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Midlife stroke risk and cognitive decline: a 10-year follow-up of the Whitehall II cohort study.

ABSTRACT: 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.

SUBMITTER: Kaffashian S

PROVIDER: S-EPMC3918666 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Midlife stroke risk and cognitive decline: a 10-year follow-up of the Whitehall II cohort study.

Kaffashian Sara S Dugravot Aline A Brunner Eric J EJ Sabia Séverine S Ankri Joël J Kivimäki Mika M Singh-Manoux Archana A

Alzheimer's & dementia : the journal of the Alzheimer's Association 20121128 5

<h4>Background</h4>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.<h4>Methods</h4>We studied 4153 men and 1657 women (mean age, 55.6 years at baseline) from the Whitehall II study, a longitudinal British coho ...[more]

PMID: 23199495

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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.

Project description:ObjectivesTo examine multiple objective and self-reported measures of motor function for their associations with mortality.DesignProspective cohort study.SettingUK 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.Participants6194 participants with motor function measures in 2007-09 (mean age 65.6, SD 5.9), 2012-13, and 2015-16.Main outcome measuresAll 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.ResultsOne 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.ConclusionMotor 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.

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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.

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Midlife stroke risk and cognitive decline: a 10-year follow-up of the Whitehall II cohort study.

Publications

Midlife stroke risk and cognitive decline: a 10-year follow-up of the Whitehall II cohort study.

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