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


RESULTS
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.
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.
Darren M
DM
Lipnicki
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.
John D
JD
Crawford
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.
Rajib
http://orcid.org/0000-0002-2267-4458
R
Dutta
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.
Anbupalam
A
Thalamuthu
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.
Nicole A
http://orcid.org/0000-0002-8630-6398
NA
Kochan
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.
Gavin
http://orcid.org/0000-0002-4315-2173
G
Andrews
Rene Rachou Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
M Fernanda
http://orcid.org/0000-0002-3474-2980
MF
Lima-Costa
Rene Rachou Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Erico
E
Castro-Costa
Department of Public Health and Primary Care, Cambridge University, Cambridge, United Kingdom.
Carol
http://orcid.org/0000-0001-5307-663X
C
Brayne
MRC Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom.|Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom.
Fiona E
http://orcid.org/0000-0002-1728-2388
FE
Matthews
Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom.
Blossom C M
BC
Stephan
Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York, United States of America.|Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Yeshiva University, New York City, New York, United States of America.
Richard B
RB
Lipton
Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York, United States of America.
Mindy J
MJ
Katz
Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier, France.|Université de Montpellier, Montpellier, France.|Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Karen
K
Ritchie
Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier, France.|Université de Montpellier, Montpellier, France.
Jacqueline
J
Scali
Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier, France.|Université de Montpellier, Montpellier, France.
Marie-Laure
ML
Ancelin
National and Kapodistrian University of Athens, Athens, Greece.|Columbia University, New York City, New York, United States of America.
Nikolaos
N
Scarmeas
Harokopio University, Athens, Greece.
Mary
M
Yannakoulia
University of Thessaly, Larissa, Greece.
Efthimios
E
Dardiotis
Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China.
Linda C W
LC
Lam
Department of Psychiatry, Tai Po Hospital, Hong Kong SAR, China.
Candy H Y
http://orcid.org/0000-0002-5083-7496
CH
Wong
Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China.
Ada W T
AW
Fung
GolgiCenci Foundation, Abbiategrasso, Milan, Italy.
Antonio
http://orcid.org/0000-0003-3954-5932
A
Guaita
GolgiCenci Foundation, Abbiategrasso, Milan, Italy.
Roberta
R
Vaccaro
GolgiCenci Foundation, Abbiategrasso, Milan, Italy.
Annalisa
A
Davin
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea.|Department of Psychiatry, Seoul National University, College of Medicine, Seoul, Korea.|Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, Korea.
Ki Woong
KW
Kim
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea.
Ji Won
JW
Han
Department of Psychiatry, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea.
Tae Hui
TH
Kim
Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra, Australia.
Kaarin J
http://orcid.org/0000-0002-9706-9316
KJ
Anstey
Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra, Australia.
Nicolas
N
Cherbuin
Centre for Research on Ageing, Health and Wellbeing, College of Medicine, Biology and Environment, The Australian National University, Canberra, Australia.
Peter
P
Butterworth
Institute of Psychiatry and LIM-23, Clinics Hospital, University of São Paulo, São Paulo, Brazil.
Marcia
M
Scazufca
Faculty of Arts and Science, Kyushu University, Kasuga City, Japan.
Shuzo
S
Kumagai
Xiangya School of Nursing, Central South University, Changsha, China.
Sanmei
S
Chen
Faculty of Socio-Environmental Studies, Fukuoka Institute of Technology, Fukuoka City, Japan.
Kenji
K
Narazaki
Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Tze Pin
http://orcid.org/0000-0001-9585-855X
TP
Ng
Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Qi
http://orcid.org/0000-0002-1965-7411
Q
Gao
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.
Simone
http://orcid.org/0000-0003-4785-0224
S
Reppermund
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.|Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia.
Henry
http://orcid.org/0000-0001-9487-6617
H
Brodaty
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain.|Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain.
Antonio
A
Lobo
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain.|Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spanish Ministry of Economy and Competitiveness, Madrid, Spain.
Raúl
R
Lopez-Anton
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain.|Department of Microbiology, Preventive Medicine and Public Health, University of Zaragoza, Spain.
Javier
J
Santabárbara
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.|Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia.
Perminder S
PS
Sachdev
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000453:epidemiology* / Q000209:etiology; D015331:Cohort Studies; D004522:Educational Status; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012737:Sex Factors
C000612345:ApoE protein, human; D001057:Apolipoproteins E