Change in lipids before onset of dementia, coronary heart disease, and mortality: A 28-year follow-up Whitehall II prospective cohort study.
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ABSTRACT: 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.
SUBMITTER: Hassen CB
PROVIDER: S-EPMC10679471 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
Publications
Change in lipids before onset of dementia, coronary heart disease, and mortality: A 28-year follow-up Whitehall II prospective cohort study.
Hassen Céline Ben CB Machado-Fragua Marcos D MD Landré Benjamin B Fayosse Aurore A Dumurgier Julien J Kivimaki Mika M Sabia Séverine S Singh-Manoux Archana A
Alzheimer's & dementia : the journal of the Alzheimer's Association 20230527 12
<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>No associations were observed in men; ...[more]
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Project description:IntroductionWe 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.MethodsA 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.ResultsObesity (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.DiscussionObesity in midlife and weight loss in the preclinical phase characterizes dementia; the current obesity epidemic may affect future dementia rates.
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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.
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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.
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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: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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Project description:IntroductionAlthough the multimorbidity-dementia association has been widely addressed, little is known on the long-term trajectory of multimorbidity (TOM) in preclinical dementia.MethodsBased on the Health and Retirement Study, burden of multimorbidity was quantified with the total number of eight long-term conditions (LTC). Patterns of TOM before dementia diagnosis were investigated with mixed-effects models.ResultsIn 1752 dementia cases and 5256 matched controls, cases showed higher and faster increasing predicted number of LTC than controls, with a significant case-control difference from 20 years prior to dementia diagnosis. Larger increases in number of LTC during preclinical phase of dementia were found in White participants, females, those whose age at dementia onset was younger, and those who were less educated.DiscussionOur findings emphasize the faster accumulation of multimorbidity in prodromal dementia than in natural aging, as well as effect modifications by age and sex.HighlightsTOM increased faster in prodromal dementia than in natural ageing.Patterns of TOM by dementia status diverged at 20 years before dementia diagnosis.Patterns of TOM were modified by age and sex.
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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:ContextObesity is associated with low-grade inflammation, but the long-term effects of weight change on inflammation are unknown.ObjectiveThe aim was to examine the association of change in weight, body mass index (BMI), and waist circumference with change in C-reactive protein (CRP) and IL-6 and to assess whether this association is modified by baseline obesity status.Design and settingThe design was a prospective cohort study among civil servants (the Whitehall II Study, UK). We used data from two clinical screenings carried out in 1991-1993 and 2002-2004 (mean follow-up, 11.3 yr).ParticipantsWe studied 2496 men and 1026 women [mean age, 49.4 (sd=6.0) yr at baseline] with measurements on inflammatory markers and anthropometry at both baseline and follow-up.Main outcome measuresWe measured change in serum CRP and IL-6 during follow-up.ResultsThe mean increases in CRP and IL-6 were 0.08 [95% confidence interval (CI), 0.07-0.09] mg/liter and 0.04 (95% CI, 0.03-0.05) pg/ml per 1-kg increase in body weight during follow-up. Study members with a BMI less than 25 kg/m2 at baseline had an average increase in CRP of 0.06 (95% CI, 0.05-0.08) mg/liter per 1-kg increase in body weight, whereas the increase in those who were overweight (25≤BMI<30 kg/m2) and obese (BMI≥30 kg/m2) was greater: 0.08 (95% CI, 0.06-0.09) mg/liter and 0.11 (95% CI, 0.07-0.14) mg/liter, respectively (P value for interaction=0.002). Similar patterns were observed for changes in BMI and waist circumference.ConclusionsThose who were overweight or obese at baseline had a greater absolute increase in CRP per unit increase in weight, BMI, and waist circumference than people who were normal weight.
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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.
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