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Objective:Studies in mice have suggested that endocannabinoid blockade using the cannabinoid receptor type 1 (CB1) blocker rimonabant prevents obesity-induced hepatic steatosis.Design and subjects:To determine effects of rimonabant on liver fat in humans, we measured liver fat content by proton magnetic resonance spectroscopy in 37 subjects who used either a CB1 blocker rimonabant or placebo in a double-blind, randomized manner. This was retrospectively compared with a historical hypocaloric diet weight loss group (n=23).Results:Weight loss averaged 8.5±1.4 kg in the rimonabant, 1.7±1.0 kg in the placebo and 7.5±0.2 kg in the hypocaloric diet group (P<0.001, rimonabant vs placebo; NS, rimonabant vs hypocaloric diet). Liver fat decreased more in the rimonabant (5.9% (2.5-14.6%) vs 1.8% (0.9-3.5%), before vs after) than in the placebo group (6.8% (2.2-15.7%) vs 4.9% (1.6-7.8%), before vs after, P<0.05). The percentage change in body weight correlated closely with the percentage loss of liver fat (r=0.70, P>0.0001). The decreases in liver fat were comparable between the rimonabant and the young historical hypocaloric diet groups.Conclusions:We conclude that, unlike in mice, in humans rimonabant decreases liver fat in proportion to weight loss. [ABSTRACT FROM AUTHOR]

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&#95;83., Competing Interests: Competing interests: AP is the Chief Scientific Officer of the FinnGen project that is funded by 13 pharmaceutical companies. HR was a full-time employee of Biogen during study planning and manuscript drafting and has stocks at Merck & Co and Biogen. MMF has received development funding from the Regional Council of Northern Savo and Business Finland for a data-driven tool related to memory disorders and healthcare decision tools, Charles River DRS Finland Ltd. and Orion Pharma have donated equipment for nonclinical cognition testing at the University of Eastern Finland. PI-M has received funding from Orion Research Foundation and Helsinki Biomedicum Foundation outside the present work. RK declares funding paid to the institution from Academy of Finland, 27 Government research funding, Saastamoinen Foundation, Vaajasalo foundation and Jane and Aatos Erkko foundation outside the present work; consulting fees from Orion Pharma; payment or honoraria from Angelini Pharma, Jazz Pharma, Lundbeck, Eisai, Orion Pharma, OmaMedical, Takeda, UCB; participation in monitoring or advisory board from Marinus Pharma and UCB; and leadership or fiduciary role in European Academy of Neurology Epilepsy scientific panel management group, European Epilepsy Reference network Epicare Steering Group and International League Against Epilepsy Career Development Commission. RS declares stocks or stock options at Orion Pharma. S-KH declares payment or honoraria and support for attending meetings or travel from Roche, consulting fees and participation in monitoring or advisory board from Novartis. TK declares payment or honoraria from Novartis Finland and Bayer Nordic SE. The authors declare no other competing financial or non-financial Interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Aaltonen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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&#95;83., Competing Interests: Competing interests statement AP is the Chief Scientific Officer of the FinnGen project that is funded by thirteen pharmaceutical companies. HR was a full-time employee of Biogen during study planning and manuscript drafting and has stocks at Merck & Co. and Biogen Inc. MMF has received development funding from the Regional Council of Northern Savo and Business Finland for a data-driven tool related to memory disorders and healthcare decision tools, Charles River DRS Finland Ltd. and Orion Pharma have donated equipment for nonclinical cognition testing at the University of Eastern Finland. PI-M has received funding from Orion Research Foundation and Helsinki Biomedicum Foundation outside the present work. RK declares funding paid to the institution from Academy of Finland, Government research funding, Saastamoinen Foundation, Vaajasalo foundation and Jane and Aatos Erkko foundation outside the present work; consulting fees from Orion Pharma; payment or honoraria from Angelini Pharma, Jazz Pharma, Lundbeck, Eisai, Orion Pharma, OmaMedical, Takeda, UCB; participation in monitoring or advisory board from Marinus Pharma and UCB; and leadership or fiduciary role in European Academy of Neurology Epilepsy scientific panel management group, European Epilepsy Reference network Epicare Steering Group and International League Against Epilepsy Career Development Commission. RS declares stocks or stock options at Orion Pharma. S-KH declares payment or honoraria and support for attending meetings or travel from Roche, consulting fees and participation in monitoring or advisory board from Novartis. TK declares payment or honoraria from Novartis Finland and Bayer Nordic SE. The authors declare no other competing financial or non-financial Interests.

Successful development of novel therapies requires that clinical trials are conducted in patient cohorts with the highest benefit-to-risk ratio. Population-based biobanks with comprehensive health and genetic data from large numbers of individuals hold promise to facilitate identification of trial participants, particularly when interventions need to start while symptoms are still mild, such as for Alzheimer's disease (AD). This study describes a process for clinical recall studies from FinnGen. We demonstrate the feasibility to systematically ascertain customized clinical data from FinnGen participants with ICD10 diagnosis of AD or mild cognitive disorder (MCD) in a single-center cross-sectional study testing blood-based biomarkers and cognitive functioning in-person, computer-based and remote. As a result, 19% (27/140) of a pre-specified FinnGen subcohort were successfully recalled and completed the study. Hospital records largely validated registry entries. For 8/12 MCD patients, other reasons than AD were identified as underlying diagnosis. Cognitive measures correlated across platforms, with highest consistencies for dementia screening (r = 0.818) and semantic fluency (r = 0.764), respectively, for in-person versus telephone-administered tests. Glial fibrillary acidic protein (GFAP) (p < 0.002) and phosphorylated-tau 181 (pTau-181) (p < 0.020) most reliably differentiated AD from MCD participants. We conclude that informative, customized clinical recall studies from FinnGen are feasible., (© 2023. Springer Nature Limited.)