Timing of onset of cognitive decline: results from Whitehall II prospective cohort study.
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ABSTRACT: Objectives
To estimate 10 year decline in cognitive function from longitudinal data in a middle aged cohort and to examine whether age cohorts can be compared with cross sectional data to infer the effect of age on cognitive decline.Design
Prospective cohort study. At study inception in 1985-8, there were 10,308 participants, representing a recruitment rate of 73%.Setting
Civil service departments in London, United Kingdom.Participants
5198 men and 2192 women, aged 45-70 at the beginning of cognitive testing in 1997-9.Main outcome measure
Tests of memory, reasoning, vocabulary, and phonemic and semantic fluency, assessed three times over 10 years.Results
All cognitive scores, except vocabulary, declined in all five age categories (age 45-49, 50-54, 55-59, 60-64, and 65-70 at baseline), with evidence of faster decline in older people. In men, the 10 year decline, shown as change/range of test × 100, in reasoning was -3.6% (95% confidence interval -4.1% to -3.0%) in those aged 45-49 at baseline and -9.6% (-10.6% to -8.6%) in those aged 65-70. In women, the corresponding decline was -3.6% (-4.6% to -2.7%) and -7.4% (-9.1% to -5.7%). Comparisons of longitudinal and cross sectional effects of age suggest that the latter overestimate decline in women because of cohort differences in education. For example, in women aged 45-49 the longitudinal analysis showed reasoning to have declined by -3.6% (-4.5% to -2.8%) but the cross sectional effects suggested a decline of -11.4% (-14.0% to -8.9%).Conclusions
Cognitive decline is already evident in middle age (age 45-49).
SUBMITTER: Singh-Manoux A
PROVIDER: S-EPMC3281313 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
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Project description:BackgroundResearch on frailty, a major contributor to heterogeneity in health, is undertaken on older adults although the processes leading to frailty are likely to begin earlier in the life course. Using repeat data spanning 25 years, we examined changes in physical and mental functioning before the onset of frailty, defined using Fried's frailty phenotype (FFP).MethodsFunctioning was measured using the Short-Form 36 General Health Survey (SF-36) on nine occasions from 1991 (age range 40-63 years) to 2015 (age range 63-85 years). The poorest of four FFP scores from 2002, 2007, 2012 and 2015 was used to classify participants as frail, pre-frail, or robust. We used linear mixed models with a backward timescale such that time 0 was the person-specific date of frailty classification for frail and pre-frail participants and the end of follow-up for robust participants. Analyses adjusted for socio-demographic factors, health behaviours, body mass index and multi-morbidity status were used to compare SF-36 physical (PCS) and mental (MCS) component summary scores over 25 years before time 0 as a function of FFP classification, with estimates extracted at time 0, -5, -10, -15, -20 and -25 years. We also used illness-death models to examine the prospective association between SF-36 component summary scores at age 50 and incident FFP-defined frailty.ResultsAmong 7044 participants of the Whitehall II cohort study included in the analysis [29% female, mean age 49.7 (SD = 6.0) at baseline in 1991], 2055 (29%) participants remained robust, and 4476 (64%) became pre-frail and 513 (7%) frail during follow-up. Frail compared with robust participants had lower SF-36 scores at t = -25 before onset of frailty with a difference of 3.4 [95% confidence interval (CI) 1.6, 5.1] in PCS and 1.8 (-0.2, 3.8) in MCS. At t = 0, the differences increased to 11.5 (10.5, 12.5) and 9.1 (8.0, 10.2), respectively. The differences in SF-36 between the robust and pre-frail groups, although smaller [at t = 0, 1.7 (1.2, 2.2) in PCS and 4.0 (3.4, 4.5) in MCS], were already observed 20 and 25 years, respectively, before the onset of pre-frailty. Prospective analyses showed that at age 50, scores in the bottom quartiles of PCS [hazard ratio (HR) compared with the top quartile = 2.39, 95% CI 1.85, 3.07] and MCS [HR = 1.49 (1.15, 1.93)] were associated with a higher risk of FFP-defined frailty at older ages.ConclusionsDifferences in trajectories of physical and mental functioning in individuals who developed physical frailty at older ages were observable 25 years before onset of FFP-defined frailty. These findings highlight the need for a life course approach in efforts to prevent frailty.
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Project description:AIM:The present study investigated the link between peripheral DNA methylation (DNAm), cognitive impairment and brain aging. METHODS:We tested the association between blood genome-wide DNAm profiles using the Illumina 450K arrays, cognitive dysfunction and brain MRI measures in selected participants of the Whitehall II imaging sub-study. RESULTS:Eight differentially methylated regions were associated with cognitive impairment. Accelerated aging based on the Hannum epigenetic clock was associated with mean diffusivity and global fractional anisotropy. We also identified modules of co-methylated loci associated with white matter hyperintensities. These co-methylation modules were enriched among pathways relevant to ?-amyloid processing and glutamatergic signaling. CONCLUSION:Our data support the notion that blood DNAm changes may have utility as a biomarker for cognitive dysfunction and brain aging.
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