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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

Darren Lipnicki 1 John Crawford 1 Rajib Dutta 1 Anbupalam Thalamuthu 1 Nicole Kochan 1 Gavin Andrews 1 M. Fernanda Lima-Costa 2 Erico Castro-Costa 2 Carol Brayne 3 Fiona Matthews 3, 4 Blossom Stephan 4 Richard Lipton 5 Mindy Katz 5 Karen Ritchie 6, 7, 8 Jacqueline Scali 6, 7 Marie-Laure Ancelin 6, 7 Nikolaos Scarmeas 9, 10 Mary Yannakoulia 11 Efthimios Dardiotis Linda Lam 12 Candy Wong 13 Ada Fung 12 Antonio Guaita Roberta Vaccaro Annalisa Davin Ki Kim 14 Ji Won Han 14 Tae Kim 15 Kaarin Anstey 16 Nicolas Cherbuin 16 Peter Butterworth 16 Marcia Scazufca 17 Shuzo Kumagai 18 Sanmei Chen 19 Kenji Narazaki 20 Tze Ng 21 Qi Gao 21 Simone Reppermund 1 Henry Brodaty 1 Antonio Lobo 22, 23 Raúl Lopez-Anton 22 Javier Santabárbara 22, 23 Perminder Sachdev 1, *
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.
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Darren Lipnicki, John Crawford, Rajib Dutta, Anbupalam Thalamuthu, Nicole Kochan, et al.. Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study. PLoS Medicine, Public Library of Science, 2017, 14 (3), pp.e1002261. ⟨10.1371/journal.pmed.1002261⟩. ⟨hal-02399392⟩



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