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Understanding individual variability in response to physical activity is key to developing more effective and personalised interventions for healthy ageing. Here, we aimed to unpack individual differences by using longitudinal data from a randomised-controlled trial of a 12-month muscle strengthening intervention in older adults. Physical function of the lower extremities was collected from 247 participants (66.3 ± 2.5 years) at four time-points. At baseline and at year 4, participants underwent 3 T MRI brain scans. K-means longitudinal clustering was used to identify patterns of change in chair stand performance over 4 years, and voxel-based morphometry was applied to map structural grey matter volume at baseline and year 4. Results identified three groups showing trajectories of poor (33.6%), mid (40.1%), and high (26.3%) performance. Baseline physical function, sex, and depressive symptoms significantly differed between trajectory groups. High performers showed greater grey matter volume in the motor cerebellum compared to the poor performers. After accounting for baseline chair stand performance, participants were re-assigned to one of four trajectory-based groups: moderate improvers (38.9%), maintainers (38.5%), improvers (13%), and decliners (9.7%). Clusters of significant grey matter differences were observed between improvers and decliners in the right supplementary motor area. Trajectory-based group assignments were unrelated to the intervention arms of the study. In conclusion, patterns of change in chair stand performance were associated with greater grey matter volumes in cerebellar and cortical motor regions. Our findings emphasise that how you start matters, as baseline chair stand performance was associated with cerebellar volume 4 years later.

Background: Several studies have applied resting-state functional MRI to examine whether functional brain connectivity is altered in migraine with aura patients. These studies had multiple limitations, including small sample sizes, and reported conflicting results. Here, we performed a large, cross-sectional brain imaging study to reproduce previous findings. Methods: We recruited women aged 30–60 years from the nationwide Danish Twin Registry. Resting-state functional MRI of women with migraine with aura, their co-twins, and unrelated migraine-free twins was performed at a single centre. We carried out an extensive series of brain connectivity data analyses. Patients were compared to migraine-free controls and to co-twins. Results: Comparisons were based on data from 160 patients, 30 co-twins, and 136 controls. Patients were similar to controls with regard to age, and several lifestyle characteristics. We replicated clear effects of age on resting-state networks. In contrast, we failed to detect any differences, and to replicate previously reported differences, in functional connectivity between migraine patients with aura and non-migraine controls or their co-twins in any of the analyses. Conclusion: Given the large sample size and the unbiased population-based design of our study, we conclude that women with migraine with aura have normal resting-state brain connectivity outside of migraine attacks.

Understanding individual variability in response to physical activity is key to developing more effective and personalised interventions for healthy ageing. Here, we aimed to unpack individual differences by using longitudinal data from a randomised-controlled trial of a 12-month muscle strengthening intervention in older adults. Physical function of the lower extremities was collected from 247 participants (66.3 ± 2.5 years) at four time-points. At baseline and at year 4, participants underwent 3 T MRI brain scans. K-means longitudinal clustering was used to identify patterns of change in chair stand performance over 4 years, and voxel-based morphometry was applied to map structural grey matter volume at baseline and year 4. Results identified three groups showing trajectories of poor (33.6%), mid (40.1%), and high (26.3%) performance. Baseline physical function, sex, and depressive symptoms significantly differed between trajectory groups. High performers showed greater grey matter volume in the motor cerebellum compared to the poor performers. After accounting for baseline chair stand performance, participants were re-assigned to one of four trajectory-based groups: moderate improvers (38.9%), maintainers (38.5%), improvers (13%), and decliners (9.7%). Clusters of significant grey matter differences were observed between improvers and decliners in the right supplementary motor area. Trajectory-based group assignments were unrelated to the intervention arms of the study. In conclusion, patterns of change in chair stand performance were associated with greater grey matter volumes in cerebellar and cortical motor regions. Our findings emphasise that how you start matters, as baseline chair stand performance was associated with cerebellar volume 4 years later.

Resistance training is an effective strategy to counteract the age-related loss of muscle mass and strength in elderly, but whether the benefits of training differ between sexes is unclear. A total of 297 elderly men and women were randomized to 1 year of heavy resistance training (HRT) or control (CON). Changes in muscle function and body composition were compared between sexes and groups. Improvements in muscle strength, body fat, muscle mass and size were observed, but the absolute improvements in muscle strength (23 Nm ± 2.3 vs 11 Nm ± 2.2, P < .01) and visceral fat content (−215 g ± 50 vs −60 g ± 21, P < .01) were greater in men. Also, the relative decrease in body fat % (−6.8% ± 1.1 vs −2.7% ± 0.7, P < .05) and fat mass (−7.9% ± 1.4 vs −2.7% ± 1.0, P < .05) was more pronounced in men. Heavy resistance training improved more than CON in most muscular and body composition parameters with greater increase in muscle strength and decrease in body fat in men. Consequently, resistance training is recommendable to counteract age-related losses of muscle mass and strength and to reduce body fat in elderly, however, with a small advantage for men in parameters that predict metabolic risk factors.

Objectives: Previous studies indicated that stress diagnoses increase the risk of dementia. However, previous results may be biased by confounding, reverse causation and misclassification. Therefore, the main aim of this study was to investigate the association between clinically diagnosed stress in midlife and later dementia risk, while addressing limitations of previous studies.Methods: The study population was selected from all individuals in Denmark born 1935-1956. Individuals diagnosed with stress in midlife (aged 37-58 years) were matched (1:5) with individuals without stress diagnoses based on sex and birthdate (N = 103,484). Data were retrieved from national registers. Cox regression models were adjusted for socio-demographic factors and different morbidities.Results: We found a 2.20 (95% CI: 1.93-2.50) times higher rate of dementia among individuals with any stress diagnosis registered in midlife compared with no stress diagnosis. Hazard rate ratios of dementia were 1.73 (95% CI: 1.13-2.65) among individuals with acute stress reactions, 2.37 (95% CI: 2.05-2.74) among individuals with adjustment disorders, and 2.20 (95% CI: 1.73-2.80) among individuals with unspecified stress reactions. Individuals with PTSD and other stress reactions had non-significantly elevated rates of dementia. Adjustment for confounding only slightly attenuated the association, and reverse causation did not appear to bias the results substantially.Conclusion: Our results support the hypothesis that severe stress in midlife is an important risk factor for dementia. This finding emphasizes the importance of identifying and treating severe stress in midlife to reduce potential detrimental consequences for brain health in later life.

Background: Physical muscle function and brain hippocampus size declines with age, accelerating after the age of 60. Strength training over a few months improves physical function, but less is known about how long-term strength training affects physical function and hippocampus volume. Therefore, we aimed to investigate the effect of 1-year strength training of two different intensities upon muscle mass, function, and hippocampus volume in retirement-age individuals. Methods: In this multidisciplinary randomized controlled trial (clinicaltrials.gov: NCT02123641), participants were allocated to either a) supervised, heavy resistance training (HRT, n = 149, 3/wk), b) moderate intensity resistance training (MIT, n = 154, 3/wk) or c) non-exercise activities (CON, n = 148). 451 participants were randomized (62-70 yrs., women 61%, approximate to 80% with a chronic medical disease) and 419 were included in the intention-to-treat analysis (n = 143, 144 and 132; HRT, MIT and CON). Changes in muscle power (primary outcome), strength and size, physical function, body composition, hippocampus volume and physical/mental well-being were analyzed. Findings: Of the participants (HRT + MIT), 83% completed training at least 2/week. Leg extensor power was unchanged in all groups, but strength training had a positive effect on isometric knee extensor strength in both groups, whereas an increased muscle mass, cross-sectional area of vastus lateralis muscle, a decreased whole-body fat percentage, visceral fat content and an improved mental health (SF-36) occurred in HRT only. Further, chair-stand performance improved in all groups, whereas hippocampus volume decreased in all groups over time with no influence of strength training. Interpretation: Together, the results indicate that leg extensor power did not respond to long-term supervised strength training, but this type of training in a mixed group of healthy and chronically diseased elderly individuals can be implemented with good com

Background: Previous studies found an association between migraine and dementia, which are two leading causes of disability. However, these studies did not differentiate between migraine types and did not investigate all prevalent dementia subtypes. The main objective of this national register-based study was to investigate whether migraine was a risk factor for dementia. Additionally, we explored potential differences in dementia risk for migraine with and without aura. Methods: We obtained data on birth cohorts born between 1935 and 1956 (n = 1,657,890) from Danish national registers. Individuals registered with migraine before age 59 (n = 18,135) were matched (1:5) on sex and birthdate with individuals without migraine (n = 1,378,346). Migraine was defined by International Classification of Diseases (ICD) diagnoses and dementia was defined by ICD diagnoses and anti-dementia medication. After matching, 62,578 individuals were eligible for analysis. For the statistical analyses, we used Cox regression models and adjusted for socio-demographic factors and several psychiatric and somatic morbidities. Results: During a median follow-up time of 6.9 (IQR: 3.6–11.2) years, 207 individuals with migraine developed dementia. Compared with individuals without migraine, we found a 50% higher rate of dementia among individuals with migraine (HR = 1.50; 95% CI: 1.28–1.76). Individuals without aura had a 19% higher rate of dementia (HR = 1.19; 95% CI: 0.84–1.70), and individuals with aura had a two times higher rate of dementia (HR = 2.11; 95% CI: 1.48–3.00). Conclusions: Our findings support the hypothesis that migraine is a midlife risk factor for dementia in later life. The higher rate of dementia in individuals with a hospital-based diagnosis of migraine with aura emphasizes the need for studies on pathological mechanisms and potential preventative measures. Furthermore, given that only hospital-based migraine diagnoses were included in this study

INTRODUCTION: Despite the understanding of allostatic load (AL) as a consequence of ongoing adaptation to stress, studies of the stress-AL association generally focus on a narrow conceptualization of stress and have thus far overlooked potential confounding by personality. The present study examined the cross-sectional association of objective and subjective stress with AL, controlling for Big Five personality traits.METHODS: Participants comprised 5,512 members of the Copenhagen Aging and Midlife Biobank aged 49-63 years (69% men). AL was measured as a summary index of 14 biomarkers of the inflammatory, cardiovascular, and metabolic system. Objective stress was assessed as self-reported major life events in adult life. Subjective stress was assessed as perceived stress within the past four weeks.RESULTS: Both stress measures were positively associated with AL, with a slightly stronger association for objective stress. Adjusting for personality traits did not significantly change these associations.CONCLUSIONS: The results suggest measures of objective and subjective stress to have independent predictive validity in the context of personality. Further, it is discussed how different operationalizations of stress and AL may account for some of the differences in observed stress-AL associations.