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Introduction: In Norway, the prevalence of dementia is higher than in demographically comparable, high income countries, but reliable incidence studies are lacking. This study calculated the incidence of age-specific dementia from 2000 to 2019., Methods: Participants from The Tromsø Study ( n  = 44,214) were included. Participants with a dementia diagnosis ( n  = 2049 cases) were identified. Poisson regression was used to calculate age-specific yearly and 5-year incidence rates from 2000 to 2019., Results: The incidence of dementia has decreased from 2000 to 2019. The trend was highly significant for ages of 60-99 years, and was similar for both sexes., Discussion: The incidence of dementia in North Norway has decreased over the past two decades similar to that in Western countries, indicating that the total prevalence is increasing due to an aging population. This decrease of incidence could introduce a reduction in future estimation of dementia prevalence., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Postoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status., Methods and Analysis: This five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 µg/kg/hour. The infusion rate will be decreased to 0.2 µg/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first.Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery., Ethics and Dissemination: This trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings., Trial Registration Number: NCT05029050., Competing Interests: Competing interests: HZ has served at scientific advisory boards and/or as a consultant for Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, CogRx and Red Abbey Labs, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Programme (outside submitted work). AJCS is advisor for Prolira, a start-up company that develops an EEG-based delirium monitor. Any (future) profits from EEG-based delirium monitoring will be used for future scientific research only. GS has participated in one advisory meeting for Biogen. HMN has received lecture fees from Vifor Pharma and Orion Pharma. The other authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Cognitive impairment is one of the main disabilities in dementia. Physical activity (PA) has been suggested as protective for dementia. However, the findings are disparate in studies, and the question of whether this is because of reverse causality is still open. We aimed to explore the association of PA with cognition in people who later developed dementia compared to those who did not., Method: Since 2001, 11,512 (55% women) participants over the age of 50 years had taken at least one cognitive test in the Tromsø Study. Of these, 1,123 (58% women) later developed dementia. The cases were extracted from hospital journals and entered into an endpoint registry. Leisure time PA (LTPA) was self-reported. Multilevel mixed-effects linear regression was used to address whether LTPA was associated with cognition, stratified by those later developing dementia, and dementia-free in a separate analysis., Results: Leisure time PA was associated with scores in cognitive tests that were 55% (z-score 0.14) higher in those who did not develop dementia. For those in a preclinical phase of dementia, there was no association with LTPA on global cognitive scores. However, in a multifactorial test on processing speed and memory, women had a positive association with processing speed and memory., Conclusion: Leisure time PA had a positive association with global cognition function only for those who did not develop dementia. In women who were developing dementia, LTPA had a positive association with processing speed and memory, while in men, there were no such associations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Johnsen, Strand, Martinaityte, Lorem and Schirmer.)

Background and Objectives: Physical capacity and cardiovascular risk profiles seem to be improving in the population. Cognition has been improving due to a birth cohort effect, but evidence is conflicting on whether this improvement remains in the latest decades and what is causing the changes in our population older than 60 years. We aimed to investigate birth cohort differences in cognition., Methods: The study comprised 9,514 participants from the Tromsø Study, an ongoing longitudinal cohort study. Participants were aged 60-87 years, born between 1914 and 1956. They did 4 cognitive tests in 3 waves during 2001-2016. Linear regression was applied and adjusted for age, education, blood pressure, smoking, hypercholesterolemia, stroke, heart attack, depression, diabetes, physical activity, alcohol use, BMI, and height., Results: Cognitive test scores were better in later-born birth cohorts for all age groups, and in both sexes, compared with earlier-born cohorts. Increased education, physical activity, alcohol intake, decreasing smoking prevalence, and increasing height were associated with one-third of this improvement across birth cohorts in women and one-half of the improvement in men., Discussion: Cognitive results were better in more recent-born birth cohorts compared with earlier born, assessed at the same age. The improvement was present in all cognitive domains, suggesting an overall improvement in cognitive performance. The 80-year-olds assessed in 2015-2016 performed like 60-year-olds assessed in 2001. The improved scores were associated with increased education level, increase in modest drinking frequency, increased physical activity, and, for men, smoking cessation and increased height., (© 2021 American Academy of Neurology.)

Background: Low serum 25-hydroxyvitamin D (25(OH)D) levels are associated with impaired cognitive function, but the effect of vitamin D supplementation on cognitive function is uncertain., Methods: 422 subjects were included in a randomized controlled trial with vitamin D (cholecalciferol) 100,000 IU given as a bolus dose followed by 20,000 IU per week versus placebo for four months. Cognitive function was evaluated with verbal recall test, coding test and tapping test., Results: 374 subjects (mean age 52 years, 198 males) had complete cognitive tests both at baseline and at end of study. Mean baseline serum 25(OH)D level was 34 nmol/L. At baseline there were no significant associations between serum 25(OH)D and the three separate cognitive tests. At the end of the study mean serum 25(OH)D levels were 89 nmol/L and 31 nmol/L in the vitamin D and placebo groups, respectively. At the end of the study, there were no statistically significant differences between the two groups regarding change in the cognitive test scores. Nor did sub-group analyses based on gender, age, baseline serum 25(OH)D and cognitive test scores reveal significant differences between the two groups at the end of the study., Conclusions: Vitamin D supplementation did not improve cognitive function during a four months intervention in mid-aged and older subjects., Trial Registration: ClinicalTrials.govNCT02750293., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Context: Vitamin D and 25-hydroxyvitamin D [25(OH)D] are stored in adipose tissue, but the clinical relevance is uncertain., Objective: To evaluate changes in serum 25(OH)D and adipose tissue vitamin D levels after stopping vitamin D supplementation., Design: A prospective, double-blind cohort follow-up study., Setting: Clinical Research Unit at University Hospital of North Norway., Patients: Seventy-six subjects were included after participation in a 3- to 5-year prevention of type 2 diabetes study and were administered 20,000 IU of vitamin D or placebo per week., Intervention: During the 12-month follow-up period, blood samples were drawn at the beginning and after 1, 3, 6, 9, and 12 months. Fat biopsies were taken at the start and end., Main Outcome Measures: Changes in 25(OH)D level in serum and 25(OH)D and vitamin D levels in adipose tissue., Results: Forty-one of 42 subjects who were given vitamin D and 33 of 34 subjects who were given placebo completed the study. At the inclusion, mean serum 25(OH)D levels were 122 and 71 nmol/L in the vitamin D and placebo groups, respectively. Serum 25(OH)D levels were significantly higher in the vitamin D group than in the placebo group throughout and were 84.5 and 73.1 nmol/L, respectively, after 12 months. In the vitamin D group, adipose tissue vitamin D levels decreased by 52% over 12 months., Conclusion: Vitamin D and 25(OH)D stored in adipose tissue after 3 to 5 years of vitamin D supplementation may have a clinically relevant effect on serum 25(OH)D level the following year., (Copyright © 2017 Endocrine Society)

Background: Bone mineral density (BMD) is determined by bone remodeling processes regulated by endocrine, autocrine and genetic mechanisms. Thus, some studies have reported that BMD is associated with single nucleotide polymorphisms (SNPs) associated with vitamin D receptor (VDR), serum 25(OH)D levels and estrogen receptor 1 (ESR1), but without consensus. Therefore, we aimed to map and compare the risk genotypes for forearm and total hip low BMD., Methods and Findings: Data were derived from a population-based study in northern Norway; the Tromsø Study. Distal forearm BMD was measured with a single x-ray absorptiometric device, while total hip BMD was measured with a dual-energy x-ray absorptiometric device. There were 7,317 and 4,082 successful analyses of distal forearm and total hip BMD, respectively, and at least one SNP of interest. We evaluated plausible BMD modulating factors and associations of BMD and SNPs related to vitamin D metabolism (FokI, Cdx2, BsmI, rs2298850, rs10741657, rs3794060, rs6013897), ApaI-BsmI-TaqI haplotypes and ESR1 SNP rs4870044., Results: Age, BMI, physical activity and smoking were significantly associated with BMD. In a linear regression model with adjustment for age and gender and with the major homozygote as reference, rs6013897 had a standardized beta coefficient (β) of -0.031 (P = 0.024) for total hip BMD. β for ESR1 SNP rs4870044 was -0.016 (P = 0.036) for forearm BMD and -0.034 (P = 0.015) for total hip BMD. The other SNPs nor serum 25(OH)D were significantly associated with BMD., Conclusions: Both forearm and total hip BMD were associated with ESR1 SNP rs4870044. Of the vitamin D-related genes, only CYP24A1 gene rs6013897 was associated with total hip BMD, but the association was weak and needs confirmation in other studies. Serum 25(OH)D was not associated with BMD in our population, probably due to the generally sufficient vitamin D levels in the population.

Objective: To determine whether 2-dimensional or 3-dimensional hepatic visualization is better for the medical students to be used while studying the clinical hepatic anatomy., Material and Methods: Twenty-nine patients who underwent surgical intervention due to focal hepatic pathology at the Department of General Surgery, University of Heidelberg, and at Clinics of Santariskes, Vilnius University Hospital were included in the retrospective cohort study. Before the surgical intervention, the computed tomography (CT) liver scan and 3-dimensional (3D) hepatic visualization were performed. A total of 58 2-dimensional and 3-dimensional digital liver images, mixed up in random sequence not to follow each other with a specially designed questionnaire, were presented to the students of Faculty of Medicine, Vilnius University. Their aim was to determine tumor-affected liver segments, to plan which liver segments should be resected, and to predict anatomical difficulties for liver resection. Results were compared with the data of real operation., Results: The students achieved better results for tumor localization analyzing 3D liver images vs. CT scans. This was especially evident determining the localization of tumor in segments 5, 6, 7, and 8 (P<0.05). Furthermore, the results of proposed extent of liver resection have been found to be better with 3D visualization (mean+/-SD - 0.794+/-0.175) in comparison with CT scans (mean+/-SD - 0.670+/-0.200), (P<0.001)., Conclusions: Computer-generated 3D visualizations of the liver images helped the medical students to determine the tumor localization and to plan the prospective liver resection operations more precisely comparing with 2D visualizations. Computer-generated 3D visualization should be used as a means of studying liver anatomy.