Gymnastik- och idrottshögskolan, GIH

BACKGROUND AND OBJECTIVES: Individuals aged 70 and older frequently experience an increased risk of deficits in both physical and cognitive functions. However, the natural progression and interrelationship of these deficits, as well as their neurologic correlates, remain unclear. We aimed to classify the data-driven physical-cognitive phenotypes and then investigate their associations with neuroimaging markers.

METHODS: This cross-sectional study included 70-year-old participants from the Gothenburg H70 Birth Cohort (2014-2016). Based on physical performance (grip strength, balance, walking speed, and chair stand) and cognitive measures (episodic memory, perceptual speed, executive function, verbal fluency, and visuospatial abilities), we applied latent class analysis to identify physical-cognitive phenotypes. Based on the brain MRI measurements, 3 groups of neuroimaging markers were involved-neurodegeneration, cerebral small vessel disease (cSVD), and microstructural white matter (WM) integrity. We performed multinomial logistic regressions to examine the differences between the physical-cognitive phenotypes.

RESULTS: In total, 1,140 participants (female: 53.3%) without dementia and disability were included in the study, with 721 (female: 52.2%) undergoing MRI scans. Three physical-cognitive phenotypes were identified: an "optimal" group characterized by high performance in both physical and cognitive functions, an "intermediate" group showing a slight reduction in both domains, and a "physical deficit" group marked by a significant reduction in physical performance. Compared with the optimal group, the other 2 groups were more likely to present with vascular risk factors. The physical deficit group had higher odds of experiencing depression compared with the intermediate group (adjusted odds ratio [aOR] 2.9, 95% CI 1.4-5.9). Compared with the optimal group, the odds of presenting all 3 severe neuroimaging markers were higher in both the intermediate (aOR 3.4, 95% CI 1.5-7.9) and physical deficit (aOR 10.3, 95% CI 2.4-45.0) groups.

DISCUSSION: This study highlights the variability in physical and cognitive performance among older adults and suggests that neuroimaging markers of neurodegeneration, cSVD, and microstructural WM integrity may account for these variations. Our findings indicate the potential for developing group-based strategies to prevent and manage age-related functional decline. Further research with larger sample sizes is needed to deepen our understanding of physical-cognitive decline patterns.

PURPOSE: The transition phase between childhood and adolescence is critical, given the observation of increased mental health issues during this period, coupled with the absence of efficient intervention tools. This study aims to examine a possible effect of physical activity on mental health symptoms in adolescents during this transitional age.

METHODS: We used data from a large-scale population-based Swedish twin sample of 14,083 individuals to investigate cross-sectional and longitudinal associations between physical activity and mental health problems during childhood and adolescence. We examine different aspects of mental health symptoms, including internalizing and externalizing symptoms. We applied generalized estimating equations to investigate the associations and explored potential familial confounding using within-twin pair analysis.

RESULTS: We found high physical activity intensity and frequency to be associated with better mental health throughout childhood and adolescence, cross-sectionally and longitudinally. Compared to those who reported low, those reporting high physical activity intensity and frequency in both childhood and/or adolescence had significantly lower symptoms of mental health at age 15. This association was statistically significant for both internalizing and externalizing symptoms. The within-twin pair analysis showed that familial confounding factors can largely explain the association with the externalizing scale, but not the internalizing scale.

DISCUSSION: Physical activity in childhood and adolescence may play an essential role in reducing the risk of developing mental health problems, especially internalizing symptoms. Implementing acceptable, low-risk, and cost-effective interventions to promote physical activity could effectively safeguard young individuals from these symptoms.

Introduction. Executive functions (EF) is essential for cognitive aging and vascular cognitive impairment. Habitual physical activity (PA) has been shown to yield positive effects on EF in aging. In this study, we aim (1) to investigate the relationship between EF and time spent in sedentary behaviour (SED), light-PA (LIPA), moderate-PA (MPA), and vigorous-PA (VPA), respectively; and (2) to examine the potential beneficial effect of combined movement behaviours.

Methods. The study consisted of 4592 participants (women: 52.6%), aged 50 to 65 years, from the Swedish CArdioPulmonary bioImage Study(SCAPIS) in Gothenburg region (data collection: 2013-2017). The Trail Making Tests (A and B) were applied to evaluate the EF. ActiGraph accelerometer was employed to evaluate the daily movement patterns objectively. After adjusting for covariates in demographic factors, cardiorespiratory fitness, and vascular risk factors, piecewise linear and linear regression models were used to examine the relationship between movement patterns and EF.

Results. In the fully adjusted model, when daily sedentary time was less than 10 hours, an increased SED time was positively associated with EF score. However, a negative association was observed between SED time and EF score when daily sedentary time exceeded 10 hours. When daily LIPA time exceeded 4 hours, LIPA time was found to have a negative association with EF score. An increase in MPA time was positively associated with EF score when daily MPA was less than 45 minutes. A significant positive association was observed between conducting daily VPA within 20 minutes and EF score. The majority of participants in our study demonstrated a movement pattern characterized by high levels of cardiorespiratory fitness, sedentary time within 10 hours, LPA more than 4 hours, MPA more than 45 minutes, and VPA more than 20 minutes. This particular movement pattern was significantly and positively associated with EF scores compared to other groups.

Discussion. The association between EF and specific movement behaviours varied depending on their daily duration. In this study, the majority of middle-aged and older adults demonstrated an active movement pattern, which was positively associated with EF. Further research is needed to investigate the underlying pathways that explain this

Blood-based biomarkers of neurodegeneration demonstrate great promise for the diagnosis and prognosis of Alzheimer's disease. Ultra-sensitive plasma assays now allow for quantification of the lower concentrations in cognitively unimpaired older adults, making it possible to investigate whether these markers can provide insight also into the early neurodegenerative processes that affect cognitive function and whether the markers are influenced by modifiable risk factors. Adopting an exploratory approach in 93 healthy older adults (65-75 years), we used structural equation modelling to investigate cross-sectional associations between multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning) and plasma amyloid beta (Aβ42/Aβ40 ratio), phosphorylated-tau 181 (ptau-181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), as well as the influence of device-measured habitual physical activity on these associations. The results showed that NfL was negatively associated with working memory, and that NfL interacted with moderate-to-vigorous physical activity in its association with episodic memory. The study has thereby demonstrated the potential of neurodegenerative plasma markers for improving understanding of normative cognitive aging and encourages future research to test the hypothesis that high levels of NfL, indicative of white matter pathology, limit the beneficial effect of physical activity on episodic memory in healthy aging.

Background: Multimodal lifestyle interventions can benefit overall health, including cognition, in populations at-risk for dementia. However, little is known about the effect of lifestyle interventions in patients with prodromal Alzheimer's disease (AD). Even less is known about dietary intake and adherence to dietary recommendations within this population making it difficult to design tailored interventions for them.

Method: A 6-month MIND-ADmini pilot randomized controlled trial (RCT) was conducted among 93 participants with prodromal AD in Sweden, Finland, Germany, and France. Three arms were included in the RCT: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management, and social stimulation); 2) multimodal lifestyle intervention + medical food product; and 3) regular health advice (control group). Adherence to dietary advice was assessed with a brief food intake questionnaire by using the Healthy Diet Index (HDI) and Mediterranean Diet Adherence Screener (MEDAS). The intake of macro- and micronutrients were analyzed on a subsample using 3-day food records.

Results: The dietary quality in the intervention groups, pooled together, improved compared to that of the control group at the end of the study, as measured with by HDI (p = 0.026) and MEDAS (p = 0.008). The lifestyle-only group improved significantly more in MEDAS (p = 0.046) and almost significantly in HDI (p = 0.052) compared to the control group, while the lifestyle + medical food group improved in both HDI (p = 0.042) and MEDAS (p = 0.007) during the study. There were no changes in macro- or micronutrient intake for the intervention groups at follow-up; however, the intakes in the control group declined in several vitamins and minerals when adjusted for energy intake.

Conclusion: These results suggest that dietary intervention as part of multimodal lifestyle interventions is feasible and results in improved dietary quality in a population with prodromal AD. Nutrient intakes remained unchanged in the intervention groups while the control group showed a decreasing nutrient density.

BACKGROUND: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.

METHODS: MIND-AD_mini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60-85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.

RESULTS: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (β_{Lifestyle×Time} = 1.11, P = 0.038; β_{Lifestyle+medical food×Time} = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.

CONCLUSIONS: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03249688.

BACKGROUND: Sarcopenia and cognitive impairment are two leading causes of disabilities.

OBJECTIVE: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients.

METHODS: 368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer's disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0-3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied.

RESULTS: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06-0.90) and AD (OR: 0.12, 95% CI: 0.03-0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45-11.92).

CONCLUSION: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with both short- and long-term risks, although it is unknown if risks vary by severity, timing, and duration of gestational hyperglycemia. We aimed to identify trajectories of random capillary glucose (RCG) levels throughout pregnancy and assess their associations with both obstetric/neonatal outcomes and children's risk of neurodevelopmental conditions (NDCs) (i.e., autism, intellectual disability, and attention-deficit/hyperactivity disorders [ADHD]).

METHODS: A population-based cohort study was conducted involving 76,228 children born to 68,768 mothers without pregestational diabetes. Group-based trajectory modeling was utilized to identify distinct glucose trajectories across RCG values throughout the course of pregnancy. The associations between these trajectory groups and obstetric/neonatal outcomes as well as children's NDCs were then assessed using generalized estimating equation models with a logit link. The Benjamini-Hochberg (BH) procedure was employed to adjust P-values for multiple comparisons, controlling the false discovery rate (FDR).

RESULTS: Five distinct glucose trajectory groups were identified, each with varying percentages diagnosed with GDM. Their associations with obstetric/neonatal outcomes as well as children's NDCs varied. For example, when compared to the "Persistently Low" group, other groups exhibited varying degrees of increased risk for large-for-gestational-age babies, with the exception of the "High in Early Pregnancy" group. Compared to the "Persistently Low" group, all other trajectory groups were associated with NDC outcomes, except the "High in Mid-Pregnancy" group. However, none of the associations with offspring NDCs remained significant after accounting for the FDR correction.

CONCLUSIONS: Persistent high glucose levels or moderately elevated glucose levels throughout pregnancy, as well as transient states of hyperglycemia in early or mid-pregnancy, were found to be associated with increased risks of specific obstetric and neonatal complications, and potentially offspring NDCs. These risks varied depending on the severity, timing, duration, and management of hyperglycemia. The findings underscore the need for continuous surveillance and individualized management strategies for women displaying different glucose trajectories during pregnancy. Limitations such as potential residual confounding, the role of mediators, and small sample size should be addressed in future studies.

The concept of reserve has been developed to account for the discontinuity between the extent of brain damage at its clinical manifestation in the form of cognitive decline or dementia. In this chapter, we discuss contributors to cognitive reserve from various stages of the life-course, including childhood, early adulthood, middle age, and late life. Evidence from observational studies as well as intervention trials is presented and assessed. We conclude by arguing that reserve formation in dementia risk is a life-course process whereby baseline cognitive abilities are subjected to modulation by subsequent experiences at diverse stages over the entire life-course. Variations among individuals in their ability to withstand age-related brain changes are ultimately dependent on their life-time accumulation of mental, physical, and lifestyle inputs into cognitive reserve.

This study aimed to quantify the relationships between the American Heart Association (AHA) Cardiovascular Health (CVH) metrics, namely AHA Life's Simple 7, and cognitive outcomes. We searched PubMed and Embase (January 1, 2010-August 24, 2022) and finally included 14 longitudinal studies (311654 participants with 8006 incident dementia cases). Random-effects meta-analysis and one-stage linear mixed-effects models were performed. Increased CVH score seemed to associate with decreased risk of incident dementia in a linear manner, but this relationship varied by the measurement age of CVH metrics. That is, midlife CVH tended to have a linear association with late-life dementia risk, whereas a J-shaped association was observed between the late-life CVH score and dementia. In addition, late-life dementia risk was reduced significantly if individuals maintained an ideal level of AHA's CVH guidelines of physical activity, fasting plasma glucose, total cholesterol, and smoking. However, our meta-analysis did not show a significant association between CVH score and global cognitive decline rate. Following AHA's CVH guidelines and maintaining CVH at an optimal level would substantially reduce the late-life dementia risk. More research is required to explore the link between a favorable CVH score and cognitive trajectories among cognitively asymptomatic older populations.

BACKGROUND: Previous evidence supports a beneficial effect of physical activity on executive function across the whole lifespan. Yet, the interrelationships of the intensities of physical activity, cardiorespiratory fitness, and executive function require further investigation in adults.

AIM: Using unfiltered accelerometry data and high-resolution intensity classification, we sought to estimate the associations of physical activity with cardiorespiratory fitness and executive function in adult office workers.

METHODS: We included 343 full-time office workers (mean age: 42.41 years, range of age: 36-49 years). Executive function was assessed using Stroop, Trail making tests (part-B), and 2-back tests, and a composite score was produced to reflect the general executive function performance. Physical activity was assessed using the Actigraph GT3X+-monitor, worn by each participant for seven days at the hip. Raw accelerometry data were processed by the 10 Hz frequency extended method and divided into 22 intensity bins and sleep time. Cardiorespiratory fitness was estimated using the submaximal Ekblom-Bak cycle ergometer test. Data were analyzed using partial least squares regressions.

RESULTS: In adults, cardiorespiratory fitness was closely correlated with a wide range of absolute physical activity intensity patterns. A higher level of executive function in adults was associated with both higher absolute physical activity intensities and cardiorespiratory fitness, which was independent of age, sex, and education levels. A very weak association between intensities, fitness, and executive function was observed in high-fit adults. Among low-fit adults, although a positive association started already toward the upper end of moderate intensity, there still appeared to be an association between intensities, cardiorespiratory fitness, and executive function. That is, cardiorespiratory fitness may mediate the association between absolute physical activity intensities and executive function up to a certain level.

CONCLUSION: The maintenance of executive function in adulthood was related to both physical activity intensities and cardiorespiratory fitness, while their interrelationship was not equal across fitness levels. It is highly recommended to consider the cardiorespiratory fitness level in future studies that focus on executive functions in aging as well when designing individualized physical activity training programs.

Introduction: This study examined the relationship between cardiorespiratory fitness (CRF) and longitudinal cognitive functioning in a cohort enriched with risk factors for Alzheimer's disease (AD).

Methods: A total of 155 enrollees in the Wisconsin Registry for Alzheimer's Prevention completed repeat comprehensive neuropsychological evaluations that assessed six cognitive domains. Peak oxygen consumption (VO2peak) was the primary measure of CRF. Random effects regression was used to investigate the effect of CRF on cognitive trajectories.

Results: Higher CRF was associated with slower decline in the cognitive domains of verbal learning and memory (P < .01) and visual learning and memory (P < .042). Secondary analyses indicated that these effects were stronger among men than women, and for noncarriers of the apolipoprotein E ε4 allele.

Discussion: Higher CRF was associated with a slower rate of the decline in episodic memory that occurs as a natural consequence of aging in a cohort enriched with risk factors for AD.

BACKGROUND: We previously reported the effects of two cluster-randomized 6-month multi-component workplace interventions, targeting reducing sedentary behavior or increasing physical activity among office workers, on movement behaviors and cardiorespiratory fitness. The primary aim of this study was to investigate the effects of these interventions on cognitive functions compared to a wait-list control group. The secondary aims were to examine if changes in cognition were related to change in cardiorespiratory fitness or movement behaviors and if age, sex, or cardiorespiratory fitness moderated these associations.

METHODS: Both interventions encompassed multi-components acting on the individual, environmental, and organizational levels and aimed to change physical activity patterns to improve mental health and cognitive function. Out of 263 included participants, 139 (mean age 43 years, 76% females) completed a neuropsychological test battery and wore accelerometers at baseline and 6-month follow-up. The intervention effect (aim 1) on cognitive composite scores (i.e., Executive Functions, Episodic Memory, Processing Speed, and Global Cognition) was investigated. Additionally, associations between changes in movement behaviors and cardiorespiratory fitness, and changes in cognition were examined (aim 2). Moreover, age, sex, and cardiorespiratory fitness level were investigated as possible moderators of change associations (aim 3).

RESULTS: Overall, cognitive performance improved from baseline to follow-up, but the change did not differ between the intervention groups and the control group. Changes in cardiorespiratory fitness or any movement behavior category did not predict changes in cognitive functions. The association between changes in time in bed and changes in both Executive Function and Global Cognition were moderated by age, such that a more positive relation was seen with increasing age. A less positive association was seen between changes in sedentary behavior and Processing Speed for men vs. women, whereas higher cardiorespiratory fitness was related to a more positive association between changes in moderate-intensity physical activity and Global Cognition.

CONCLUSION: The lack of an intervention effect on cognitive functions was expected since the intervention did not change movement behavior or fitness. Age, sex, and cardiorespiratory fitness level might moderate the relationships between movement behaviors and cognitive functions changes.

TRIAL REGISTRATION: ISRCTN92968402 . Registered 09/04/2018.

Brain-derived neurotrophic factor (BDNF) and cortisol are both capable of modulating synaptic plasticity, but it is unknown how physical activity-induced changes in their plasma levels relate to corticospinal plasticity in humans. Sixteen inactive middle-aged men and women participated in three separate interventions consisting of 3hours prolonged sitting (SIT); 3hours sitting interrupted every 30minutes with frequent short physical activity breaks (FPA); and 2.5hours prolonged sitting followed by 25minutes of moderate intensity exercise (EXE). These 3hour sessions were each followed by a 30min period of paired associative stimulation over the primary motor cortex (PAS). Blood samples were taken and corticospinal excitability measured at baseline, pre PAS, 5min and 30min post PAS. Here we report levels of plasma BDNF and cortisol over three activity conditions and relate these levels to previously published changes in corticospinal excitability of a non-activated thumb muscle. There was no interaction between time and condition in BDNF, but cortisol levels were significantly higher after EXE compared to after SIT and FPA. Higher cortisol levels at pre PAS predicted larger increases in corticospinal excitability from baseline to all subsequent time points in the FPA condition only, while levels of BDNF at pre PAS did not predict such changes in any of the conditions. Neither BDNF nor cortisol modified changes from pre PAS to the subsequent time points, suggesting that the increased corticospinal excitability was not mediated though an augmented effect of the PAS protocol. The relationship between cortisol and plasticity has been suggested to be U-shaped. This is possibly why the moderately high levels of cortisol seen in the FPA condition were positively associated with changes AURC, while the higher cortisol levels seen after EXE were not. A better understanding of the mechanisms for how feasible physical activity breaks affect neuroplasticity can inform the theoretical framework for how work environments and schedules should be designed. DATA AVAILABILITY: Data are available from the corresponding author upon reasonable request.

BACKGROUND: The potential impact of migraine on cognitive aging among older adults remains controversial.

OBJECTIVE: To examine the relationship of migraine and subtypes with cognitive decline and dementia in an older Swedish population.

METHODS: This population-based study included 3069 participants (age≥60) from the Swedish National study on Aging and Care in Kungsholmen, Stockholm. Baseline examination was conducted in 2001-2004, and participants were followed every 3 or 6 years until 2013-2016. Data were collected through face-to-face interviews, clinical examinations, laboratory tests, and linkage with registers. Global cognitive function was measured with the Mini-Mental State Examination (MMSE). Dementia was diagnosed according to the DSM-IV criteria. Migraine and subtypes were defined following the international classification system. Data were analyzed using logistic regression, Cox regression, and linear mixed-effects models.

RESULTS: At baseline, 305 participants were defined with non-migraine headache and 352 with migraine. The cross-sectional analysis showed that the multivariable-adjusted odds ratio (95% confidence interval) of prevalent dementia was 0.49 (0.20-1.21) for migraine and 0.66 (0.26-1.66) for migraine without aura. The longitudinal analysis showed that the multivariable-adjusted hazard ratios of incident dementia associated with migraine and subtypes ranged 0.68-0.89 (p > 0.05). Furthermore, migraine and subtypes were not significantly associated with either baseline MMSE score or MMSE changes during follow-ups (p > 0.05). The nonsignificant associations did not vary substantially by age, APOEɛ4 allele, cerebrovascular disease, and antimigraine treatment (p for interactions > 0.05).

CONCLUSION: This study shows no evidence supporting the associations of migraine and its subtypes with cognitive decline and dementia among older adults.

Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric—fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO—is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer’s disease (AD). Age was significantly associated with all but one diffusion parameters and regions of interest. NDI and MD in the cingulate region adjacent to the cingulate cortex showed a significant association with a composite measure of Executive Function and was proven to partially mediate the relationship between aging and Executive Function decline. These results suggest that both DTI and NODDI parameters are sensitive to age-related differences in white matter regions vulnerable to aging, particularly among older adults at risk for AD.

A knowledge gap remains in understanding how to improve the intervention effectiveness in office workers targeting physically active (PA) behavior. We aim to identify the modifying effect of executive function (EF) on the intervention effectiveness targeting PA-behaviors, and to verify whether the observed effect varies by Job Demand Control (JDC) categories. This workplace-based intervention study included 245 participants who were randomized into a control group and two intervention arms—promoting physical activity (iPA) group or reducing sedentary behavior (iSED) group. The interventions were conducted through counselling-based cognitive behavioral therapy and team activities over 6 months. PA-behaviors were measured by an accelerometer. EF was assessed by the Trail Making Test-B, Stroop, and n-back test. The JDC categories were measured by the demand control questionnaire. Higher EF level at baseline was significantly associated with the intervention effect on increased sleep time (β-coefficient: 3.33, p = 0.003) and decreased sedentary time (−2.76, p = 0.049) in the iSED-group. Participants with active jobs (high job demands, high control) presented significantly increased light-intensity PA in the iSED-group in comparison to the control group. Among participants with a high level of EF and active jobs, relative to the control group, the iPA-group showed a substantial increase in light-intensity PA (1.58, p = 0.036) and the iSED-group showed a tendency of reducing sedentary behavior (−5.35, p = 0.054). The findings suggest that office workers with a high EF and active jobs may benefit most from an intervention study targeting PA-behaviors.

Background: Poor social health is likely associated with cognitive decline and risk of dementia; however, studies show inconsistent results. Additionally, few studies separate social health components or control for mental health.

Objective: To investigate whether loneliness and social support are independently associated with cognitive decline and risk of dementia, and whether depressive symptoms confound the association.

Methods: We included 4,514 participants from the population-based Rotterdam Study (RS; aged 71±7SD years) followed up to 14 years (median 10.8, interquartile range 7.4-11.6), and 2,112 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; aged 72±10SD years) followed up to 10 years (mean 5.9±1.6SD). At baseline, participants were free of major depression and scored on the Mini-Mental State Examination (MMSE) ≥26 for RS and ≥25 for SNAC-K. We investigated loneliness, perceived social support, and structural social support (specifically marital status and number of children). In both cohorts, dementia was diagnosed and cognitive function was repeatedly assessed with MMSE and a global cognitive factor (g-factor).

Results: Loneliness was prospectively associated with a decline in the MMSE in both cohorts. Consistently, persons who were lonely had an increased risk of developing dementia (RS: HR 1.34, 95%CI 1.08-1.67; SNAC-K: HR 2.16, 95%CI 1.12-4.17). Adjustment for depressive symptoms and exclusion of the first 5 years of follow-up did not alter results. Neither perceived or structural social support was associated with cognitive decline or dementia risk.

Conclusion: Loneliness, not social support, predicted cognitive decline and incident dementia independently of depressive symptoms.

BACKGROUND: The purpose of this study was to examine the associations between combined and individual cerebral small vessel disease (cSVD) markers on future walking speed over 9 years; and to explore whether these associations varied by the presence of cardiovascular risk factors (CRFs).

METHODS: This population-based cohort study included 331 adults, aged ≥60 years, without limitation in walking speed (≥0.8 m/s). At baseline, cSVD markers, including white matter hyperintensities (WMH), lacunes, and perivascular spaces (PVS), were assessed on magnetic resonance imaging. The modifiable CRFs (physical inactivity, heavy alcohol consumption, smoking, hypertension, high total cholesterol, diabetes, and overweight/obese) were combined into a score. The association between baseline cSVD markers and the decline in walking speed was examined using linear mixed-effects models, whereas Cox proportional hazards models were used to estimate the association with walking speed limitation (defined as < 0.8 m/s) over the follow-up.

RESULTS: Over the follow-up period, 76 (23.0%) persons developed walking speed limitation. Participants in the highest tertile of the combined cSVD marker score had a hazard ratio (HR) of 3.78 (95% confidence interval [CI] 1.70-8.45) for walking speed limitation compared with people in the lowest score tertile, even after adjusting for socio-demographics, CRFs, cognitive function, and chronic conditions. When investigating the cSVD markers individually, having the highest burden of WMH was associated with a significantly faster decline in walking speed (β coefficient - 0.020; 95% CI -0.035-0.004) and a greater HR of walking speed limitation (HR 2.78; 95% CI 1.31-5.89) compared with having the lowest WMH burden. Similar results were obtained for the highest tertile of PVS (HR 2.13; 95% CI 1.04-4.36). Lacunes were associated with walking speed limitation, but only in men. Having ≥4 CRFs and high WMH volume simultaneously, showed a greater risk of walking speed limitation compared with having ≥4 CRFs and low WMH burden. CRFs did not modify the associations between lacunes or PVS and walking speed.

CONCLUSIONS: Combined cSVD markers strongly predict walking speed limitation in healthy older adults, independent of cognitive function, with WMH and PVS being the strongest contributors. Improving cardiovascular health may help to mitigate the negative effects of WMH on future walking speed.

Background: Modifiable vascular risk factors have been associated with late-life cognitive impairment. The Life Simple 7 (LS7) score comprises seven cardiovascular health metrics: smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure. Objective: To investigate the association between individual and composite LS7 metrics and rate of cognitive decline, and potential differences in these associations between young-old and old-old individuals. Methods: This cohort study included 1,950 participants aged >= 60 years (M= 70.7 years) from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic and semantic memory, verbal fluency, processing speed, global cognition) across 12 years. The LS7 score was assessed at baseline and categorized as poor, intermediate, or optimal. Level and change in cognitive performance as a function of LS7 categories were estimated using linear mixed-effects models. Results: Having an optimal LS7 total score was associated with better performance (expressed in standard deviation units) at baseline for perceptual speed (beta=0.21, 95% CI 0.12-0.29), verbal fluency (beta=0.08, 0.00-0.16), and global cognition (beta = 0.06, 0.00-0.12) compared to the poor group. Age-stratified analyses revealed associations for cognitive level and change only in the young-old (< 78 years) group. For the specific metrics, diverging patterns were observed for young-old and old-old individuals. Conclusion: Meeting the LS7 criteria for ideal cardiovascular health in younger old age is associated with slower rate of cognitive decline. However, the LS7 criteria may have a different meaning for cognitive function in very old adults.

Knowledge about associations between school-based initiatives and physical activity patterns is limited. The purpose of this paper was to examine associations between factors in the school environment, physical activity and sedentary time during school time. The cross-sectional study included 1139 adolescents aged 13–14 from 34 schools. Physical activity and sedentary time were measured using hip-worn accelerometers. Factors in the school environment included health policy, a mobile phone ban during breaks, organized physical activities during breaks and activity breaks during lessons reported by teachers. The frequency and duration of breaks and physical education (PE) lessons were collected from school schedules. The results showed significant associations between health policy (β = 3.87, 95% confidence interval (CI): 2.37, 5.23), the mobile phone ban (β = 2.51, 95% CI: 1.29, 3.94) and PE; total duration (β = 0.08, 95% CI: 0.05, 0.11), average duration (β = 0.08, 95% CI: 0.01, 0.13) and frequency (β = 1.73, 95% CI: 0.50, 3.04) and moderate-vigorous physical activity. There were negative associations between health policy (β = −6.41, 95% CI: −10.24, −2.67), the mobile phone ban (β = −3.75, 95% CI: −7.25, −0.77) and PE; total duration (β = −0.15, 95% CI: −0.23, −0.08) and average duration (β = −0.14, 95% CI: −0.27, −0.03) and time spent sedentary. Adolescents attending schools with health policies, mobile phone bans and more time for PE showed higher levels of physical activity and lower sedentary time.

Background and Objectives: Cognitive reserve (CR) is meant to account for the mismatch between brain damage and cognitive decline or dementia. Generally, CR has been operationalized using proxy variables indicating exposure to enriching activities (activity-based CR). An alternative approach defines CR as residual variance in cognition, not explained by the brain status (residual-based CR). The aim of this study is to compare activity-based and residual-based CR measures in their association with cognitive trajectories and dementia. Furthermore, we seek to examine if the two measures modify the impact of brain integrity on cognitive trajectories and if they predict dementia incidence independent of brain status.

Methods: We used data on 430 older adults aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, followed for 12 years. Residual-based reserve was computed from a regression predicting episodic memory with a brain-integrity index incorporating six structural neuroimaging markers (white-matter hyperintensities volume, whole-brain gray matter volume, hippocampal volume, lateral ventricular volume, lacunes, and perivascular spaces), age, and sex. Activity-based reserve incorporated education, work complexity, social network, and leisure activities. Cognition was assessed with a composite of perceptual speed, semantic memory, letter-, and category fluency. Dementia was clinically diagnosed in accordance with DSM-IV criteria. Linear mixed models were used for cognitive change analyses. Interactions tested if reserve measures modified the association between brain-integrity and cognitive change. Cox proportional hazard models, adjusted for brain-integrity index, assessed dementia risk.

Results: Both reserve measures were associated with cognitive trajectories [β × time (top tertile, ref.: bottom tertile) = 0.013; 95% CI: -0.126, -0.004 (residual-based) and 0.011; 95% CI: -0.001, 0.024, (activity-based)]. Residual-based, but not activity-based reserve mitigated the impact of brain integrity on cognitive decline [β (top tertile × time × brain integrity) = -0.021; 95% CI: -0.043, 0.001] and predicted 12-year dementia incidence, after accounting for the brain-integrity status [HR (top tertile) = 0.23; 95% CI: 0.09, 0.58].

Interpretation: The operationalization of reserve based on residual cognitive performance may represent a more direct measure of CR than an activity-based approach. Ultimately, the two models of CR serve largely different aims. Accounting for brain integrity is essential in any model of reserve.

The role of orthostatic hypotension (OH) in the continuum of cognitive aging remains to be clarified. We sought to investigate the associations of OH with dementia, cognitive impairment, no dementia (CIND), and CIND progression to dementia in older adults while considering orthostatic symptoms. This population-based cohort study included 2532 baseline (2001–2004) dementia-free participants (age ≥60 years; 62.6% women) in the SNAC-K (Swedish National Study on Aging and Care in Kungsholmen) who were regularly examined over 12 years. We further divided the participants into a baseline CIND-free cohort and a CIND cohort. OH was defined as a decrease by ≥20/10 mmHg in systolic/diastolic blood pressure upon standing and further divided into asymptomatic and symptomatic OH. Dementia was diagnosed following the international criteria. CIND was defined as scoring ≥1.5 SDs below age group-specific means in ≥1 cognitive domain. Data were analyzed with flexible parametric survival models, controlling for confounding factors. Of the 2532 participants, 615 were defined with OH at baseline, and 322 were diagnosed with dementia during the entire follow-up period. OH was associated with an adjusted hazard ratio of 1.40 for dementia (95% CI, 1.10–1.76), 1.15 (0.94–1.40) for CIND, and 1.54 (1.05–2.25) for CIND progression to dementia. The associations of dementia and CIND progression to dementia with asymptomatic OH were similar to overall OH, whereas symptomatic OH was only associated with CIND progression to dementia. Our study suggests that OH, even asymptomatic OH, is associated with increased risk of dementia and accelerated progression from CIND to dementia in older adults.

Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer's disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40-89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13-8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (β=-1.43), hippocampus (-1.25), superior frontal gyrus (-1.70), middle frontal gyrus (-1.99), posterior cingulate (-2.46), and precuneus (-2.14), with all P-values < 0.01. Compared with male-ɛ4 carriers, female-ɛ4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-ɛ4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-ɛ4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.

BACKGROUND AND PURPOSE: Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to examine the association between AF and cerebral small vessel disease markers among older adults.

METHODS: Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001-2004) and follow-ups (2004-2007 and 2007-2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models.

RESULTS: At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (β coefficient=0.45 [95% CI, 0.04-0.86]) and lateral ventricular volume (0.58 [0.13-1.02]). There was no significant association of AF with annual changes in perivascular spaces number (β coefficient=0.53 [95% CI, -0.27 to 1.34]) or lacune number (-0.01 [-0.07 to 0.05]).

CONCLUSIONS: Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.

Intervention studies aiming at changing movement behavior have usually not accounted for the compositional nature of time-use data. Compositional data analysis (CoDA) has been suggested as a useful strategy for analyzing such data. The aim of this study was to examine the effects of two multi-component interventions on 24-h movement behavior (using CoDA) and on cardiorespiratory fitness among office workers; one focusing on reducing sedentariness and the other on increasing physical activity. Office workers (n = 263) were cluster randomized into one of two 6-month intervention groups, or a control group. Time spent in sedentary behavior, light-intensity, moderate and vigorous physical activity, and time in bed were assessed using accelerometers and diaries, both for 24 h in total, and for work and leisure time separately. Cardiorespiratory fitness was estimated using a sub-maximal cycle ergometer test. Intervention effects were analyzed using linear mixed models. No intervention effects were found, either for 24-h behaviors in total, or for work and leisure time behaviors separately. Cardiorespiratory fitness did not change significantly. Despite a thorough analysis of 24-h behaviors using CoDA, no intervention effects were found, neither for behaviors in total, nor for work and leisure time behaviors separately. Cardiorespiratory fitness did not change significantly. Although the design of the multi-component interventions was based on theoretical frameworks, and included cognitive behavioral therapy counselling, which has been proven effective in other populations, issues related to implementation of and compliance with some intervention components may have led to the observed lack of intervention effect.

INTRODUCTION: Stroke, especially ischemic stroke's (IS) link with Alzheimer's disease (AD) remains unclear.

METHODS: This prospective cohort study included 2459 AD- and cerebrovascular disease-free older adults at baseline (mean age 71.9 ± 10.3 years, Stockholm, Sweden). Using Cox regressions, shared risk factors (SRFs) and shared protective factors (SPFs) between AD and IS were recognized when their hazard ratios in both AD and IS models were significant and in the same direction.

RESULTS: During the follow-up period of up to 15 years, 132 AD and 260 IS mutually exclusive cases were identified. SRFs were low education, sedentary lifestyle, and heart diseases. High levels of psychological well-being, actively engaging in leisure activities, and a rich social network were SPFs. Having ≥1 SPF reduced 47% of AD and 28% of IS risk among people with a low risk profile (<2 SRFs), and 38% of AD and 31% of IS risk with a high risk profile (≥2 SRFs). In total, 57.8% of AD/IS cases could be prevented if individuals have ≥1 SPF and no SRF.

DISCUSSION: AD and IS share risk/protective profiles, and SPFs seem to counteract the adverse effects of SRFs on both AD and IS.

BACKGROUND: The patterns of blood pressure trajectory (i.e., change over time) over life-course remain to be explored. In this study, we aim to determine the trajectories of systolic blood pressure (SBP) from adulthood to late life and to assess its impact on the risk of cardiovascular diseases (CVDs).

METHODS: Based on the China Health and Nutrition Survey, a total of 3566 participants aged 20-50 years at baseline (1989) with at least three SBP measurements during 1989-2011 were included. SBP was measured through physical examination, and socio-demographic factors, lifestyles, medications, and CVDs were based on self-reported questionnaire. Latent class growth modeling was performed to examine SBP trajectory. Odds ratio (OR) and 95% confidence interval (CI) from logistic regression was used to determine the association between SBP trajectory and CVDs.

RESULTS: Five trajectory groups of SBP were identified: Class 1: rapid increase (n = 113, 3.2%); Class 2: slight increase (n = 1958, 54.9%); Class 3: stable (n = 614, 17.2%); Class 4: increase (n = 800, 22.4%); Class 5: fluctuant (n = 81, 2.3%). After adjustment of demographic factors, baseline SBP, and lifestyles, compared with the "slight increase" group, the OR (95% CI) of CVDs was 0.65 (0.32, 1.28) for "stable" group, 2.24 (1.40, 3.58) for "increase" group, 3.95 (1.81, 8.62) for "rapid increase" group, and 4.32 (1.76, 10.57) for "fluctuant" group. After stratified by use of antihypertensive drugs, the association was only significant for "rapid increase" group among those using antihypertensive drugs with OR (95% CI) of 2.81 (1.01, 7.77).

CONCLUSIONS: Having a rapidly increasing SBP over life-course is associated with a higher risk of CVDs. This implies the importance of monitoring lifetime change of blood pressure for the prevention of CVDs.

Introduction: The impact of prediabetes and diabetes on stroke and the development of dementia after a stroke remain unclear. Methods: A total of 2655 dementia-free participants (including a stroke-free cohort and a prevalent stroke cohort) were followed-up for 12 years. Dementia and post-stroke dementia were determined by clinical examinations and national registry data. Diabetes was ascertained via medical examination, medication use, medical records, or glycated hemoglobin (HbA1c) >= 6.5%. Prediabetes was defined as H bA1c >= 5.7% in diabetes-free participants. Results: In the stroke-free cohort, 236 participants developed ischemic stroke, and 47 developed post-stroke dementia. Diabetes was associated with ischemic stroke (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.16 to 2.67) and post-stroke dementia (HR 2.56, 95% CI 1.04 to 6.25). In the prevalent stroke cohort, diabetes was also related to dementia risk. Prediabetes was not significantly related to stroke or post-stroke dementia. Discussion: Diabetes, but not prediabetes, is associated with an increased risk of ischemic stroke and post-stroke dementia.

BACKGROUND: Prevention and control of cardiometabolic conditions and cardiovascular disease (CVD) in China may contribute to sustainable CVD reduction globally, given the fact that one-fifth of the worldwide population is in China. Knowing the distribution of behavioral risk factors (e.g., smoking and physical inactivity), especially at a national level in China, would be extremely relevant to the field of public health and CVD prevention. The objectives of this study were to investigate the nationwide prevalence of obesity, smoking, heavy drinking, and physical inactivity in Chinese adults, and further explore whether cardiometabolic conditions would modify the distribution of behavioral risk factors.

METHODS: This population-based study is based on the China Health and Retirement Longitudinal Study (2011-2012), including 17,302 adults (≥45 years, mean age 59.67 years, female 51.66%) from 25 provinces in China. Data on demographics, lifestyle factors, health status and history of diseases were collected via structured interviews and laboratory tests. Smoking, heavy drinking, obesity, and physical inactivity were defined following standard guidelines. We performed descriptive analysis and logistic regressions in this study.

RESULTS: The overall prevalence of heavy drinking, obesity, current smoking, and physical inactivity among middle-aged and older adults was 7.23% (95% confidence interval 6.53-7.29%), 11.53% (10.43-12.62%), 27.46% (26.30-28.62%), and 44.06% (41.19-46.92%), respectively. The prevalence varied between rural and urban areas as well as among geographic areas, with higher prevalence in the Northern and Northeastern regions. Heavy drinking and obesity were significantly associated with incident hypertension, diabetes, and high cholesterol; while current smoking was significantly associated with incident hypertension. Compared with healthy individuals, participants who self-reported a diagnosis of hypertension, high cholesterol, or diabetes were less likely to smoke currently and drink alcohol heavily, but more likely to be physically inactive and obese.

CONCLUSIONS: Among Chinese middle-aged and older adults, the prevalence of behavioral risk factors varies by geographic region. Further effort is required to improve physical activity and fitness for Chinese adults, especially those with cardiometabolic conditions.

OBJECTIVE: To explore the differential associations of neurodegeneration and microvascular lesion load with cognitive decline and dementia in older people and the modifying effect of the APOE genotype on these associations.

METHODS: A sample of 436 participants (age ≥ 60 years) was derived from the population-based Swedish National study on Aging and Care in Kungsholmen, Stockholm, and clinically examined at baseline (2001-2003) and 3 occasions during the 9-year follow-up. At baseline, we assessed microvascular lesion load using a summary score for MRI markers of lacunes, white matter hyperintensities (WMHs), and perivascular spaces and neurodegeneration load for markers of enlarged ventricles, smaller hippocampus, and smaller gray matter. We assessed cognitive function using the Mini-Mental State Examination (MMSE) test and diagnosed dementia following the Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. We analyzed data using linear mixed-effects, mediation, and random-effects Cox models.

RESULTS: During the follow-up, 46 participants were diagnosed with dementia. Per 1-point increase in microvascular lesion and neurodegeneration score (range 0-3) was associated with multiple adjusted β-coefficients of -0.35 (95% confidence interval, -0.51 to -0.20) and -0.44 (-0.56 to -0.32), respectively, for the MMSE score and multiple adjusted hazard ratios of 1.68 (1.12-2.51) and 2.35 (1.58-3.52), respectively, for dementia; carrying APOE ε4 reinforced the associations with MMSE decline. WMH volume changes during the follow-up mediated 66.9% and 12.7% of the total association of MMSE decline with the baseline microvascular score and neurodegeneration score, respectively.

CONCLUSIONS: Both cerebral microvascular lesion and neurodegeneration loads are strongly associated with cognitive decline and dementia. The cognitive decline due to microvascular lesions is exacerbated by APOE ε4 and is largely attributed to progression and development of microvascular lesions.