Association between changes in cardiovascular health and the risk of multimorbidity: community-based cohort studies in the UK and Finland.

Background: Better cardiovascular health is associated with lower risk of various chronic diseases, but its association with multimorbidity is poorly understood. We aimed to examine whether change in cardiovascular health is associated with multimorbidity risk. Methods: The primary analysis was conducted in the Whitehall II multiwave prospective cohort study (UK) and the validation analysis in the Finnish Public Sector cohort study (Finland). Change in cardiovascular health was assessed using the American Heart Association Life's Simple 7 (LS7) and Life's Essential 8 (LE8) at baseline and re-assessments, using objective measures in Whitehall II and self-reports and pharmacy claims in the Finnish Public Sector cohort study, respectively. Multimorbidity was defined as the presence of two or more of 12 chronic diseases during follow-up. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox's proportional hazard models with age as time scale, adjusting for sex, education, occupation, marital status, and ethnicity. Findings: In the primary analysis among 9715 participants, mean age was 44.8 (standard deviation 6.0) years and 67.6% participants were men at baseline. During the median follow-up of 31.4 (interquartile range 26.8-32.3) years, 2751 participants developed multimorbidity. The hazard of multimorbidity decreased by 8% (HR 0.92, 95% CI 0.88-0.96) per ideal LS7 metric increment over 5 years and by 14% (HR 0.86, 95% CI 0.80-0.93) per ten points increase in LE8 score over 10 years. These findings were replicated in the validation analysis among 75,377 participants in terms of 4-year change in cardiovascular health. Interpretation: Improvement in cardiovascular health was associated with lower multimorbidity risk in two community-based cohort studies. Interventions improving cardiovascular health of the community may contribute to multimorbidity prevention. Funding: None.

Cross-sectional and longitudinal associations of obesity with disability between age 50 and 90 in the SHARE study.

BACKGROUND: Obesity is associated with disability but whether age and ageing modify this association remains unclear. We examined whether this association changes between 50 and 90 years, and whether change in disability rates over 14 years differs by body mass index (BMI) categories. METHODS: BMI and ADL-disability data on 28,453 individuals from 6 waves (2004-2018, SHARE study) were used to examine the cross-sectional absolute and relative associations, extracted at age 50, 60, 70, 80, and 90 years using logistic mixed models. Then baseline BMI and change in disability rates over 14-years were examined using logistic-mixed models. RESULTS: At age 50, the probabilities of ADL disability in individuals with BMI 30-34.9 and ≥35 kg/m² were 0.07 (0.06, 0.09) and 0.11 (0.09, 0.12), increasing to 0.47 (0.44, 0.50) and 0.55 (0.50, 0.60) at age 90; the increase in both these groups was greater than that in the normal-weight group (p for increase with age<0.001). On the relative scale the OR at age 50 in these obesity groups was 2.37 (1.79, 3.13) and 5.03 (3.38, 7.48), decreasing to 1.51 (1.20, 1.89) and 2.19 (1.50, 3.21) at age 90; p for decrease with age=0.05 and 0.02 respectively. The 14-year increase in probability of disability was greatest in those with BMI≥35 kg/m² at age 50, 60, and 70 at baseline: differences in increase compared to normal weight were 0.08 (0.02, 0.14), 0.11 (0.07, 0.15), and 0.09 (0.02, 0.16) respectively. CONCLUSIONS: ADL disability is increasingly prevalent with age in individuals with obesity. Relative measures of change obscure the association between obesity and disability due to age-related increase in disability rates in all groups.

Age at cardiovascular disease onset, dementia risk, and the role of lifestyle factors.

INTRODUCTION: We first examined the role of age at cardiovascular disease (CVD) onset for incident dementia, and then examined whether lifestyle factors at guideline-recommended levels in individuals with CVD mitigates dementia risk. METHODS: We used population-based data (Whitehall II: n = 10,308/baseline 1985-1988/examinations every 4-5 years). Lifestyle factors (non-smoking, body mass index [BMI], physical activity, diet) were extracted post-CVD. RESULTS: Over a median of 31.6 years, 3275 (32.1%) developed CVD. At age 70, risk of dementia was higher in individuals with CVD onset before (hazard ratio [HR] of incident dementia for participants with CVD before age 60, using participants without CVD at age 70 as the reference: 1.56, 95% confidence interal [CI] 1.18-2.08) but not after 60 years. In participants with CVD, a greater number of lifestyle factors at recommended levels post-CVD was associated with a lower dementia risk (per lifestyle factor at recommended level HR: 0.73, 95% CI 0.59-0.92). DISCUSSION: Our results suggest that early onset CVD is associated with a higher dementia risk at older ages. In those with CVD, the dementia risk was lower if lifestyle factors are at recommended levels following CVD diagnosis. HIGHLIGHTS: CVD in midlife but not in late life is associated with a higher risk of dementia. Dementia risk in CVD patients is lower if their lifestyle factors are at recommended levels. These findings provide evidence to promote CVD prevention in midlife or earlier. Study findings also show the importance of a healthy lifestyle in those with CVD.

Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study.

BACKGROUND: Metabolically healthy obesity is hypothesized to be a benign condition but whether this is the case for dementia remains debated. We examined the role of age at assessment of metabolic-obesity phenotypes in associations with incident dementia. METHODS: Obesity (body mass index ≥ 30 kg/m2) and poor metabolic health (≥ 2 of elevated serum triglycerides, low HDL-C, elevated blood pressure, and elevated serum fasting glucose) were used to define four metabolic-obesity phenotypes (metabolically healthy (MHNO) and unhealthy non-obesity (MUNO), metabolically healthy (MHO) and unhealthy obesity (MUO)) at < 60, 60 to < 70, and ≥ 70 years using 6 waves of data from the Whitehall II study and their associations with incident dementia was examined using Cox regression. RESULTS: Analyses with exposures measured < 60, 60 to < 70, and ≥ 70 years involved 410 (5.8%), 379 (5.6%), and 262 (7.4%) incident dementia cases over a median follow-up of 20.8, 10.3, and 4.2 years respectively. In analyses of individual components, obesity before 60 years (HR 1.41, 95% CI: [1.08, 1.85]) but not at older ages was associated with dementia; unhealthy metabolic status when present < 60 years (HR 1.33, 95% CI: [1.08, 1.62]) and 60 to < 70 years (HR 1.32, 95% CI: [1.07, 1.62]) was associated with dementia. Compared to the metabolically healthy non-obesity group, the risk of dementia was higher in those with metabolically healthy obesity before 60 years (1.69; 95% CI: [1.16, 2.45]); this was not the case when metabolic-obesity phenotype was present at 60 to < 70 years or ≥ 70 years. Analyses at older ages were on smaller numbers due to death and drop-out but inverse probability weighting to account for missing data yielded similar results. CONCLUSIONS: Individuals with metabolically healthy obesity before age 60 had a higher risk of incident dementia over a 27-year follow-up; the excess risk dissipates when metabolic health and obesity are measured after 70 years.

Is the number of ideal cardiovascular health metrics in midlife associated with lower risk of cancer? Evidence from 3 European prospective cohorts.

BACKGROUND: Primordial prevention may be a relevant strategy for the prevention of cancer. Given the commonality of risk factors and mechanisms between cancer and cardiovascular disease, we examined the associations between the number of ideal cardiovascular health metrics in midlife and incident cancer. METHODS: In 3 European cohorts (NutriNet-Santé and GAZEL, France; Whitehall II, United Kingdom), the number of ideal cardiovascular health metrics was determined at baseline (range 0-7). Follow-up for cancer events was until October 2020 (NutriNet-Santé), March 2017 (Whitehall II) and December 2015 (GAZEL). Cox regression was conducted in each cohort, and results were thereafter pooled using a random-effects model. RESULTS: Data were available on 39 718 participants. A total of 16 237 were from NutriNet-Santé (mean age 51.3 yr; 28% men), 9418 were from Whitehall II (mean age 44.8 yr; 68% men) and 14 063 were from GAZEL (mean age 45.2 yr; 75% men). The median follow-up was 8.1 years in NutriNet-Santé, 29.6 years in Whitehall II and 24.8 years in GAZEL, and yielded a total of 4889 cancer events. A greater number of ideal cardiovascular health metrics was associated with a lower overall cancer risk in each cohort, with an aggregate hazard ratio (HR) per 1 increment in number of ideal metrics of 0.91 (95% confidence interval [CI] 0.88-0.93). This association remained after removal of the smoking metric (aggregate HR per unit increment in number of ideal metrics: 0.94, 95% CI 0.90-0.97), and site-specific analysis demonstrated a significant association with lung cancer. INTERPRETATION: A greater number of ideal cardiovascular health metrics in midlife was associated with lower cancer risk, notably lung cancer. Primordial prevention of cardiovascular risk factors in midlife may be a complementary strategy to prevent the onset of cancer.

Role of age and sex in the association between BMI and functional limitations in stroke patients: Cross-sectional analysis in three European and US cohorts.

BACKGROUND: A U- or J-shaped association between BMI and different post-stroke outcomes is suggested. Thus, the aim is to evaluate the association between BMI with ADL, IADL and mobility limitations in the ageing post-stroke population at different ages, as well as the differences in this association by sex. METHODS: A total of 5,468 participants with stroke and 21,872 without stroke over 50 years of age were assessed for the number of limitations in basic or instrumental activities of daily living (ADL/IADL) as well as mobility tasks. The association between BMI at the interview (continuous time-dependent variable) and the level of limitations was assessed using a linear mixed model stratified by sex and stroke status. RESULTS: The association between BMI and ADL/IADL and mobility limitations were found to be significant in both men and women regardless of stroke status (p<0.001 for all). The association differs between those who have suffered a stroke and those who have not (p<0.001 for all). In ADL/IADL limitations, men with stroke showed a transition from an inverted J-shape to a U-shape association with age. In women, the BMI showed a less pronounced association between BMI and ADL/IADL limitations compared to men but with similar trends. A effect of sex was observed in the association between BMI and mobility, with women with and without stroke showing a linear association that differed from the inverted J-shaped or U-shaped association of men. CONCLUSION: Our results suggest that BMI is associated with limitations in ADL, IADL and mobility in stroke patients. In addition, this association differs between men and women and is also influenced by age.

Change in lipids before onset of dementia, coronary heart disease, and mortality: A 28-year follow-up Whitehall II prospective cohort study.

INTRODUCTION: The association of lipids with dementia remains a subject of debate. Using data from 7,672 participants of the Whitehall II prospective cohort study, we examined whether timing of exposure, length of follow-up, or sex modifies this association. METHODS: Twelve markers of lipid levels were measured from fasting blood and eight among them a further five times. We performed time-to-event as well as trajectory analyses. RESULTS: No associations were observed in men; in women most lipids were associated with the risk of dementia, but only for events occurring after the first 20 years of follow-up. Differences in lipid trajectories in men emerged only in the years immediately before diagnosis whereas in women total cholesterol (TC), LDL-cholesterol (LDL-C), non-HDL-cholesterol (non-HDL-C), TC/HDL-C, and LDL-C/HDL-C were higher in midlife among dementia cases before declining progressively. DISCUSSION: Abnormal lipid levels in midlife seem to be associated with a higher risk of dementia in women.

Association of physical activity, sedentary behaviour, and daylight exposure with sleep in an ageing population: findings from the Whitehall accelerometer sub-study.

BACKGROUND: Ageing is accompanied by changes in sleep, while poor sleep is suggested as a risk factor for several health outcomes. Non-pharmacological approaches have been proposed to improve sleep in elderly; their impact remains to be investigated. The aim of this study was to examine the independent day-to-day associations of physical behaviours and daylight exposure with sleep characteristics among older adults. METHODS: Data were drawn from 3942 participants (age range: 60-83 years; 27% women) from the Whitehall II accelerometer sub-study. Day-to-day associations of objectively-assessed daytime physical behaviours (sedentary behaviour, light-intensity physical activity (LIPA), moderate-to-vigorous physical activity (MVPA), mean acceleration, physical activity chronotype) and daylight exposure (proportion of waking window with light exposure > 1000 lx and light chronotype) with sleep characteristics were examined using mixed models. RESULTS: A 10%-increase in proportion of the waking period spent sedentary was associated with 5.12-minute (4.31, 5.92) later sleep onset and 1.76-minute shorter sleep duration (95%confidence interval: 0.86, 2.66). Similar increases in LIPA and MVPA were associated with 6.69 (5.67, 7.71) and 4.15 (2.49, 5.81) earlier sleep onset respectively and around 2-minute longer sleep duration (2.02 (0.87, 3.17) and 2.23 (0.36, 4.11), respectively), although the association was attenuated for MVPA after adjustment for daylight exposure (1.11 (- 0.84, 3.06)). A 3-hour later physical activity chronotype was associated with a 4.79-minute later sleep onset (4.15, 5.43) and 2.73-minute shorter sleep duration (1.99, 3.47). A 10%-increase in proportion of waking period exposed to light> 1000 lx was associated with 1.36-minute longer sleep (0.69, 2.03), independently from mean acceleration. Associations found for sleep duration were also evident for duration of the sleep windows with slightly larger effect size (for example, 3.60 (2.37, 4.82) minutes for 10%-increase in LIPA), resulting in associations with sleep efficiency in the opposite direction (for example, - 0.29% (- 0.42, - 0.16) for 10%-increase in LIPA). Overall, associations were stronger for women than for men. CONCLUSIONS: In this study, higher levels of physical activity and daylight exposure were associated with slightly longer sleep in older adults. Given the small effect sizes of the associations, increased physical activity and daylight exposure might not be enough to improve sleep.

Circulating serum metabolites as predictors of dementia: a machine learning approach in a 21-year follow-up of the Whitehall II cohort study.

BACKGROUND: Age is the strongest risk factor for dementia and there is considerable interest in identifying scalable, blood-based biomarkers in predicting dementia. We examined the role of midlife serum metabolites using a machine learning approach and determined whether the selected metabolites improved prediction accuracy beyond the effect of age. METHODS: Five thousand three hundred seventy-four participants from the Whitehall II study, mean age 55.8 (standard deviation (SD) 6.0) years in 1997-1999 when 233 metabolites were quantified using nuclear magnetic resonance metabolomics. Participants were followed for a median 21.0 (IQR 20.4, 21.7) years for clinically-diagnosed dementia (N=329). Elastic net penalized Cox regression with 100 repetitions of nested cross-validation was used to select models that improved prediction accuracy for incident dementia compared to an age-only model. Risk scores reflecting the frequency with which predictors appeared in the selected models were constructed, and their predictive accuracy was examined using Royston's R2, Akaike's information criterion, sensitivity, specificity, C-statistic and calibration. RESULTS: Sixteen of the 100 models had a better c-statistic compared to an age-only model and 15 metabolites were selected at least once in all 16 models with glucose present in all models. Five risk scores, reflecting the frequency of selection of metabolites, and a 1-SD increment in all five risk scores was associated with higher dementia risk (HR between 3.13 and 3.26). Three of these, constituted of 4, 5 and 15 metabolites, had better prediction accuracy (c-statistic from 0.788 to 0.796) compared to an age-only model (c-statistic 0.780), all p<0.05. CONCLUSIONS: Although there was robust evidence for the role of glucose in dementia, metabolites measured in midlife made only a modest contribution to dementia prediction once age was taken into account.

Pre-stroke Disability and Long-Term Functional Limitations in Stroke Survivors: Findings From More of 12 Years of Follow-Up Across Three International Surveys of Aging.

Background: Almost 50% of the post-stroke disabled population already have a premorbid disability before stroke. These patients may be offered a different care pathway in the acute and subacute phase than those without pre-morbid disability. Therefore, the aim of this study was to assess the association of the severity of premorbid disability with change of limitations in basic and instrumental activities of daily living (ADL/IADL) 1 year after stroke and over the following decade. Methods: Among 3,432 participants from HRS, SHARE and ELSA cohorts with a first stroke, ADL/IADL limitations were measured at 1-2 years prior to stroke, at 1 year post-stroke, and during the chronic phase. Modified Ranking Scale (P-mRS) was used to categorize the participants by level of premorbid disability (1-2 years pre-stroke). Change in ADL/IADL limitations by P-mRS level (0-1, 2-3, and 4-5) was assessed using a piecewise linear mixed model with a breakpoint set at 1 year post-stroke, stratified by median age groups. Results: Increase in ADL limitations at 1 year post-stroke was less pronounced in P-mRS ≥2 (p < 0.005). After years of relative stability, limitations of ADL increased for all P-mRS levels (p = 0.003). In those aged ≥75 years at stroke event, the increase was similar irrespective of P-mRS (p = 0.090). There were no significant differences in IADL trajectories between P-mRS levels (p ≥ 0.127). Conclusion: These results suggest similar trajectories of functional limitations between P-mRS levels up to 9 years post-stroke, highlighting the possible benefit of including patients with pre-morbid disability to certain treatments during the acute phase.

Association of Metabolic Syndrome With Incident Dementia: Role of Number and Age at Measurement of Components in a 28-Year Follow-up of the Whitehall II Cohort Study.

OBJECTIVE: Previous research suggests an inconsistent association between Metabolic syndrome (MetS) and incident dementia. We examined the role of number of MetS components and age at their assessment for incident dementia. RESEARCH DESIGN AND METHODS: MetS components (fasting glucose, triglycerides, waist circumference, blood pressure, and HDL cholesterol) on 7,265, 6,660, and 3,608 participants at <60, 60 to <70, and ≥70 years of age were used to examine associations with incident dementia using cause-specific Cox regression. RESULTS: Analyses of MetS measured at <60, 60 to <70, and ≥70 years involved 393 (5.4%), 497 (7.5%), and 284 (7.9%) dementia cases over a median follow-up of 20.8, 10.4, and 4.2 years, respectively. Every additional MetS component before 60 (hazard ratio [HR] 1.13 [95% CI 1.05, 1.23]) and 60 to <70 (HR 1.08 [95% CI 1.00, 1.16]) but not ≥70 years (HR 1.04 [95% CI 0.96, 1.13]) was associated with higher dementia risk. MetS defined conventionally (≥3 components) before 60 years (HR 1.23 [95% CI 0.96, 1.57]), between 60 and 70 years (HR 1.14 [95% CI 0.91, 1.42]), or >70 years of age (HR 1.10 [95% CI 0.86, 1.40]) was not associated with incident dementia. Multistate models showed higher risk of dementia in those with ≥1 (HR 1.99 [95% CI 1.08, 3.66]) and ≥2 MetS components (HR 1.69 [95% CI 1.12, 2.56]) before 60 years of age, even when they remained free of cardiovascular disease over the follow-up. CONCLUSIONS: Risk of incident dementia increases with every additional MetS component present in midlife rather than after accumulation of three components; only part of this risk is mediated by cardiovascular disease.

Individual Barriers to an Active Lifestyle at Older Ages Among Whitehall II Study Participants After 20 Years of Follow-up.

Importance: Identification of individual-level barriers associated with decreased activity in older age is essential to inform effective strategies for preventing the health outcomes associated with high sedentary behavior and lack of physical activity during aging. Objective: To assess cross-sectional and prospective associations of a large set of factors with objectively assessed sedentary time and physical activity at older age. Design, Setting, and Participants: This population-based cohort study was conducted among participants in the Whitehall II accelerometer substudy with accelerometer data assessed in 2012 to 2013. Among 4880 participants invited to the accelerometer substudy, 4006 individuals had valid accelerometer data. Among them, 3808 participants also had factors assessed in 1991 to 1993 (mean [SD] follow-up time, 20.3 [0.5] years), 3782 participants had factors assessed in 2002 to 2004 (mean [SD] follow-up time, 9.1 [0.3] years), and 3896 participants had factors assessed in 2012 to 2013 (mean follow up time, 0 years). Data were analyzed from May 2020 through July 2021. Exposures: Sociodemographic factors (ie, age, sex, race and ethnicity, occupational position, and marital status), behavioral factors (ie, smoking, alcohol intake, and fruit and vegetable intake), and health-related factors (ie, body mass index, 36-Item Short Form Health Survey (SF-36) physical and mental component summary scores [PCS and MCS], and number of chronic conditions) were assessed among 3808 individuals in 1991 to 1993; 3782 individuals in 2002 to 2004; and 3896 individuals in 2012 to 2013. High alcohol intake was defined as more than 14 units of alcohol per week, and high fruit and vegetable intake was defined as twice daily or more. Main Outcomes and Measures: Accelerometer-assessed time spent in sedentary behavior, light-intensity physical activity (LIPA), and moderate to vigorous physical activity (MVPA) in 2012 to 2013 were analyzed in 2021 using multivariate linear regressions. Results: A total of 3896 participants (986 [25.3%] women; age range, 60-83 years; mean [SD] age, 69.4 [5.7] years) had accelerometer data and exposure factors available in 2012 to 2013. Older age, not being married or cohabiting, having overweight, having obesity, more chronic conditions, and poorer SF-36 PCS, assessed in midlife or later life, were associated with increased sedentary time at the expense of time in physical activity. Mean time differences ranged from 9.8 min/d (95% CI, 4.1 to 15.6 min/d) of sedentary behavior per 10-point decrease in SF-36 PCS to 51.4 min/d (95% CI, 37.2 to65.7 min/d) of sedentary behavior for obesity vs reference range weight, from -6.2 min/d (95% CI, -8.4 to -4.1 min/d) of LIPA per 5 years of age to -28.0 min/d (95% CI, -38.6 to -17.4 min/d) of LIPA for obesity vs reference range weight, and from -5.3 min/d (95% CI, -8.2 to -2.4 min/d) of MVPA per new chronic condition to -23.4 min/d (95% CI, -29.2 to -17.6 min/d) of MVPA for obesity vs reference range weight in 20-year prospective analyses for men. There was also evidence of clustering of behavioral factors: high alcohol intake, high fruit and vegetable consumption, and no current smoking were associated with decreased sedentary time (mean time difference in cross-sectional analysis in men: -12.7 min/d [95% CI, -19.8 to -5.5 min/d]; -6.0 min/d [95% CI, -12.3 to -0.2]; and -37.4 min/d [95% CI, - 56.0 to -18.8 min/d], respectively) and more physical activity. Conclusions and Relevance: This study found a large range of individual-level barriers associated with a less active lifestyle in older age, including sociodemographic, behavioral, and health-related factors. These barriers were already evident in midlife, suggesting the importance of early implementation of targeted interventions to promote physical activity and reduce sedentary time.

Association of APOE ε4 with cerebral gray matter volumes in non-demented older adults: The MEMENTO cohort study.

Data on 2,045 non-demented individuals with memory complaints were drawn from the Memento cohort study to examine the association between Apolipoprotein E ε4 allele (APOE4) and regional brain gray matter volumes. Linear regression was used to examine the association of APOE4 and measures of regional gray matter volumes in cross-sectional analysis and change therein using longitudinal analyses based on two brain MRI performed at baseline and at two-year follow-up. Overall, in analyses adjusted for age, sex, and intracranial volume, the presence of APOE4 was associated with lower total gray matter volume at baseline and with a higher atrophy rate over the follow-up. The hippocampus and entorhinal cortex were the two gray matter regions most associated with APOE4. Further adjustment for cardiovascular risk factors had little impact on these associations. There was an interaction between age, APOE4 status and total brain volume atrophy rate, with evidence of an earlier age at onset of atrophy in hippocampal volume in APOE4 carriers compared to non-carriers. Those results are in accordance with the role of medial temporal structures in the greater risk of dementia observed in people carrying the APOE4 allele.

Association between age at onset of multimorbidity and incidence of dementia: 30 year follow-up in Whitehall II prospective cohort study.

OBJECTIVE: To examine the association of midlife and late life multimorbidity, including severity of multimorbidity, with incident dementia. DESIGN: Prospective cohort study. SETTING: Civil service departments in London (Whitehall II study, study inception in 1985-88). PARTICIPANTS: 10 095 participants, aged 35 to 55 at baseline. MAIN OUTCOME MEASURE: Incident dementia at follow-up between 1985 and 2019. Cause specific Cox proportional hazards regression was used to examine the association of multimorbidity overall and at age 55, 60, 65, and 70 with subsequent dementia, taking into account the competing risk of death. RESULTS: The prevalence of multimorbidity (≥2 chronic diseases) was 6.6% (655/9937) at age 55 and 31.7% (2464/7783) at age 70; 639 cases of incident dementia occurred over a median follow-up of 31.7 years. After adjustment for sociodemographic factors and health behaviours, multimorbidity at age 55 was associated with subsequent risk of dementia (difference in incidence rate per 1000 person years 1.56, 95% confidence interval 0.62 to 2.77; hazard ratio 2.44, 95% confidence interval 1.82 to 3.26). The association weakened progressively with older age at onset of multimorbidity. At age 65, onset of multimorbidity before age 55 was associated with 3.86 (1.80 to 6.52) per 1000 person years higher incidence of dementia (hazard ratio 2.46, 1.80 to 2.26) and onset between 60 and 65 was associated with 1.85 (0.64 to 3.39) per 1000 person years higher incidence (1.51, 1.16 to 1.97). Severity of multimorbidity (≥3 chronic diseases) at age 55 was associated with a 5.22 (1.14 to 11.95) per 1000 person years higher incidence of dementia (hazard ratio 4.96, 2.54 to 9.67); the same analyses at age 70 showed 4.49 (2.33 to 7.19) per 1000 person years higher incidence (1.65, 1.25 to 2.18). CONCLUSION: Multimorbidity, particularly when onset is in midlife rather than late life, has a robust association with subsequent dementia. The increasingly younger age at onset of multimorbidity makes prevention of multimorbidity in people with a first chronic disease important.

Association between kidney function and incidence of dementia: 10-year follow-up of the Whitehall II cohort study.

BACKGROUND: Cognitive dysfunction is common in haemodialysis patients but whether poor kidney function in the general population is also associated with higher risk of dementia remains unclear. OBJECTIVE: To examine the association of kidney function with incident dementia in community dwelling older adults. DESIGN: Whitehall II prospective study. SETTING: Population-based study on 6,050 adults, mean age 65.8 in 2007-2009. METHODS: Poor kidney function, defined as estimated Glomerular Filtration Rate (eGFR) <60 ml/min/1.73 m2 in 2007-2009, and adverse change in eGFR was defined as decrease ≥4 ml/min/1.73 m2 between 2007-2009 and 2012-2013.Incident dementia was ascertained through linkage to electronic health records, and Cox regression was used to examine associations with dementia. RESULTS: A total of 306 cases of dementia were recorded over a mean follow-up of 10 years. Baseline eGFR <60 was associated with a hazard ratio (HR) for dementia of 1.37 (95% CI 1.02, 1.85) in analysis adjusted for sociodemographic factors, hypertension, obesity, stroke, diabetes and cardiovascular disease/medication. Removing stroke cases at baseline and censoring them over the follow-up yielded an HR of 1.42 (95% CI 1.00, 2.00) for the association between CKD and dementia. Decline of eGFR ≥4 between 2007-2009 and 2012-2013 was associated with incidence of dementia over a 6.3 year mean follow-up (HR: 1.37; 95% CI 1.02, 1.85), with somewhat stronger associations when analyses were restricted to those with eGFR ≥60 in 2007-2009 (1.56; 95% CI: 1.12, 2.19). CONCLUSION: Poor and declining kidney function in older adults is associated with a higher risk of dementia that is not attributable to stroke and persists after accounting for major cardiometabolic conditions.

Objectively Measured Total Sedentary Time and Pattern of Sedentary Accumulation in Older Adults: Associations With Incident Cardiovascular Disease and All-Cause Mortality.

BACKGROUND: We examined associations of total duration and pattern of accumulation of objectively measured sedentary behavior (SB) with incident cardiovascular disease (CVD) and all-cause mortality among older adults. METHODS: Total sedentary time and 8 sedentary accumulation pattern metrics were extracted from accelerometer data of 3 991 Whitehall II study participants aged 60-83 years in 2012-2013. Incident CVD and all-cause mortality were ascertained up to March 2019. RESULTS: Two hundred and ninety-nine CVD cases and 260 deaths were recorded over a mean (standard deviation [SD]) follow-up of 6.2 (1.3) and 6.4 (0.8) years, respectively. Adjusting for sociodemographic and behavioral factors, 1-SD (100.2 minutes) increase in total sedentary time was associated with 20% higher CVD risk (hazard ratio [95% confidence interval]: 1.20 [1.05-1.37]). More fragmented SB was associated with reduced CVD risk (eg, 0.86 [0.76-0.97] for 1-SD [6.2] increase in breaks per sedentary hour). Associations were not evident once health-related factors and moderate-to-vigorous physical activity (MVPA) were considered. For all-cause mortality, associations with more fragmented SB (eg, 0.73 [0.59-0.91] for breaks per sedentary hour) were found only among the youngest older group (<74 years; p for interaction with age < .01) independently from all covariates. CONCLUSIONS: In this study, no associations of total sedentary time and sedentary accumulation patterns with incident CVD and all-cause mortality were found in the total sample once MVPA was considered. Our findings of reduced mortality risk with less total and more fragmented SB independent from MVPA among individuals <74 years need to be replicated to support the recent recommendations to reduce and fragment SB.

Long-Term Evolution of Functional Limitations in Stroke Survivors Compared With Stroke-Free Controls: Findings From 15 Years of Follow-Up Across 3 International Surveys of Aging.

BACKGROUND AND PURPOSE: In the chronic phase 2 to 5 years poststroke, limitations in activities of daily living (ADL) and instrumental ADL (IADL) initially plateau before steady increasing. However, the impact of age and differences in initial levels of disability on the evolution of these limitations remains unclear. As such, this study aims to evaluate differences in long-term evolution of ADL/IADL limitations between stroke survivors and stroke-free population, and how limitations differ by initial level of disability for stroke survivors. METHODS: Thirty-three thousand six hundred sixty participants (5610 first-ever stroke cases with no recurrence during follow-up and 28 050 stroke-free controls) aged ≥50 from the Health and Retirement Study, Survey of Health, Ageing and Retirement in Europe, and English Longitudinal Study of Ageing were assessed for number of ADL/IADL limitations during the poststroke chronic phase (for cases) and over follow-up years 1996 to 2018 (for controls). Three thousand seven hundred eighteen stroke cases were additionally categorized by disability level using the modified Rankin Scale score of 1 to 2 years poststroke. Evolution of ADL/IADL limitations was assessed in stroke cases and controls and by modified Rankin Scale score (0-1, 2-3, 4-5) using linear mixed models. Models were stratified by age group (50-74 and ≥75 years) and adjusted for baseline characteristics, health behaviors, BMI, and comorbidities. RESULTS: Findings showed relative stability of ADL/IADL limitations during 3 to 6 years poststroke followed by an increase for both populations, which was faster for younger stroke cases, suggesting a differential age-effect (P<0.001). Disability level at 1 to 2 years poststroke influenced the evolution of limitations over time, especially for severe disability (modified Rankin Scale score, 4-5) associated with a reduction in limitations at 5 to 6 years poststroke. CONCLUSIONS: Our findings showed that during the poststroke chronic phase functional limitations first plateau and then increase and the evolution differs by disability severity. These results highlight the importance of adaptive long-term health and social care measures for stroke survivors.

Terminal decline in objective and self-reported measures of motor function before death: 10 year follow-up of Whitehall II cohort study.

OBJECTIVES: To examine multiple objective and self-reported measures of motor function for their associations with mortality. DESIGN: Prospective cohort study. SETTING: UK based Whitehall II cohort study, which recruited participants aged 35-55 years in 1985-88; motor function component was added at the 2007-09 wave. PARTICIPANTS: 6194 participants with motor function measures in 2007-09 (mean age 65.6, SD 5.9), 2012-13, and 2015-16. MAIN OUTCOME MEASURES: All cause mortality between 2007 and 2019 in relation to objective measures (walking speed, grip strength, and timed chair rises) and self-reported measures (physical component summary score of the SF-36 and limitations in basic and instrumental activities of daily living (ADL)) of motor function. RESULTS: One sex specific standard deviation poorer motor function in 2007-09 (cases/total, 610/5645) was associated with an increased mortality risk of 22% (95% confidence interval 12% to 33%) for walking speed, 15% (6% to 25%) for grip strength, 14% (7% to 23%) for timed chair rises, and 17% (8% to 26%) for physical component summary score over a mean 10.6 year follow-up. Having basic/instrumental ADL limitations was associated with a 30% (7% to 58%) increased mortality risk. These associations were progressively stronger when measures were drawn from 2012-13 (mean follow-up 6.8 years) and 2015-16 (mean follow-up 3.7 years). Analysis of trajectories showed poorer motor function in decedents (n=484) than survivors (n=6194) up to 10 years before death for timed chair rises (standardised difference 0.35, 95% confidence interval 0.12 to 0.59; equivalent to a 1.2 (men) and 1.3 (women) second difference), nine years for walking speed (0.21, 0.05 to 0.36; 5.5 (men) and 5.3 (women) cm/s difference), six years for grip strength (0.10, 0.01 to 0.20; 0.9 (men) and 0.6 (women) kg difference), seven years for physical component summary score (0.15, 0.05 to 0.25; 1.2 (men) and 1.6 (women) score difference), and four years for basic/instrumental ADL limitations (prevalence difference 2%, 0% to 4%). These differences increased in the period leading to death for timed chair rises, physical component summary score, and ADL limitations. CONCLUSION: Motor function in early old age has a robust association with mortality, with evidence of terminal decline emerging early in measures of overall motor function (timed chair rises and physical component summary score) and late in basic/instrumental ADL limitations.

Association of daily composition of physical activity and sedentary behaviour with incidence of cardiovascular disease in older adults.

BACKGROUND: Moderate-to-vigorous physical activity (MVPA) is proposed as key for cardiovascular diseases (CVD) prevention. At older ages, the role of sedentary behaviour (SB) and light intensity physical activity (LIPA) remains unclear. Evidence so far is based on studies examining movement behaviours as independent entities ignoring their co-dependency. This study examines the association between daily composition of objectively-assessed movement behaviours (MVPA, LIPA, SB) and incident CVD in older adults. METHODS: Whitehall II accelerometer sub-study participants free of CVD at baseline (N = 3319, 26.7% women, mean age = 68.9 years in 2012-2013) wore a wrist-accelerometer from which times in SB, LIPA, and MVPA during waking period were extracted over 7 days. Compositional Cox regression was used to estimate the hazard ratio (HR) for incident CVD for daily compositions of movement behaviours characterized by 10 (20 or 30) minutes greater duration in one movement behaviour accompanied by decrease in another behaviour, while keeping the third behaviour constant, compared to reference composition. Analyses were adjusted for sociodemographic, lifestyle, cardiometabolic risk factors and multimorbidity index. RESULTS: Of the 3319 participants, 299 had an incident CVD over a mean (SD) follow-up of 6.2 (1.3) years. Compared to daily movement behaviour composition with MVPA at recommended 21 min per day (150 min/week), composition with additional 10 min of MVPA and 10 min less SB was associated with smaller risk reduction - 8% (HR, 0.92; 95% CI, 0.87-0.99) - than the 14% increase in risk associated with a composition of similarly reduced time in MVPA and more time in SB (HR, 1.14; 95% CI, 1.02-1.27). For a given MVPA duration, the CVD risk did not differ as a function of LIPA and SB durations. CONCLUSIONS: Among older adults, an increase in MVPA duration at the expense of time in either SB or LIPA was found associated with lower incidence of CVD. This study lends support to public health guidelines encouraging increase in MVPA or at least maintain MVPA at current duration.