Longitudinal leisure-time physical activity profiles throughout adulthood and related characteristics: a 36-year follow-up study of the older Finnish Twin Cohort.

BACKGROUND: Personalized interventions aiming to increase physical activity in individuals are effective. However, from a public health perspective, it would be important to stimulate physical activity in larger groups of people who share the vulnerability to be physically inactive throughout adulthood. To find these high-risk groups, we identified 36-year leisure-time physical activity profiles from young adulthood to late midlife in females and males. Moreover, we uncovered which anthropometric-, demographic-, lifestyle-, and health-related characteristics were associated with these physical activity profiles. METHODS: We included 2,778 females and 1,938 males from the population-based older Finnish Twin Cohort Study, who responded to health and behavior surveys at the mean ages of 24, 30, 40 and 60. Latent profile analysis was used to identify longitudinal leisure-time physical activity profiles. RESULTS: We found five longitudinal leisure-time physical activity profiles for both females and males. Females' profiles were: 1) Low increasing moderate (29%), 2) Moderate stable (23%), 3) Very low increasing low (20%), 4) Low stable (20%) and 5) High increasing high (9%). Males' profiles were: 1) Low increasing moderate (29%), 2) Low stable very low (26%), 3) Moderate decreasing low (21%), 4) High fluctuating high (17%) and 5) Very low stable (8%). In both females and males, lower leisure-time physical activity profiles were associated with lower education, higher body mass index, smoking, poorer perceived health, higher sedentary time, high blood pressure, and a higher risk for type 2 diabetes. Furthermore, lower leisure-time physical activity was linked to a higher risk of depression in females. CONCLUSIONS: We found several longitudinal leisure-time physical activity profiles with unique changes in both sexes. Fewer profiles in females than in males remained or became low physically active during the 36-year follow-up. We observed that lower education, higher body mass index, and more smoking already in young adulthood were associated with low leisure-time physical activity profiles. However, the fact that several longitudinal profiles demonstrated a change in their physical activity behavior over time implies the potential for public health interventions to improve leisure-time physical activity levels.

Adolescent leisure-time physical activity and eating disorders: a longitudinal population-based twin study.

PURPOSE: High levels of physical activity have been documented in eating disorder patients. Our aim was to examine whether adolescent leisure-time physical activity is prospectively associated with eating disorders in adolescence and young adulthood. METHODS: Finnish twins born in 1983-1987 reported their physical activity frequency at ages 12, 14, and 17. A subsample of participants underwent structured, retrospective interviews for eating disorders at the mean age of 22.4 years. Associations between female twins' physical activity and future eating disorders (571-683 twins/wave) were investigated with the Cox proportional hazards model. To illustrate the physical activity similarity of the co-twins in a twin pair, we used cross-tabulation of eating disorder-discordant twin pairs (13-24 pairs/wave). RESULTS: After adjusting for several covariates, we found no statistically significant longitudinal association between physical activity and eating disorders. This applied when all eating disorders were combined but also when assessed separately as restrictive and non-restrictive eating disorders. Co-twins' physical activity in adolescence tended to be similar irrespective of their future eating disorder, supporting the results of the regression analysis. CONCLUSION: We observed no evidence of adolescent physical activity frequency being prospectively associated with eating disorders in female twins. Further longitudinal studies with larger sample sizes and more detailed physical activity data are needed. LEVEL OF EVIDENCE: III, evidence obtained from cohort or case-control analytic studies.

Better late than never: Diagnosis of recurrent atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) comprising microangiopathic hemolytic anemia, consumptive thrombocytopenia, and end-organ damage. Risk of end-stage renal disease is increased as HUS usually manifests in native and transplanted kidneys. In transplants, while de novo disease can be seen, recurrent disease is more common. The etiology is variable, being either primary or secondary. aHUS often constitutes a diagnostic and therapeutic challenge, which may lead to a considerable delay in the diagnosis and treatment. During the last decades, great progress has been made in understanding the mechanisms and therapeutic options of this devastating condition. We present a case of a 50-year-old female who received her first kidney transplant from her mother at the age of 9 years. She experienced recurrent losses of transplants, and only after the loss of her fourth transplant did the diagnosis of aHUS become evident.

Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts.

BACKGROUND: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. METHODS: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. RESULTS: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. CONCLUSIONS: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

Exploring the relationships between adolescent alcohol misuse and later life health outcomes.

BACKGROUND: We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well-being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. METHOD: The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self-rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co-twin comparison models were applied and included covariates from adolescence and early midlife. RESULTS: There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (ß = 0.03, 95% CI [0.03, 0.04]), self-rated health (ß = -0.02, 95% CI [-0.03, -0.01]), and life satisfaction (ß = -0.03, CI [-0.04, -0.02]). These serial mediation effects were robust in co-twin comparison analyses. CONCLUSIONS: These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan.

Letermovir treatment for CMV infection in kidney and pancreas transplantation: A valuable option for complicated cases.

Cytomegalovirus (CMV) infection remains a major challenge in solid organ transplantation. Ganciclovir has changed the prognosis, but with the expense of possible viral resistance. New antiviral drugs, such as letermovir, have not been studied sufficiently in kidney and pancreas transplant recipients. We reviewed abdominal organ transplants recipients with CMV infection from the national transplant registry and identified patients treated with letermovir from electronic medical records. We report on letermovir treatment in one kidney and three simultaneous pancreas and kidney (SPK) transplant patients with refractory or ganciclovir-resistant CMV infection (UL54/ UL97 mutation). In SPK patients, persistent leukopenia undermined immunosuppressive and antiviral treatment, favoring life-threatening bacterial infections or ganciclovir resistance. All patients achieved viral clearance after letermovir monotherapy of 1.5-6 months. Letermovir was well tolerated and leukopenia resolved. Adjustments of calcineurin inhibitor doses were challenging. One acute rejection occurred because of under immunosuppression. After the end of treatment, recurrent low-grade CMV-DNAemia was common requiring reinitiating antiviral therapy to achieve viral clearance. To conclude, letermovir was a well-tolerated valuable option for the treatment of refractory or resistant CMV infection in kidney and pancreas transplantation.

Physical activity and health: Findings from Finnish monozygotic twin pairs discordant for physical activity.

Genetic and early environmental differences including early health habits associate with future health. To provide insight on the causal nature of these associations, monozygotic (MZ) twin pairs discordant for health habits provide an interesting natural experiment. Twin pairs discordant for leisure-time physical activity (LTPA) in early adult life is thus a powerful study design to investigate the associations between long-term LTPA and indicators of health and wellbeing. We have identified 17 LTPA discordant twin pairs from two Finnish twin cohorts and summarize key findings of these studies in this paper. The carefully characterized rare long-term LTPA discordant MZ twin pairs have participated in multi-dimensional clinical examinations. Key findings highlight that compared with less active twins in such MZ twin pairs, the twins with higher long-term LTPA have higher physical fitness, reduced body fat, reduced visceral fat, reduced liver fat, increased lumen diameters of conduit arteries to the lower limbs, increased bone mineral density in loaded bone areas, and an increased number of large high-density lipoprotein particles. The findings increase our understanding on the possible site-specific and system-level effects of long-term LTPA.

Motives for physical activity in older men and women: A twin study using accelerometer-measured physical activity.

Motives for physical activity may vary considerably by age, sex, and the level of physical activity. We aimed to examine motives for physical activity in older men and women with different physical activity levels as well as whether genetic and/or environmental factors explain those motives. Finnish twins (mean age 72.9 years, 262 full twin pairs) self-reported their motives for physical activity. Time spent on moderate-to-vigorous physical activity was monitored using a hip-worn accelerometer. Comparisons between the different physical activity groups of older twins (n = 764-791/motive dimension) were analyzed using the Wald test, and effect sizes were calculated as Cohen's d. Quantitative genetic modeling was used to estimate genetic and environmental contributions. For both sexes, the most frequently reported motives for physical activity were physical fitness, health maintenance, and psychological well-being. Conforming to others' expectations was more important for men than for women (P < .001, Cohen's d = 0.38), while appearance (P = .001 Cohen's d = -0.24) and psychological well-being (P = .02, Cohen's d = -0.17) were highlighted by women. Most of the motive dimensions differed significantly between the physically active and inactive individuals. It was estimated that 5%-42% of the variation in motives was contributed by genetic factors and 58%-95% by environmental factors. The result that environmental factors contribute in a great deal to motives indicates that interventions to motivate physically inactive older individuals to be physically active can be successful. However, personalized interventions are needed because sex and the level of physical activity were found to be associated with older individuals' motives for physical activity.

FinnTwin16: A Longitudinal Study from Age 16 of a Population-Based Finnish Twin Cohort.

The purpose of this review is to provide a detailed and updated description of the FinnTwin16 (FT16) study and its future directions. The Finnish Twin Cohort comprises three different cohorts: the Older Twin Cohort established in the 1970s and the FinnTwin12 and FT16 initiated in the 1990s. FT16 was initiated in 1991 to identify the genetic and environmental precursors of alcoholism, but later the scope of the project expanded to studying the determinants of various health-related behaviors and diseases in different stages of life. The main areas addressed are alcohol use and its consequences, smoking, physical activity, overall physical health, eating behaviors and eating disorders, weight development, obesity, life satisfaction and personality. To date, five waves of data collection have been completed and the sixth is now planned. Data from the FT16 cohort have contributed to several hundred studies and many substudies, with more detailed phenotyping and collection of omics data completed or underway. FT16 has also contributed to many national and international collaborations.

FinnTwin12 Cohort: An Updated Review.

This review offers an update on research conducted with FinnTwin12 (FT12), the youngest of the three Finnish Twin Cohorts. FT12 was designed as a two-stage study. In the first stage, we conducted multiwave questionnaire research enrolling all eligible twins born in Finland during 1983-1987 along with their biological parents. In stage 2, we intensively studied a subset of these twins with in-school assessments at age 12 and semistructured poly-diagnostic interviews at age 14. At baseline, parents of intensively studied twins were administered the adult version of the interview. Laboratory studies with repeat interviews, neuropsychological tests, and collection of DNA were made of intensively studied twins during follow-up in early adulthood. The basic aim of the FT12 study design was to obtain information on individual, familial and school/neighborhood risks for substance use/abuse prior to the onset of regular tobacco and alcohol use and then track trajectories of use and abuse and their consequences into adulthood. But the longitudinal assessments were not narrowly limited to this basic aim, and with multiwave, multirater assessments from ages 11 to 12, the study has created a richly informative data set for analyses of gene-environment interactions of both candidate genes and genomewide measures with measured risk-relevant environments. Because 25 years have elapsed since the start of the study, we are planning a fifth-wave follow-up assessment.

Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.

Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project.

A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.

The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits.

For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

Physical Activity and Cognitive Decline Among Older Adults: A Systematic Review and Meta-Analysis.

Importance: Physical activity is associated with the risk for cognitive decline, but much of the evidence in this domain comes from studies with short follow-ups, which is prone to reverse causation bias. Objective: To examine how length of follow-up, baseline age, physical activity amount, and study quality modify the longitudinal associations of physical activity with cognition. Data Sources: Observational studies of adults with a prospective follow-up of at least 1 year, a valid baseline cognitive measure or midlife cohort, and an estimate of the association of baseline physical activity and follow-up cognition were sought from PsycInfo, Scopus, CINAHL, Web of Science, SPORTDiscus, and PubMed, with the final search conducted on November 2, 2022. Study Selection: Two independent researchers screened titles with abstracts and full-text reports. Data Extraction and Synthesis: Two reviewers independently assessed study quality and extracted data. Pooled estimates of association were calculated with random-effects meta-analyses. An extensive set of moderators, funnel plots, and scatter plots of physical activity amount were examined. This study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Pooled estimates of the associations between physical activity and global cognition, as well as specific cognitive domains, were examined. Results: A total of 104 studies with 341 471 participants were assessed. Analysis of binary outcomes included 45 studies with 102 452 individuals, analysis of follow-up global cognition included 14 studies with 41 045 individuals, and analysis of change in global cognition included 25 studies with 67 463 individuals. Physical activity was associated with a decreased incidence of cognitive impairment or decline after correction for funnel plot asymmetry (pooled risk ratio, 0.97; 95% CI, 0.97-0.99), but there was no significant association in follow-ups longer than 10 years. Physical activity was associated with follow-up global cognition (standardized regression coefficient, 0.03; 95% CI, 0.02-0.03) and change in global cognition (standardized regression coefficient, 0.01; 95% CI, 0.01 to 0.02) from trim-and-fill analyses, with no clear dose-response or moderation by follow-up length, baseline age, study quality or adjustment for baseline cognition. The specific cognitive domains associated with physical activity were episodic memory (standardized regression coefficient, 0.03; 95% CI, 0.02-0.04) and verbal fluency (standardized regression coefficient, 0.05; 95% CI, 0.03-0.08). Conclusions and Relevance: In this meta-analysis of the association of physical activity with cognitive decline, physical activity was associated with better late-life cognition, but the association was weak. However, even a weak association is important from a population health perspective.

TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer's disease.

INTRODUCTION: A better understanding of the earliest stages of Alzheimer's disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria. METHODS AND ANALYSIS: A multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN. ETHICS AND DISSEMINATION: This recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

Genetic and environmental influences on longitudinal changes in leisure-time physical activity from adolescence to young adulthood.

The aim of this study was to estimate genetic and environmental influences on the longitudinal evolution of leisure-time physical activity habits from adolescence to young adulthood. Data were gathered at four time points, at mean ages 16.2, 17.1, 18.6, and 24.5 years. At baseline, the sample comprised 5,216 monozygotic and dizygotic twins, born 1975-1979, and, at the last follow-up point, of 4,531 monozygotic and dizygotic twins. Physical activity volume was assessed as frequency of leisure-time physical activity and participants were categorized into three groups: inactive, moderately active, and active. Genetic and environmental influences were estimated using a multivariate, longitudinal Cholesky decomposition with a 'multifactorial liability threshold' approach. The results suggest that, in both sexes the heritability of leisure-time physical activity remained moderate (~43-52%) during adolescence, declining to ~30% in young adulthood. Shared environmental influences increased from adolescence (~18-26%) to young adulthood (43% in men and 49% in women). Specific environmental influences remained relatively stable during the total follow-up (~20-30%). New genetic, shared, and specific environmental influences at every follow-up point were suggested by the low correlations across occasions. In conclusion, the study demonstrated gender differences in genetic influences in the evolution of leisure-time physical activity habits from adolescence to young adulthood. However, shared environmental influences, especially in women, were crucial in explaining longitudinal changes in leisure-time physical activity. These outcomes emphasize the need of gender-specific measures to promote physical activity habits during young adulthood.

Accelerometer-measured physical activity and sedentary behavior in nonagenarians: Associations with self-reported physical activity, anthropometric, sociodemographic, health and cognitive characteristics.

BACKGROUND: Research on device-based physical activity in the oldest-old adults is scarce. We examined accelerometer-measured physical activity and sedentary behavior in nonagenarians. We also investigated how the accelerometer characteristics associate with nonagenarians' self-reported physical activity, anthropometric, sociodemographic, health and cognitive characteristics. METHODS: Nonagenarians from a population-based cohort study (N = 38, mean age 91.2) used accelerometers during the waking hours for seven days. They also participated in a health survey and cognitive telephone interview. The Wald test and Pearson and polyserial correlations were used to analyze the data. RESULTS: The participants' average day consisted of 2931 steps, 11 minutes of moderate-to-vigorous physical activity and 13.6 hours of sedentary time. Physical activity bouts less than 3 minutes per day and sedentary time bouts of 20-60 minutes per day were the most common. No sex differences were found. Many accelerometer-measured and self-reported physical activity characteristics correlated positively (correlations ≥0.34, p-values <0.05). The low levels of many accelerometer-measured physical activity characteristics associated with low education (correlations ≥0.25, p-values <0.05), dizziness (correlations ≤-0.42, p-values <0.01) and fear of falling (correlations ≤-0.45, p-values <0.01). Fear of falling was also associated with accelerometer-measured sedentary behavior characteristics (correlations -0.42 or ≥0.43). CONCLUSIONS: Nonagenarians were mostly sedentary and low in physical activity, but individual variability existed. Accelerometer-measured and self-reported physical activity had a good consistency. Education, dizziness and fear of falling were consistently related to accelerometer-measured characteristics in nonagenarians.

TWINGEN - protocol for an observational clinical biobank recall and biomarker study to identify individuals with high risk of Alzheimer's disease.

Introduction: A better understanding of the earliest stages of Alzheimer's disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among Finnish biobank donors according to TWINGEN study criteria. Methods and analysis: A multi-center study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behavior and sleep. A sub-cohort are being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. TWINGEN data will be transferred to Finnish Institute of Health and Welfare (THL) biobank and we aim to further to transfer it to the FinnGen study where it will be combined with health registry data for prediction of AD. Ethics and dissemination: This recall study consists of FTC/THL/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

[The puzzle of glomerulonephritides is closer to be saved]. / Glomerulonefriittien arvoitus on ratkeamassa.

Glomerulonephritides are a mixed group of kidney diseases, the diagnosis and classification of which being based on renal biopsy. Over the last few years revolutionary findings on the pathogenesis of these diseases have been made. Above all the previously obscure immunopathogenesis of focal segmental glomerulosclerosis and membranous nephropathy have begun to unravel. New ideas are bringing new diagnostic methods to the diagnostics and monitoring of these diseases. At the same time their treatments are increasingly focusing on the underlying immunological phenomena.

Outcome of idiopathic membranous nephropathy using targeted stepwise immunosuppressive treatment strategy.

BACKGROUND: The natural course of idiopathic membranous nephropathy (IMN) is variable and the role of immunosuppressive therapy is controversial. In our centre, the strategy has been conservative: the immunomodulating treatment (glucocorticoids and/or cyclosporine A) has been targeted to patients at high risk of developing progressive renal disease and the cytotoxic drugs have been used cautiously. The aim of this retrospective observational study was to evaluate the efficacy of this strategy. METHODS: We evaluated the clinical course and outcome of IMN patients diagnosed between 1993 and 2003. Risk assessment was done during an observation period of ≥6 months after the initial renal biopsy. Patients were followed up until death, the development of end-stage renal disease (ESRD) or the last clinical visit (before December 2006). Treatments and their side effects were recorded. RESULTS: One hundred and forty-two patients with membranous nephropathy were diagnosed of which 81 were idiopathic. The clinical course of 76 IMN patients (38 high risk and 38 low risk) were followed up [mean duration 66 ± 40 (median 59) months]. Thirty-five patients were treated with immunosuppressive drugs, and at last follow-up, 71% of them were in complete or partial remission. The overall response rate of this therapy was 83%. 11% of the high-risk patients had reached ESRD. For the high-risk patients, 10-year survival (alive with glomerular filtration rate >10 mL/min/1.73 m(2)) was 79%. No major side effects were observed. CONCLUSIONS: This study suggests that targeted, stepwise, cytotoxic drug-sparing immunosuppressive treatment in IMN was associated with favourable renal, as well as overall survival among patient at risk of developing ESRD.