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      Identifying the lifetime cognitive and socioeconomic antecedents of cognitive state: seven decades of follow-up in a British birth cohort study

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          Abstract

          Objectives

          The life course determinants of midlife and later life cognitive function have been studied using longitudinal population-based cohort data, but far less is known about whether the pattern of these pathways is similar or distinct for clinically relevant cognitive state. We investigated this for Addenbrooke’s Cognitive Examination third edition (ACE-III), used in clinical settings to screen for cognitive impairment and dementia.

          Design

          Longitudinal birth cohort study.

          Setting

          Residential addresses in England, Wales and Scotland.

          Participants

          1762 community-dwelling men and women of European heritage, enrolled since birth in the Medical Research Council (MRC) National Survey of Health and Development (the British 1946 birth cohort).

          Primary outcome

          ACE-III.

          Results

          Path modelling estimated direct and indirect associations between apolipoprotein E ( APOE) status, father’s social class, childhood cognition, education, midlife occupational complexity, midlife verbal ability (National Adult Reading Test; NART), and the total ACE-III score. Controlling for sex, there was a direct negative association between APOE ε4 and the ACE-III score (β=−0.04 [–0.08 to –0.002], p=0.04), but not between APOE ε4 and childhood cognition (β=0.03 [–0.006 to 0.069], p=0.10) or the NART (β=0.0005 [–0.03 to 0.03], p=0.97). The strongest influences on the ACE-III were from childhood cognition (β=0.20 [0.14 to 0.26], p<0.001) and the NART (β=0.35 [0.29 to 0.41], p<0.001); educational attainment and occupational complexity were modestly and independently associated with the ACE-III (β=0.08 [0.03 to 0.14], p=0.002 and β=0.05 [0.01 to 0.10], p=0.02, respectively).

          Conclusions

          The ACE-III in the general population shows a pattern of life course antecedents that is similar to neuropsychological measures of cognitive function, and may be used to represent normal cognitive ageing as well as a screen for cognitive impairment and dementia.

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          Most cited references19

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          • Article: found

          Validation of the Addenbrooke's Cognitive Examination III in Frontotemporal Dementia and Alzheimer's Disease

          Background/Aims: The aims of this study were to validate the newly developed version of the Addenbrooke's Cognitive Examination (ACE-III) against standardised neuropsychological tests and its predecessor (ACE-R) in early dementia. Methods: A total of 61 patients with dementia (frontotemporal dementia, FTD, n = 33, and Alzheimer's disease, AD, n = 28) and 25 controls were included in the study. Results: ACE-III cognitive domains correlated significantly with standardised neuropsychological tests used in the assessment of attention, language, verbal memory and visuospatial function. The ACE-III also compared very favourably with its predecessor, the ACE-R, with similar levels of sensitivity and specificity. Conclusion: The results of this study provide objective validation of the ACE-III as a screening tool for cognitive deficits in FTD and AD.
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            Sex differences in cognitive trajectories in clinically normal older adults.

            Age effects on cognitive functioning are well-documented, but effects of sex on trajectories of cognitive aging are less clear. We examined cognitive ability across a variety of measures for 1,065 to 2,127 participants (mean baseline age 64.1 to 69.7 years) from the Baltimore Longitudinal Study of Aging who were repeatedly tested over a mean follow-up interval of 3.0 to 9.0 years with a mean of 2.3 to 4.4 assessments. Memory and other cognitive tests were administered at each visit, assessing mental status, verbal learning and memory, figural memory, language, attention, perceptuomotor speed and integration, executive function, and visuospatial ability. Importantly, participants free from cognitive impairment at all time points were used in the analyses. Results showed that for all tests, higher age at baseline was significantly associated with lower scores, and performance declined over time. In addition, advancing age was associated with accelerated longitudinal declines in performance (trend for mental status). After adjusting for age, education, and race, sex differences were observed across most tests of specific cognitive abilities examined. At baseline, males outperformed females on the 2 tasks of visuospatial ability, and females outperformed males in most other tests of cognition. Sex differences in cognitive change over time indicated steeper rates of decline for men on measures of mental status, perceptuomotor speed and integration, and visuospatial ability, but no measures on which women showed significantly steeper declines. Our results highlight greater resilience to age-related cognitive decline in older women compared with men.
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              The effects of apolipoprotein E on non-impaired cognitive functioning: a meta-analysis.

              Nearly twice as many participants are represented in the current literature than were available at the time of the last major meta-analytic neurocognitive examination of apolipoprotein E (ApoE) epsilon allele combinations [Small, B.J., Rosnick, C.B., Fratiglioni, L., Backman, L., 2004. Apolipoprotein E and cognitive performance: a meta-analysis. Psychol. Aging 19, 592-600]. The meta-analysis in the current study sought to specifically examine (1) small effects and (2) possible moderating variables associated with ApoE allele combinations that may have been undiscoverable in previous examinations of smaller data sets. A total of 77 studies, representing 40,942 cognitively healthy adults were identified for inclusion in the current meta-analysis (random effects design). Results were congruent with the previous meta-analytic findings indicating that carriers of ApoE allele 4 (ɛ4) perform significantly worse on measures of episodic memory, executive functioning, and overall global cognitive ability. In addition, the current analysis revealed a small effect suggesting that ApoE allele 4 adversely impacts perceptual speed. In contrast to earlier studies, the results also indicate that increases in age result in significantly larger differences between ApoE ɛ4 carriers and ApoE non-ɛ4 carriers on measures of episodic memory and global cognitive ability. ApoE ɛ4 exerts broad, but specific, adverse small effects on a range of neurocognitive functions in cognitively healthy adults. Copyright © 2009 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2019
                24 April 2019
                : 9
                : 4
                : e024404
                Affiliations
                [1 ] departmentMRC Unit for Lifelong Health and Ageing at UCL , UCL , London, UK
                [2 ] departmentEpidemiology and Public Health , University College London , London, UK
                [3 ] departmentNational Hospital for Neurology and Neurosurgery , University College London Hospitals NHS Foundation Trust , London, UK
                Author notes
                [Correspondence to ] M Richards; m.richards@ 123456ucl.ac.uk
                Author information
                http://orcid.org/0000-0002-3800-4416
                http://orcid.org/0000-0001-7386-2857
                Article
                bmjopen-2018-024404
                10.1136/bmjopen-2018-024404
                6502022
                31023749
                dca3a62a-455c-49f8-a6a1-d9d04df8836f
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

                History
                : 30 May 2018
                : 05 February 2019
                : 12 February 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Funded by: Alzheimer’s Research UK;
                Funded by: FundRef http://dx.doi.org/10.13039/501100000265, Medical Research Council;
                Categories
                Epidemiology
                Research
                1506
                1692
                Custom metadata
                unlocked

                Medicine
                epidemiology,dementia,old age psychiatry
                Medicine
                epidemiology, dementia, old age psychiatry

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