a 4-year period ending in 2002, all living, contactable, interviewable, and consenting twins in the Swedish Twin Registry (N = 31 406) born between January 1, 1935, and December 31, 1958, underwent screening for a range of disorders, including AN. Information collected systematically in 1972 to 1973, before the onset of AN, was used to examine prospective risk factors for AN. SETTING: Population-based sample of twins in Sweden. PARTICIPANTS: Cases of AN were identified as those individuals who met full DSM-IV criteria by means of clinical interview of the Swedish Twin Registry, who had a hospital discharge diagnosis of AN, or who had a cause-of-death certificate including an AN diagnosis. RESULTS: The overall prevalence of AN was 1.20% and 0.29% for female and male participants, respectively. The prevalence of AN in both sexes was greater among those born after 1945. Individuals with lifetime AN reported lower body mass index, greater physical activity, and better health satisfaction than those without lifetime AN. Anorexia nervosa was inversely associated with the development of overweight (odds ratio, 0.29; 95% confidence interval [CI], 0.16-0.54 [P<.001]). The heritability of narrowly defined DSM-IV AN (additive genetic effects) was estimated to be a(2) = 0.56 (95% CI, 0.00-0.87), with the remaining variance attributable to shared environment (c(2) = 0.05; 95% CI, 0.00-0.64) and unique environment (e(2) = 0.38; 95% CI, 0.13-0.84). Neuroticism measured about 3 decades before the diagnostic assessment was significantly associated with the development of later AN (odds ratio, 1.62; 95% CI, 1.27-2.05 [P<.001]). CONCLUSIONS: The prevalence of AN was higher in both male and female participants born after 1945. Individuals who survive AN and who no longer have body mass indexes in the AN range appear to be at lower risk for the development of overweight. Prospectively assessed neuroticism was associated with the subsequent development of AN, the liability to which is under considerable genetic influence.

Anorexia Nervosa↗

Importance of genetic influences on chronic widespread pain.

OBJECTIVE: To estimate the relative importance of genetic and environmental factors in chronic widespread pain, and to assess whether there are sex differences in the type or magnitude of these influences. METHODS: Data were collected from a national sample of twins > or = 42 years of age, all of whom were participants in the Swedish Twin Registry. The presence of chronic widespread pain was assessed via computer-assisted telephone interviews, which were conducted between 1998 and 2002, using the American College of Rheumatology criteria for fibromyalgia. No clinical examinations were performed. In preliminary analyses, probandwise concordance rates and tetrachoric correlations were calculated. Structural equation modeling was then performed to estimate additive genetic, shared environmental, and nonshared environmental sources of variability in susceptibility for the development of chronic widespread pain. RESULTS: Of 61,355 eligible twins, 44,897 individuals (73.2%) responded to the interview. Both members of 15,950 pairs responded to the items regarding pain symptoms; of these pairs, 4,170 were monozygotic, 5,881 were same-sex dizygotic, and 5,755 were opposite-sex dizygotic. The prevalence of chronic widespread pain was 4.1%, and the ratio of women to men was 3.3 to 1. Probandwise concordance rates and tetrachoric correlations suggested modest genetic influences for both women and men. Genetic and shared environmental influences explained approximately half of the total variance, with no indication of sex differences in either the type or magnitude of these influences. CONCLUSION: Individual differences in the likelihood of developing chronic widespread pain reflect modest genetic influences. There are no significant sex differences in the type or expression of the genes responsible for chronic widespread pain or in the magnitude of the relative importance of these influences on chronic widespread pain.

Chronic Disease↗

Longitudinal change in memory performance associated with HTR2A polymorphism.

We present a fresh approach to evaluating association with candidate genes and cognitive change by testing association for parameters describing individual growth curves from twins. Moderate genetic influences on memory in aging adults has been shown in quantitative genetic studies. A recently reported, association of a HTR2A polymorphism with episodic memory in young unrelated adults led us to investigate the association between a nearby polymorphism and longitudinal memory performance in the Swedish Adoption/Twin Study of Aging (SATSA). Analysis of growth curve parameters suggests that both how well individuals perform on figural memory at age 65 years and nonlinear change in figural memory performance across age are associated with HTR2A. Individuals with two copies of the common G allele demonstrated higher figural memory performance longitudinally than those with the less frequent A allele, with performance trajectories differing by 2-6% per year. These findings imply a role for the 5-HT2A serotonin receptor on the formation of episodic memories in older adults.

Age Distribution↗

Personality and risk of cognitive impairment 25 years later.

The authors examined the relationship between personality and cognitive impairment in 4,039 members of the Swedish Twin Registry. Neuroticism and extraversion scores were collected in 1973 at midlife, and cognitive impairment was assessed in the same group 25 years later. Data were analyzed with case-control and co-twin control designs. Greater neuroticism was associated with higher risk of cognitive impairment in the results from case-control, but not from co-twin, analyses. Compared with both extraversion and introversion, moderate extraversion was associated with lower risk of cognitive impairment in both case-control and co-twin designs, as was the combination of high neuroticism and low extraversion. Findings are discussed in the context of theories related to personality, psychological distress, arousal, and cognitive function.

Aged↗