Timing of onset of cognitive decline: Results from Whitehall II prospective cohort study

Institut National de la Santé et de la Recherche Médicale, U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, 94807 Villejuif Cedex, France.
BMJ (online) (Impact Factor: 17.45). 01/2012; 344(jan04 4):d7622. DOI: 10.1136/bmj.d7622
Source: PubMed


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.
Prospective cohort study. At study inception in 1985-8, there were 10,308 participants, representing a recruitment rate of 73%.
Civil service departments in London, United Kingdom.
5198 men and 2192 women, aged 45-70 at the beginning of cognitive testing in 1997-9.
Tests of memory, reasoning, vocabulary, and phonemic and semantic fluency, assessed three times over 10 years.
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%).
Cognitive decline is already evident in middle age (age 45-49).

Download full-text


Available from: Archana Singh-Manoux, Oct 04, 2015
21 Reads
  • Source
    • "It was observed that the regions involved in memory systems, that is, hippocampus and caudate showed an increase in heterogeneity (HFA t ) along with a significant increase in the average FA t (Fig. 10, Table IV). Thus, these regions showed a neural degeneration with age implying a possible decrease in performance on memory related tasks, as has been recorded in other published works [Singh-Manoux et al., 2012; West Figure 9. Cortical gray matter heterogeneity (HFAt) in the three functional zones (primary, paralimbic, and association—left to right) for both the hemispheres. Statistically significant increase can be seen in the primary and the association zones, but not in the paralimbic areas. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Many studies have observed altered neurofunctional and structural organization in the aging brain. These observations from functional neuroimaging studies show a shift in brain activity from the posterior to the anterior regions with aging (PASA model), as well as a decrease in cortical thickness, which is more pronounced in the frontal lobe followed by the parietal, occipital, and temporal lobes (retrogenesis model). However, very little work has been done using diffusion MRI (dMRI) with respect to examining the structural tissue alterations underlying these neurofunctional changes in the gray matter. Thus, for the first time, we propose to examine gray matter changes using diffusion MRI in the context of aging. In this work, we propose a novel dMRI based measure of gray matter “heterogeneity” that elucidates these functional and structural models (PASA and retrogenesis) of aging from the viewpoint of diffusion MRI. In a cohort of 85 subjects (all males, ages 15–55 years), we show very high correlation between age and “heterogeneity” (a measure of structural layout of tissue in a region-of-interest) in specific brain regions. We examine gray matter alterations by grouping brain regions into anatomical lobes as well as functional zones. Our findings from dMRI data connects the functional and structural domains and confirms the “retrogenesis” hypothesis of gray matter alterations while lending support to the neurofunctional PASA model of aging in addition to showing the preservation of paralimbic areas during healthy aging. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
    Human Brain Mapping 08/2014; 35(8). DOI:10.1002/hbm.22441 · 5.97 Impact Factor
  • Source
    • "There is considerable inter-individual variation in how these capabilities change with age. While some domains of cognitive function, such as verbal ability and general knowledge, show little change with advancing age, in general, fluid cognitive abilities, such as reasoning, executive function, processing speed and memory decline from midlife or even earlier (Park and Reuter-Lorenz 2009; Singh-Manoux et al. 2012). Gait is a complex motor function that tends to deteriorate in later life, although it is unclear how early in the life course these changes start. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cross-sectional studies show that older people with better cognition tend to walk faster. Whether this association reflects an influence of fluid cognition upon walking speed, vice versa, a bidirectional relationship or the effect of common causes is unclear. We used linear mixed effects models to examine the dynamic relationship between usual walking speed and fluid cognition, as measured by executive function, verbal memory and processing speed, in 2,654 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. There was a bidirectional relationship between walking speed and fluid cognition. After adjusting for age and sex, better performance on executive function, memory and processing speed was associated with less yearly decline in walking speed over the 6-year follow-up period; faster walking speed was associated with less yearly decline in each cognitive domain; and less yearly decline in each cognitive domain was associated with less yearly decline in walking speed. Effect sizes were small. After further adjustment for other covariates, effect sizes were attenuated but most remained statistically significant. We found some evidence that walking speed and the fluid cognitive domains of executive function and processing speed may change in parallel with increasing age. Investigation of the association between walking speed and cognition earlier in life is needed to better understand the origins of this relation and inform the development and timing of interventions.
    Journal of the American Aging Association 08/2014; 36(4):9682. DOI:10.1007/s11357-014-9682-8 · 3.39 Impact Factor
  • Source
    • "Short-term verbal memory was assessed with 20 one- or two-syllable words, presented orally at 2-second intervals, and the participants had 2 minutes to recall these words in writing.22 "
    [Show abstract] [Hide abstract]
    ABSTRACT: To examine the association between alcohol consumption in midlife and subsequent cognitive decline. Data are from 5,054 men and 2,099 women from the Whitehall II cohort study with a mean age of 56 years (range 44-69 years) at first cognitive assessment. Alcohol consumption was assessed 3 times in the 10 years preceding the first cognitive assessment (1997-1999). Cognitive tests were repeated in 2002-2004 and 2007-2009. The cognitive test battery included 4 tests assessing memory and executive function; a global cognitive score summarized performances across these tests. Linear mixed models were used to assess the association between alcohol consumption and cognitive decline, expressed as z scores (mean = 0, SD = 1). In men, there were no differences in cognitive decline among alcohol abstainers, quitters, and light or moderate alcohol drinkers (<20 g/d). However, alcohol consumption ≥36 g/d was associated with faster decline in all cognitive domains compared with consumption between 0.1 and 19.9 g/d: mean difference (95% confidence interval) in 10-year decline in the global cognitive score = -0.10 (-0.16, -0.04), executive function = -0.06 (-0.12, 0.00), and memory = -0.16 (-0.26, -0.05). In women, compared with those drinking 0.1 to 9.9 g/d of alcohol, 10-year abstainers showed faster decline in the global cognitive score (-0.21 [-0.37, -0.04]) and executive function (-0.17 [-0.32, -0.01]). Excessive alcohol consumption in men (≥36 g/d) was associated with faster cognitive decline compared with light to moderate alcohol consumption.
    Neurology 01/2014; 82(4). DOI:10.1212/WNL.0000000000000063 · 8.29 Impact Factor
Show more