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.

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.

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.

Midlife dietary patterns and mortality in the population-based study of Swedish twins.

BACKGROUND: We examined midlife dietary patterns in relation to (1) sociodemographic and health-related characteristics and (2) survival. METHODS: A two-step cluster analysis of a 12-item food questionnaire was used to derive dietary patterns in a cohort of 16 649 members of the Swedish Twin Registry, a prospective, population-based study of twins. The average age at baseline (1967) was 55.5 years; the follow-up for all-cause mortality extended until 2011 (26.8±12.35 years or 345,127 person-years) via death records. RESULTS: Four dietary patterns (classes) distinguishable by demographic and health characteristics emerged: Moderate Intake and Starch Diet (Class 1), Moderate Intake Diet with Low Flour-Based Foods (Class 2), Meat and Starch Diet (Class 3) and Low Meat Intake Diet (Class 4). Membership in Class 3 was associated with 7% increased risk of mortality compared with Class 2 independent of baseline age, cohort, sex and body mass index. These results were mostly explained by sociodemographic and lifestyle factors. When follow-up was restricted to those in the study for 20+ years, both Classes 1 and 3 conferred increased risk of mortality compared with Class 2, independent of covariates. Analyses conducted within twin pairs revealed similar results. CONCLUSIONS: Midlife diet over-represented by meat and starch-based foods may increase the risk of mortality, whereas the diet low in starch may be beneficial. These results appear to be independent of factors shared by twins, as well as at least partially a function of social and lifestyle factors, particularly marital status and smoking.

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.

Midlife overweight and obesity increase late-life dementia risk: a population-based twin study.

OBJECTIVE: The relation of overweight to dementia is controversial. We aimed to examine the association of midlife overweight and obesity with dementia, Alzheimer disease (AD), and vascular dementia (VaD) in late life, and to verify the hypothesis that genetic and early-life environmental factors contribute to the observed association. METHODS: From the Swedish Twin Registry, 8,534 twin individuals aged ≥65 (mean age 74.4) were assessed to detect dementia cases (DSM-IV criteria). Height and weight at midlife (mean age 43.4) were available in the Registry. Data were analyzed as follows: 1) unmatched case-control analysis for all twins using generalized estimating equation (GEE) models and 2) cotwin matched case-control approach for dementia-discordant twin pairs by conditional logistic regression taking into account lifespan vascular disorders and diabetes. RESULTS: Among all participants, dementia was diagnosed in 350 subjects, and 114 persons had questionable dementia. Overweight (body mass index [BMI] >25-30) and obesity (BMI >30) at midlife were present in 2,541 (29.8%) individuals. In fully adjusted GEE models, compared with normal BMI (20-25), overweight and obesity at midlife were related to dementia with odds ratios (ORs) (95% CIs) of 1.71 (1.30-2.25) and 3.88 (2.12-7.11), respectively. Conditional logistic regression analysis in 137 dementia-discordant twin pairs led to an attenuated midlife BMI-dementia association. The difference in ORs from the GEE and the matched case-control analysis was statistically significant (p = 0.019). CONCLUSIONS: Both overweight and obesity at midlife independently increase the risk of dementia, AD, and VaD. Genetic and early-life environmental factors may contribute to the midlife high adiposity-dementia association.

'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.

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.

Clinical indices of familial depression in the Swedish Twin Registry.

OBJECTIVE: Although familial factors certainly contribute to the etiology of major depression (MD), further information is needed about which clinical features of depressive illness index the familial vulnerability in MD. METHOD: Lifetime MD and associated clinical features were assessed at personal interview in 27 230 individual twins, including 4080 onsets of MD, from the Swedish National Twin Registry. Analyses were conducted using Cox proportional hazards models. RESULTS: Three clinical variables in a depressed twin predicted the hazard ratio for MD in the cotwin. In the order of the strength of the association, these were: number of endorsed A criteria, age at onset, and number of episodes. CONCLUSION: Certain clinical features of MD are significant, albeit modest, indices of the familial vulnerability to MD. Individuals with a high familial/genetic risk for MD tend to have an early age at onset, meet most of the symptomatic DSM criteria and suffer recurrences.

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.

Gender differences in heritability of depressive symptoms in the elderly.

BACKGROUND: The present study aimed to investigate the relative importance of genetic and environmental influences on depressive symptoms in the elderly. METHOD: Depressive symptoms were assessed through the Center for Epidemiological Studies-Depression (CES-D) scale. The CES-D scale was administered to 959 twin pairs (123 female MZs, 90 male MZs, 207 same-sex female DZs, 109 same-sex male DZs and 430 opposite-sex DZs) aged 50 years or older (mean age 72 years). A dichotomous depressed state variable was constructed based on CES-D cut-offs and self-reported use of antidepressant medication. Structural equation models were fitted to the data to dissect genetic and environmental variance components. RESULTS: The sex-specific heritability estimates for depressive symptoms were 14% for males and 29% for females and 23% when constrained to be equal for men and women. The prevalence of clinically significant depressive symptoms was 16% for men and 24% for women. Heritability estimates for the dichotomous depressed state measure were 7% for males and 49% for females in the full model and 33% when constrained to be equal. CONCLUSION: Our results suggest that depressive symptoms in the elderly are moderately heritable, with a higher heritability for women than men, although differences in heritability estimates were not statistically significant.

Association between depressed mood in the elderly and a 5-HTR2A gene variant.

The aim of this study was to investigate any possible association between depressed mood in the elderly and two candidate SNPs in the serotonin system: one in the 5-HTR2A gene promotor (-1438 G/A) and one in the 5-HT transporter gene (-925 C/A). DNA from a population-based Swedish twin sample (N = 1,592; mean age = 73) was genotyped using Pryosequencing trade mark. An association was found between the 5-HTR2A gene promotor polymorphism and depressed mood (OR: 1.5, CI: 1.1-2.1) for the A/A genotype in the total sample. When the sample was analyzed by gender, a significant association (OR: 2.4, CI: 1.4-4.4) was found for males and the A/A genotype, but not for females. The 5-HT transporter gene was not associated with depressed mood in this elderly population. These results suggest that there might be different genetic mechanisms for males and females contributing to the development of depressed mood in the elderly.

Deficits in controlled processing may predict dementia: a twin study.

This study tested for differential patterns of cognitive decline in 33 twin pairs for which both were nondemented, but 1 member of the pair went on to develop dementia. Compared with their nondemented twin partners, twins who later developed dementia already showed poorer performance on tests of memory and attention, visuospatial-reasoning skills, and perceptual speed and the Mini-Mental State Examination (MMSE). The authors suggest that this cluster of tests reflects deficits in controlled rather than automatic cognitive processes. Nondemented twin partners of the twins who became demented were also compared with 33 matched controls selected from pairs in which both members remained nondemented. Nondemented twin partners scored lower than matched controls on tests of verbal ability, memory and attention, and perceptual speed and the MMSE. This finding indicates that nondemented twin partners of demented twins are at elevated risk themselves for becoming demented, and further suggests that certain areas of cognition are compromised prior to diagnosis of dementia.

Education and the risk of Alzheimer's disease: findings from the study of dementia in Swedish twins.

The association between dementia and education was studied in 143 twin pairs discordant for dementia, using a matched-pair design, and in 221 dementia cases and 442 unrelated controls from the same twin registry, using a case-control design. Low education was defined as 6 years or less of schooling. Case-control analyses with prevalent cases showed low education to be a risk for Alzheimer's disease but not dementia in general. Low education did not significantly predict incident cases. In the matched-pairs analysis, which controls for genetic and other familial influences, differences in education between demented twins and twin partners were not statistically significant. However, for Alzheimer's disease, odds ratios resulting from matched pairs and case-control analyses were similar. Twins' comparative reports about intellectual involvement earlier in their lives suggest a long-standing difference on this dimension, with less involvement by the twin who became demented.

A longitudinal analysis of anxiety and depressive symptoms.

The authors modeled depressive and anxiety symptom data from 1,391 participants in a longitudinal study of middle-aged and older Swedish twins (M age = 60.9 years, SD = 13.3). Although anxiety and depression were highly correlated, a model with distinct Anxiety and Depression factors fit the data better than models with Positive and Negative Affect factors or a single Mental Health factor. Lack of well-being was associated with anxiety rather than depression. Over two 3-year intervals, anxiety symptoms led to depressive symptoms, but the relationship was not reciprocal. Anxiety symptoms were more stable than depression. These findings provide additional support for the idea that anxiety symptoms may reflect a personality trait such as neuroticism more than do depressive symptoms and suggest that low positive affect may not be as specific to depression among older adults as in younger people.

Symptoms of depression in the oldest old: a longitudinal study.

This study examined depressive symptoms in a population-based, longitudinal sample of people aged 80 and older to determine initial prevalence of depressive symptoms and changes over time. Depressive symptomatology was assessed with the Center for Epidemiologic Studies-Depression scale (CES-D). The sample was drawn from the OCTO-Twin study, which examined 702 Swedish twins over age 80 in which both members of the pair were still surviving. For the present study, one member of each twin pair was randomly selected, resulting in a sample of 351. A comprehensive biobehavioral assessment was conducted at three time points over 4 years. Depressive symptoms were initially relatively low and decreased significantly between Wave 1 and Wave 2. At Wave 3, depressive symptoms increased slightly but not significantly. Participants who received a dementia diagnosis at some point in the study did not differ significantly on initial CES-D scores when compared to those participants who never received such a diagnosis. Lack of well-being, as opposed to negative affect, was the biggest contributor to the overall depression score at each of the three waves of measurement. Predictors of negative affect for this sample included activities of daily living, subjective health, and performance on the cognitive test, block design. None of these predictors were significant for lack of well-being.

Age-related differences and change in positive and negative affect over 23 years.

Positive and negative affect, measured by the Bradburn Affect Balance Scale, were studied in a longitudinal sample spanning from 1971 to 1994. The sample (N = 2,804) represented 4 generations of families. Linear trend analyses compared generations over time for positive and negative affect and also examined the possible influences of neuroticism and extraversion on initial levels of affect and patterns of change in affect. Negative affect decreased with age for all generations, although the rate was attenuated among the oldest adults. Higher neuroticism scores also attenuated the decrease in negative affect across time. For positive affect, the younger and middle-aged adults showed marked stability, but the older group evidenced a small decrease over time. Higher levels of extraversion were related to more stability in positive affect.