Combined effect of physical activity and leisure time sitting on long-term risk of incident obesity and metabolic risk factor clustering

Aims/hypothesis Our study aimed to investigate the combined effects of moderate-to-vigorous physical activity and leisure time sitting on the long-term risk of obesity and clustering of metabolic risk factors. Methods The duration of moderate and vigorous physical activity and of leisure time sitting was assessed by questionnaire between 1997 and 1999 among 3,670 participants from the Whitehall II cohort study (73% male; mean age 56 years). Multivariable-adjusted logistic regression models examined associations of physical activity and leisure time sitting tertiles with odds of incident obesity (BMI ≥ 30 kg/m2) and incident metabolic risk factor clustering (two or more of the following: low HDL-cholesterol, high triacylglycerol, hypertension, hyperglycaemia, insulin resistance) at 5 and 10 year follow-ups. Results Physical activity, but not leisure time sitting, was associated with incident obesity. The lowest odds of incident obesity after 5 years were observed for individuals reporting both high physical activity and low leisure time sitting (OR = 0.26; 95% CI 0.11, 0.64), with weaker effects after 10 years. Compared with individuals in the low physical activity/high leisure time sitting group, those with intermediate levels of both physical activity and leisure time sitting had lower odds of incident metabolic risk factor clustering after 5 years (OR 0.53; 95% CI 0.36, 0.78), with similar odds after 10 years. Conclusions/interpretation Both high levels of physical activity and low levels of leisure time sitting may be required to substantially reduce the risk of obesity. Associations with developing metabolic risk factor clustering were less clear

Healthy obesity and objective physical activity

Background: Disease risk is lower in metabolically healthy obese adults than in their unhealthy obese counterparts. Studies considering physical activity as a modifiable determinant of healthy obesity have relied on self-reported measures, which are prone to inaccuracies and do not capture all movements that contribute to health. Objective: We aimed to examine differences in total and moderate-to-vigorous physical activity between healthy and unhealthy obese groups by using both self-report and wrist-worn accelerometer assessments. Design: Cross-sectional analyses were based on 3457 adults aged 60–82 y (77% male) participating in the British Whitehall II cohort study in 2012–2013. Normal-weight, overweight, and obese adults were considered “healthy” if they had <2 of the following risk factors: low HDL cholesterol, hypertension, high blood glucose, high triacylglycerol, and insulin resistance. Differences across groups in total physical activity, based on questionnaire and wrist-worn triaxial accelerometer assessments (GENEActiv), were examined by using linear regression. The likelihood of meeting 2010 World Health Organization recommendations for moderate-to-vigorous activity (≥2.5 h/wk) was compared by using prevalence ratios. Results: Of 3457 adults, 616 were obese [body mass index (in kg/m2) ≥30]; 161 (26%) of those were healthy obese. Obese adults were less physically active than were normal-weight adults, regardless of metabolic health status or method of physical activity assessment. Healthy obese adults had higher total physical activity than did unhealthy obese adults only when assessed by accelerometer (P = 0.002). Healthy obese adults were less likely to meet recommendations for moderate-to-vigorous physical activity than were healthy normal-weight adults based on accelerometer assessment (prevalence ratio: 0.59; 95% CI: 0.43, 0.79) but were not more likely to meet these recommendations than were unhealthy obese adults (prevalence ratio: 1.26; 95% CI: 0.89, 1.80). Conclusions: Higher total physical activity in healthy than in unhealthy obese adults is evident only when measured objectively, which suggests that physical activity has a greater role in promoting health among obese populations than previously thought

Aortic Pulse Wave Velocity as Adjunct Risk Marker for Assessing Cardiovascular Disease Risk : Prospective Study

Peer reviewe

Inter- and intra-individual variation in brain structural-cognition relationships in aging

The sources of inter- and intra-individual variability in age-related cognitive decline remain poorly understood. We examined the association between 20-year trajectories of cognitive decline and multimodal brain structure and morphology in older age. We used the Whitehall II Study, an extensively characterised cohort with 3T brain magnetic resonance images acquired at older age (mean age = 69.52 ± 4.9) and 5 repeated cognitive performance assessments between mid-life (mean age = 53.2 ±4.9 years) and late-life (mean age = 67.7 ± 4.9). Using non-negative matrix factorization, we identified 10 brain components integrating cortical thickness, surface area, fractional anisotropy, and mean and radial diffusivities. We observed two latent variables describing distinct brain-cognition associations. The first describes variations in 5 structural components associated with low mid-life performance across multiple cognitive domains, decline in reasoning, but maintenance of fluency abilities. The second describes variations in 6 structural components associated with low mid-life performance in fluency and memory, but retention of multiple abilities. Expression of latent variables predicts future cognition 3.2 years later (mean age = 70.87 ± 4.9). This data-driven approach highlights brain-cognition relationships wherein individuals degrees of cognitive decline and maintenance across diverse cognitive functions are both positively and negatively associated with markers of cortical structure

Association of Midlife Cardiovascular Risk Profiles with Cerebral Perfusion at Older Ages

© 2019 AMA. All rights reserved. Importance: Poor cardiovascular health is an established risk factor for dementia, but little is known about its association with brain physiology in older adults. Objective: To examine the association of cardiovascular risk factors, measured repeatedly during a 20-year period, with cerebral perfusion at older ages. Design, Setting, and Participants: In this longitudinal cohort study, individuals were selected from the Whitehall II Imaging Substudy. Participants were included if they had no clinical diagnosis of dementia, had no gross brain structural abnormalities on magnetic resonance imaging scans, and had received pseudocontinuous arterial spin labeling magnetic resonance imaging. Cardiovascular risk was measured at 5-year intervals across 5 phases from September 1991 to October 2013. Arterial spin labeling scans were acquired between April 2014 and December 2014. Data analysis was performed from June 2016 to September 2018. Exposures: Framingham Risk Score (FRS) for cardiovascular disease, comprising age, sex, high-density lipoprotein cholesterol level, total cholesterol level, systolic blood pressure, use of antihypertensive medications, cigarette smoking, and diabetes, was assessed at 5 visits. Main Outcomes and Measures: Cerebral blood flow (CBF; in milliliters per 100 g of tissue per minute) was quantified with pseudocontinuous arterial spin labeling magnetic resonance imaging. Results: Of 116 adult participants, 99 (85.3%) were men. At the first examination, mean (SD) age was 47.1 (5.0) years; at the last examination, mean (SD) age was 67.4 (4.9) years. Mean (SD) age at MRI scan was 69.3 (5.0) years. Log-FRS increased with time (B = 0.058; 95% CI, 0.044 to 0.072;

Does Poorer Pulmonary Function Accelerate Arterial Stiffening?: A Cohort Study With Repeated Measurements of Carotid-Femoral Pulse Wave Velocity.

Whether poorer pulmonary function accelerates progression of arterial stiffness remains unknown as prior observational studies have not examined longitudinal changes in arterial stiffness in relation to earlier pulmonary function. Data (N=5342, 26% female) were drawn from the Whitehall II cohort study. Participants completed repeated assessments of forced expiratory volume in 1 second (FEV1, L) and carotid-femoral pulse wave velocity (cf-PWV, m/s) over 5 years. The effect of FEV1 on later cf-PWV and its progression was estimated using linear mixed-effects modeling. Possible explanatory mechanisms, such as mediation by low-grade systemic inflammation, common-cause explanation by preexisting cardiometabolic risk factors, and reverse-causation bias, were assessed. Poorer pulmonary function was associated with later higher cf-PWV and its subsequent progression (cf-PWV 5-year change 0.09, 95% CI 0.03-0.17 per SD lower FEV1) after adjustment for age, sex, ethnicity, heart rate, and mean arterial pressure. Decrease in pulmonary function was associated with later higher cf-PWV (0.17, 95% CI 0.04-0.30 in the top compared to bottom quartile of decline in FEV1). There was no evidence to support mediation by circulating CRP (C-reactive protein) or IL (interleukin)-6. Furthermore, arterial stiffness was not associated with later FEV1 after accounting for cardiometabolic status. In conclusion, poorer pulmonary function predicted future arterial stiffness. These findings support pulmonary function as a clinically important risk factor for arterial stiffness and provide justification for future intervention studies for pulmonary function based on its relationship with arterial stiffness.The Whitehall II study is supported by the British Heart Foundation (RG/16/11/32334), UK Medical Research Council (K013351) and US National Institute on Aging (R01AG013196; R01AG034454; R01AG056477). M. Kivimaki is additionally supported by the UK Medical Research Council (S011676), NordForsk (the Nordic Research Programme on Health and Welfare), the Academy of Finland (311492), and Helsinki Institute of Life Scienc

Association of aortic stiffness with cognitive decline: Whitehall II longitudinal cohort study

Abstract: Aortic stiffness is associated with an increased risk of cardio- and cerebrovascular disease and mortality and may increase risk of dementia. The aim of the present study is to examine the association between arterial stiffness and cognitive decline in a large prospective cohort study with three repeated cognitive assessment over 7 years of follow-up. Aortic pulse wave velocity (PWV) was measured among 4300 participants (mean ± standard deviation age 65.1 ± 5.2 years) in 2007–2009 and categorized based on the tertiles: (lowest third: 8.91 m/s). A global cognitive score was calculated in 2007–2009, 2012–2013, and 2015–2016 based on responses to memory, reasoning and fluency tests. Standardized global cognitive score (mean = 0, SD = 1) in highest third versus lowest third of PWV category was lower at baseline (− 0.12, 95% CI − 0.18, − 0.06). Accelerated 7-year cognitive decline was observed among individuals with the highest PWV [difference in 7-year cognitive change for highest third versus lowest third PWV: − 0.06, 95% CI − 0.11, − 0.01, P < 0.01]. Higher aortic stiffness was associated with faster cognitive decline. Clinicians may be able to use arterial stiffness severity as an indicator to administer prompt treatments to prevent or delay the onset of cognitive decline or dementia. Future studies need to determine whether early intervention of vascular stiffness is effective in delaying these outcomes

Vascular risk status as a predictor of later-life depressive symptoms: A cohort study

Background: Common etiology of vascular diseases and later-life depression may provide important synergies for prevention. We examined whether standard clinical risk profiles developed for vascular diseases also predict depressive symptoms in older adults. Methods: Data were drawn from the Whitehall II study with baseline examination in 1991; follow-up screenings in 1997, 2003, and 2008; and additional disease ascertainment from hospital data and registry linkage on 5318 participants (mean age 54.8 years, 31% women) without depressive symptoms at baseline. Vascular risk was assessed with the Framingham Cardiovascular, Coronary Heart Disease, and Stroke Risk Scores. New depressive symptoms at each follow-up screening were identified by General Health Questionnaire caseness, a Center for Epidemiologic Studies Depression Scale score <16, and use of antidepressant medication. Results: Diagnosed vascular disease (that is, coronary heart disease or stroke) was associated with an increased risk for depressive symptoms, age- and sex-adjusted odds ratios from 1.5 (95% confidence interval 1.0-2.2) to 2.0 (1.4-3.0), depending on the indicator of depressive symptoms. Among participants without manifest vascular disease, the Stroke Risk Score was associated with Center for Epidemiologic Studies Depression Scale depressive symptoms before age 65 (age- and sex-adjusted odds ratio per 10% absolute change in the score = 3.1 [1.5-6.5]), but none of the risk scores predicted new-onset depressive symptoms in those aged <65 (odds ratios from.8 to 1.2). Conclusions: These data suggest that public health measures to improve vascular risk status will influence the incidence of later-life depressive symptoms via reduced rates of manifest vascular disease

Alcohol consumption and cognitive performance: a <scp>M</scp> endelian randomization study

Aims: To use Mendelian randomization to assess whether alcohol intake was causally associated with cognitive function. Design: Mendelian randomization using a genetic variant related to alcohol intake (ADH1B rs1229984) was used to obtain unbiased estimates of the association between alcohol intake and cognitive performance. Setting: Europe. Participants: More than 34000 adults. Measurements: Any versus no alcohol intake and units of intake in the previous week was measured by questionnaire. Cognitive function was assessed in terms of immediate and delayed word recall, verbal fluency and processing speed. Findings: Having consumed any versus no alcohol was associated with higher scores by 0.17 standard deviations (SD) [95% confidence interval (CI)=0.15, 0.20] for immediate recall, 0.17 SD (95% CI=0.14, 0.19) for delayed recall, 0.17 SD (95% CI=0.14, 0.19) for verbal fluency and 0.12 SD (95% CI=0.09, 0.15) for processing speed. The minor allele of rs1229984 was associated with reduced odds of consuming any alcohol (odds ratio=0.87; 95% CI=0.80, 0.95; P=0.001; R2=0.1%; F-statistic=47). In Mendelian randomization analysis, the minor allele was not associated with any cognitive test score, and instrumental variable analysis suggested no causal association between alcohol consumption and cognition: -0.74 SD (95% CI=-1.88, 0.41) for immediate recall, -1.09 SD (95% CI=-2.38, 0.21) for delayed recall, -0.63 SD (95% CI=-1.78, 0.53) for verbal fluency and -0.16 SD (95% CI=-1.29, 0.97) for processing speed. Conclusions: The Mendelian randomization analysis did not provide strong evidence of a causal association between alcohol consumption and cognitive ability

Association of Type 2 Diabetes, According to the Number of Risk Factors Within Target Range, With Structural Brain Abnormalities, Cognitive Performance, and Risk of Dementia

OBJECTIVE: Type 2 diabetes is associated with increased risks of cognitive dysfunction and brain abnormalities. The extent to which risk factor modification can mitigate these risks is unclear. We investigated the associations between incident dementia, cognitive performance, and brain abnormalities among individuals with type 2 diabetes, according to the number of risk factors on target, compared with control subjects without diabetes. RESEARCH DESIGN AND METHODS: Prospective data were from UK Biobank of 87,856 individuals (n = 10,663 diabetes, n = 77,193 control subjects; baseline 2006-2010), with dementia follow-up until February 2018. Individuals with diabetes were categorized according to the number of seven selected risk factors within the guideline-recommended target range (nonsmoking; guideline-recommended levels of glycated hemoglobin, blood pressure, BMI, albuminuria, physical activity, and diet). Outcomes were incident dementia, domain-specific cognitive performance, white matter hyperintensities, and total brain volume. RESULTS: After a mean follow-up of 9.0 years, 147 individuals (1.4%) with diabetes and 412 control subjects (0.5%) had incident dementia. Among individuals with diabetes, excess dementia risk decreased stepwise for a higher number of risk factors on target. Compared with control subjects (incidence rate per 1,000 person-years 0.62 [95% CI 0.56; 0.68]), individuals with diabetes who had five to seven risk factors on target had no significant excess dementia risk (absolute rate difference per 1,000 person-years 0.20 [-0.11; 0.52]; hazard ratio 1.32 [0.89; 1.95]). Similarly, differences in processing speed, executive function, and brain volumes were progressively smaller for a higher number of risk factors on target. These results were replicated in the Maastricht Study. CONCLUSIONS: Among individuals with diabetes, excess dementia risk, lower cognitive performance, and brain abnormalities decreased stepwise for a higher number of risk factors on target