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December 03, 2019; 93 (23) ArticleOpen Access

Cognition at age 70

Life course predictors and associations with brain pathologies

Kirsty Lu, Jennifer M. Nicholas, Jessica D. Collins, Sarah-Naomi James, Thomas D. Parker, Christopher A. Lane, Ashvini Keshavan, Sarah E. Keuss, Sarah M. Buchanan, Heidi Murray-Smith, David M. Cash, Carole H. Sudre, Ian B. Malone, William Coath, Andrew Wong, Susie M.D. Henley, Sebastian J. Crutch, Nick C. Fox, Marcus Richards, Jonathan M. Schott
First published October 30, 2019, DOI: https://doi.org/10.1212/WNL.0000000000008534
Kirsty Lu
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Jennifer M. Nicholas
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Jessica D. Collins
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Sarah-Naomi James
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Thomas D. Parker
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Christopher A. Lane
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Ashvini Keshavan
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Sarah E. Keuss
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Sarah M. Buchanan
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Heidi Murray-Smith
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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David M. Cash
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Carole H. Sudre
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Ian B. Malone
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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William Coath
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Andrew Wong
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Susie M.D. Henley
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Sebastian J. Crutch
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Nick C. Fox
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Marcus Richards
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Jonathan M. Schott
From the Dementia Research Centre (K.L., J.D.C., T.D.P., C.A.L., A.K., S.E.K., S.M.B., H.M.-S., D.M.C., C.H.S., I.B.M., W.C., S.M.D.H., S.J.C., N.C.F., J.M.S.), UCL Queen Square Institute of Neurology, University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine; MRC Unit for Lifelong Health and Ageing at UCL (S.-N.J., A.W., M.R.); and School of Biomedical Engineering and Imaging Sciences (D.M.C., C.H.S.), King's College London, UK.
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Citation
Cognition at age 70
Kirsty Lu, Jennifer M. Nicholas, Jessica D. Collins, Sarah-Naomi James, Thomas D. Parker, Christopher A. Lane, Ashvini Keshavan, Sarah E. Keuss, Sarah M. Buchanan, Heidi Murray-Smith, David M. Cash, Carole H. Sudre, Ian B. Malone, William Coath, Andrew Wong, Susie M.D. Henley, Sebastian J. Crutch, Nick C. Fox, Marcus Richards, Jonathan M. Schott
Neurology Dec 2019, 93 (23) e2144-e2156; DOI: 10.1212/WNL.0000000000008534

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Abstract

Objective To investigate predictors of performance on a range of cognitive measures including the Preclinical Alzheimer Cognitive Composite (PACC) and test for associations between cognition and dementia biomarkers in Insight 46, a substudy of the Medical Research Council National Survey of Health and Development.

Methods A total of 502 individuals born in the same week in 1946 underwent cognitive assessment at age 69–71 years, including an adapted version of the PACC and a test of nonverbal reasoning. Performance was characterized with respect to sex, childhood cognitive ability, education, and socioeconomic position (SEP). In a subsample of 406 cognitively normal participants, associations were investigated between cognition and β-amyloid (Aβ) positivity (determined from Aβ-PET imaging), whole brain volumes, white matter hyperintensity volumes (WMHV), and APOE ε4.

Results Childhood cognitive ability was strongly associated with cognitive scores including the PACC more than 60 years later, and there were independent effects of education and SEP. Sex differences were observed on every PACC subtest. In cognitively normal participants, Aβ positivity and WMHV were independently associated with lower PACC scores, and Aβ positivity was associated with poorer nonverbal reasoning. Aβ positivity and WMHV were not associated with sex, childhood cognitive ability, education, or SEP. Normative data for 339 cognitively normal Aβ-negative participants are provided.

Conclusions This study adds to emerging evidence that subtle cognitive differences associated with Aβ deposition are detectable in older adults, at an age when dementia prevalence is very low. The independent associations of childhood cognitive ability, education, and SEP with cognitive performance at age 70 have implications for interpretation of cognitive data in later life.

Glossary

Aβ=
β-amyloid;
AD=
Alzheimer disease;
CI=
confidence interval;
DSST=
Digit Symbol Substitution Test;
FCSRT=
Free and Cued Selective Reminding Test;
FNAME-12=
12-item Face-Name test;
MCI=
mild cognitive impairment;
MMSE=
Mini-Mental State Examination;
NSHD=
National Survey of Health and Development;
PACC=
Preclinical Alzheimer Cognitive Composite;
SEP=
socioeconomic position;
SPM=
statistical parametric mapping;
SUVR=
standard uptake volume ratio;
TIV=
total intracranial volume;
WMHV=
white matter hyperintensity volume

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • The Article Processing Charge was funded by the MRC/Wellcome Trust.

  • Received February 8, 2019.
  • Accepted in final form June 12, 2019.
  • Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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