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1. Dose‐response relationship between late‐life physical activity and incident dementia: A pooled analysis of 10 cohort studies of memory in an international consortium

Author

Wu, Wanqing, Ding, Ding, Zhao, Qianhua, Xiao, Zhenxu, Luo, Jianfeng, Ganguli, Mary, Hughes, Tiffany F, Jacobsen, Erin, Haan, Mary N, Dang, Kristine, Lima‐Costa, Maria Fernanda, Blay, Sergio Luis, Castro‐Costa, Erico, Ng, Tze Pin, Gwee, Xinyi, Gao, Qi, Gureje, Oye, Ojagbemi, Akin, Bello, Toyin, Shahar, Suzana, Ludin, Arimi Fitri Mat, Rivan, Nurul Fatin Malek, Scarmeas, Nikolaos, Anastasiou, Costas A, Yannakoulia, Mary, Brodaty, Henry, Crawford, John D, Lipton, Richard B, Derby, Carol A, Katz, Mindy J, Lipnicki, Darren M, Sachdev, Perminder S, and Consortium, for Cohort Studies of Memory in an International

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Acquired Cognitive Impairment, Aging, Rehabilitation, Clinical Research, Dementia, Prevention, Brain Disorders, Neurological, Humans, Aged, Cohort Studies, Proportional Hazards Models, Risk Factors, cohort, dementia, dose-response, physical activity, pooled analysis, population-based, for Cohort Studies of Memory in an International Consortium, Neurosciences, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionThough consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear.MethodsWe harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults.ResultsUsing no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week).DiscussionThis cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

Published
2023

2. Does parity matter in women’s risk of dementia? A COSMIC collaboration cohort study

Author

Bae, Jong Bin, Lipnicki, Darren M, Han, Ji Won, Sachdev, Perminder S, Kim, Tae Hui, Kwak, Kyung Phil, Kim, Bong Jo, Kim, Shin Gyeom, Kim, Jeong Lan, Moon, Seok Woo, Park, Joon Hyuk, Ryu, Seung-Ho, Youn, Jong Chul, Lee, Dong Young, Lee, Dong Woo, Lee, Seok Bum, Lee, Jung Jae, Jhoo, Jin Hyeong, Llibre-Rodriguez, Juan J, Llibre-Guerra, Jorge J, Valhuerdi-Cepero, Adolfo J, Ritchie, Karen, Ancelin, Marie-Laure, Carriere, Isabelle, Skoog, Ingmar, Najar, Jenna, Sterner, Therese Rydberg, Scarmeas, Nikolaos, Yannakoulia, Mary, Dardiotis, Efthimios, Meguro, Kenichi, Kasai, Mari, Nakamura, Kei, Riedel-Heller, Steffi, Roehr, Susanne, Pabst, Alexander, van Boxtel, Martin, Köhler, Sebastian, Ding, Ding, Zhao, Qianhua, Liang, Xiaoniu, Scazufca, Marcia, Lobo, Antonio, De-la-Cámara, Concepción, Lobo, Elena, and Kim, Ki Woong

Subjects
Alzheimer's Disease, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Neurodegenerative, Prevention, Neurosciences, Dementia, Aging, Acquired Cognitive Impairment, Neurological, Cohort Studies, Female, Humans, Middle Aged, Parity, Risk Factors, Alzheimer's disease, Risk factors, Women, for Cohort Studies of Memory in an International Consortium, Alzheimer’s disease, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundDementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied.MethodsWe harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype.ResultsAcross all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia.ConclusionParity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes.

Published
2020

3. A cross‐national study of depression in preclinical dementia: A COSMIC collaboration study

Author

Carles, Sophie, Carrière, Isabelle, Reppermund, Simone, Davin, Annalisa, Guaita, Antonio, Vaccaro, Roberta, Ganguli, Mary, Jacobsen, Erin P, Beer, Joanne C, Riedel‐Heller, Steffi G, Roehr, Susanne, Pabst, Alexander, Haan, Mary N, Brodaty, Henry, Kochan, Nicole A, Trollor, Julian N, Kim, Ki Woong, Han, Ji Won, Suh, Seung Wan, Lobo, Antonio, De Camara, Concepción, Lobo, Elena, Lipnicki, Darren M, Sachdev, Perminder S, Ancelin, Marie‐Laure, Ritchie, Karen, and Consortium, for Cohort Studies of Memory in an International

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Brain Disorders, Mental Health, Aging, Depression, Alzheimer's Disease, Acquired Cognitive Impairment, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurological, Aged, Aged, 80 and over, Cohort Studies, Female, Humans, Incidence, Longitudinal Studies, Male, Prodromal Symptoms, dementia, depression, incidence, for Cohort Studies of Memory in an International Consortium, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionDepression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain.MethodsLongitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics.ResultsA common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates.DiscussionThe results support the hypothesis that depression occurring in the preclinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.

Published
2020

4. Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment

Author

Makkar, Steve R, Lipnicki, Darren M, Crawford, John D, Kochan, Nicole A, Castro-Costa, Erico, Lima-Costa, Maria Fernanda, Diniz, Breno Satler, Brayne, Carol, Stephan, Blossom, Matthews, Fiona, Llibre-Rodriguez, Juan J, Llibre-Guerra, Jorge J, Valhuerdi-Cepero, Adolfo J, Lipton, Richard B, Katz, Mindy J, Zammit, Andrea, Ritchie, Karen, Carles, Sophie, Carriere, Isabelle, Scarmeas, Nikolaos, Yannakoulia, Mary, Kosmidis, Mary, Lam, Linda, Fung, Ada, Chan, Wai Chi, Guaita, Antonio, Vaccaro, Roberta, Davin, Annalisa, Kim, Ki Woong, Han, Ji Won, Suh, Seung Wan, Riedel-Heller, Steffi G, Roehr, Susanne, Pabst, Alexander, Ganguli, Mary, Hughes, Tiffany F, Jacobsen, Erin P, Anstey, Kaarin J, Cherbuin, Nicolas, Haan, Mary N, Aiello, Allison E, Dang, Kristina, Kumagai, Shuzo, Narazaki, Kenji, Chen, Sanmei, Ng, Tze Pin, Gao, Qi, Nyunt, Ma Shwe Zin, Meguro, Kenichi, Yamaguchi, Satoshi, Ishii, Hiroshi, Lobo, Antonio, Escolar, Elena Lobo, De la Cámara, Concepción, Brodaty, Henry, Trollor, Julian N, Leung, Yvonne, Lo, Jessica W, Sachdev, Perminder, and Consortium, for Cohort Studies of Memory in an International

Subjects
Public Health, Health Sciences, Women's Health, Aging, Neurosciences, Neurodegenerative, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Behavioral and Social Science, Alzheimer's Disease, Brain Disorders, Dementia, Quality Education, Aged, Aged, 80 and over, Apolipoprotein E4, Cognitive Dysfunction, Educational Status, Ethnicity, Female, Humans, Longitudinal Studies, Male, Risk Factors, Cognitive decline, Education, Ageing, Sex, Age, for Cohort Studies of Memory in an International Consortium, Clinical Sciences, Geriatrics, Clinical sciences, Public health
Abstract

BackgroundWe examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).MethodsParticipants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.ResultsCompared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P

Published
2020

5. Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

Author

Lipnicki, Darren M, Makkar, Steve R, Crawford, John D, Thalamuthu, Anbupalam, Kochan, Nicole A, Lima-Costa, Maria Fernanda, Castro-Costa, Erico, Ferri, Cleusa Pinheiro, Brayne, Carol, Stephan, Blossom, Llibre-Rodriguez, Juan J, Llibre-Guerra, Jorge J, Valhuerdi-Cepero, Adolfo J, Lipton, Richard B, Katz, Mindy J, Derby, Carol A, Ritchie, Karen, Ancelin, Marie-Laure, Carrière, Isabelle, Scarmeas, Nikolaos, Yannakoulia, Mary, Hadjigeorgiou, Georgios M, Lam, Linda, Chan, Wai-Chi, Fung, Ada, Guaita, Antonio, Vaccaro, Roberta, Davin, Annalisa, Kim, Ki Woong, Han, Ji Won, Suh, Seung Wan, Riedel-Heller, Steffi G, Roehr, Susanne, Pabst, Alexander, van Boxtel, Martin, Köhler, Sebastian, Deckers, Kay, Ganguli, Mary, Jacobsen, Erin P, Hughes, Tiffany F, Anstey, Kaarin J, Cherbuin, Nicolas, Haan, Mary N, Aiello, Allison E, Dang, Kristina, Kumagai, Shuzo, Chen, Tao, Narazaki, Kenji, Ng, Tze Pin, Gao, Qi, Nyunt, Ma Shwe Zin, Scazufca, Marcia, Brodaty, Henry, Numbers, Katya, Trollor, Julian N, Meguro, Kenichi, Yamaguchi, Satoshi, Ishii, Hiroshi, Lobo, Antonio, Lopez-Anton, Raul, Santabárbara, Javier, Leung, Yvonne, Lo, Jessica W, Popovic, Gordana, Sachdev, Perminder S, and for Cohort Studies of Memory in an International Consortium (COSMIC)

Subjects
for Cohort Studies of Memory in an International Consortium, Humans, Diabetes Mellitus, Exercise, Risk Assessment, Risk Factors, Smoking, Cognition, Age Factors, Comorbidity, Health Education, Aged, Aged, 80 and over, Middle Aged, Ethnic Groups, Female, Male, Stroke, Cognitive Dysfunction, and over, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundWith no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.Methods and findingsWe harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife.ConclusionsThese results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

Published
2019

6. Does parity matter in women’s risk of dementia? A COSMIC collaboration cohort study

Author

Shin Gyeom Kim, John D. Crawford, Jorge J. Llibre-Guerra, Marie-Laure Ancelin, Murali Krishna, Richard B. Lipton, Jeong Lan Kim, Mindy J. Katz, Jong Bin Bae, Mari Kasai, Susanne Roehr, Iraj Nabipour, Toshiharu Ninimiya, Jin Hyeong Jhoo, Concepción De-la-Cámara, Antonio Lobo, Edwin S. Lowe, Perminder S. Sachdev, Hugh C. Hendrie, Marcia Scazufca, Ronald C. Petersen, Darren M. Lipnicki, Tze Pin Ng, Seungho Ryu, Erico Castro-Costa, Shuzo Kumagai, Bagher Larijani, Jenna Najar, Nicole A. Kochan, Bong Jo Kim, Jessica W. Lo, Suzana Shahar, Juan J. Llibre-Rodriguez, Seok Woo Moon, Elena Lobo, Sebastian Köhler, Ji Won Han, Kenneth Rockwood, Richard Walker, Adolfo J. Valhuerdi-Cepero, Henry Brodaty, Efthimios Dardiotis, Ding Ding, Alexander Pabst, Dong Young Lee, Nikolaos Scarmeas, Louisa Jorm, Antonio Guaita, Kyung Phil Kwak, Jong Chul Youn, Tae Hui Kim, Mary Ganguli, Joon Hyuk Park, Michael Crowe, Isabelle Carrière, Martin P.J. van Boxtel, Kenichi Meguro, Steve R. Makkar, Karen Ritchie, Kaarin J. Anstey, Mary Yannakoulia, Dong Woo Lee, Xiao Shifu, Anbupalam Thalamuthu, Pierre-Marie Preux, Therese Rydberg Sterner, Ki Woong Kim, Yvonne Leung, Nicole Schupf, Liang Kung Chen, Richard Mayeux, Mary N. Haan, Qianhua Zhao, Jung Jae Lee, Linda Lam, Kei Nakamura, Maëlenn Guerchet, Seok Bum Lee, Xiaoniu Liang, Jacqueline C. Dominguez, Ingmar Skoog, Steffi G. Riedel-Heller, Yuda Turana, 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), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatrie & Neuropsychologie, Section Neuropsychology, RS: FPN NPPP I, and RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience

Subjects
Aging, [SDV]Life Sciences [q-bio], PREMATURE, lcsh:Medicine, Neurodegenerative, Medical and Health Sciences, Cohort Studies, 0302 clinical medicine, Epidemiology, Childbirth, 030212 general & internal medicine, ESTRADIOL, POPULATION, education.field_of_study, General Medicine, ASSOCIATION, Middle Aged, Alzheimer's disease, 3. Good health, PREVALENCE, ALZHEIMERS-DISEASE, Parity, PREGNANCY, Neurological, Cohort, Female, HEALTH, Alzheimer’s disease, Research Article, Cohort study, medicine.medical_specialty, Population, 03 medical and health sciences, Clinical Research, General & Internal Medicine, mental disorders, Acquired Cognitive Impairment, medicine, Humans, Dementia, Women, Vascular dementia, education, business.industry, Prevention, lcsh:R, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Odds ratio, PROFILES, medicine.disease, Brain Disorders, for Cohort Studies of Memory in an International Consortium, ATHEROSCLEROSIS, Risk factors, business, 030217 neurology & neurosurgery, Demography
Abstract

Background Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. Results Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10–1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38–6.47) and Latin America (OR = 1.49, 95% CI = 1.04–2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33–3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81–26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07–3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44–8.35) in Asia. Conclusion Parity is associated with women’s risk of dementia, though this is not uniform across regions and dementia subtypes.

Published
2020
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7. Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment

Author

Makkar, S.R., Lipnicki, D.M., Crawford, J.D., Kochan, N.A., Castro-Costa, E., Lima-Costa, M.F., Diniz, B.S., Brayne, C., Stephan, B., Matthews, F., Llibre-Rodriguez, J.J., Llibre-Guerra, J.J., Valhuerdi-Cepero, A.J., Lipton, R.B., Katz, M.J., Zammit, A., Ritchie, K., Carles, S., Carriere, I., Scarmeas, N., Yannakoulia, M., Kosmidis, M., Lam, L., Fung, A., Chan, W.C., Guaita, A., Vaccaro, R., Davin, A., Kim, K.W., Han, J.W., Suh, S.W., Riedel-Heller, S.G., Roehr, S., Pabst, A., Ganguli, M., Hughes, T.F., Jacobsen, E.P., Anstey, K.J., Cherbuin, N., Haan, M.N., Aiello, A.E., Dang, K., Kumagai, S., Narazaki, K., Chen, S., Ng, T.P., Gao, Q., Nyunt, M.S.Z., Meguro, K., Yamaguchi, S., Ishii, H., Lobo, A., Lobo Escolar, E., De la Cámara, C., Brodaty, H., Trollor, J.N., Leung, Y., Lo, J.W., Sachdev, P., for, Cohort, Studies, of, Memory, in, an, International, Consortium, (COSMIC), University of New South Wales [Sydney] (UNSW), Fiocruz Minas - René Rachou Research Center / Instituto René Rachou [Belo Horizonte, Brésil], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), University of Toronto, University of Cambridge [UK] (CAM), Newcastle University [Newcastle], University of Havana (Universidad de la Habana) (UH), University of California [San Francisco] (UCSF), University of California, Universidad de Matanzas, 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), University of Edinburgh, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Colombière, Columbia University [New York], National and Kapodistrian University of Athens (NKUA), Harokopio University of Athens, Aristotle University of Thessaloniki, The Chinese University of Hong Kong [Hong Kong], The Hong Kong Polytechnic University [Hong Kong] (POLYU), The University of Hong Kong (HKU), Golgi Cenci Foundation, Seoul National University College of Natural Sciences, Seoul National University Bundang Hospital (SNUBH), Universität Leipzig [Leipzig], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Youngstown State University (YSU), Australian National University (ANU), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Kyushu University [Fukuoka], Fukuoka Institute of Technology (FIT), National Center for Global Health and Medicine [Japan] (NCGM), National University of Singapore (NUS), Tohoku University [Sendai], and University of Zaragoza - Universidad de Zaragoza [Zaragoza]

Subjects
Apolipoprotein E, Male, Aging, Health (social science), Apolipoprotein B, [SDV]Life Sciences [q-bio], Apolipoprotein E4, Ethnic group, Cognitive decline, MESH: Cognitive Dysfunction, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Risk Factors, Risk Factors, 80 and over, Ethnicity, Medicine, 030212 general & internal medicine, Longitudinal Studies, MESH: Apolipoprotein E4, Cognitive impairment, MESH: Longitudinal Studies, Aged, 80 and over, MESH: Aged, biology, Hazard ratio, Educational Status, MESH: Ethnic Groups, Female, Sex, Clinical Sciences, Article, Education, 03 medical and health sciences, Age, Clinical Research, Acquired Cognitive Impairment, Humans, Cognitive Dysfunction, Aged, MESH: Humans, 030214 geriatrics, business.industry, Prevention, Neurosciences, Educational attainment, MESH: Male, Brain Disorders, Quality Education, Ageing, for Cohort Studies of Memory in an International Consortium, Geriatrics, biology.protein, Dementia, Geriatrics and Gerontology, business, MESH: Educational Status, Gerontology, MESH: Female, Demography
Abstract

International audience; Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers.Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.

Published
2020
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8. Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study

Author

Mary N. Haan, Allison E. Aiello, Erico Castro-Costa, Julian N. Trollor, Linda Lam, Jessica W. Lo, Jorge J. Llibre-Guerra, Ki Woong Kim, Katya Numbers, Kenji Narazaki, Carol Brayne, Antonio Guaita, Satoshi Yamaguchi, Annalisa Davin, Antonio Lobo, Raúl López-Antón, Adolfo J. Valhuerdi-Cepero, Marcia Scazufca, Kenichi Meguro, Seung Wan Suh, Roberta Vaccaro, Martin P.J. van Boxtel, Shuzo Kumagai, Georgios M. Hadjigeorgiou, Perminder S. Sachdev, Isabelle Carrière, Carol A. Derby, Steve R. Makkar, Tze Pin Ng, Kristina Dang, Kaarin J. Anstey, Qi Gao, Anbupalam Thalamuthu, Steffi G. Riedel-Heller, Tiffany F. Hughes, Javier Santabárbara, Kay Deckers, Mary Yannakoulia, Cleusa P. Ferri, Marie-Laure Ancelin, Ji Won Han, Gordana C. Popovic, Richard B. Lipton, Ma Shwe Zin Nyunt, Blossom C. M. Stephan, Mary Ganguli, Wai Chi Chan, Karen Ritchie, Mindy J. Katz, Henry Brodaty, Alexander Pabst, Yvonne Leung, Ada Fung, Erin Jacobsen, Darren M. Lipnicki, Hiroshi Ishii, Juan J. Llibre-Rodriguez, Sebastian Köhler, Nicolas Cherbuin, Nicole A. Kochan, Nikolaos Scarmeas, Susanne Roehr, Tao Chen, Maria Fernanda Lima-Costa, John D. Crawford, Psychiatrie & Neuropsychologie, Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, Hadjigeorgiou, Georgios M. [0000-0001-5386-4273], Yannakoulia, Mary [0000-0003-2171-7337], Scarmeas, Nikolaos [0000-0001-6453-8908], Herrada, Anthony, University of New South Wales [Sydney] (UNSW), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Federal University of Sao Paulo (Unifesp), University of Cambridge [UK] (CAM), Newcastle University [Newcastle], University of Havana (Universidad de la Habana) (UH), University of California (UC), Universidad de Matanzas, 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, University of Cyprus [Nicosia] (UCY), The Chinese University of Hong Kong [Hong Kong], The University of Hong Kong (HKU), The Hong Kong Polytechnic University [Hong Kong] (POLYU), Seoul National University [Seoul] (SNU), Universität Leipzig [Leipzig], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Youngstown State University (YSU), Australian National University (ANU), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Kyushu University, Fukuoka Institute of Technology (FIT), National University of Singapore (NUS), Universidade de São Paulo = University of São Paulo (USP), Tohoku University [Sendai], 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) (PSS, HB), the National Institute On Aging of the National Institutes of Health under Award Number RF1AG057531 (PSS, MG, RBL, KR, KWK, HB), and philanthropic contributions to The Dementia Momentum Fund (UNSW Project ID PS38235) (PSS, HB). Funding for each of the contributing studies is as follows: The Brazilian Ministry of Health (Department of Science and Technology), the Brazilian Ministry of Science and Technology (National Fund for Scientific and Technological Development, Funding of Studies, Brazilian National Research Council) and the Minas Gerais State Research Foundation (MFLC, ECC), Major awards from the Medical Research Council and the Department of Health, UK (CB), The Wellcome Trust Foundation (GR066133 and GR08002) and the Cuban Ministry of Public Health (JJLR), Supported in part by National Institutes of Health grants NIA 2 P01 AG03949, the Leonard and Sylvia Marx Foundation, and the Czap Foundation (RBL, MJK), Novartis (KR, MLA), IIRG-09133014 from the Alzheimer’s Association, 189 10276/8/9/2011 from the ESPA-EU program Excellence Grant (ARISTEIA), which is co-funded by the European Social Fund and Greek National resources, and ΔΥ2β/οικ.51657/14.4.2009 from the Ministry for Health and Social Solidarity (Greece) (NS), The Mei Family Trust (LL), Financed with own funds and supported in part by 'Federazione Alzheimer Italia', Milan, Italy (AG), The Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea [Grant No. HI09C1379 (A092077)] (KWK), The Interdisciplinary Centre for Clinical Research at the University of Leipzig (Interdisziplinäres Zentrum für Klinische Forschung/IZKF, grant 01KS9504) (SGRH), Grant # R01AG07562 from the National Institute on Aging, National Institutes of Health, United States Department of Health and Human Services (MG), National Health and Medical Research Council of Australia grants 973302, 179805, 157125 and 1002160 (KA), NIH grants AG12975, T32 AG049663, ES023451 (MNH), Carolina Population Center (CPC) Funding: CPC Center grant (the P2C Center grant from NIH): P2C HD050924. CPC NICHD-NRSA Population Research Training (the T32 Training grant from NIH): T32 HD007168, Biosocial Training Grant: T32 HD091058 (AEA), JSPS KAKENHI Grant Number JP17K09146 (SK), Agency for Science Technology and Research (A*STAR) Biomedical Research Council (BMRC) [Grants: 03/1/21/17/214 and 08/1/21/19/567] and the National Medical Research Council [Grant: NMRC/1108/2007] (TPN), The Wellcome Trust Foundation and FAPESP, São Paulo, Brazill (MS), National Health & Medical Research Council of Australia Program Grant (ID 350833) (PSS, HB), Supported by grants from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness, Madrid, Spain (grants 94/1562, 97/1321E, 98/0103, 01/0255, 03/0815, 06/0617, G03/128), and the Fondo Europeo de Desarrollo Regional (FEDER) of the European Union and Gobierno de Aragón, Group #19 (AL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funders., Tsai, Alexander C, University of California, University of Cyprus [Nicosia], Kyushu University [Fukuoka], Universidade de São Paulo (USP), Lipnicki, Darren M [0000-0002-1684-3577], Kochan, Nicole A [0000-0002-8630-6398], Ferri, Cleusa Pinheiro [0000-0002-1815-7685], Brayne, Carol [0000-0001-5307-663X], Stephan, Blossom [0000-0002-1235-360X], Llibre-Guerra, Jorge J [0000-0002-2137-7750], Ritchie, Karen [0000-0002-0688-8982], Chan, Wai-Chi [0000-0002-7324-0553], Fung, Ada [0000-0001-7439-3503], Guaita, Antonio [0000-0003-3954-5932], Kim, Ki Woong [0000-0002-1103-3858], Han, Ji Won [0000-0003-2418-4257], Riedel-Heller, Steffi G [0000-0003-4321-6090], Roehr, Susanne [0000-0001-9385-0669], van Boxtel, Martin [0000-0002-3221-2150], Köhler, Sebastian [0000-0002-2398-0609], Deckers, Kay [0000-0003-1339-2974], Ganguli, Mary [0000-0003-2762-7105], Jacobsen, Erin P [0000-0002-4599-6214], Anstey, Kaarin J [0000-0002-9706-9316], Cherbuin, Nicolas [0000-0001-6481-0748], Haan, Mary N [0000-0001-9312-4501], Aiello, Allison E [0000-0001-7029-2537], Ng, Tze Pin [0000-0001-9585-855X], Gao, Qi [0000-0002-1965-7411], Scazufca, Marcia [0000-0002-4545-006X], Numbers, Katya [0000-0002-7009-2401], Ishii, Hiroshi [0000-0001-9829-7743], Lopez-Anton, Raul [0000-0002-3360-7015], Leung, Yvonne [0000-0001-9110-7054], Lo, Jessica W [0000-0003-4778-8360], Popovic, Gordana [0000-0002-1376-1058], Sachdev, Perminder S [0000-0002-9595-3220], and Apollo - University of Cambridge Repository

Subjects
Male, Aging, MESH: Cognition, Epidemiology, Comorbidity, Cardiovascular Medicine, Cardiovascular, MESH: Risk Assessment, Pathology and Laboratory Medicine, Vascular Medicine, MESH: Health Education, 0302 clinical medicine, Endocrinology, Cognition, 80 and over, Ethnicity, Public and Occupational Health, Aetiology, MESH: Cognitive Dysfunction/ethnology, Health Education, POPULATION, Cognitive Impairment, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, Depression, General Medicine, 3. Good health, ALZHEIMERS-DISEASE, Hyperlipidemia, Neurology, Cardiovascular Diseases, Medicine, social and economic factors, Cohort study, Endocrine Disorders, Cerebrovascular Diseases, Hypercholesterolemia, and over, Risk Assessment, 03 medical and health sciences, Signs and Symptoms, Clinical Research, Diabetes Mellitus, Humans, Cognitive Dysfunction, Risk factor, education, OLDER-ADULTS, MESH: Smoking/adverse effects, Exercise, Aged, MESH: Age Factors, GENDER-DIFFERENCES, MESH: Humans, Prevention, Biology and Life Sciences, Physical Activity, Prevention of disease and conditions, medicine.disease, for Cohort Studies of Memory in an International Consortium, RISK-FACTORS, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Dementia, MESH: Female, Body mass index, Demography, Neuroscience, and promotion of well-being, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MESH: Comorbidity, 030204 cardiovascular system & hematology, Medical and Health Sciences, MESH: Cognitive Dysfunction/psychology, MESH: Aged, 80 and over, MESH: Risk Factors, Risk Factors, Medicine and Health Sciences, 030212 general & internal medicine, Cognitive decline, Stroke, MESH: Aged, 2. Zero hunger, MESH: Cognitive Dysfunction/diagnosis, Cognitive Neurology, Smoking, Age Factors, Middle Aged, PREVALENCE, COMMUNITY, Mental Health, SEX, Female, MESH: Ethnic Groups/psychology, Research Article, Cognitive Neuroscience, Population, Ethnic Groups, MESH: Smoking/ethnology, MINI-MENTAL-STATE, 2.3 Psychological, Diagnostic Medicine, General & Internal Medicine, Behavioral and Social Science, Mental Health and Psychiatry, Acquired Cognitive Impairment, medicine, business.industry, Neurosciences, MESH: Male, Brain Disorders, Good Health and Well Being, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Exercise, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medical Risk Factors, Metabolic Disorders, Cognitive Science, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Diabetes Mellitus/ethnology, MESH: Stroke/ethnology
Abstract

Background With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. Methods and findings We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54–105 (mean = 72.7) years and without dementia at baseline. Studies had 2–15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = −0.1, SE = 0.01), APOE*4 carriage (B = −0.31, SE = 0.11), depression (B = −0.11, SE = 0.06), diabetes (B = −0.23, SE = 0.10), current smoking (B = −0.20, SE = 0.08), and history of stroke (B = −0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = −0.07, SE = 0.01), APOE*4 carriage (B = −0.41, SE = 0.18), and diabetes (B = −0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = −0.24, SE = 0.12), and between diabetes and cognitive decline (B = −0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. Conclusions These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences., Darren Lipnicki and the Sydney COSMIC team analysed cognitive performance and risk factor data from older people from 15 countries to assess associations between risk factors and late-life cognition, Author summary Why was this study done? There is a growing global burden associated with cognitive decline and dementia. Evidence for modifiable risk factors that could be targeted to reduce this burden needs to be improved. Risk factors for cognitive decline and dementia might differ between ethno-regional groups. What did the researchers do and find? We analyzed cognitive performance and risk factor data from 48,522 older individuals, provided by 20 studies of aging representing 15 countries (Australia, Brazil, Cuba, France, Germany, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, The Netherlands, the United Kingdom, and the United States). Cognitive performance was measured as Mini-Mental State Examination (MMSE) and global cognition scores. When controlling for confounding risk factors, the apolipoprotein E ε4 allele (APOE*4), depression, diabetes, current smoking, and history of stroke were associated with poorer cognitive performance, and higher levels of education and vigorous physical activity were associated with better performance. Age, APOE*4, and diabetes were associated with faster cognitive decline. Compared to white people, Asian people showed stronger associations between having ever smoked and cognitive performance, and between diabetes and cognitive decline. What do these findings mean? Modifiable risk factors associated with cognitive decline include education, smoking, physical activity, diabetes, and stroke. If these associations are determined to be causal, interventions targeting these factors may help reduce the global burden of cognitive decline and dementia. Interventions may require tailoring to particular ethno-regional groups.

Published
2019
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