Skip to main content
Education and the Moderating Roles of Age, Sex, Ethnicity and Apolipoprotein Epsilon 4 on the Risk of Cognitive Impairment – Carolina Center for Population Aging and Health

Education and the Moderating Roles of Age, Sex, Ethnicity and Apolipoprotein Epsilon 4 on the Risk of Cognitive Impairment


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, et al. (2020). Education and the Moderating Roles of Age, Sex, Ethnicity and Apolipoprotein Epsilon 4 on the Risk of Cognitive Impairment. Archives of Gerontology and Geriatrics, 91, 104112. PMCID: PMC7724926


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.


Reference Type

Journal Article

Year Published


Journal Title

Archives of Gerontology and Geriatrics


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
Lobo Escolar, Elena
De la Cámara, Concepción
Brodaty, Henry
Trollor, Julian N.
Leung, Yvonne
Lo, Jessica W.
Sachdev, Perminder for Cohort Studies of Memory in an International Consortium (COSMIC),

Article Type




Data Set/Study





Aiello - 0000-0001-7029-2537