The Heritability of Level and Rate-of-Change in Cognitive Functioning in Danish Twins Aged 70 Years and Older

To investigate heritable influences on overall level and rate-of-change in cognitive ability, biometric growth models were fit to cognitive data from nearly 1000 Danish twins age 70 years and older. Twins are participants in the ongoing Longitudinal Study of Aging Danish Twins, a cohort-sequential study of twins assessed every 2 years for up to four waves. Cognitive ability was assessed by five brief cognitive tasks: a fluency measure, forward and backward digit span, and immediate and delayed list recall. Model-fitting results indicated that although the overall level of cognitive functioning was highly heritable ( h 2 =.76, 95% confidence interval of .68 to .82), the rate of linear change was not ( h 2 =.06, 95% confidence interval of .00 to .57). These findings suggest that the search for specific genes might reasonably focus on average level of cognitive performance, whereas specific environmental influences might account for cognitive change.     

Alanine aminotransferase, γ‐glutamyltransferase (GGT) and all‐cause mortality: results from a population‐based Danish twins study alanine aminotransferase,GGT and mortality in elderly twins

Background/Aims: Alanine aminotransferase (ALT) and γ‐glutamyltransferase (GGT) are widely used markers of liver disease. Several population‐based cohort studies have found associations of these liver enzymes with all‐cause mortality. None of these studies controlled for genetic variation as well as fetal and early life exposure, whether environmental or genetic. Methods: We studied the associations of ALT and GGT with all‐cause mortality using data for 686 twins (73–94 years old) included in the Longitudinal Study of Aging Danish Twins. Results: An increase in 1 logged U/L of GGT was associated with a 15% increase in the hazard ratio (HR) for mortality [95% confidence interval (CI) 0.99, 1.32] but there was no strong evidence of an association of ALT with all‐cause mortality (HR=1.07, 95% CI 0.82, 1.40) when controlling for potential confounders. In this analysis, the study population was treated as individuals, with similarities between twins accounted for by using robust standard errors. However, an intrapair analysis in which the proportion of twin pairs in which the twin with the higher level of ALT or GGT died first was compared with 50% (expected under the null hypothesis), found no strong evidence that higher ALT or GGT was associated with earlier death within twin pairs; the results were consistent in both monozygotic and dizygotic twins. Conclusions: γ‐glutamyltransferase but not ALT predicts mortality among older Danish twins when using traditional methods for controlling for potential confounders and existing diabetes and cardiovascular disease. Environmental developmental origins may explain the association, but larger twin studies are required to replicate our findings.     

Physical activity in adolescence and smoking in young adulthood: a prospective twin cohort study

AIMS: To control for familial confounds, we studied the association between adolescent physical activity and later smoking in twin siblings discordant for their baseline physical activity. DESIGN AND MEASUREMENTS: In this prospective population-based twin study, we asked whether persistent physical activity/inactivity in adolescence (assessed at 16, 17 and 18.5 years) predicted questionnaire-reported daily smoking at ages 22-27. Twins who, on the three baseline questionnaires, consistently reported frequent leisure physical activity (more than three times weekly) were classified as persistent exercisers, those who exercised less than three times monthly were called persistently inactive, others were occasional exercisers. SETTING: Finland. PARTICIPANTS: A total of 4240 individuals, including 1870 twin pairs. Findings In analyses of individual twins, compared to persistent activity, persistent physical inactivity predicted increased risk of daily smoking (age- and sex-adjusted odds ratio 5.53, 95% confidence interval 3.88-7.88, P < 0.001). The risk remained elevated even after excluding all those who had smoked 50 cigarettes or more life-time at baseline and adjusted for educational level in adolescence. In within-pair analyses compared to the active members of discordant twin pairs, the physically inactive co-twins had increased risk of future daily smoking (sex-adjusted odds ratio 3.39, 95% confidence interval 1.56-7.39, P = 0.002). CONCLUSIONS: Persistent physical inactivity in adolescence relates to adult smoking, even after familial factors are taken into account.     

Genetic and environmental influences on self-reported reduced hearing in the old and oldest old

OBJECTIVES: The aim of the present twin study was to estimate the relative importance of genetic and environmental factors in variation in self-reported reduced hearing among the old and the oldest old. DESIGN: Self-reported hearing abilities of older twins assessed at intake interview in a population-based longitudinal survey. SETTING: Denmark. PARTICIPANTS: Twins age 75 and older identified in the population-based Danish Twin Registry in 1995. An interview was conducted with 77% of 3,099 individuals in the study population. In 1997 and 1999, a follow-up contact to the survivors was made and an additional 2,778 twins, age 70-76, were included in the study. MEASUREMENTS: Reduced hearing was assessed by the same question in all interview waves. Heritability (proportion of the population variance attributable to genetic variation) was estimated using structural-equation analyses. RESULTS: The prevalence of self-reported reduced hearing corresponded to previous studies and showed the expected age and sex dependence. Concordance rates, odds ratios, and correlations were consistently higher for monozygotic twin pairs than for dizygotic twin pairs in all age and sex categories, indicating heritable effects. Structural-equation analyses revealed a substantial heritability for self-reported reduced hearing of 40% (95% CI = 19-53%). The remaining variation could be attributed to individuals' nonfamilial environments. CONCLUSION: We found that genetic factors play an important role in self-reported reduced hearing in both men and women age 70 and older. Because self-reports of reduced hearing involve misclassification, this estimate of the genetic influence on hearing disabilities is probably conservative. Hence, genetic and environmental factors play a substantial role in reduced hearing among the old and oldest old. This suggests that clinical epidemiological studies of age-related hearing loss should include not only information on environmental exposures but also on family history of hearing loss and, if possible, biological samples for future studies of candidate genes for hearing loss.     

Ankylosing spondylitis in Danish and Norwegian twins: occurrence and the relative importance of genetic vs. environmental effectors in disease causation

OBJECTIVE: To estimate the influence of genetic effects in the aetiology and pathogenesis of ankylosing spondylitis (AS). METHODS: The study comprised one Norwegian and two Danish nationwide twin surveys. In 1994 and 2002, respectively, 37,388 and 46,331 Danish twin individuals were asked by questionnaire if they had AS. Similarly, in 1998, 12,718 Norwegian twins were asked if they had AS using a questionnaire phrased according to the Danish survey. Twins reporting AS were categorized according to the modified New York criteria. RESULTS: A total of 113 twin individuals reported AS, of whom 81 (72.3%) participated in validation of the diagnosis. After validation, 39 probands were diagnosed with AS. Subsequent invitation of co-twins resulted in 27 complete pairs. The point prevalence and the annual incidence of AS was 0.1% and 3/100,000 person-years (pyr) among the Danish twins. The positive predictive value of self-reported AS was 49.3%. Probandwise concordance rates on AS were (2/5) 40% in monozygotic (MZ) and (1/23) 4% in dizygotic (DZ) twins [difference 35% (95% CI 2.9-72.8), p = 0.26]. Heredity analysis including previously published and the present HLA-B27-positive twin pairs indicated that additive genetic effects account for 94% (95% CI 0.56-0.99) of the variance in the causation of AS. CONCLUSION: Self-reported AS needs careful validation. The occurrence of AS in a Danish twin population was 0.1% and accords well with previous studies on singletons in hospital settings. The present study adds to previous evidence of a major genetic effect in the pathogenesis of AS.     

Sources of Influence on Rate of Cognitive Change Over Time in Swedish Twins: An Application of Latent Growth Models

The use of latent growth models to examine influence on individual differences on ability level versus rate of change were examined for measures of fluid ability, memory, and perceptual speed in a sample of twins from the Swedish Adoption/Twin Study of Aging. Results indicated a larger amount of individual variation for average ability level (i.e., intercept) than rate of change (i.e., slope) for all three traits: Block Design, Thurstone's Picture Memory, and Symbol Digit. Generally, genetic influences were of greater importance to individual variation in ability level whereas variation for rate of change exhibited a larger environmental component. These findings support theories of increasing environmental influences with age. When genetic and environmental sources of covariation between educational attainment and pulmonary function with latent growth parameters were considered, the sources of covariation between the latent cognitive growth model parameters (i.e., intercept and slope) and both covariates were primarily genetic for ability level (intercepts) but environmental for rate of change (slopes). Such findings suggest that the forces important to timing or entry into cognitive decline may reflect stochastic processes or external environmental factors, primarily nonshared, that may differentially hasten cognitive decline in twins. These same forces may overlap with those that influence higher or lower educational attainment or those leading to better or worse pulmonary functioning.     

Early-onset depressive disorders predict the use of addictive substances in adolescence: a prospective study of adolescent Finnish twins

Aims To explore the developmental relationships between early‐onset depressive disorders and later use of addictive substances. Design, setting and participants A sample of 1545 adolescent twins was drawn from a prospective, longitudinal study of Finnish adolescent twins with baseline assessments at age 14 years and follow‐up at age 17.5 years. Measurements At baseline, DSM‐IV diagnoses were assessed with a professionally administered adolescent version of Semi‐Structured Assessment for Genetics of Alcoholism (C‐SSAGA‐A). At follow‐up, substance use outcomes were assessed via self‐reported questionnaire. Findings Early‐onset depressive disorders predicted daily smoking [odds ratio (OR) 2.29, 95% confidence interval (CI) 1.49–3.50, P < 0.001], smokeless tobacco use (OR = 2.00, 95% CI 1.32–3.04, P = 0.001), frequent illicit drug use (OR = 4.71, 95% CI 1.95–11.37, P = 0.001), frequent alcohol use (OR = 2.02, 95% CI 1.04–3.92, P = 0.037) and recurrent intoxication (OR = 1.83, 95% CI 1.18–2.85, P = 0.007) 3 years later. ORs remained significant after adjustment for comorbidity and exclusion of baseline users. In within‐family analysis of depression‐discordant co‐twins (analyses that control for shared genetic and familial background factors), early‐onset depressive disorders at age 14 predicted significantly frequent use of smokeless tobacco and alcohol at age 17.5. Conclusions Our results suggest important predictive associations between early‐onset depressive disorders and addictive substance use, and these associations appear to be independent of shared familial influences.     

Impact of Geriatrician-Performed Comprehensive Geriatric Care on Medication Use and Cognitive Function in Older Adults Referred to a Non-Hospital-Based Rehabilitation Unit

Background and Purpose

Eighty-eight percent of older adults referred to Danish non-hospital-based rehabilitation units used ≥5 regular drugs per day at the beginning of rehabilitation. The aim of the study was to explore whether geriatrician-performed comprehensive geriatric care had an impact on medication use and cognitive function in older adults after a 90-day follow-up.

Cognitive Decline and Risk of Dementia in Individuals With Heart Failure: A Systematic Review and Meta-analysis

BackgroundWe sought to determine the association between heart failure (HF) and cognitive change and dementia.Methods and ResultsSystematic search of three electronic databases was performed and 29 eligible studies involving approximately 3 million participants were identified. Twelve studies examined dementia and 20 cognitive change, but only a subset of studies could be included in the meta-analysis. These findings indicated that HF was not significantly associated with dementia (n = 8, hazard ratio 1.18, 95% confidence interval 0.93–1.50), but increased the risk of cognitive impairment (n = 3, hazard ratio 1.80, 95% confidence interval 1.14–2.86) . Additionally, HF was associated with poorer mean cognitive performance in global cognition (Hedges’ g –0.73, 95% confidence interval –1.12 to –0.35), memory (Hedges’ g –0.57, 95% confidence interval –0.72 to –0.42), executive function (Hedges’ g –0.58, 95% confidence interval –0.72 to –0.43), attention/speed (Hedges’ g –0.50, 95% confidence interval –0.63 to –0.37) and language (Hedges’ g –0.61, 95% confidence interval –1.05 to –0.17).ConclusionsPatients with HF perform worse on all cognitive tests and have an increased risk of cognitive impairment. These findings highlight the need for clinicians to consider cognition as part of routine care for patients with HF.     

Communication between identical twins: health behavior and social factors are associated with longevity that is greater among identical than fraternal U.S. World War II veteran twins

BACKGROUND: Longevity is greater for identical twins than for fraternal twins from the same population. Factors that are explanatory for this difference are not known. METHODS: Multivariate survival analysis is applied to current mortality data for 26,974 male twins with known zygosities of the National Academy of Science-National Research Council World War II Veteran Twins Registry, and this analysis is applied to their health and social behavior and personal histories, as collected from two survey questionnaires distributed in 1967 and 1983 (with 14,300 and 9475 responses received, respectively). To explain this difference in longevity, social, health, and personal history factors are evaluated for associations with longevity. RESULTS: Survival functions of identical and fraternal twins differed significantly (p<.0001). Median lifetimes were 82 years for identical and 80.5 years for fraternal twins. The correlation between lifetimes of identical twin partners was greater than that of fraternal twins. For identical but not for fraternal twins, the risk of mortality was significantly lower for twin partners who communicated 1 or more times per month, compared with those who communicated less frequently (relative risk.80, 95% confidence interval 0.68-0.94, p=.008, with control for other factors associated with longevity: smoking, exercise, a current marriage, living with both parents until age 15 or older, and having a live co-twin). Distributions of communication, exercise level, and smoking prevalence were more beneficial with regard to longevity for identical than for fraternal twins as a group. CONCLUSIONS: Frequent communication between identical but not fraternal twin partners, and both level of exercise and prevalence of smoking, distributed more beneficially in terms of longevity for identical compared with fraternal twins, are explanatory for the greater longevity of identical than fraternal twins.     

Dizziness and the genetic influences on subjective experiences to initial cigarette use

Aim To examine individual differences in positive and negative subjective experiences to initial cigarette use. Design Retrospective self‐reports of initial subjective experiences were examined to estimate the genetic and environmental influences and the extent of their covariation across different effects. Participants Data was drawn from 2482 young adult same‐and opposite sex twins‐ and siblings participating in the National Longitudinal Study of Adolescent Health. Measurement Subjective experiences were retrospectively collected using the Early Smoking Experience (ESE) questionnaire. Findings Positive experiences evidenced moderate heritable contributions (40%, 95% CI: 0.22 to 0.56), as did an overall hedonic measure (34%, 95% CI: 0.22 to 0.46) and dizziness (34%, 95% CI: 0.15 to 0.52). Negative experiences evidenced small heritable contributions (13%, 95% CI: 0.00 to 0.36). Individual specific environmental influences were strong and accounted for the remaining proportion of observed variation in these experiences. Multivariate genetic modeling identified a moderately heritable underlying factor (37%, 95% CI: 0.22 to 0.52) that influenced the covariation of diverse subjective experiences and loaded most heavily on dizziness. Positive experiences also evidence residual genetic influences that were uncorrelated with other subjective experiences. Conclusions How a person experiences their initial few cigarettes is due to both heritable contributions and environmental experiences unique to the person. The covariation of diverse subjective experiences appears to be due to a heritable latent sensitivity to the chemicals contained in an average cigarette and is best indexed by dizziness.     

Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group

BACKGROUND: The long-term effect of type 2 diabetes on cognitive function is uncertain. OBJECTIVE: To determine whether older women with diabetes have an increased risk of cognitive impairment and cognitive decline. DESIGN: Prospective cohort study. SETTING: Four research centers in the United States (Baltimore, Md; Portland, Ore; Minneapolis, Minn; and the Monongahela Valley, Pennsylvania). PARTICIPANTS: Community-dwelling white women 65 years and older (n = 9679). MEASUREMENTS: Physician-diagnosed diabetes and other aspects of health history were assessed by interview. Three tests of cognitive function, the Digit Symbol test, the Trails B test, and a modified version of the Mini-Mental State Examination (m-MMSE), were administered at baseline and 3 to 6 years later. Change in cognitive function was defined by the change in the score for each test. Major cognitive decline was defined as the worst 10th percentile change in the score for each test. RESULTS: Women with diabetes (n = 682 [7.0%]) had lower baseline scores than those without diabetes on all 3 tests of cognitive function (Digit Symbol and Trials B tests, P<.01; m-MMSE, P = .03) and experienced an accelerated cognitive decline as measured by the Digit Symbol test (P<.01) and m-MMSE (P = .03). Diabetes was also associated with increased odds of major cognitive decline as determined by scores on the Digit Symbol (odds ratio = 1.63; 95% confidence interval, 1.20-2.23) and Trails B (odds ratio, 1.74; 95% confidence interval, 1.27-2.39) tests when controlled for age, education, depression, stroke, visual impairment, heart disease, hypertension, physical activity, estrogen use, and smoking. Women who had diabetes for more than 15 years had a 57% to 114% greater risk of major cognitive decline than women without diabetes. CONCLUSION: Diabetes is associated with lower levels of cognitive function and greater cognitive decline among older women.     

Relationship between functional loss before hospital admission and mortality in elderly persons with medical illness

OBJECTIVE: This hospital-based prospective study tests the hypothesis that, in a large group of hospitalized elderly patients, those who report functional decline between pre-illness baseline and hospital admission have a higher risk of death. METHODS: Nine hundred fifty elderly ambulant patients (F = 69.3%; mean age 78.3 +/- 8.5 years) were consecutively admitted to a geriatric ward (Poliambulanza Hospital, Brescia, Italy) during a 15-month period. Number and severity of somatic diseases, Charlson Index score, APACHE II score, level of serum albumin, cognitive status (by Mini-Mental State Examination), and depression score (by Geriatric Depression Scale), were assessed on admission and evaluated as potential prognostic factors. Functional status (by Barthel Index) was assessed by self-report on admission. Preadmission function was also assessed by self-report at the time of admission. Impairment of function due to an acute event is measured as the difference between performances on admission and 2 weeks before the acute event. Six-month survival was the main outcome variable. RESULTS: Factors related to mortality in bivariate analysis were: male sex, age over 80, cancer, congestive heart failure, pulmonary diseases, elevated Charlson Index score, and (independently) dementia (Mini-Mental State Examination < 18), APACHE-Acute Physiology Score , albumin level <3.5 g/dL, and anemia. After controlling for these variables and for Barthel Index score 2 weeks before the acute event, change in function due to the acute disease is independently related to 6-month mortality (minor functional change [<30 Barthel Index Point] relative risk: 1.3, 95% confidence interval, 0.6-3.0 and major functional change [major functional decrement] relative risk: 2.8, 95% confidence interval, 1.3-5.7). CONCLUSIONS: Disease-induced disability may reflect a condition of biological inability to react to acute diseases (i.e., frailty), and should be assessed as a relevant prognostic indicator.     

Genetic factors and susceptibility to falls in older women

OBJECTIVES: To determine whether genetic influences account for individual differences in susceptibility to falls in older women. DESIGN: Prospective twin cohort study. SETTING: Research laboratory and residential environment. PARTICIPANTS: Ninety-nine monozygotic (MZ) and 114 dizygotic (DZ) female twin pairs aged 63 to 76 from the Finnish Twin Cohort study. MEASUREMENTS: The participants recorded their falls on a calendar for an average+/-standard deviation of 344+/-41 days. Reported falls were verified via telephone interview, and circumstances, causes, and consequences of the fall were asked about. RESULTS: The total number of falls was 434, of which 188 were injurious; 91 participants had two or more falls. Casewise concordance was 0.61 (95% confidence interval (CI)=0.49-0.72) for MZ twins and 0.49 (95% CI=0.37-0.62) for DZ twins for at least one fall, 0.38 (95% CI=0.23-0.53) for MZ and 0.33 (95% CI=0.17-0.50) for DZ twins for at least one injurious fall, and 0.43 (95% CI=0.26-0.60) for MZ and 0.36 (95% CI=0.17-0.55) for DZ twins for recurrent falls. On average, the proportion of familial influences accounting for the individual differences in susceptibility to at least one fall was 30% and to recurrent falls was 40%; nongenetic familial and nonfamilial factors alone accounted for susceptibility to at least one injurious fall. CONCLUSION: In community-dwelling older women, familial factors underlie the risk of falling but not the risk of injurious falls.     

Hair loss among elderly men: etiology and impact on perceived age

BACKGROUND: Androgenetic alopecia is the most common type of hair loss in men, but little is known about the etiology of androgenetic alopecia in elderly men and its impact on perceived age. Here we used a population-based twin study of men aged 70+ to assess the magnitude of the genetic component affecting hair loss and to examine the association between baldness and perceived age. METHODS: In the fourth wave of The Longitudinal Study of Aging Danish Twins we obtained digital photos of the face and photos of the vertex area of 739 elderly male twins, including 148 intact twin pairs. The degree of baldness and perceived age were assessed in each twin by five and nine nurses, respectively. The heritability of balding was estimated using structural-equation analysis, and it was tested whether baldness was associated with estimations of age. RESULTS: The intrapair correlation of degree of balding was consistently higher for monozygotic than for dizygotic twin pairs regardless of the baldness categorization used, and structural-equation analysis revealed a heritability of 79% (95% confidence interval, 0.40--0.85) for the mean baldness index. The remaining variation could be attributed to non-shared environmental effects. There was only a very weak and statistically nonsignificant association between baldness and overestimation of age. CONCLUSIONS: The majority of the variation in baldness in elderly men can be explained by genetic factors, and hair quantity has little impact on perceived age in elderly men.     

Mortality in patients with ulcerative colitis in Leicestershire, 1972–1989

The mortality in 1014 patients with ulcerative proctocolitis diagnosed while resident in Leicestershire identified in a population-based study from 1972 to 1989 was assessed. Ninety-two Europeans and one South Asian died. The standardized mortality ratio (SMR) in South Asians was 26 (95% confidence interval 0–147). In Europeans the overall mortality was not increased, the SMR was 93 (95% confidence interval 75–114). The SMR did not differ between established disease extents, but was highest in those patients in whom the extent was undefined (SMR=237, 95% confidence interval 130–397). Comparison of SMRs and survival curves showed no difference in mortality in patients diagnosed from 1972 to 1980 and from 1981 to 1989. Mortality was similar in patients who had colectomy and those who had not (SMR=130, 95% confidence interval 71–219, X² ₁=1.2, NS). Mortality did not change during the study. These findings should be made available to patients and their families.     

Twin study of depressive symptoms among older african-american women

This study examines factors associated with depressive symptoms in a genetically informative sample of African-American female twins aged 65 years and older. A telephone interview was conducted with 180 pairs of twins. Questions included demographics, health behaviors, health status, activities of daily living (ADLs), instrumental ADLs, and depressive symptoms as measured by the Center for Epidemiologic Studies-Depression scale. Regression methods for clustered data were used to examine the associations. In univariate analyses, ADLs (odds ratio or OR = 1.4, 95% confidence interval or CI = 1.1-1.7), fractures (OR = 4.4, 95% CI = 1.3-15.6), and vision problems (OR = 1.9, 95% CI = 1.0-3.8) were significantly associated with depressive symptoms. In multivariable analyses, ADLs (OR = 1.4, 95% CI = 1.2-1.7) and vision problems (OR = 2.0, 95% CI = 1.2-3.5) remained significantly associated with depressive symptoms. A within-pair analysis, controlling for genetic or familial influences, produced similar results. The results suggest that efforts targeted at reducing levels of disability may reduce depressive symptoms in this population.     

Sources of influence on rate of cognitive change over time in Swedish twins: an application of latent growth models

The use of latent growth models to examine influence on individual differences on ability level versus rate of change were examined for measures of fluid ability, memory, and perceptual speed in a sample of twins from the Swedish Adoption/Twin Study of Aging. Results indicated a larger amount of individual variation for average ability level (i.e., intercept) than rate of change (i.e., slope) for all three traits: Block Design, Thurstone's Picture Memory, and Symbol Digit. Generally, genetic influences were of greater importance to individual variation in ability level whereas variation for rate of change exhibited a larger environmental component. These findings support theories of increasing environmental influences with age. When genetic and environmental sources of covariation between educational attainment and pulmonary function with latent growth parameters were considered, the sources of covariation between the latent cognitive growth model parameters (i.e., intercept and slope) and both covariates were primarily genetic for ability level (intercepts) but environmental for rate of change (slopes). Such findings suggest that the forces important to timing or entry into cognitive decline may reflect stochastic processes or external environmental factors, primarily nonshared, that may differentially hasten cognitive decline in twins. These same forces may overlap with those that influence higher or lower educational attainment or those leading to better or worse pulmonary functioning.     

Depressive Symptoms and Incident Cognitive Impairment in Cognitively Well-Functioning Older Men and Women

OBJECTIVES: To investigate whether the effect of depressive symptoms on the risk of cognitive decline and incident cognitive impairment (CI) in cognitively well-functioning older persons differed between men and women and whether sex differences in cerebrovascular factors might explain this.
DESIGN: Prospective cohort study.
SETTING: General community.
PARTICIPANTS: One thousand four hundred eighty-seven well-functioning Chinese older adults (Mini-Mental State Examination (MMSE) score ≥24) assessed at baseline for the presence of depressive symptoms (Geriatric Depression Scale score ≥5), and covariates (age, apolipoprotein E ɛ4, education, smoking, alcohol drinking, and vascular risk factors and diseases).
MAIN OUTCOME MEASURES: Incident CI and change in MMSE were assessed at 2-year follow-up.
RESULTS: In the whole sample, participants with depression showed significantly more incident CI than those without (5.7% vs 2.6%, P =.04; adjusted odds ratio (OR)=2.29, 95% confidence interval (CI)=1.05–5.00. Significantly higher OR was observed only in men (OR=4.75, 95% CI=1.22–18.5) and not for women (OR=1.29). There was a correspondingly greater rate of cognitive decline in participants with depressive symptoms that was observed to be marked only in men and not in women. The association was accentuated in subgroups with hypertension or vascular factors, but the sex differences in association were consistently observed.
CONCLUSION: The association between depressive symptoms and risk of cognitive decline was observed only in men and was not explained by sex differences in vascular factors. The comorbid presence of underlying cerebral vascular pathology or multi-infarct disease was possibly not a mediating factor but might amplify the process of cognitive decline.     

A population-based study of chronic autoimmune hypothyroidism in Danish twins

Hashimoto's thyroiditis (HT), atrophic thyroiditis (AT), and Graves' disease are autoimmune thyroid diseases in which genetic factors are suspected to play an important role in disease susceptibility. In a recent population-based twin study we rendered it probable that a substantial part of the susceptibility to Graves' disease is attributable to genetic factors. At present there are no population-based twin studies supporting such a genetic influence in the etiology of HT/AT. To elucidate whether there is a genetic influence in the etiology of HT/AT, we studied the distribution of HT/AT in a population-based sample of 2945 Danish female-female twin pairs (5890 individuals) born between 1953 and 1972. Information on hypothyroidism was obtained from a nationwide questionnaire survey in 1994. Information from hospitals, out-patient clinics, general practitioners, and specialists was sought to verify the diagnosis. The overall prevalence of autoimmune hypothyroidism was 0.41% (24 of 5890). The prevalence did not differ between monozygotic and dizygotic twins (0.42% and 0.40%, respectively). The crude proband-wise concordance rates were significantly higher for monozygotic compared to dizygotic twin pairs: 0.55 (95% confidence interval, 0.23-0.83) vs. 0.0 (95% confidence interval, 0.0-0.25; P = 0.01). All of the healthy cotwins (n = 15) of twins with clinically overt autoimmune hypothyroidism were biochemically euthyroid. Overall, regardless of zygosity 53% (8 of 15) of the healthy cotwins were positive for antithyroid antibodies. The prevalence of autoantibodies among the monozygotic cotwins was 80% (4 of 5) and 40% (4 of 10) among dizygotic cotwins (P = 0.36). In conclusion, the higher concordance rate in monozygotic compared to dizygotic pairs indicates that genetic factors play a role in the etiology of HT/AT among Caucasian women living in areas with borderline iodine deficiency. However, the fact that the concordance rate among MZ twins was below 1 suggests that environmental factors also are of etiological importance.