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Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

Identifieur interne : 002754 ( Pmc/Curation ); précédent : 002753; suivant : 002755

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

Auteurs : Darren M. Lipnicki [Australie] ; John D. Crawford [Australie] ; Rajib Dutta [Australie] ; Anbupalam Thalamuthu [Australie] ; Nicole A. Kochan [Australie] ; Gavin Andrews [Australie] ; M. Fernanda Lima-Costa [Brésil] ; Erico Castro-Costa [Brésil] ; Carol Brayne [Royaume-Uni] ; Fiona E. Matthews [Royaume-Uni] ; Blossom C. M. Stephan [Royaume-Uni] ; Richard B. Lipton [États-Unis] ; Mindy J. Katz [États-Unis] ; Karen Ritchie [France, Royaume-Uni] ; Jacqueline Scali [France] ; Marie-Laure Ancelin [France] ; Nikolaos Scarmeas [Grèce, États-Unis] ; Mary Yannakoulia [Grèce] ; Efthimios Dardiotis [Grèce] ; Linda C. W. Lam [République populaire de Chine] ; Candy H. Y. Wong [République populaire de Chine] ; Ada W. T. Fung [République populaire de Chine] ; Antonio Guaita [Italie] ; Roberta Vaccaro [Italie] ; Annalisa Davin [Italie] ; Ki Woong Kim [Corée du Sud] ; Ji Won Han [Corée du Sud] ; Tae Hui Kim [Corée du Sud] ; Kaarin J. Anstey [Australie] ; Nicolas Cherbuin [Australie] ; Peter Butterworth [Australie] ; Marcia Scazufca [Brésil] ; Shuzo Kumagai [Japon] ; Sanmei Chen [République populaire de Chine] ; Kenji Narazaki [Japon] ; Tze Pin Ng [Singapour] ; Qi Gao [Singapour] ; Simone Reppermund [Australie] ; Henry Brodaty [Australie] ; Antonio Lobo [Espagne] ; Raúl Lopez-Anton [Espagne] ; Javier Santabárbara [Espagne] ; Perminder S. Sachdev [Australie]

Source :

RBID : PMC:5360220

Abstract

Background

The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline.

Methods and findings

We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China.

Conclusions

Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.


Url:
DOI: 10.1371/journal.pmed.1002261
PubMed: 28323832
PubMed Central: 5360220

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Le document en format XML

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<name sortKey="Dutta, Rajib" sort="Dutta, Rajib" uniqKey="Dutta R" first="Rajib" last="Dutta">Rajib Dutta</name>
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<name sortKey="Andrews, Gavin" sort="Andrews, Gavin" uniqKey="Andrews G" first="Gavin" last="Andrews">Gavin Andrews</name>
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<name sortKey="Lima Costa, M Fernanda" sort="Lima Costa, M Fernanda" uniqKey="Lima Costa M" first="M. Fernanda" last="Lima-Costa">M. Fernanda Lima-Costa</name>
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<addr-line>Rene Rachou Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil</addr-line>
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<name sortKey="Castro Costa, Erico" sort="Castro Costa, Erico" uniqKey="Castro Costa E" first="Erico" last="Castro-Costa">Erico Castro-Costa</name>
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<addr-line>Rene Rachou Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil</addr-line>
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<name sortKey="Brayne, Carol" sort="Brayne, Carol" uniqKey="Brayne C" first="Carol" last="Brayne">Carol Brayne</name>
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<addr-line>Department of Public Health and Primary Care, Cambridge University, Cambridge, United Kingdom</addr-line>
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<country xml:lang="fr">Royaume-Uni</country>
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<name sortKey="Matthews, Fiona E" sort="Matthews, Fiona E" uniqKey="Matthews F" first="Fiona E." last="Matthews">Fiona E. Matthews</name>
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<addr-line>Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom</addr-line>
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<name sortKey="Stephan, Blossom C M" sort="Stephan, Blossom C M" uniqKey="Stephan B" first="Blossom C. M." last="Stephan">Blossom C. M. Stephan</name>
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<name sortKey="Lipton, Richard B" sort="Lipton, Richard B" uniqKey="Lipton R" first="Richard B." last="Lipton">Richard B. Lipton</name>
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<addr-line>Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York, United States of America</addr-line>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York</wicri:regionArea>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Yeshiva University, New York City, New York</wicri:regionArea>
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<name sortKey="Katz, Mindy J" sort="Katz, Mindy J" uniqKey="Katz M" first="Mindy J." last="Katz">Mindy J. Katz</name>
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<addr-line>Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York, United States of America</addr-line>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York</wicri:regionArea>
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<name sortKey="Ritchie, Karen" sort="Ritchie, Karen" uniqKey="Ritchie K" first="Karen" last="Ritchie">Karen Ritchie</name>
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<name sortKey="Scali, Jacqueline" sort="Scali, Jacqueline" uniqKey="Scali J" first="Jacqueline" last="Scali">Jacqueline Scali</name>
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<addr-line>Université de Montpellier, Montpellier, France</addr-line>
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<name sortKey="Ancelin, Marie Laure" sort="Ancelin, Marie Laure" uniqKey="Ancelin M" first="Marie-Laure" last="Ancelin">Marie-Laure Ancelin</name>
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<country xml:lang="fr">France</country>
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<addr-line>Université de Montpellier, Montpellier, France</addr-line>
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<country xml:lang="fr">France</country>
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<name sortKey="Scarmeas, Nikolaos" sort="Scarmeas, Nikolaos" uniqKey="Scarmeas N" first="Nikolaos" last="Scarmeas">Nikolaos Scarmeas</name>
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<addr-line>National and Kapodistrian University of Athens, Athens, Greece</addr-line>
</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>National and Kapodistrian University of Athens, Athens</wicri:regionArea>
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<affiliation wicri:level="1">
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<addr-line>Columbia University, New York City, New York, United States of America</addr-line>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Columbia University, New York City, New York</wicri:regionArea>
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<name sortKey="Yannakoulia, Mary" sort="Yannakoulia, Mary" uniqKey="Yannakoulia M" first="Mary" last="Yannakoulia">Mary Yannakoulia</name>
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<nlm:aff id="aff013">
<addr-line>Harokopio University, Athens, Greece</addr-line>
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<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Harokopio University, Athens</wicri:regionArea>
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<name sortKey="Dardiotis, Efthimios" sort="Dardiotis, Efthimios" uniqKey="Dardiotis E" first="Efthimios" last="Dardiotis">Efthimios Dardiotis</name>
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<addr-line>University of Thessaly, Larissa, Greece</addr-line>
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<country xml:lang="fr">Grèce</country>
<wicri:regionArea>University of Thessaly, Larissa</wicri:regionArea>
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<name sortKey="Lam, Linda C W" sort="Lam, Linda C W" uniqKey="Lam L" first="Linda C. W." last="Lam">Linda C. W. Lam</name>
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<addr-line>Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR</wicri:regionArea>
</affiliation>
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<author>
<name sortKey="Wong, Candy H Y" sort="Wong, Candy H Y" uniqKey="Wong C" first="Candy H. Y." last="Wong">Candy H. Y. Wong</name>
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<nlm:aff id="aff016">
<addr-line>Department of Psychiatry, Tai Po Hospital, Hong Kong SAR, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Psychiatry, Tai Po Hospital, Hong Kong SAR</wicri:regionArea>
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</author>
<author>
<name sortKey="Fung, Ada W T" sort="Fung, Ada W T" uniqKey="Fung A" first="Ada W. T." last="Fung">Ada W. T. Fung</name>
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<nlm:aff id="aff015">
<addr-line>Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Guaita, Antonio" sort="Guaita, Antonio" uniqKey="Guaita A" first="Antonio" last="Guaita">Antonio Guaita</name>
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<nlm:aff id="aff017">
<addr-line>GolgiCenci Foundation, Abbiategrasso, Milan, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>GolgiCenci Foundation, Abbiategrasso, Milan</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Vaccaro, Roberta" sort="Vaccaro, Roberta" uniqKey="Vaccaro R" first="Roberta" last="Vaccaro">Roberta Vaccaro</name>
<affiliation wicri:level="1">
<nlm:aff id="aff017">
<addr-line>GolgiCenci Foundation, Abbiategrasso, Milan, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>GolgiCenci Foundation, Abbiategrasso, Milan</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Davin, Annalisa" sort="Davin, Annalisa" uniqKey="Davin A" first="Annalisa" last="Davin">Annalisa Davin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff017">
<addr-line>GolgiCenci Foundation, Abbiategrasso, Milan, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>GolgiCenci Foundation, Abbiategrasso, Milan</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kim, Ki Woong" sort="Kim, Ki Woong" uniqKey="Kim K" first="Ki Woong" last="Kim">Ki Woong Kim</name>
<affiliation wicri:level="1">
<nlm:aff id="aff018">
<addr-line>Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea</addr-line>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff019">
<addr-line>Department of Psychiatry, Seoul National University, College of Medicine, Seoul, Korea</addr-line>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Psychiatry, Seoul National University, College of Medicine, Seoul</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff020">
<addr-line>Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, Korea</addr-line>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Han, Ji Won" sort="Han, Ji Won" uniqKey="Han J" first="Ji Won" last="Han">Ji Won Han</name>
<affiliation wicri:level="1">
<nlm:aff id="aff018">
<addr-line>Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea</addr-line>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kim, Tae Hui" sort="Kim, Tae Hui" uniqKey="Kim T" first="Tae Hui" last="Kim">Tae Hui Kim</name>
<affiliation wicri:level="1">
<nlm:aff id="aff021">
<addr-line>Department of Psychiatry, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea</addr-line>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Psychiatry, Yonsei University Wonju Severance Christian Hospital, Wonju</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Anstey, Kaarin J" sort="Anstey, Kaarin J" uniqKey="Anstey K" first="Kaarin J." last="Anstey">Kaarin J. Anstey</name>
<affiliation wicri:level="1">
<nlm:aff id="aff022">
<addr-line>Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cherbuin, Nicolas" sort="Cherbuin, Nicolas" uniqKey="Cherbuin N" first="Nicolas" last="Cherbuin">Nicolas Cherbuin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff022">
<addr-line>Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra</wicri:regionArea>
</affiliation>
</author>
<author>
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<country xml:lang="fr">Australie</country>
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<country xml:lang="fr">Brésil</country>
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<name sortKey="Chen, Sanmei" sort="Chen, Sanmei" uniqKey="Chen S" first="Sanmei" last="Chen">Sanmei Chen</name>
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<nlm:aff id="aff025">
<addr-line>Xiangya School of Nursing, Central South University, Changsha, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Xiangya School of Nursing, Central South University, Changsha</wicri:regionArea>
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<author>
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<nlm:aff id="aff026">
<addr-line>Faculty of Socio-Environmental Studies, Fukuoka Institute of Technology, Fukuoka City, Japan</addr-line>
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<country xml:lang="fr">Japon</country>
<wicri:regionArea>Faculty of Socio-Environmental Studies, Fukuoka Institute of Technology, Fukuoka City</wicri:regionArea>
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<addr-line>Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
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<name sortKey="Gao, Qi" sort="Gao, Qi" uniqKey="Gao Q" first="Qi" last="Gao">Qi Gao</name>
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<nlm:aff id="aff027">
<addr-line>Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore</wicri:regionArea>
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<name sortKey="Reppermund, Simone" sort="Reppermund, Simone" uniqKey="Reppermund S" first="Simone" last="Reppermund">Simone Reppermund</name>
<affiliation wicri:level="1">
<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
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<name sortKey="Brodaty, Henry" sort="Brodaty, Henry" uniqKey="Brodaty H" first="Henry" last="Brodaty">Henry Brodaty</name>
<affiliation wicri:level="1">
<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff028">
<addr-line>Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Dementia Collaborative Research Centre, University of New South Wales, Sydney</wicri:regionArea>
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<author>
<name sortKey="Lobo, Antonio" sort="Lobo, Antonio" uniqKey="Lobo A" first="Antonio" last="Lobo">Antonio Lobo</name>
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<nlm:aff id="aff029">
<addr-line>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff030">
<addr-line>Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lopez Anton, Raul" sort="Lopez Anton, Raul" uniqKey="Lopez Anton R" first="Raúl" last="Lopez-Anton">Raúl Lopez-Anton</name>
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<nlm:aff id="aff029">
<addr-line>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff031">
<addr-line>Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spanish Ministry of Economy and Competitiveness, Madrid, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spanish Ministry of Economy and Competitiveness, Madrid</wicri:regionArea>
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</author>
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<name sortKey="Santabarbara, Javier" sort="Santabarbara, Javier" uniqKey="Santabarbara J" first="Javier" last="Santabárbara">Javier Santabárbara</name>
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<nlm:aff id="aff029">
<addr-line>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff032">
<addr-line>Department of Microbiology, Preventive Medicine and Public Health, University of Zaragoza, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Microbiology, Preventive Medicine and Public Health, University of Zaragoza</wicri:regionArea>
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<name sortKey="Sachdev, Perminder S" sort="Sachdev, Perminder S" uniqKey="Sachdev P" first="Perminder S." last="Sachdev">Perminder S. Sachdev</name>
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<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff028">
<addr-line>Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Dementia Collaborative Research Centre, University of New South Wales, Sydney</wicri:regionArea>
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<title xml:lang="en" level="a" type="main">Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study</title>
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<name sortKey="Lipnicki, Darren M" sort="Lipnicki, Darren M" uniqKey="Lipnicki D" first="Darren M." last="Lipnicki">Darren M. Lipnicki</name>
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<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
</affiliation>
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<name sortKey="Crawford, John D" sort="Crawford, John D" uniqKey="Crawford J" first="John D." last="Crawford">John D. Crawford</name>
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<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
</affiliation>
</author>
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<name sortKey="Dutta, Rajib" sort="Dutta, Rajib" uniqKey="Dutta R" first="Rajib" last="Dutta">Rajib Dutta</name>
<affiliation wicri:level="1">
<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
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<name sortKey="Thalamuthu, Anbupalam" sort="Thalamuthu, Anbupalam" uniqKey="Thalamuthu A" first="Anbupalam" last="Thalamuthu">Anbupalam Thalamuthu</name>
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<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
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<name sortKey="Kochan, Nicole A" sort="Kochan, Nicole A" uniqKey="Kochan N" first="Nicole A." last="Kochan">Nicole A. Kochan</name>
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<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
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<name sortKey="Andrews, Gavin" sort="Andrews, Gavin" uniqKey="Andrews G" first="Gavin" last="Andrews">Gavin Andrews</name>
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<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
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<name sortKey="Lima Costa, M Fernanda" sort="Lima Costa, M Fernanda" uniqKey="Lima Costa M" first="M. Fernanda" last="Lima-Costa">M. Fernanda Lima-Costa</name>
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<nlm:aff id="aff002">
<addr-line>Rene Rachou Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Rene Rachou Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro</wicri:regionArea>
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<name sortKey="Castro Costa, Erico" sort="Castro Costa, Erico" uniqKey="Castro Costa E" first="Erico" last="Castro-Costa">Erico Castro-Costa</name>
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<nlm:aff id="aff002">
<addr-line>Rene Rachou Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Rene Rachou Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro</wicri:regionArea>
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<name sortKey="Brayne, Carol" sort="Brayne, Carol" uniqKey="Brayne C" first="Carol" last="Brayne">Carol Brayne</name>
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<nlm:aff id="aff003">
<addr-line>Department of Public Health and Primary Care, Cambridge University, Cambridge, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Public Health and Primary Care, Cambridge University, Cambridge</wicri:regionArea>
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</author>
<author>
<name sortKey="Matthews, Fiona E" sort="Matthews, Fiona E" uniqKey="Matthews F" first="Fiona E." last="Matthews">Fiona E. Matthews</name>
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<nlm:aff id="aff004">
<addr-line>MRC Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Biostatistics Unit, Institute of Public Health, Cambridge</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff005">
<addr-line>Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Health and Society, Newcastle University, Newcastle upon Tyne</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Stephan, Blossom C M" sort="Stephan, Blossom C M" uniqKey="Stephan B" first="Blossom C. M." last="Stephan">Blossom C. M. Stephan</name>
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<nlm:aff id="aff005">
<addr-line>Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Health and Society, Newcastle University, Newcastle upon Tyne</wicri:regionArea>
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</author>
<author>
<name sortKey="Lipton, Richard B" sort="Lipton, Richard B" uniqKey="Lipton R" first="Richard B." last="Lipton">Richard B. Lipton</name>
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<nlm:aff id="aff006">
<addr-line>Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff007">
<addr-line>Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Yeshiva University, New York City, New York, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Yeshiva University, New York City, New York</wicri:regionArea>
</affiliation>
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<author>
<name sortKey="Katz, Mindy J" sort="Katz, Mindy J" uniqKey="Katz M" first="Mindy J." last="Katz">Mindy J. Katz</name>
<affiliation wicri:level="1">
<nlm:aff id="aff006">
<addr-line>Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York</wicri:regionArea>
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</author>
<author>
<name sortKey="Ritchie, Karen" sort="Ritchie, Karen" uniqKey="Ritchie K" first="Karen" last="Ritchie">Karen Ritchie</name>
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<nlm:aff id="aff008">
<addr-line>Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff009">
<addr-line>Université de Montpellier, Montpellier, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université de Montpellier, Montpellier</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff010">
<addr-line>Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Scali, Jacqueline" sort="Scali, Jacqueline" uniqKey="Scali J" first="Jacqueline" last="Scali">Jacqueline Scali</name>
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<nlm:aff id="aff008">
<addr-line>Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff009">
<addr-line>Université de Montpellier, Montpellier, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université de Montpellier, Montpellier</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Ancelin, Marie Laure" sort="Ancelin, Marie Laure" uniqKey="Ancelin M" first="Marie-Laure" last="Ancelin">Marie-Laure Ancelin</name>
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<nlm:aff id="aff008">
<addr-line>Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff009">
<addr-line>Université de Montpellier, Montpellier, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université de Montpellier, Montpellier</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Scarmeas, Nikolaos" sort="Scarmeas, Nikolaos" uniqKey="Scarmeas N" first="Nikolaos" last="Scarmeas">Nikolaos Scarmeas</name>
<affiliation wicri:level="1">
<nlm:aff id="aff011">
<addr-line>National and Kapodistrian University of Athens, Athens, Greece</addr-line>
</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>National and Kapodistrian University of Athens, Athens</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff012">
<addr-line>Columbia University, New York City, New York, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Columbia University, New York City, New York</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Yannakoulia, Mary" sort="Yannakoulia, Mary" uniqKey="Yannakoulia M" first="Mary" last="Yannakoulia">Mary Yannakoulia</name>
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<nlm:aff id="aff013">
<addr-line>Harokopio University, Athens, Greece</addr-line>
</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Harokopio University, Athens</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Dardiotis, Efthimios" sort="Dardiotis, Efthimios" uniqKey="Dardiotis E" first="Efthimios" last="Dardiotis">Efthimios Dardiotis</name>
<affiliation wicri:level="1">
<nlm:aff id="aff014">
<addr-line>University of Thessaly, Larissa, Greece</addr-line>
</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>University of Thessaly, Larissa</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lam, Linda C W" sort="Lam, Linda C W" uniqKey="Lam L" first="Linda C. W." last="Lam">Linda C. W. Lam</name>
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<nlm:aff id="aff015">
<addr-line>Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wong, Candy H Y" sort="Wong, Candy H Y" uniqKey="Wong C" first="Candy H. Y." last="Wong">Candy H. Y. Wong</name>
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<nlm:aff id="aff016">
<addr-line>Department of Psychiatry, Tai Po Hospital, Hong Kong SAR, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Psychiatry, Tai Po Hospital, Hong Kong SAR</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Fung, Ada W T" sort="Fung, Ada W T" uniqKey="Fung A" first="Ada W. T." last="Fung">Ada W. T. Fung</name>
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<nlm:aff id="aff015">
<addr-line>Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Guaita, Antonio" sort="Guaita, Antonio" uniqKey="Guaita A" first="Antonio" last="Guaita">Antonio Guaita</name>
<affiliation wicri:level="1">
<nlm:aff id="aff017">
<addr-line>GolgiCenci Foundation, Abbiategrasso, Milan, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>GolgiCenci Foundation, Abbiategrasso, Milan</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Vaccaro, Roberta" sort="Vaccaro, Roberta" uniqKey="Vaccaro R" first="Roberta" last="Vaccaro">Roberta Vaccaro</name>
<affiliation wicri:level="1">
<nlm:aff id="aff017">
<addr-line>GolgiCenci Foundation, Abbiategrasso, Milan, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>GolgiCenci Foundation, Abbiategrasso, Milan</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Davin, Annalisa" sort="Davin, Annalisa" uniqKey="Davin A" first="Annalisa" last="Davin">Annalisa Davin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff017">
<addr-line>GolgiCenci Foundation, Abbiategrasso, Milan, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>GolgiCenci Foundation, Abbiategrasso, Milan</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kim, Ki Woong" sort="Kim, Ki Woong" uniqKey="Kim K" first="Ki Woong" last="Kim">Ki Woong Kim</name>
<affiliation wicri:level="1">
<nlm:aff id="aff018">
<addr-line>Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea</addr-line>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff019">
<addr-line>Department of Psychiatry, Seoul National University, College of Medicine, Seoul, Korea</addr-line>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Psychiatry, Seoul National University, College of Medicine, Seoul</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff020">
<addr-line>Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, Korea</addr-line>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Han, Ji Won" sort="Han, Ji Won" uniqKey="Han J" first="Ji Won" last="Han">Ji Won Han</name>
<affiliation wicri:level="1">
<nlm:aff id="aff018">
<addr-line>Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea</addr-line>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kim, Tae Hui" sort="Kim, Tae Hui" uniqKey="Kim T" first="Tae Hui" last="Kim">Tae Hui Kim</name>
<affiliation wicri:level="1">
<nlm:aff id="aff021">
<addr-line>Department of Psychiatry, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea</addr-line>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Psychiatry, Yonsei University Wonju Severance Christian Hospital, Wonju</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Anstey, Kaarin J" sort="Anstey, Kaarin J" uniqKey="Anstey K" first="Kaarin J." last="Anstey">Kaarin J. Anstey</name>
<affiliation wicri:level="1">
<nlm:aff id="aff022">
<addr-line>Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cherbuin, Nicolas" sort="Cherbuin, Nicolas" uniqKey="Cherbuin N" first="Nicolas" last="Cherbuin">Nicolas Cherbuin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff022">
<addr-line>Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Butterworth, Peter" sort="Butterworth, Peter" uniqKey="Butterworth P" first="Peter" last="Butterworth">Peter Butterworth</name>
<affiliation wicri:level="1">
<nlm:aff id="aff022">
<addr-line>Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Scazufca, Marcia" sort="Scazufca, Marcia" uniqKey="Scazufca M" first="Marcia" last="Scazufca">Marcia Scazufca</name>
<affiliation wicri:level="1">
<nlm:aff id="aff023">
<addr-line>Institute of Psychiatry and LIM-23, Clinics Hospital, University of São Paulo, São Paulo, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Institute of Psychiatry and LIM-23, Clinics Hospital, University of São Paulo, São Paulo</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kumagai, Shuzo" sort="Kumagai, Shuzo" uniqKey="Kumagai S" first="Shuzo" last="Kumagai">Shuzo Kumagai</name>
<affiliation wicri:level="1">
<nlm:aff id="aff024">
<addr-line>Faculty of Arts and Science, Kyushu University, Kasuga City, Japan</addr-line>
</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Faculty of Arts and Science, Kyushu University, Kasuga City</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Chen, Sanmei" sort="Chen, Sanmei" uniqKey="Chen S" first="Sanmei" last="Chen">Sanmei Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff025">
<addr-line>Xiangya School of Nursing, Central South University, Changsha, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Xiangya School of Nursing, Central South University, Changsha</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Narazaki, Kenji" sort="Narazaki, Kenji" uniqKey="Narazaki K" first="Kenji" last="Narazaki">Kenji Narazaki</name>
<affiliation wicri:level="1">
<nlm:aff id="aff026">
<addr-line>Faculty of Socio-Environmental Studies, Fukuoka Institute of Technology, Fukuoka City, Japan</addr-line>
</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Faculty of Socio-Environmental Studies, Fukuoka Institute of Technology, Fukuoka City</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Ng, Tze Pin" sort="Ng, Tze Pin" uniqKey="Ng T" first="Tze Pin" last="Ng">Tze Pin Ng</name>
<affiliation wicri:level="1">
<nlm:aff id="aff027">
<addr-line>Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Gao, Qi" sort="Gao, Qi" uniqKey="Gao Q" first="Qi" last="Gao">Qi Gao</name>
<affiliation wicri:level="1">
<nlm:aff id="aff027">
<addr-line>Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Reppermund, Simone" sort="Reppermund, Simone" uniqKey="Reppermund S" first="Simone" last="Reppermund">Simone Reppermund</name>
<affiliation wicri:level="1">
<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Brodaty, Henry" sort="Brodaty, Henry" uniqKey="Brodaty H" first="Henry" last="Brodaty">Henry Brodaty</name>
<affiliation wicri:level="1">
<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff028">
<addr-line>Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Dementia Collaborative Research Centre, University of New South Wales, Sydney</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lobo, Antonio" sort="Lobo, Antonio" uniqKey="Lobo A" first="Antonio" last="Lobo">Antonio Lobo</name>
<affiliation wicri:level="1">
<nlm:aff id="aff029">
<addr-line>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff030">
<addr-line>Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lopez Anton, Raul" sort="Lopez Anton, Raul" uniqKey="Lopez Anton R" first="Raúl" last="Lopez-Anton">Raúl Lopez-Anton</name>
<affiliation wicri:level="1">
<nlm:aff id="aff029">
<addr-line>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff031">
<addr-line>Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spanish Ministry of Economy and Competitiveness, Madrid, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spanish Ministry of Economy and Competitiveness, Madrid</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Santabarbara, Javier" sort="Santabarbara, Javier" uniqKey="Santabarbara J" first="Javier" last="Santabárbara">Javier Santabárbara</name>
<affiliation wicri:level="1">
<nlm:aff id="aff029">
<addr-line>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff032">
<addr-line>Department of Microbiology, Preventive Medicine and Public Health, University of Zaragoza, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Microbiology, Preventive Medicine and Public Health, University of Zaragoza</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Sachdev, Perminder S" sort="Sachdev, Perminder S" uniqKey="Sachdev P" first="Perminder S." last="Sachdev">Perminder S. Sachdev</name>
<affiliation wicri:level="1">
<nlm:aff id="aff001">
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff028">
<addr-line>Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Dementia Collaborative Research Centre, University of New South Wales, Sydney</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">PLoS Medicine</title>
<idno type="ISSN">1549-1277</idno>
<idno type="eISSN">1549-1676</idno>
<imprint>
<date when="2017">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec id="sec001">
<title>Background</title>
<p>The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (
<italic>APOE*4</italic>
) carrier status were associated with decline.</p>
</sec>
<sec id="sec002">
<title>Methods and findings</title>
<p>We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16],
<italic>p</italic>
< 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03],
<italic>p</italic>
= 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (
<italic>p</italic>
= 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12],
<italic>p</italic>
< 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02],
<italic>p</italic>
= 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035],
<italic>p</italic>
< 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006],
<italic>p</italic>
= 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003],
<italic>p</italic>
= 0.001).
<italic>APOE*4</italic>
carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01],
<italic>p</italic>
= 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China.</p>
</sec>
<sec id="sec003">
<title>Conclusions</title>
<p>Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and
<italic>APOE</italic>
genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.</p>
</sec>
</div>
</front>
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<article-id pub-id-type="pmc">5360220</article-id>
<article-id pub-id-type="doi">10.1371/journal.pmed.1002261</article-id>
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<subject>Biology and Life Sciences</subject>
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<subject>Neuroscience</subject>
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<subject>Cognitive Neuroscience</subject>
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<subject>Dementia</subject>
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<subject>Medicine and Health Sciences</subject>
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<subject>Dementia</subject>
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<subject>Neuroscience</subject>
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<subject>Biology and Life Sciences</subject>
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<subject>Biology and Life Sciences</subject>
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<subject>Meta-Analysis</subject>
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<subject>Statistics (Mathematics)</subject>
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<subject>Cognitive Psychology</subject>
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</subj-group>
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<subject>Earth Sciences</subject>
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<article-title>Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study</article-title>
<alt-title alt-title-type="running-head">Age-related cognitive decline in diverse international regions</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Lipnicki</surname>
<given-names>Darren M.</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Crawford</surname>
<given-names>John D.</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-2267-4458</contrib-id>
<name>
<surname>Dutta</surname>
<given-names>Rajib</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Thalamuthu</surname>
<given-names>Anbupalam</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8630-6398</contrib-id>
<name>
<surname>Kochan</surname>
<given-names>Nicole A.</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0002-4315-2173</contrib-id>
<name>
<surname>Andrews</surname>
<given-names>Gavin</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-3474-2980</contrib-id>
<name>
<surname>Lima-Costa</surname>
<given-names>M. Fernanda</given-names>
</name>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Castro-Costa</surname>
<given-names>Erico</given-names>
</name>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0001-5307-663X</contrib-id>
<name>
<surname>Brayne</surname>
<given-names>Carol</given-names>
</name>
<xref ref-type="aff" rid="aff003">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-1728-2388</contrib-id>
<name>
<surname>Matthews</surname>
<given-names>Fiona E.</given-names>
</name>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Stephan</surname>
<given-names>Blossom C. M.</given-names>
</name>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lipton</surname>
<given-names>Richard B.</given-names>
</name>
<xref ref-type="aff" rid="aff006">
<sup>6</sup>
</xref>
<xref ref-type="aff" rid="aff007">
<sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Katz</surname>
<given-names>Mindy J.</given-names>
</name>
<xref ref-type="aff" rid="aff006">
<sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ritchie</surname>
<given-names>Karen</given-names>
</name>
<xref ref-type="aff" rid="aff008">
<sup>8</sup>
</xref>
<xref ref-type="aff" rid="aff009">
<sup>9</sup>
</xref>
<xref ref-type="aff" rid="aff010">
<sup>10</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Scali</surname>
<given-names>Jacqueline</given-names>
</name>
<xref ref-type="aff" rid="aff008">
<sup>8</sup>
</xref>
<xref ref-type="aff" rid="aff009">
<sup>9</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ancelin</surname>
<given-names>Marie-Laure</given-names>
</name>
<xref ref-type="aff" rid="aff008">
<sup>8</sup>
</xref>
<xref ref-type="aff" rid="aff009">
<sup>9</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Scarmeas</surname>
<given-names>Nikolaos</given-names>
</name>
<xref ref-type="aff" rid="aff011">
<sup>11</sup>
</xref>
<xref ref-type="aff" rid="aff012">
<sup>12</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yannakoulia</surname>
<given-names>Mary</given-names>
</name>
<xref ref-type="aff" rid="aff013">
<sup>13</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Dardiotis</surname>
<given-names>Efthimios</given-names>
</name>
<xref ref-type="aff" rid="aff014">
<sup>14</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lam</surname>
<given-names>Linda C. W.</given-names>
</name>
<xref ref-type="aff" rid="aff015">
<sup>15</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-5083-7496</contrib-id>
<name>
<surname>Wong</surname>
<given-names>Candy H. Y.</given-names>
</name>
<xref ref-type="aff" rid="aff016">
<sup>16</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fung</surname>
<given-names>Ada W. T.</given-names>
</name>
<xref ref-type="aff" rid="aff015">
<sup>15</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-3954-5932</contrib-id>
<name>
<surname>Guaita</surname>
<given-names>Antonio</given-names>
</name>
<xref ref-type="aff" rid="aff017">
<sup>17</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Vaccaro</surname>
<given-names>Roberta</given-names>
</name>
<xref ref-type="aff" rid="aff017">
<sup>17</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Davin</surname>
<given-names>Annalisa</given-names>
</name>
<xref ref-type="aff" rid="aff017">
<sup>17</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Ki Woong</given-names>
</name>
<xref ref-type="aff" rid="aff018">
<sup>18</sup>
</xref>
<xref ref-type="aff" rid="aff019">
<sup>19</sup>
</xref>
<xref ref-type="aff" rid="aff020">
<sup>20</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Han</surname>
<given-names>Ji Won</given-names>
</name>
<xref ref-type="aff" rid="aff018">
<sup>18</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Tae Hui</given-names>
</name>
<xref ref-type="aff" rid="aff021">
<sup>21</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-9706-9316</contrib-id>
<name>
<surname>Anstey</surname>
<given-names>Kaarin J.</given-names>
</name>
<xref ref-type="aff" rid="aff022">
<sup>22</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cherbuin</surname>
<given-names>Nicolas</given-names>
</name>
<xref ref-type="aff" rid="aff022">
<sup>22</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Butterworth</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="aff022">
<sup>22</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Scazufca</surname>
<given-names>Marcia</given-names>
</name>
<xref ref-type="aff" rid="aff023">
<sup>23</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kumagai</surname>
<given-names>Shuzo</given-names>
</name>
<xref ref-type="aff" rid="aff024">
<sup>24</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Sanmei</given-names>
</name>
<xref ref-type="aff" rid="aff025">
<sup>25</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Narazaki</surname>
<given-names>Kenji</given-names>
</name>
<xref ref-type="aff" rid="aff026">
<sup>26</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0001-9585-855X</contrib-id>
<name>
<surname>Ng</surname>
<given-names>Tze Pin</given-names>
</name>
<xref ref-type="aff" rid="aff027">
<sup>27</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-1965-7411</contrib-id>
<name>
<surname>Gao</surname>
<given-names>Qi</given-names>
</name>
<xref ref-type="aff" rid="aff027">
<sup>27</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-4785-0224</contrib-id>
<name>
<surname>Reppermund</surname>
<given-names>Simone</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0001-9487-6617</contrib-id>
<name>
<surname>Brodaty</surname>
<given-names>Henry</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff028">
<sup>28</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lobo</surname>
<given-names>Antonio</given-names>
</name>
<xref ref-type="aff" rid="aff029">
<sup>29</sup>
</xref>
<xref ref-type="aff" rid="aff030">
<sup>30</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lopez-Anton</surname>
<given-names>Raúl</given-names>
</name>
<xref ref-type="aff" rid="aff029">
<sup>29</sup>
</xref>
<xref ref-type="aff" rid="aff031">
<sup>31</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Santabárbara</surname>
<given-names>Javier</given-names>
</name>
<xref ref-type="aff" rid="aff029">
<sup>29</sup>
</xref>
<xref ref-type="aff" rid="aff032">
<sup>32</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sachdev</surname>
<given-names>Perminder S.</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff028">
<sup>28</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
<contrib contrib-type="author">
<collab>Cohort Studies of Memory in an International Consortium (COSMIC)</collab>
<xref ref-type="author-notes" rid="fn001">
<sup></sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff001">
<label>1</label>
<addr-line>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia</addr-line>
</aff>
<aff id="aff002">
<label>2</label>
<addr-line>Rene Rachou Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil</addr-line>
</aff>
<aff id="aff003">
<label>3</label>
<addr-line>Department of Public Health and Primary Care, Cambridge University, Cambridge, United Kingdom</addr-line>
</aff>
<aff id="aff004">
<label>4</label>
<addr-line>MRC Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom</addr-line>
</aff>
<aff id="aff005">
<label>5</label>
<addr-line>Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom</addr-line>
</aff>
<aff id="aff006">
<label>6</label>
<addr-line>Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York, United States of America</addr-line>
</aff>
<aff id="aff007">
<label>7</label>
<addr-line>Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Yeshiva University, New York City, New York, United States of America</addr-line>
</aff>
<aff id="aff008">
<label>8</label>
<addr-line>Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier, France</addr-line>
</aff>
<aff id="aff009">
<label>9</label>
<addr-line>Université de Montpellier, Montpellier, France</addr-line>
</aff>
<aff id="aff010">
<label>10</label>
<addr-line>Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom</addr-line>
</aff>
<aff id="aff011">
<label>11</label>
<addr-line>National and Kapodistrian University of Athens, Athens, Greece</addr-line>
</aff>
<aff id="aff012">
<label>12</label>
<addr-line>Columbia University, New York City, New York, United States of America</addr-line>
</aff>
<aff id="aff013">
<label>13</label>
<addr-line>Harokopio University, Athens, Greece</addr-line>
</aff>
<aff id="aff014">
<label>14</label>
<addr-line>University of Thessaly, Larissa, Greece</addr-line>
</aff>
<aff id="aff015">
<label>15</label>
<addr-line>Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China</addr-line>
</aff>
<aff id="aff016">
<label>16</label>
<addr-line>Department of Psychiatry, Tai Po Hospital, Hong Kong SAR, China</addr-line>
</aff>
<aff id="aff017">
<label>17</label>
<addr-line>GolgiCenci Foundation, Abbiategrasso, Milan, Italy</addr-line>
</aff>
<aff id="aff018">
<label>18</label>
<addr-line>Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea</addr-line>
</aff>
<aff id="aff019">
<label>19</label>
<addr-line>Department of Psychiatry, Seoul National University, College of Medicine, Seoul, Korea</addr-line>
</aff>
<aff id="aff020">
<label>20</label>
<addr-line>Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, Korea</addr-line>
</aff>
<aff id="aff021">
<label>21</label>
<addr-line>Department of Psychiatry, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea</addr-line>
</aff>
<aff id="aff022">
<label>22</label>
<addr-line>Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra, Australia</addr-line>
</aff>
<aff id="aff023">
<label>23</label>
<addr-line>Institute of Psychiatry and LIM-23, Clinics Hospital, University of São Paulo, São Paulo, Brazil</addr-line>
</aff>
<aff id="aff024">
<label>24</label>
<addr-line>Faculty of Arts and Science, Kyushu University, Kasuga City, Japan</addr-line>
</aff>
<aff id="aff025">
<label>25</label>
<addr-line>Xiangya School of Nursing, Central South University, Changsha, China</addr-line>
</aff>
<aff id="aff026">
<label>26</label>
<addr-line>Faculty of Socio-Environmental Studies, Fukuoka Institute of Technology, Fukuoka City, Japan</addr-line>
</aff>
<aff id="aff027">
<label>27</label>
<addr-line>Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</addr-line>
</aff>
<aff id="aff028">
<label>28</label>
<addr-line>Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia</addr-line>
</aff>
<aff id="aff029">
<label>29</label>
<addr-line>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain</addr-line>
</aff>
<aff id="aff030">
<label>30</label>
<addr-line>Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain</addr-line>
</aff>
<aff id="aff031">
<label>31</label>
<addr-line>Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spanish Ministry of Economy and Competitiveness, Madrid, Spain</addr-line>
</aff>
<aff id="aff032">
<label>32</label>
<addr-line>Department of Microbiology, Preventive Medicine and Public Health, University of Zaragoza, Spain</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Miller</surname>
<given-names>Bruce L.</given-names>
</name>
<role>Academic Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">
<addr-line>University of California San Francisco Memory and Aging Center, UNITED STATES</addr-line>
</aff>
<author-notes>
<fn fn-type="COI-statement" id="coi001">
<p>I have read the journal's policy and the authors of this manuscript have the following competing interests: JDC is supported by the National Health and Medical Research Council of Australia (NHMRC Program Grant ID 568969). CB is a member of the Editorial Board of PLOS Medicine. FEM is a member of the Editorial Board of PLOS Medicine. RBL is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York and receives research support from the NIH; receives support from the Migraine Research Foundation and the National Headache Foundation and serves on the editorial board of Neurology and as senior advisor to Headache; has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics; serves as consultant, advisory board member, or has received honoraria from American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Colucid, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKlein (formerly Novartis), Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta; and receives royalties from Wolff’s Headache, 8th Edition, Oxford Press University, 2009, Wiley and Informa. MJK is funded by NIH/NIA and the following private foundations: Czap Foundation, Sylvia and Leonard Marx Foundation and also receives consultation fees from Eli Lilly and Company. HB has received departmental grants for drug trials from Lilly, Merck, Sanofi, Servier and Tau Therapeutics; is on the advisory board for Nutricia and has been asked to be an advisor to Lundbeck, Otuska and Eli Lilly; and is on clinical advisory committees for Montefiore Homes and Cranbrook Care, both of which operate residential/ long-term care homes. AL has received honoraria or travel fees from Lundbeck and Sanofi. PSS would like to acknowledge financial support from the National Health & Medical Research Council (APP1093083), the Vincent Fairfax Foundation and the Yulgilbar Foundation for COSMIC. All other authors declare no competing interests.</p>
</fn>
<fn fn-type="con">
<p>
<list list-type="simple">
<list-item>
<p>
<bold>Conceptualization:</bold>
PSS DML JDC NAK SK CB FEM BCMS CHYW LCWL MFLC ECC KJA AL NS ED MY RBL MJK GA KWK MS.</p>
</list-item>
<list-item>
<p>
<bold>Data curation:</bold>
DML JDC RD AT AWTF NC SK SC KN TPN QG CHYW LCWL JSc CB FEM BCMS THK MFLC ECC KJA RLA JSa MJK JWH KWK PB MS.</p>
</list-item>
<list-item>
<p>
<bold>Formal analysis:</bold>
RD AT SC NAK CHYW LCWL MFLC ECC RLA JSa NS MY JWH KWK MS FEM BCMS.</p>
</list-item>
<list-item>
<p>
<bold>Funding acquisition:</bold>
PSS.</p>
</list-item>
<list-item>
<p>
<bold>Investigation:</bold>
AWTF NC SK SC KN TPN QG CHYW LCWL AG RV AD MLA HB THK NAK MFLC ECC KJA AL RLA JSa NS ED MY KR RBL MJK SR JWH GA KWK PB MS CB FEM BCMS.</p>
</list-item>
<list-item>
<p>
<bold>Methodology:</bold>
JDC AT SK SC KN TPN QG CB FEM LCWL KJA NS ED MY KWK MS.</p>
</list-item>
<list-item>
<p>
<bold>Project administration:</bold>
DML.</p>
</list-item>
<list-item>
<p>
<bold>Software:</bold>
JSa MJK KWK MS FEM BCMS.</p>
</list-item>
<list-item>
<p>
<bold>Supervision:</bold>
PSS.</p>
</list-item>
<list-item>
<p>
<bold>Validation:</bold>
CB FEM BCMS LCWL JSc MLA MFLC ECC KJA AL RLA JSa RBL MJK JWH KWK MS.</p>
</list-item>
<list-item>
<p>
<bold>Visualization:</bold>
AT.</p>
</list-item>
<list-item>
<p>
<bold>Writing – original draft:</bold>
DML JDC PSS.</p>
</list-item>
<list-item>
<p>
<bold>Writing – review & editing:</bold>
DML PSS JDC RD AT NAK GA MFLC ECC CB FEM BCMS RBL MJK KR JSc MLA NS MY ED LCWL CHYW AWTF AG RV AD KWK JWH THK KJA NC PB MS KS CS KN TPN QG SR HB AL RLA JSa.</p>
</list-item>
</list>
</p>
</fn>
<fn fn-type="other" id="fn001">
<p>¶ Membership of the Cohort Studies of Memory in an International Consortium (COSMIC) is provided in the Acknowledgments.</p>
</fn>
<corresp id="cor001">* E-mail:
<email>p.sachdev@unsw.edu.au</email>
</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>21</day>
<month>3</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="collection">
<month>3</month>
<year>2017</year>
</pub-date>
<volume>14</volume>
<issue>3</issue>
<elocation-id>e1002261</elocation-id>
<history>
<date date-type="received">
<day>16</day>
<month>10</month>
<year>2016</year>
</date>
<date date-type="accepted">
<day>10</day>
<month>2</month>
<year>2017</year>
</date>
</history>
<permissions>
<copyright-statement>© 2017 Lipnicki et al</copyright-statement>
<copyright-year>2017</copyright-year>
<copyright-holder>Lipnicki et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="pmed.1002261.pdf"></self-uri>
<abstract>
<sec id="sec001">
<title>Background</title>
<p>The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (
<italic>APOE*4</italic>
) carrier status were associated with decline.</p>
</sec>
<sec id="sec002">
<title>Methods and findings</title>
<p>We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16],
<italic>p</italic>
< 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03],
<italic>p</italic>
= 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (
<italic>p</italic>
= 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12],
<italic>p</italic>
< 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02],
<italic>p</italic>
= 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035],
<italic>p</italic>
< 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006],
<italic>p</italic>
= 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003],
<italic>p</italic>
= 0.001).
<italic>APOE*4</italic>
carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01],
<italic>p</italic>
= 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China.</p>
</sec>
<sec id="sec003">
<title>Conclusions</title>
<p>Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and
<italic>APOE</italic>
genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.</p>
</sec>
</abstract>
<abstract abstract-type="toc">
<p>In a collaborative cohort study, Darren Lipnicki and colleagues investigate associations between age-related cognitive decline and sex, education, and apolipoprotein E genotype across ethnocultural groups and geographic regions.</p>
</abstract>
<abstract abstract-type="summary">
<title>Author summary</title>
<sec id="sec004">
<title>Why was this study done?</title>
<list list-type="bullet">
<list-item>
<p>The prevalence of dementia varies around the world, but it is not known whether international differences in rates of cognitive decline contribute to this.</p>
</list-item>
<list-item>
<p>The extent to which risk and protective factors such as sex, education, and apolipoprotein E ε4 allele (
<italic>APOE*4</italic>
) carrier status have different associations with dementia in different ethnocultural groups and geographic regions is also not known.</p>
</list-item>
</list>
</sec>
<sec id="sec005">
<title>What did the researchers do and find?</title>
<list list-type="bullet">
<list-item>
<p>We analyzed cognitive performance data from 42,170 mostly elderly individuals, provided by 14 studies of aging representing 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States).</p>
</list-item>
<list-item>
<p>The Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores all declined with age, and rates of decline accelerated with age.</p>
</list-item>
<list-item>
<p>The 14 studies showed different rates of decline, and decline in MMSE scores was faster for Asians than whites, females than males, and
<italic>APOE*4</italic>
carriers than non-carriers.
<italic>APOE*4</italic>
carriers also declined faster than non-carriers on test of memory, processing speed, and language.</p>
</list-item>
</list>
</sec>
<sec id="sec006">
<title>What do these findings mean?</title>
<list list-type="bullet">
<list-item>
<p>International differences in rates of cognitive decline might contribute to the global variation in dementia prevalence.</p>
</list-item>
<list-item>
<p>Further research is needed to determine whether cardiovascular health, lifestyle, and other risk factors for dementia have different associations with cognitive decline in different ethnocultural groups and geographic regions.</p>
</list-item>
</list>
</sec>
</abstract>
<funding-group>
<funding-statement>Funding for COSMIC comes from a National Health and Medical Research Council of Australia Program Grant (ID 1093083) and philanthropic contributions to The Dementia Momentum Fund (PSS). Funding for each of the contributing studies is as follows: The Brazilian Ministry of Health and Ministry of Science and Technology (MFLC, ECC); Major awards from the UK Medical Research Council and the Department of Health (CB, FEM, BCMS); National Institute on Health/National Institute on Aging grants (5P01 AG003949, 1R03 AG045474; RBL, MJK); Novartis (KR, JS, MLA); Alzheimer’s Association (IIRG-09-133014), ESPA-EU program Excellence Grant (ARISTEIA), which is co-funded by the European Social Fund and Greek National resources (189 10276/8/9/2011), and Ministry for Health and Social Solidarity, Greece (ΔΥ2β/οικ.51657/14.4.2009; NS, MY, ED); Mr. Lai Seung Hung & Mrs. Lai Chan Pui Ngong Dementia in Hong Kong Research Fund, and an educational fund from Eisai (LCWL, CHYW, AWTF); Fondazione Golgi Cenci and Federazione Alzheimer Italia (AG, RV, AD); Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea [Grant No. HI09C1379 (A092077); KWK, JWH, THK]; National Health and Medical Research Council of Australia (Grants 973302, 179805, 157125 and 1002160; KJA, NC, PB); Wellcome Trust (grant code GR066133MA) and FAPESP-Brazil (grant code 2004/12694-8; MS); Health and Labour Sciences Research Grant from the Ministry of Health, Labour and Welfare of Japan (H25-Ninchisho-Ippan-004) and a research grant from Sasaguri town, Fukuoka, Japan (SK, SC, KN); Research grants (No. 03/ 121/17/214 and No. 08/1/21/19/567) from the Biomedical Research Council, Agency for Science, Technology and Research (A_STAR) in Singapore (TPN, QG); National Health & Medical Research Council of Australia Program Grant (ID 350833; PSS, DML, NAK, JDC, AT, GA, SR, HB); Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spanish Ministry of Health, Madrid, Spain (Grants 94/ 1562, 97/1321E, 98/0103, 01/0255, 03/0815, 06/0617, and G03/128) and Pfizer Foundation, Madrid (AL, RLA, JS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts>
<fig-count count="3"></fig-count>
<table-count count="2"></table-count>
<page-count count="21"></page-count>
</counts>
<custom-meta-group>
<custom-meta id="data-availability">
<meta-name>Data Availability</meta-name>
<meta-value>Data cannot be shared openly based on the terms of each study, however researchers may apply to the COSMIC Scientific Steering Committee by contacting Dr Kristan Kang (
<email>k.kang@unsw.edu.au</email>
).</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes>
<title>Data Availability</title>
<p>Data cannot be shared openly based on the terms of each study, however researchers may apply to the COSMIC Scientific Steering Committee by contacting Dr Kristan Kang (
<email>k.kang@unsw.edu.au</email>
).</p>
</notes>
</front>
</pmc>
</record>

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