Sleep dysregulation is a feature of dementia but it remains unclear whether sleep duration prior to old age is associated with dementia incidence. Using data from 7959 participants of the Whitehall ...II study, we examined the association between sleep duration and incidence of dementia (521 diagnosed cases) using a 25-year follow-up. Here we report higher dementia risk associated with a sleep duration of six hours or less at age 50 and 60, compared with a normal (7 h) sleep duration, although this was imprecisely estimated for sleep duration at age 70 (hazard ratios (HR) 1.22 (95% confidence interval 1.01-1.48), 1.37 (1.10-1.72), and 1.24 (0.98-1.57), respectively). Persistent short sleep duration at age 50, 60, and 70 compared to persistent normal sleep duration was also associated with a 30% increased dementia risk independently of sociodemographic, behavioural, cardiometabolic, and mental health factors. These findings suggest that short sleep duration in midlife is associated with an increased risk of late-onset dementia.
We examined whether obesity at ages 50, 60, and 70 years is associated with subsequent dementia. Changes in body mass index (BMI) for more than 28 years before dementia diagnosis were compared with ...changes in BMI in those free of dementia.
A total of 10,308 adults (33% women) aged 35 to 55 years in 1985 were followed up until 2015. BMI was assessed six times and 329 cases of dementia were recorded.
Obesity (BMI ≥30 kg/m2) at age 50 years (hazard ratio = 1.93; 1.35–2.75) but not at 60 or 70 years was associated with risk of dementia. Trajectories of BMI differed in those with dementia compared with all others (P < .0001) or to matched control subjects (P < .0001) such that BMI in dementia cases was higher from 28 years (P = .001) to 16 years (P = .05) and lower starting 8 years before diagnosis.
Obesity in midlife and weight loss in the preclinical phase characterizes dementia; the current obesity epidemic may affect future dementia rates.
To assess whether AF is a risk factor for cognitive dysfunction we used prospective data on AF, repeat cognitive scores, and dementia incidence in adults followed over 45 to 85 years.
Data are drawn ...from the Whitehall II study, N = 10 308 at study recruitment in 1985. A battery of cognitive tests was administered four times (1997-2013) to 7428 participants (414 cases of AF), aged 45-69 years in 1997. Compared with AF-free participants, those with longer exposure to AF (5, 10, or 15 years) experienced faster cognitive decline after adjustment for sociodemographic, behavioural, and chronic diseases (P for trend = 0.01). Incident stroke or coronary heart disease individually did not explain the excess cognitive decline; however, this relationship was impacted when considering them together (P for trend 0.09). Analysis of incident dementia (N = 274/9302 without AF; N = 50/912 with AF) showed AF was associated with higher risk of dementia in Cox regression adjusted for sociodemographic factors, health behaviours and chronic diseases hazard ratio (HR): 1.87; 95% confidence interval (CI): 1.37, 2.55. Multistate models showed AF to increase risk of dementia in those free of stroke (HR: 1.67; 95% CI: 1.17, 2.38) but not those free of stroke and coronary heart disease (HR: 1.29; 95% CI: 0.74, 2.24) over the follow-up.
In adults aged 45-85 years AF is associated with accelerated cognitive decline and higher risk of dementia even at ages when AF incidence is low. At least in part, this was explained by incident cardiovascular disease in patients with AF.
Multimorbidity is increasingly common and is associated with adverse health outcomes, highlighting the need to broaden the single-disease framework that dominates medical research. We examined the ...role of midlife clinical characteristics, socioeconomic position, and behavioural factors in the development of cardiometabolic multimorbidity (at least 2 of diabetes, coronary heart disease, and stroke), along with how these factors modify risk of mortality.
Data on 8,270 men and women were drawn from the Whitehall II cohort study, with mean follow-up of 23.7 years (1985 to 2017). Three sets of risk factors were assessed at age 50 years, each on a 5-point scale: clinical profile (hypertension, hypercholesterolemia, overweight/obesity, family history of cardiometabolic disease), occupational position, and behavioural factors (smoking, alcohol consumption, diet, physical activity). The outcomes examined were cardiometabolic disease (diabetes, coronary heart disease, stroke), cardiometabolic multimorbidity, and mortality. We used multi-state models to examine the role of risk factors in 5 components of the cardiometabolic disease trajectory: from healthy state to first cardiometabolic disease, from first cardiometabolic disease to cardiometabolic multimorbidity, from healthy state to death, from first cardiometabolic disease to death, and from cardiometabolic multimorbidity to death. A total of 2,501 participants developed 1 of the 3 cardiometabolic diseases, 511 developed cardiometabolic multimorbidity, and 1,406 died. When behavioural and clinical risk factors were considered individually, only smoking was associated with all five transitions. In a model containing all 3 risk factor scales, midlife clinical profile was the strongest predictor of first cardiometabolic disease (hazard ratio for the least versus most favourable profile: 3.74; 95% CI: 3.14-4.45) among disease-free participants. Among participants with 1 cardiometabolic disease, adverse midlife socioeconomic (1.54; 95% CI: 1.10-2.15) and behavioural factors (2.00; 95% CI: 1.40-2.85), but not clinical characteristics, were associated with progression to cardiometabolic multimorbidity. Only midlife behavioural factors predicted mortality among participants with cardiometabolic disease (2.12; 95% CI: 1.41-3.18) or cardiometabolic multimorbidity (3.47; 95% CI: 1.81-6.66). A limitation is that the study was not large enough to estimate transitions between each disease and subsequent outcomes and between all possible pairs of diseases.
The importance of specific midlife factors in disease progression, from disease-free state to single disease, multimorbidity, and death, varies depending on the disease stage. While clinical risk factors at age 50 determine the risk of incident cardiometabolic disease in a disease-free population, midlife socioeconomic and behavioural factors are stronger predictors of progression to multimorbidity and mortality in people with cardiometabolic disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sleep duration has been shown to be associated with individual chronic diseases but its association with multimorbidity, common in older adults, remains poorly understood. We examined whether sleep ...duration is associated with incidence of a first chronic disease, subsequent multimorbidity and mortality using data spanning 25 years.
Data were drawn from the prospective Whitehall II cohort study, established in 1985 on 10,308 persons employed in the London offices of the British civil service. Self-reported sleep duration was measured 6 times between 1985 and 2016, and data on sleep duration was extracted at age 50 (mean age (standard deviation) = 50.6 (2.6)), 60 (60.3 (2.2)), and 70 (69.2 (1.9)). Incidence of multimorbidity was defined as having 2 or more of 13 chronic diseases, follow-up up to March 2019. Cox regression, separate analyses at each age, was used to examine associations of sleep duration at age 50, 60, and 70 with incident multimorbidity. Multistate models were used to examine the association of sleep duration at age 50 with onset of a first chronic disease, progression to incident multimorbidity, and death. Analyses were adjusted for sociodemographic, behavioral, and health-related factors. A total of 7,864 (32.5% women) participants free of multimorbidity had data on sleep duration at age 50; 544 (6.9%) reported sleeping ≤5 hours, 2,562 (32.6%) 6 hours, 3,589 (45.6%) 7 hours, 1,092 (13.9%) 8 hours, and 77 (1.0%) ≥9 hours. Compared to 7-hour sleep, sleep duration ≤5 hours was associated with higher multimorbidity risk (hazard ratio: 1.30, 95% confidence interval = 1.12 to 1.50; p < 0.001). This was also the case for short sleep duration at age 60 (1.32, 1.13 to 1.55; p < 0.001) and 70 (1.40, 1.16 to 1.68; p < 0.001). Sleep duration ≥9 hours at age 60 (1.54, 1.15 to 2.06; p = 0.003) and 70 (1.51, 1.10 to 2.08; p = 0.01) but not 50 (1.39, 0.98 to 1.96; p = 0.07) was associated with incident multimorbidity. Among 7,217 participants free of chronic disease at age 50 (mean follow-up = 25.2 years), 4,446 developed a first chronic disease, 2,297 progressed to multimorbidity, and 787 subsequently died. Compared to 7-hour sleep, sleeping ≤5 hours at age 50 was associated with an increased risk of a first chronic disease (1.20, 1.06 to 1.35; p = 0.003) and, among those who developed a first disease, with subsequent multimorbidity (1.21, 1.03 to 1.42; p = 0.02). Sleep duration ≥9 hours was not associated with these transitions. No association was found between sleep duration and mortality among those with existing chronic diseases. The study limitations include the small number of cases in the long sleep category, not allowing conclusions to be drawn for this category, the self-reported nature of sleep data, the potential for reverse causality that could arise from undiagnosed conditions at sleep measures, and the small proportion of non-white participants, limiting generalization of findings.
In this study, we observed short sleep duration to be associated with risk of chronic disease and subsequent multimorbidity but not with progression to death. There was no robust evidence of an increased risk of chronic disease among those with long sleep duration at age 50. Our findings suggest an association between short sleep duration and multimorbidity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AbstractObjectiveTo test the hypotheses that physical activity in midlife is not associated with a reduced risk of dementia and that the preclinical phase of dementia is characterised by a decline in ...physical activity.DesignProspective cohort study with a mean follow-up of 27 years.SettingCivil service departments in London (Whitehall II study).Participants10 308 participants aged 35-55 years at study inception (1985-88). Exposures included time spent in mild, moderate to vigorous, and total physical activity assessed seven times between 1985 and 2013 and categorised as “recommended” if duration of moderate to vigorous physical activity was 2.5 hours/week or more.Main outcome measuresA battery of cognitive tests was administered up to four times from 1997 to 2013, and incident dementia cases (n=329) were identified through linkage to hospital, mental health services, and mortality registers until 2015.ResultsMixed effects models showed no association between physical activity and subsequent 15 year cognitive decline. Similarly, Cox regression showed no association between physical activity and risk of dementia over an average 27 year follow-up (hazard ratio in the “recommended” physical activity category 1.00, 95% confidence interval 0.80 to 1.24). For trajectories of hours/week of total, mild, and moderate to vigorous physical activity in people with dementia compared with those without dementia (all others), no differences were observed between 28 and 10 years before diagnosis of dementia. However, physical activity in people with dementia began to decline up to nine years before diagnosis (difference in moderate to vigorous physical activity −0.39 hours/week; P=0.05), and the difference became more pronounced (−1.03 hours/week; P=0.005) at diagnosis.ConclusionThis study found no evidence of a neuroprotective effect of physical activity. Previous findings showing a lower risk of dementia in physically active people may be attributable to reverse causation—that is, due to a decline in physical activity levels in the preclinical phase of dementia.
IMPORTANCE: Trends in type 2 diabetes show an increase in prevalence along with younger age of onset. While vascular complications of early-onset type 2 diabetes are known, the associations with ...dementia remains unclear. OBJECTIVE: To determine whether younger age at diabetes onset is more strongly associated with incidence of dementia. DESIGN, SETTING, AND PARTICIPANTS: Population-based study in the UK, the Whitehall II prospective cohort study, established in 1985-1988, with clinical examinations in 1991-1993, 1997-1999, 2002-2004, 2007-2009, 2012-2013, and 2015-2016, and linkage to electronic health records until March 2019. The date of final follow-up was March 31, 2019. EXPOSURES: Type 2 diabetes, defined as a fasting blood glucose level greater than or equal to 126 mg/dL at clinical examination, physician-diagnosed type 2 diabetes, use of diabetes medication, or hospital record of diabetes between 1985 and 2019. MAIN OUTCOMES AND MEASURES: Incident dementia ascertained through linkage to electronic health records. RESULTS: Among 10 095 participants (67.3% men; aged 35-55 years in 1985-1988), a total of 1710 cases of diabetes and 639 cases of dementia were recorded over a median follow-up of 31.7 years. Dementia rates per 1000 person-years were 8.9 in participants without diabetes at age 70 years, and rates were 10.0 per 1000 person-years for participants with diabetes onset up to 5 years earlier, 13.0 for 6 to 10 years earlier, and 18.3 for more than 10 years earlier. In multivariable-adjusted analyses, compared with participants without diabetes at age 70, the hazard ratio (HR) of dementia in participants with diabetes onset more than 10 years earlier was 2.12 (95% CI, 1.50-3.00), 1.49 (95% CI, 0.95-2.32) for diabetes onset 6 to 10 years earlier, and 1.11 (95% CI, 0.70-1.76) for diabetes onset 5 years earlier or less; linear trend test (P < .001) indicated a graded association between age at onset of type 2 diabetes and dementia. At age 70, every 5-year younger age at onset of type 2 diabetes was significantly associated with an HR of dementia of 1.24 (95% CI, 1.06-1.46) in analyses adjusted for sociodemographic factors, health behaviors, and health-related measures. CONCLUSIONS AND RELEVANCE: In this longitudinal cohort study with a median follow-up of 31.7 years, younger age at onset of diabetes was significantly associated with higher risk of subsequent dementia.
AbstractObjectiveTo examine the association between alcohol consumption and risk of dementia.DesignProspective cohort study.SettingCivil service departments in London (Whitehall II ...study).Participants9087 participants aged 35-55 years at study inception (1985/88).Main outcome measuresIncident dementia, identified through linkage to hospital, mental health services, and mortality registers until 2017. Measures of alcohol consumption were the mean from three assessments between 1985/88 and 1991/93 (midlife), categorised as abstinence, 1-14 units/week, and >14 units/week; 17 year trajectories of alcohol consumption based on five assessments of alcohol consumption between 1985/88 and 2002/04; CAGE questionnaire for alcohol dependence assessed in 1991/93; and hospital admission for alcohol related chronic diseases between 1991 and 2017.Results397 cases of dementia were recorded over a mean follow-up of 23 years. Abstinence in midlife was associated with a higher risk of dementia (hazard ratio 1.47, 95% confidence interval 1.15 to 1.89) compared with consumption of 1-14 units/week. Among those drinking >14 units/week, a 7 unit increase in alcohol consumption was associated with a 17% (95% confidence interval 4% to 32%) increase in risk of dementia. CAGE score >2 (hazard ratio 2.19, 1.29 to 3.71) and alcohol related hospital admission (4.28, 2.72 to 6.73) were also associated with an increased risk of dementia. Alcohol consumption trajectories from midlife to early old age showed long term abstinence (1.74, 1.31 to 2.30), decrease in consumption (1.55, 1.08 to 2.22), and long term consumption >14 units/week (1.40, 1.02 to 1.93) to be associated with a higher risk of dementia compared with long term consumption of 1-14 units/week. Analysis using multistate models suggested that the excess risk of dementia associated with abstinence in midlife was partly explained by cardiometabolic disease over the follow-up as the hazard ratio of dementia in abstainers without cardiometabolic disease was 1.33 (0.88 to 2.02) compared with 1.47 (1.15 to 1.89) in the entire population.ConclusionThe risk of dementia was increased in people who abstained from alcohol in midlife or consumed >14 units/week. In several countries, guidelines define thresholds for harmful alcohol consumption much higher than 14 units/week. The present findings encourage the downward revision of such guidelines to promote cognitive health at older ages.
AbstractObjectiveTo examine the association of midlife and late life multimorbidity, including severity of multimorbidity, with incident dementia.DesignProspective cohort study.SettingCivil service ...departments in London (Whitehall II study, study inception in 1985-88).Participants10 095 participants, aged 35 to 55 at baseline.Main outcome measureIncident 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.ResultsThe 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).ConclusionMultimorbidity, 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.
Social inequalities in mortality persist in high-income countries with universal health care, and the mechanisms by which these inequalities are generated remain unclear. We aimed to examine whether ...social inequalities were present before or after the onset of adverse health conditions (multimorbidity, frailty, and disability).
Our analysis was based on data from the ongoing Whitehall II cohort study, which enrolled British civil servants aged 35–55 years in 1985–88. Participants were assessed for three indicators of socioeconomic status (education, occupational position, and literacy) at age 50 years. Participants underwent clinical examinations (in 2002–04, 2007–09, 2012–13, and 2015–16) for assessment of frailty (two or more of low physical activity, slow walking speed, poor grip strength, weight loss, and exhaustion) and disability (two or more difficulties in bathing, dressing, going to the toilet, transferring, feeding, and walking). In addition, electronic health records were used to assess the incidence of multimorbidity (two or more of diabetes, coronary heart disease, stroke, chronic obstructive pulmonary disease, depression, arthritis, cancer, dementia, and Parkinson's disease) and mortality. In analyses adjusted for sociodemographic factors, we used multistate models to examine social inequalities in transitions from healthy state to adverse health conditions and subsequently to mortality.
Of 10 308 individuals in the Whitehall II study cohort, 6425 had relevant data available at 50 years and to the end of follow-up on Aug 31, 2017, and were included in our analysis. Participants were followed up for a median of 23·6 years (IQR 19·6–28·9). 1694 (26·4%) of 6425 participants developed multimorbidity, 1733 (27·0%) became frail, 692 (10·8%) had a disability, and 611 (9·5%) died. Multimorbidity (hazard ratio HR 4·12 95% CI 3·41–4·98), frailty (HR 2·38 95% CI 1·93–2·93), and disability (HR 1·73 95% CI 1·34–2·22) were associated with increased risk of mortality; these associations were not modified by socioeconomic status. In multistate models, occupation was the socioeconomic status indicator that was most strongly associated with inequalities in the transition from healthy state to multimorbidity (HR 1·54 95% CI 1·37–1·73), to frailty (HR 2·08 95% CI 1·85–2·33), and to disability (HR 1·44 95% CI 1·18–1·74). Socioeconomic status indicators did not affect transitions to mortality in those with multimorbidity, frailty, or disability.
Socioeconomic status affects the risk of multimorbidity, frailty, and disability, but does not affect the risk of mortality after the onset of these adverse health conditions. Therefore, primary prevention is key to reducing social inequalities in mortality. Of the three adverse health conditions, multimorbidity had the strongest association with mortality, making it a central target for improving population health.
UK Medical Research Council; National Institute on Aging, National Institutes of Health; British Heart Foundation.
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