Tze Pin Ng, Erico Castro-Costa, John D. Crawford, Annalisa Davin, Mary Yannakoulia, Simone Reppermund, Candy H. Y. Wong, Tae Hui Kim, Roberta Vaccaro, Gavin Andrews, Qi Gao, Anbupalam Thalamuthu, Kaarin J. Anstey, Antonio Lobo, Mindy J. Katz, Ji Won Han, Darren M. Lipnicki, Javier Santabárbara, Peter Butterworth, Ki Woong Kim, Carol Brayne, Efthimios Dardiotis, Linda C. W. Lam, Rajib Kumar Dutta, Fiona E. Matthews, Nicole A. Kochan, Marie-Laure Ancelin, Raúl López-Antón, Blossom C. M. Stephan, Marcia Scazufca, Shuzo Kumagai, Nikolaos Scarmeas, Henry Brodaty, Ada W.T. Fung, M. Fernanda Lima-Costa, Nicolas Cherbuin, Kenji Narazaki, Jacqueline Scali, Richard B. Lipton, Karen Ritchie, Sanmei Chen, Antonio Guaita, Perminder S. Sachdev, Dutta, Rajib [0000-0002-2267-4458], Kochan, Nicole A [0000-0002-8630-6398], Andrews, Gavin [0000-0002-4315-2173], Lima-Costa, M Fernanda [0000-0002-3474-2980], Brayne, Carol [0000-0001-5307-663X], Matthews, Fiona E [0000-0002-1728-2388], Wong, Candy HY [0000-0002-5083-7496], Guaita, Antonio [0000-0003-3954-5932], Anstey, Kaarin J [0000-0002-9706-9316], Ng, Tze Pin [0000-0001-9585-855X], Gao, Qi [0000-0002-1965-7411], Reppermund, Simone [0000-0003-4785-0224], Brodaty, Henry [0000-0001-9487-6617], Apollo - University of Cambridge Repository, University of New South Wales [Sydney] (UNSW), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), University of Cambridge [UK] (CAM), Newcastle University [Newcastle], Albert Einstein College of Medicine [New York], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Edinburgh, National and Kapodistrian University of Athens (NKUA), Columbia University [New York], Harokopio University of Athens, The Chinese University of Hong Kong [Hong Kong], Tai Po Hospital, Seoul National University [Seoul] (SNU), Yonsei University, Australian National University (ANU), University of São Paulo (USP), Kyushu University [Fukuoka], Central South University [Changsha], Fukuoka Institute of Technology (FIT), National University of Singapore (NUS), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Zaragoza - Universidad de Zaragoza [Zaragoza], 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., and Matthews, Fiona [0000-0002-1728-2388]
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., 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., Author summary Why was this study done? The prevalence of dementia varies around the world, but it is not known whether international differences in rates of cognitive decline contribute to this. The extent to which risk and protective factors such as sex, education, and apolipoprotein E ε4 allele (APOE*4) carrier status have different associations with dementia in different ethnocultural groups and geographic regions is also not known. What did the researchers do and find? 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). 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. The 14 studies showed different rates of decline, and decline in MMSE scores was faster for Asians than whites, females than males, and APOE*4 carriers than non-carriers. APOE*4 carriers also declined faster than non-carriers on test of memory, processing speed, and language. What do these findings mean? International differences in rates of cognitive decline might contribute to the global variation in dementia prevalence. 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.