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

Date Published: March 21, 2017

Publisher: Public Library of Science

Author(s): Darren M. Lipnicki, John D. Crawford, Rajib Dutta, Anbupalam Thalamuthu, Nicole A. Kochan, Gavin Andrews, M. Fernanda Lima-Costa, Erico Castro-Costa, Carol Brayne, Fiona E. Matthews, Blossom C. M. Stephan, Richard B. Lipton, Mindy J. Katz, Karen Ritchie, Jacqueline Scali, Marie-Laure Ancelin, Nikolaos Scarmeas, Mary Yannakoulia, Efthimios Dardiotis, Linda C. W. Lam, Candy H. Y. Wong, Ada W. T. Fung, Antonio Guaita, Roberta Vaccaro, Annalisa Davin, Ki Woong Kim, Ji Won Han, Tae Hui Kim, Kaarin J. Anstey, Nicolas Cherbuin, Peter Butterworth, Marcia Scazufca, Shuzo Kumagai, Sanmei Chen, Kenji Narazaki, Tze Pin Ng, Qi Gao, Simone Reppermund, Henry Brodaty, Antonio Lobo, Raúl Lopez-Anton, Javier Santabárbara, Perminder S. Sachdev, Bruce L. Miller

Abstract: BackgroundThe 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 findingsWe 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.ConclusionsCognitive 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.

Partial Text: The age-specific prevalence of dementia varies around the world, reportedly being the highest in Latin America and lowest in sub-Saharan Africa [1]. While age-specific prevalence is a good indicator of the population burden of dementia, the relative risk of dementia in different countries is better reflected in the age-specific incidence data. Unfortunately, such data are frequently lacking, especially in low- and middle-income countries. A reasonable proxy for dementia incidence is the rate of cognitive decline, with the expectation that more rapid cognitive decline will lead to higher rates of dementia in one population than another. Differences in the rates of cognitive decline may also contribute to global variation in late-life cognitive deficits less severe than dementia, such as the prevalence of mild cognitive impairment (MCI), which varies even when applying uniform diagnostic criteria [2], and performance on immediate word list recall tasks [3].

We used individual participant-level data provided by members of the COSMIC collaboration to investigate rates of cognitive decline in 14 longitudinal population-based studies of cognitive aging, representing 12 countries and 5 continents. We also investigated the extent to which sex, education, and APOE*4 carrier status were associated with cognitive performance and decline across these diverse ethnocultural groups and geographic regions. Our findings were minimally affected when repeating our analyses with cases of baseline dementia removed, probably in large part because the overall proportion of these cases was low (3.3%).

In conclusion, we found that cognitive performance consistently declined with age, and more rapidly with increasing age, across cohorts from a diverse range of ethnocultural groups and geographical regions. Similar patterns of results were found for analyses that either included or excluded individuals with dementia at baseline. The strengths of the observed associations varied across the cohorts, and there were also some small differences between groups of cohorts classified as white or Asian. This suggests that different rates of cognitive decline might contribute, via different rates of incident dementia, to the global variation in dementia prevalence. Given the diversity of cohorts and our large overall sample size (more than 42,000 individuals), the associations with sex, education, and APOE genotype we found should help to clarify the contributions of these factors to cognitive ageing on a global scale. We intend for future research with COSMIC cohorts to explore how risk factors not investigated in the current study, including other genetic, epigenetic, cardiovascular, and lifestyle-related factors, contribute to cognitive decline and neurocognitive disorders, and to determine the extent to which their associations vary internationally. We also aim to feature populations from ethnocultural groups and geographical regions for which the current study lacked data, including Africa, India, and mainland China. This will provide important information for developing efficacious interventions to prevent or minimize cognitive impairment and dementia in the rapidly aging population worldwide.



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