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.

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.

Associations Between Engagement with the BitHabit Digital Lifestyle Intervention and Changes in Type 2 Diabetes Risk Factors.

Type 2 diabetes (T2D) can be prevented or delayed through a healthy lifestyle. Digital behavior change interventions (DBCIs) may offer cost-effective and scalable means to support lifestyle changes. This study investigated associations between user engagement with a habit-formation-based DBCI, the BitHabit app, and changes in T2D risk factors over 12 months in 963 participants at risk of T2D. User engagement was characterized by calculating use metrics from the BitHabit log data. User ratings were used as a subjective measure of engagement. The use metrics and user ratings were the strongest associated with improvements in diet quality. Weak positive associations were observed between the use metrics and changes in waist circumference and body mass index. No associations were found with changes in physical activity, fasting plasma glucose, or plasma glucose two hours after an oral glucose tolerance test. To conclude, increased use of the BitHabit app can have beneficial impacts on T2D risk factors, especially on diet quality.

Physical activity and aerobic fitness show different associations with brain processes underlying anticipatory selective visuospatial attention in adolescents.

Current knowledge about the underlying brain processes of exercise-related benefits on executive functions and the specific contributions of physical activity and aerobic fitness during adolescence is inconclusive. We explored whether and how physical activity and aerobic fitness are associated with the oscillatory dynamics underlying anticipatory spatial attention. We studied whether the link between physical exercise level and cognitive control in adolescents is mediated by task-related oscillatory activity. Magnetoencephalographic alpha oscillations during a modified Posner's cueing paradigm were measured in 59 adolescents (37 females and 22 males, 12-17 years). Accelerometer-measured physical activity and aerobic fitness (20-m shuttle run test) were used to divide the sample into higher- and lower-performing groups. The interhemispheric alpha asymmetry during selective attention was larger in the high than in the low physical activity group, but there was no difference between the high and low aerobic fitness groups. Exploratory mediation analysis suggested that anticipatory interhemispheric asymmetry mediates the association between physical activity status and drift rate in the selective attention task. Higher physical activity was related to increased cue-induced asymmetry, which in turn was associated with less efficient processing of information. Behaviorally, more physically active males showed stronger dependence on the cue, while more fit females showed more efficient processing of information. Our findings suggest that physical activity may be associated with a neural marker of anticipatory attention in adolescents. These findings might help to explain the varying results regarding the association of physical activity and aerobic fitness with attention and inhibition in adolescents.

Physical activity and aerobic fitness in relation to local and interhemispheric functional connectivity in adolescents' brains.

INTRODUCTION: Adolescents have experienced decreased aerobic fitness levels and insufficient physical activity levels over the past decades. While both physical activity and aerobic fitness are related to physical and mental health, little is known concerning how they manifest in the brain during this stage of development, characterized by significant physical and psychosocial changes. The aim of the study is to examine the associations between both physical activity and aerobic fitness with brains' functional connectivity. METHODS: Here, we examined how physical activity and aerobic fitness are associated with local and interhemispheric functional connectivity of the adolescent brain (n = 59), as measured with resting-state functional magnetic resonance imaging. Physical activity was measured by hip-worn accelerometers, and aerobic fitness by a maximal 20-m shuttle run test. RESULTS: We found that higher levels of moderate-to-vigorous intensity physical activity, but not aerobic fitness, were linked to increased local functional connectivity as measured by regional homogeneity in 13-16-year-old participants. However, we did not find evidence for significant associations between adolescents' physical activity or aerobic fitness and interhemispheric connectivity, as indicated by homotopic connectivity. CONCLUSIONS: These results suggest that physical activity, but not aerobic fitness, is related to local functional connectivity in adolescents. Moreover, physical activity shows an association with a specific brain area involved in motor functions but did not display any widespread associations with other brain regions. These results can advance our understanding of the behavior-brain associations in adolescents.

Physical activity, aerobic fitness, and brain white matter: Their role for executive functions in adolescence.

Physical activity and exercise beneficially link to brain properties and cognitive functions in older adults, but the findings concerning adolescents remain tentative. During adolescence, the brain undergoes significant changes, which are especially pronounced in white matter. Studies provide contradictory evidence regarding the influence of physical activity or aerobic-exercise on executive functions in youth. Little is also known about the link between both fitness and physical activity with the brain's white matter during puberty. We investigated the connection between aerobic fitness and physical activity with the white matter in 59 adolescents. We further determined whether white matter interacts with the connection of fitness or physical activity with core executive functions. Our results show that only the level of aerobic fitness, but not of physical activity relates to white matter. Furthermore, the white matter of the corpus callosum and the right superior corona radiata moderates the links of aerobic fitness and physical activity with working memory. Our results suggest that aerobic fitness and physical activity have an unequal contribution to the white matter properties in adolescents. We propose that the differences in white matter properties could underlie the variations in the relationship between either physical activity or aerobic fitness with working memory.

Aerobic fitness, but not physical activity, is associated with grey matter volume in adolescents.

Higher levels of aerobic fitness and physical activity are linked to beneficial effects on brain health, especially in older adults. The generalizability of these earlier results to young individuals is not straightforward, because physiological responses (such as cardiovascular responses) to exercise may depend on age. Earlier studies have mostly focused on the effects of either physical activity or aerobic fitness on the brain. Yet, while physical activity indicates the amount of activity, aerobic fitness is an adaptive state or attribute that an individual has or achieves. Here, by measuring both physical activity and aerobic fitness in the same study, we aimed to differentiate the association between these two measures and grey matter volume specifically. Magnetic resonance imaging scans were used to study volumes of 30 regions of interest located in the frontal, motor and subcortical areas of 60 adolescents (12.7-16.2 years old). Moderate-to-vigorous intensity physical activity (MVPA) was measured with hip-worn accelerometers and aerobic fitness was assessed with a 20-m shuttle run. Multiple regression analyses revealed a negative association between aerobic fitness and left superior frontal cortex volume and a positive association between aerobic fitness and the left pallidum volume. No associations were found between MVPA and any brain region of interest. These results demonstrate unequal contribution of physical activity and aerobic fitness on grey matter volumes, with inherent or achieved capacity (aerobic fitness) showing clearer associations than physical activity.

Physiological adaptations to resistance training in rats selectively bred for low and high response to aerobic exercise training.

NEW FINDINGS: What is the central question of this study? Can phenotypic traits associated with low response to one mode of training be extrapolated to other exercise-inducible phenotypes? The present study investigated whether rats that are low responders to endurance training are also low responders to resistance training. What is the main finding and its importance? After resistance training, rats that are high responders to aerobic exercise training improved more in maximal strength compared with low-responder rats. However, the greater gain in strength in high-responder rats was not accompanied by muscle hypertrophy, suggesting that the responses observed could be mainly neural in origin. ABSTRACT: The purpose of this study was to determine whether rats selectively bred for low and high response to aerobic exercise training co-segregate for differences in muscle adaptations to ladder-climbing resistance training. Five high-responder (HRT) and five low-responder (LRT) rats completed the resistance training, while six HRT and six LRT rats served as sedentary control animals. Before and after the 6 week intervention, body composition was determined by dual energy X-ray absorptiometry. Before tissue harvesting, the right triceps surae muscles were loaded by electrical stimulation. Muscle fibre cross-sectional areas, nuclei per cell, phosphorylation status of selected signalling proteins of mTOR and Smad pathways, and muscle protein, DNA and RNA concentrations were determined for the right gastrocnemius muscle. The daily protein synthesis rate was determined by the deuterium oxide method from the left quadriceps femoris muscle. Tissue weights of fore- and hindlimb muscles were measured. In response to resistance training, maximal carrying capacity was greater in HRT (∼3.3 times body mass) than LRT (∼2.5 times body mass), indicating greater improvements of strength in HRT. However, muscle hypertrophy that could be related to greater strength gains in HRT was not observed. Furthermore, noteworthy changes within the experimental groups or differences between groups were not observed in the present measures. The lack of hypertrophic muscular adaptations despite considerable increases in muscular strength suggest that adaptations to the present ladder-climbing training in HRT and LRT rats were largely induced by neural adaptations.

Changes in corticospinal excitability during an acute bout of resistance exercise in the elbow flexors.

PURPOSE: Hypertrophic resistance exercise (HRE) induces central and peripheral fatigue. However, more detailed information about changes in corticospinal excitability remains to be elucidated. METHODS: Eleven volunteers participated in the upper arm HRE which included one repetition maximum (1 RM) control contractions and three sets of 13 RM (SET1-3). Transcranial magnetic stimulation (TMS) was applied during maximal isometric voluntary contraction (MVC) at the end of each set and during control contractions to study changes in corticospinal excitability. Electrical stimulation was used in order to measure peripheral changes. RESULTS: MVC decreased after each set when compared to control contractions. Motor evoked potential (MEP) were 138.7 ± 52.7 % (p < 0.05), 130.4 ± 44.7 and 113.1 ± 31.4 % after SET1, SET2 and SET3, respectively, when compared to pre-exercise value. A significant reduction in MEP area between SET1 and SET3 (p < 0.05) was observed while silent period (SP) duration increased (~151-165 ms, p < 0.05) simultaneously between these sets. TMS-evoked twitch force during MVC increased significantly following each set when compared to pre-exercise value. Simultaneously, a significant reduction was observed in resting twitch force over the sets. CONCLUSIONS: The results of this study clearly support the existence of both central and peripheral fatigue during HRE of elbow flexors. However, changes in the MEP area and SP suggest that during HRE of the elbow flexors, the corticospinal excitability increases first, until at some point, supraspinal fatigue takes over.

Effect of weighted vest suit worn during daily activities on running speed, jumping power, and agility in young men.

Previous weighted vest interventions using exercise in addition to hypergravity have been successful in improving postural balance and power production capacity. The purpose of this study was to investigate if hypergravity alone in daily activities excluding sporting activities is effective in improving neuromuscular performance in young adults. Eight male subjects (age = 32 [SD: 6] years, height = 178 [5] cm, and body mass = 81 [8] kg) wore weighted vests 3 d·wk for 3 weeks during waking hours, excluding sporting activities. Control group comprised 9 male subjects (age = 32 [6] years, height = 179 [5] cm, and body mass = 83 [9] kg). Performance was assessed with countermovement jump (body mass normalized peak power), figure-of-8 running test (running time), and running velocity test at baseline and at the end of the intervention. At baseline, the groups did not differ from each other (multivariate analysis of variance [MANOVA] p = 0.828). A significant group × time interaction (MANOVA F = 5.1, p = 0.015) was observed for performance variables. Analysis of covariance indicated that the intervention improved the figure-of-8 running time (p = 0.016) (-2.2 vs. 0.5%), whereas normalized peak power (0.0 vs. 1.6%) and running velocity (1.3 vs. 0.1%) were unaffected (p ≥ 0.095). Wearing weighted vests was effective in slightly improving agility-related performance in young men. Because the effect was small, applying hypergravity only during exercise probably suffices. It appears that a proper volume and intensity of hypergravity could be in the order of 5-10% body weight vest worn during up to 50% of the training sessions for a period of 3-4 weeks.