Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study
Creators: name: Lipnick, Darren M.
name: Crawford, John D.
name: Dutta, Rajib
name: Thalamuthu, Anbupalam
name: Kochan, Nicole A.
name: Andrews, Gavin
name: Lima-Costa, M. Fernanda
name: Castro-Costa, Erico
name: Brayne, Carol
name: Matthews, Fiona E.
name: Stephan, Blossom C. M.
name: Lipton, Richard B.
name: Katz, Mindy J.
name: Ritchie, Karen
name: Scali, Jacqueline
name: Ancelin, Marie-Laure
name: Scarmeas, Nikolaos
name: Yannakoulia, Mary
name: Dardiotis, Efthimios
name: Lam, Linda C. W.
name: Wong, Candy H. Y.
name: Fung, Ada W. T.
name: Guaita, Antonio
name: Vaccaro, Roberta
name: Davin, Annalisa
name: Kim, Ki Woong
name: Han, Ji Won
name: Kim, Tae Hui
name: Anstey, Kaarin J.
name: Cherbuin, Nicolas
name: Butterworth, Peter
name: Scazufca, Marcia
name: Kumagai, Shuzo
name: Chen, Sanmei
name: Narazaki, Kenji
name: Ng, Tze Pin
name: Gao, Qi
name: Reppermund, Simone
name: Brodaty, Henry
name: Lobo, Antonio
name: Lopez-Anton, Rau´L
name: Santaba´Rbara, Javier
name: Sachdev, Perminder S.
name: Cohort Studies Of Memory In An International Consortium
Publisher: name: Columbia University
Year: 2017
Subjects: subject: Cognitive neuroscience
subject: Apolipoprotein E gene
subject: Aging
subject: Genetics
subject: FOS: Biological sciences

description: 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 &lt; 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 &lt; 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 &lt; 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.