Obesity trajectories and risk of dementia: 28 years of follow-up in the Whitehall II Study.
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ABSTRACT:
SUBMITTER: Singh-Manoux A
PROVIDER: S-EPMC5805839 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
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Obesity trajectories and risk of dementia: 28 years of follow-up in the Whitehall II Study.
Singh-Manoux Archana A Dugravot Aline A Shipley Martin M Brunner Eric J EJ Elbaz Alexis A Sabia Séverine S Kivimaki Mika M
Alzheimer's & dementia : the journal of the Alzheimer's Association 20170921 2
<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Obesity (BMI ≥30 kg/m<sup>2</sup>) at age 50 ye ...[more]
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Project description:Objective To 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.Design Prospective cohort study with a mean follow-up of 27 years.Setting Civil service departments in London (Whitehall II study).Participants 10?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 measures A 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.Results Mixed 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.Conclusion This 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.
| S-EPMC5480222 | biostudies-literature
Project description:BackgroundThere is need to identify targets for preventing or delaying dementia. Social contact is a potential target for clinical and public health studies, but previous observational studies had short follow-up, making findings susceptible to reverse causation bias. We therefore examined the association of social contact with subsequent incident dementia and cognition with 28 years' follow-up.Methods and findingsWe conducted a retrospective analysis of the Whitehall II longitudinal prospective cohort study of employees of London civil service departments, aged 35-55 at baseline assessment in 1985-1988 and followed to 2017. Social contact was measured six times through a self-report questionnaire about frequency of contact with non-cohabiting relatives and friends. Dementia status was ascertained from three linked clinical and mortality databases, and cognition was assessed five times using tests of verbal memory, verbal fluency, and reasoning. Cox regression models with inverse probability weighting to account for attrition and missingness examined the association between social contact at age 50, 60, and 70 years and subsequent incident dementia. Mixed linear models examined the association of midlife social contact between 45 and 55 years and cognitive trajectory during the subsequent 14 years. Analyses were adjusted for age, sex, ethnicity, socioeconomic status, education, health behaviours, employment status, and marital status. Of 10,308 Whitehall II study participants, 10,228 provided social contact data (mean age 44.9 years [standard deviation (SD) 6.1 years] at baseline; 33.1% female; 89.1% white ethnicity). More frequent social contact at age 60 years was associated with lower dementia risk (hazard ratio [HR] for each SD higher social contact frequency = 0.88 [95% CI 0.79, 0.98], p = 0.02); effect size of the association of social contact at 50 or 70 years with dementia was similar (0.92 [95% CI 0.83, 1.02], p = 0.13 and 0.91 [95% CI 0.78, 1.06], p = 0.23, respectively) but not statistically significant. The association between social contact and incident dementia was driven by contact with friends (HR = 0.90 [95% CI 0.81, 1.00], p = 0.05), but no association was found for contact with relatives. More frequent social contact during midlife was associated with better subsequent cognitive trajectory: global cognitive function was 0.07 (95% CI 0.03, 0.11), p = 0.002 SDs higher for those with the highest versus lowest tertile of social contact frequency, and this difference was maintained over 14 years follow-up. Results were consistent in a series of post hoc analyses, designed to assess potential biases. A limitation of our study is ascertainment of dementia status from electronic health records rather than in-person assessment of diagnostic status, with the possibility that milder dementia cases were more likely to be missed.ConclusionsFindings from this study suggest a protective effect of social contact against dementia and that more frequent contact confers higher cognitive reserve, although it is possible that the ability to maintain more social contact may be a marker of cognitive reserve. Future intervention studies should seek to examine whether improving social contact frequency is feasible, acceptable, and efficacious in changing cognitive outcomes.
| S-EPMC6677303 | biostudies-literature
Project description:ObjectiveTo 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.
| S-EPMC6066998 | biostudies-literature
Project description:ImportanceNeuropsychiatric symptoms, depressive symptoms in particular, are common in patients with dementia but whether depressive symptoms in adulthood increases the risk for dementia remains the subject of debate.ObjectiveTo characterize the trajectory of depressive symptoms over 28 years prior to dementia diagnosis to determine whether depressive symptoms carry risk for dementia.Design, setting, and participantsUp to 10 308 persons, aged 35 to 55 years, were recruited to the Whitehall II cohort study in 1985, with the end of follow-up in 2015. Data analysis for this study in a UK general community was conducted from October to December 2016.ExposuresDepressive symptoms assessed on 9 occasions between 1985 and 2012 using the General Health Questionnaire.Main outcomes and measuresIncidence of dementia (n = 322) between 1985 and 2015.ResultsOf the 10 189 persons included in the study, 6838 were men (67%) and 3351 were women (33%). Those reporting depressive symptoms in 1985 (mean follow-up, 27 years) did not have significantly increased risk for dementia (hazard ratio [HR], 1.21; 95% CI, 0.95-1.54) in Cox regression adjusted for sociodemographic covariates, health behaviors, and chronic conditions. However, those with depressive symptoms in 2003 (mean follow-up, 11 years) had an increased risk (HR, 1.72; 95% CI, 1.21-2.44). Those with chronic/recurring depressive symptoms (≥2 of 3 occasions) in the early study phase (mean follow-up, 22 years) did not have excess risk (HR, 1.02; 95% CI, 0.72-1.44) but those with chronic/recurring symptoms in the late phase (mean follow-up, 11 years) did have higher risk for dementia (HR, 1.67; 95% CI, 1.11-2.49). Analysis of retrospective depressive trajectories over 28 years, using mixed models and a backward time scale, shows that in those with dementia, differences in depressive symptoms compared with those without dementia became apparent 11 years (difference, 0.61; 95% CI, 0.09-1.13; P = .02) before dementia diagnosis and became more than 9 times larger at the year of diagnosis (difference, 5.81; 95% CI, 4.81-6.81; P < .001).Conclusions and relevanceDepressive symptoms in the early phase of the study corresponding to midlife, even when chronic/recurring, do not increase the risk for dementia. Along with our analysis of depressive trajectories over 28 years, these results suggest that depressive symptoms are a prodromal feature of dementia or that the 2 share common causes. The findings do not support the hypothesis that depressive symptoms increase the risk for dementia.
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Project description:BackgroundCognitive 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.ObjectiveTo examine the association of kidney function with incident dementia in community dwelling older adults.DesignWhitehall II prospective study.SettingPopulation-based study on 6,050 adults, mean age 65.8 in 2007-2009.MethodsPoor 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.ResultsA 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).ConclusionPoor 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.
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Project description:BackgroundApproximately 25% of the general population carries at least one ε4 allele of the Apolipoprotein E (APOE ε4), the strongest genetic risk factor for late onset Alzheimer's disease. Beyond its association with late-onset dementia, the association between APOE ε4 and change in cognition over the adult life course remains uncertain. This study aims to examine whether the association between Apolipoprotein E (APOE) ε4 zygosity and cognition function is modified between midlife and old age.MethodsA cohort study of 5561 participants (mean age 55.5 (SD = 5.9) years, 27.1% women) with APOE genotyping and repeated cognitive tests for reasoning, memory, and semantic and phonemic fluency, during a mean (SD) follow-up of 20.2 (2.8) years (the Whitehall II study). We used joint models to examine the association of APOE genotype with cognitive function trajectories between 45 and 85 years taking drop-out, dementia, and death into account and Fine and Gray models to examine associations with dementia.ResultsCompared to non-carriers, heterozygote (prevalence 25%) and homozygote (prevalence 2%) APOE ε4 carriers had increased risk of dementia, sub-distribution hazard ratios 2.19 (95% CI 1.73, 2.77) and 5.97 (95% CI 3.85, 9.28) respectively. Using data spanning 45-85 years with non-ε4 carriers as the reference, ε4 homozygotes had poorer global cognitive score starting from 65 years; ε4 heterozygotes had better scores between 45 and 55 years, then no difference until poorer cognitive scores from 75 years onwards. In analysis of individual cognitive tests, better cognitive performance in the younger ε4 heterozygotes was primarily attributable to executive function.ConclusionsBoth heterozygous and homozygous ε4 carriers had poorer cognition and greater risk of dementia at older ages. Our findings show some support for a complex antagonist pleiotropic effect of APOE ε4 heterozygosity over the adult life course, characterized by cognitive advantage in midlife.
| S-EPMC7784268 | biostudies-literature
Project description:Alzheimer disease is the most common form of dementia in the elderly, and the complex relationships among risk factors produce highly variable natural histories from normal cognition through the prodromal stage of mild cognitive impairment (MCI) to clinical dementia. We used a novel statistical approach, mixed membership trajectory models, to capture the variety of such pathways in 652 participants in the Cardiovascular Health Study Cognition Study over 22 years of follow-up (1992-2014). We identified 3 trajectories: a "healthy" profile with a peak probability of MCI between 95 and 100 years of age and only a 50% probability of dementia by age 100; an "intermediate" profile with a peak probability of MCI between 85 and 90 years of age and progression to dementia between 90 and 95 years; and an "unhealthy" profile with a peak probability of progressing to MCI between ages 75 and 80 years and to dementia between the ages of 80 and 85 years. Hypertension, education, race, and the ϵ4 allele of the apolipoprotein E gene all affected the closeness of an individual to 1 or more of the canonical trajectories. These results provide new insights into the natural history of Alzheimer disease and evidence for a potential difference in the pathophysiology of the development of dementia.
| S-EPMC4528953 | biostudies-literature
Project description:Stroke is associated with an increased risk of dementia. However, it is unclear whether risk of stroke in those free of stroke, particularly in nonelderly populations, leads to differential rates of cognitive decline. Our aim was to assess whether risk of stroke in mid life is associated with cognitive decline over 10 years of follow-up.We studied 4153 men and 1657 women (mean age, 55.6 years at baseline) from the Whitehall II study, a longitudinal British cohort study. We used the Framingham Stroke Risk Profile (FSRP), which incorporates age, sex, systolic blood pressure, diabetes mellitus, smoking, prior cardiovascular disease, atrial fibrillation, left ventricular hypertrophy, and use of antihypertensive medication. Cognitive tests included reasoning, memory, verbal fluency, and vocabulary assessed three times over 10 years. Longitudinal associations between FSRP and its components were tested using mixed-effects models, and rates of cognitive change over 10 years were estimated.Higher stroke risk was associated with faster decline in verbal fluency, vocabulary, and global cognition. For example, for global cognition there was a greater decline in the highest FSRP quartile (-0.25 of a standard deviation; 95% confidence interval: -0.28 to -0.21) compared with the lowest risk quartile (P = .03). No association was observed for memory and reasoning. Of the individual components of FSRP, only diabetes mellitus was associated independently with faster cognitive decline (? = -0.06; 95% confidence interval, -0.01 to 0.003; P = .03).Elevated stroke risk at midlife is associated with accelerated cognitive decline over 10 years. Aggregation of risk factors may be especially important in this association.
| S-EPMC3918666 | biostudies-literature
Project description:ObjectivesTo examine the association between the Life Simple 7 cardiovascular health score at age 50 and incidence of dementia.DesignProspective cohort study.SettingCivil service departments in London (Whitehall II study; study inception 1985-88).Participants7899 participants with data on the cardiovascular health score at age 50.ExposuresThe cardiovascular health score included four behavioural (smoking, diet, physical activity, body mass index) and three biological (fasting glucose, blood cholesterol, blood pressure) metrics, coded on a three point scale (0, 1, 2). The cardiovascular health score was the sum of seven metrics (score range 0-14) and was categorised into poor (scores 0-6), intermediate (7-11), and optimal (12-14) cardiovascular health.Main outcome measureIncident dementia, identified through linkage to hospital, mental health services, and mortality registers until 2017.Results347 incident cases of dementia were recorded over a median follow-up of 24.7 years. Compared with an incidence rate of dementia of 3.2 (95% confidence interval 2.5 to 4.0) per 1000 person years among the group with poor cardiovascular health, the absolute rate differences per 1000 person years were -1.5 (95% confidence interval -2.3 to -0.7) for the group with intermediate cardiovascular health and -1.9 (-2.8 to -1.1) for the group with optimal cardiovascular health. Higher cardiovascular health score was associated with a lower risk of dementia (hazard ratio 0.89 (0.85 to 0.95) per 1 point increment in the cardiovascular health score). Similar associations with dementia were observed for the behavioural and biological subscales (hazard ratios per 1 point increment in the subscores 0.87 (0.81 to 0.93) and 0.91 (0.83 to 1.00), respectively). The association between cardiovascular health at age 50 and dementia was also seen in people who remained free of cardiovascular disease over the follow-up (hazard ratio 0.89 (0.84 to 0.95) per 1 point increment in the cardiovascular health score).ConclusionAdherence to the Life Simple 7 ideal cardiovascular health recommendations in midlife was associated with a lower risk of dementia later in life.
| S-EPMC6664261 | biostudies-literature
Project description:ObjectiveTo 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.
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