Gene-environment interplay in depressive symptoms: moderation by age, sex, and physical illness.

BACKGROUND: Numerous factors influence late-life depressive symptoms in adults, many not thoroughly characterized. We addressed whether genetic and environmental influences on depressive symptoms differed by age, sex, and physical illness. METHOD: The analysis sample included 24 436 twins aged 40-90 years drawn from the Interplay of Genes and Environment across Multiple Studies (IGEMS) Consortium. Biometric analyses tested age, sex, and physical illness moderation of genetic and environmental variance in depressive symptoms. RESULTS: Women reported greater depressive symptoms than men. After age 60, there was an accelerating increase in depressive symptom scores with age, but this did not appreciably affect genetic and environmental variances. Overlap in genetic influences between physical illness and depressive symptoms was greater in men than in women. Additionally, in men extent of overlap was greater with worse physical illness (the genetic correlation ranged from near 0.00 for the least physical illness to nearly 0.60 with physical illness 2 s.d. above the mean). For men and women, the same environmental factors that influenced depressive symptoms also influenced physical illness. CONCLUSIONS: Findings suggested that genetic factors play a larger part in the association between depressive symptoms and physical illness for men than for women. For both sexes, across all ages, physical illness may similarly trigger social and health limitations that contribute to depressive symptoms.

Body mass index across midlife and cognitive change in late life.

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 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. 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. CONCLUSION: 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.

'A no means no'--measuring depression using a single-item question versus Hospital Anxiety and Depression Scale (HADS-D).

BACKGROUND: Depression often develops undetected; to make treatment possible, a single-item screening question may be useful. PATIENTS AND METHODS: We attempted to compare the accuracy of the single-item question 'Are you depressed?' with the seven-item Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) among 1192 Swedish testicular cancer survivors. RESULTS: We obtained information from 974 men (82%). Fifty-nine men (6%) answered 'Yes' to the question 'Are you depressed?' while 118 (12%) answered 'I don't know' and 794 (82%) answered 'No'. Among the 794 men who answered 'No' to the question 'Are you depressed?', 790 (99.5%) were not considered as depressed according to HADS-D 11+. Of those answering 'Yes', 34% (20/59) were identified as depressed according to the same cut-off. Sensitivity of 'Yes' compared with HADS-D > or =11 was 61%, rising to 88% when 'Yes' and 'I don't know' were combined. CONCLUSION: In a population of men with a prevalence of depression similar to that of the normal population, almost none of those responding 'No' to the written question 'Are you depressed?' were depressed according to HADS-D > or =11. Adding the category 'I don't know' increases sensitivity in detecting depression.

Introduction and evaluation of a novel multi-camera surface topography system.

BACKGROUND: Surface topography can be used for the evaluation of spinal deformities without any radiation. However, so far this technique is limited to posterior trunk measurements due to the use of a single posterior camera. RESEARCH QUESTION: Purpose of this study was to introduce a new multi camera surface topography system and to test its reliability and validity. METHODS: The surface topograph uses a two-camera system for imaging and evaluating the subjects front and back simultaneously. Inter- and intra-rater reliability was tested on 40 human subjects by two observers. For validation human, subjects were scanned by MRI and surface-topography. For additional validation we used a phantom with an anthropomorphic body which was scanned by CT and surface topography. RESULTS: Inter- (0.97-0.99) and intra-rater reliability (0.81-0.98) testing revealed good and excellent results in the detection of the body surface structures and measurement of areas and volumes. CT based validation revealed good correspondence between systems in the imaging and evaluation of the phantom model (0.61-10.52 %). Results on validation of human subjects revealed good to moderate results in the detection and measurements of almost all body surface structures (1.36-13.34 %). Only measurements using jugular notch as a reference showed moderate results in validity (0.62-27.5%) testing. SIGNIFICANCE: We have introduced a novel and innovative surface topography system that allows for simultaneous anterior and posterior trunk measurements. The results of our reliability and validity tests are satisfactory. However, in particular around the jugular notch region further improvements in the surface topography reconstruction are needed.

Overweight in midlife and risk of dementia: a 40-year follow-up study.

OBJECTIVE: This study examines whether overweight in midlife increases dementia risk later in life. METHODS: In 1963 body mass index was assessed in 1152 participants of The Swedish Twin Registry, at the age of 45-65 years. These participants were later screened for dementia in a prospective study with up to 40 years follow-up. A total of 312 participants were diagnosed with dementia. RESULTS: Logistic regression analyses adjusted for demographic factors, smoking and alcohol habits, indicated that men and women categorized as overweight in their midlife had an elevated risk of dementia (OR=1.59; 95% CI: 1.21-2.07, P=0.002), Alzheimer's disease (OR=1.71; 95% CI: 1.24-2.35, P=0.003), and vascular dementia (OR=1.55; 95% CI: 0.98-2.47, P=0.059). Further adjustments for diabetes and vascular diseases did not substantially affect the associations, except for vascular dementia (OR=1.36; 95% CI: 0.82-2.56, P=0.116), reflecting the significance of diabetes and vascular diseases in the etiology of vascular dementia. There was no significant interaction between overweight and APOE epsilon4 status, indicating that having both risk factors does not have a multiplicative effect with regard to dementia risk. CONCLUSIONS: This study gives further support to the notion that overweight in midlife increases later risk of dementia. The risk is increased for both Alzheimer's disease and vascular dementia, and follows the same pattern for men and women.

Development of a new 360-degree surface topography application.

BACKGROUND: Surface-topography has been used for almost two decades in the radiation-free clinical evaluation of spinal posture. So far, it was limited to the analysis of back surface and spine. In order to better understand, diagnose and treat complex spinal pathologies, it is important to measure the whole torso. RESEARCH QUESTION: Purpose of this study was to introduce and test an application that allows 360° reconstruction and analysis of the patient's torso. METHODS: The application uses the information gathered from eight distinct scans and angles. For validation we used an Alderson phantom as an anthropomorphic body. Defined areas and volumes were measured by CT and surface-topography. Inter- and intra-rater reliability was tested in 35 healthy subjects by two observers. RESULTS: The results revealed good correspondence between systems in the imaging and evaluation of the Alderson model (5.3-0.5%). Inter- (0.9-0.98) and intra-rater reliability (0.8-0.95) testing revealed good and excellent results in the detection of almost all body surface structures and measurement of areas and volumes. Only area and volume measurements using jugular notch as a reference showed partly moderate results in reliability (0.62-0.93) testing. SIGNIFICANCE: We were able to introduce a novel 360° torso scan application using surface topography to reconstruct torso measurements. The results of our study showed its high validity and reliability. In the future, this application needs to be tested in patients with spinal pathologies. In summary, this new application may help to better understand, diagnose and treat patients with pathologies of torso and spine.

Comparison of two different designs of forefoot off-loader shoes and their influence on gait and spinal posture.

BACKGROUND: The purpose of forefoot off-loader shoes (FOS) is to unload the operated region of the foot in order to allow early mobilization and rehabilitation. However, little is known about the actual biomechanical effects of different designs of FOS on gait, pelvis and spine. RESEARCH QUESTION: Aim of this study was to analyse and compare the effects of two different designs of forefoot unloader shoes. METHODS: Ortho-Wedge (FOS A) and Relief-Dual® (FOS B) were evaluated in this study during standing and while walking. Changes of the pelvic position and spinal posture were measured with a surface topography system and an instrumented treadmill. Gait phases were detected automatically by a built-in pressure plate. RESULTS: Both FOS resulted in a significant increase of pelvic obliquity, pelvic torsion, lateral deviation and surface rotation (p < 0.001) while standing. Between both shoe models, pelvic obliquity and lateral deviation (p < 0.05) were significantly different. During walking, both FOS had a significant effect on spine and pelvis (p < 0.05), however only minor differences were found between the designs. All gait parameters were affected more, wearing FOS A than B. Step length were significantly longer by wearing FOS (p < 0.005). However stance phase raised and swing phase is reduced on the leg wearing FOS A (p < 0.001). SIGNIFICANCE: The study showed that FOS lead to significant changes in pelvic position and spinal posture during standing and while walking. A compensating shoe on the contralateral side is therefore recommend. Gait parameters however were affected more by the traditional FOS A half-shoe. The sole- design and shape of FOS B leads to a more physiological roll-over of the foot.

Genetic susceptibility to cardiovascular disease and risk of dementia.

Several studies have shown cardiovascular disease (CVD) to be associated with dementia, but it is not clear whether CVD per se increases the risk of dementia or whether the association is due to shared risk factors. We tested how a genetic risk score (GRS) for coronary artery disease (CAD) affects dementia risk after CVD in 13 231 Swedish twins. We also utilized summarized genome-wide association data to study genetic overlap between CAD and Alzheimer´s disease (AD), and additionally between shared risk factors and each disease. There was no direct effect of a CAD GRS on dementia (hazard ratio 0.99, 95% confidence interval (CI): 0.98-1.01). However, the GRS for CAD modified the association between CVD and dementia within 3 years of CVD diagnosis, ranging from a hazard ratio of 1.59 (95% CI: 1.05-2.41) in the first GRS quartile to 1.91 (95% CI: 1.28-2.86) in the fourth GRS quartile. Using summary statistics, we found no genetic overlap between CAD and AD. We did, however, find that both AD and CAD share a significant genetic overlap with lipids, but that the overlap arose from clearly distinct gene clusters. In conclusion, genetic susceptibility to CAD was found to modify the association between CVD and dementia, most likely through associations with shared risk factors.

Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models.

Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers. Female EFAD transgenic mice (5xFAD+/-/human APOE ɛ3 or ɛ4+/+) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral ß-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aß deposits, both exacerbated by APOE ɛ4. Moreover, nPM exposure increased Aß oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ɛ4 carriers. The underlying mechanisms may involve increased cerebral Aß production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.

Women, Co-occurring Disorders, and Violence Study: evaluation design and study population.

The Women, Co-occurring Disorders, and Violence Study (WCDVS) was a multi-site cooperative study to evaluate new service models for women with co-occurring mental health and substance use disorders and a history of physical and/or sexual abuse. Despite common features in the service interventions and evaluation procedures, diversity across the nine sites plus differences introduced by non-random assignment led to numerous methodological challenges. This article describes the design, measurement, and analysis decisions behind the WCDVS and lays the foundation for understanding participant-level outcomes and service costs. This article also describes the study population, as recruited and following attrition at the 6-month follow-up, in order to address the threat of selection bias to inferences drawn from this multi-site study.

Use of twin cohorts for research in Alzheimer's disease.

The causes of Alzheimer's disease (AD) remain a mystery despite the recent identification of several putative environmental risk factors and the discovery of several linked genetic loci and point mutations associated with the disease. Particularly uncertain is the generalizability of the genetic findings to the common forms of disease encountered in clinical practice or population research. Twin studies of AD can illuminate causal mechanisms, both genetic and environmental. This consensus document explores the rationale for such twin studies, as well as a number of methodologic problems that render them difficult to implement or interpret. We review existing twin studies of AD and note several ambitious new studies. Finally, we delineate several practical strategies for the near future of twin research in AD.

Multiple-threshold models for genetic influences on age of onset for Alzheimer disease: findings in Swedish twins.

Twin studies of dementia have typically used relatively simple 2 x 2 contingency tables with one threshold to estimate the relative importance of genetic variance for liability to disease. These designs are inadequate for addressing issues of age at onset, censoring of data, and distinguishing shared environmental effects from age effects. Meyer and Breitner [1998: Am J Med Genet 81:92-97] applied a multiple-threshold model to the NAS-NRC Twin Panel (average age of onset, 63.5 years) and report that additive genetic effects and shared environmental effects account for 37% and 35% of the variation, respectively, in age of onset for Alzheimer disease. We apply a modified version of their model to the Study of Dementia in Swedish Twins (average age of onset, 75 years) and find that genetic effects account for 57%-78% of the variance, whereas shared environmental effects are of no importance. Heritability is lower when thresholds are freely estimated rather than fixed to the population prevalences. We interpret the findings to suggest that models with free thresholds confound influences on longevity with influences for the disease. Multiple-threshold models, however, do not confound age effects with shared environmental influences.

Application of life table analysis to the onset of dementia in a genetically informative design.

The primary objective of this study was to estimate the survival function for time to onset of dementia in initially unaffected twins from when their partner (index proband) was diagnosed with dementia of the Alzheimer's type. Survival functions generated by life table analyses were compared by zygosity and gender. Sixty-one twin pairs where at least one member had been diagnosed with dementia of Alzheimer's type were included in the analyses. Additionally, both members of the twin pair had to be alive at the time the index proband was diagnosed with dementia. The probability of remaining cognitively intact within the first three years after the proband was diagnosed was high (0.93, 95% CI 0.89, 1.0), but after 15 years the probability of remaining intact was low (0.34, 95% CI 0.16, 0.52). Age of onset of the index proband was a significant covariate in the survival functions. There were significant differences in the survival functions for monozygotic (MZ) and dizygotic (DZ) co-twins (chi2 = 3.86, 1, P < 0.05), evidencing a genetic component for age of onset for dementia, but there were no significant differences between men and women.

Heritability for Alzheimer's disease: the study of dementia in Swedish twins.

BACKGROUND: Alzheimer's disease has been thought to have familial and sporadic forms, and several genetic defects have been identified that chiefly explain early-onset familial cases. In this study, our purpose was to detect all cases of dementia in an established twin registry and to estimate total extent of genetic contribution to liability to Alzheimer's disease. METHODS: At the first stage, members of the registry were screened for dementia, using in-person or telephone mental status testing. At the second stage, those who screened positively and their partners were referred for clinical work-ups, including neuropsychological assessment, physician examination, laboratory tests, and neuroimaging. Clinical diagnoses were assigned at a multidisciplinary consensus conference. Probandwise concordance rates were examined by zygosity, and structural modeling was applied to the data to estimate genetic and environmental influences, using both single- and multiple-threshold models. RESULTS: Sixty-five pairs were identified in which one or both was demented. The probandwise concordance rate for Alzheimer's disease among monozygotic pairs was 67%; the corresponding figure for dizygotic pairs was 22%. Heritability of liability to Alzheimer's disease was estimated to be .74; to any dementia, .43. The other variance is attributable to environmental influences. CONCLUSIONS: Findings indicate a substantial genetic effect for these predominantly late-onset Alzheimer's disease cases. At the same time, structural modeling results and large intra-pair differences in age of onset suggest that environmental factors are also important in determining whether and when an individual may develop dementia.

Maternal plasma and amniotic fluid levels of estradiol, estrone, progesterone, and prolactin in early pregnancy.

During the 16th to 20th weeks of gestation, maternal plasma (mean) level of estradiol is 5.2 ng/mL; estrone, 3.0 ng/mL; estriol, 2.1 ng/mL; progesterone, 4235 ng/dL; and prolactin, 74 ng/mL. Amniotic fluid levels are: estradiol, 446.8 pg/mL; estrone, 234.1 pg/mL; progesterone, 5200 ng/dL; and prolactin, 2633.5 ng/mL. Maternal prolactin concentrations correlate with plasma estradiol. Amniotic fluid prolactin levels correlate significantly with maternal plasma concentrations of estradiol and estrone. The mechanisms for the possible relationship between maternal estradiol and pituitary and decidual tissue production of prolactin are discussed.

Progesterone levels in amniotic fluid and maternal plasma in prostaglandin F2alpha-induced midtrimester abortion.

Progesterone concentrations in amniotic fluid and maternal plasma were determined in 11 midtrimester pregnant patients following the intraamniotic administration of prostaglandin F2alpha. Samples were obtained at 3-hour intervals until abortion or spontaneous rupture of membranes occurred or fetal heart tones disappeared. In amniotic fluid, the mean progesterone concentrations increased throughout the sampling period. The plasma progesterone levels declined by about one-third of basal values in the first 3 hours after prostaglandin administration. The paradoxic increase in amniotic fluid progesterone is probably secondary to alterations in uterine blood flow and intrauterine pressure.

Increased survival due to radioactive estradiol in mice with C3HBA or BW 10232 tumors.

The influence of progesterone and estradiol labeled with tritium was studied in mice inoculated with transplantable mammary adenocarcinomas C3HBA or BW 10232. Tumor size, tumor growth rate, and host survival were measured. Radioactive [3H]estradiol administration increased survival time and inhibited tumor growth in mice inoculated with these tumor lines. Tumor growth retardation depended on the amount of radioactivity injected and nonradioactive estradiol was without any salutary effect on tumor size or host survival. Neither survival times nor tumor growth rate were altered by radioactive [3H]progesterone. The underlying mechanism(s) is (are) referable to ionizing radiation by the specific carrier estradiol or to an isotope effect of [3H]estradiol.

The relationship between long-distance running, plasma progesterone, and luteal phase length.

The chronic effects of long-distance running upon the menstrual cycle were studied in a healthy, ovulatory 30-year-old woman. Luteal phase plasma concentrations of follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, and progesterone were compared during a control and a training cycle. The luteal phase was shorter in cycles of greater mileage. Mid-luteal phase plasma progesterone concentrations were significantly lower during training.

Genetic and behavioral risk factors for self-reported joint pain among a population-based sample of Swedish twins.

Self-reported joint pain, a typical manifestation of osteoarthritis, was examined using 335 twin pairs from the Swedish Adoption/Twin Study of Aging to estimate relative genetic and environmental influences on self-reported joint pain and to examine the relationships between joint pain, health behavior, and psychological variables. Findings suggest that family resemblance for self-reported joint pain represents similar environments more than genetic similarity. Data from the early 1970s, including exercise, physical activity at work, obesity, and neuroticism, were used to predict joint pain in 1993. For men, moderate amounts of exercise decreased the likelihood of joint pain, but strenuous amounts of physical activity in the workplace had the opposite effect. For women, exercise and physical activity were not significant predictors, but past obesity and higher levels of neuroticism increased the likelihood of reporting joint pain in 1993.

Psychosocial interventions for individuals with dementia: an integration of theory, therapy, and a clinical understanding of dementia.

We reviewed six psychosocial interventions for individuals with dementia. Interventions are described in terms of theoretical basis, how knowledge about dementia is incorporated, techniques, and empirical support. Psychodynamic approaches appear helpful for understanding intrapsychic concerns of demented individuals. Support groups and cognitive/behavioral therapy assist early stage individuals to build coping strategies and reduce distress. Reminiscence and life review provide mild to moderate stage individuals with interpersonal connections. Behavioral approaches and memory training target specific cognitive and behavioral impairments and help to optimize remaining abilities. Reality orientation reflects a similar goal, yet is probably more useful for its interpersonal functions.