Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2025-01-03T21:21:35.615Z Has data issue: false hasContentIssue false
  • English
  • Français

APOE Effects on Late Life Cognitive Trajectories in Diverse Racial/Ethnic Groups

Published online by Cambridge University Press:  04 March 2022

Michelle L. Chan Open the ORCID record for Michelle L. Chan [Opens in a new window] ,
Oanh L. Meyer ,
Sarah T. Farias ,
Rachel A. Whitmer ,
Kumar Rajan ,
John Olichney ,
David Johnson  and
Dan Mungas Open the ORCID record for Dan Mungas [Opens in a new window]
Michelle L. Chan*
Affiliation:
Department of Neurology, University of California, Davis, USA
Oanh L. Meyer
Affiliation:
Department of Neurology, University of California, Davis, USA
Sarah T. Farias
Affiliation:
Department of Neurology, University of California, Davis, USA
Rachel A. Whitmer
Affiliation:
Department of Public Health Sciences, University of California, Davis, USA
Kumar Rajan
Affiliation:
Department of Public Health Sciences, University of California, Davis, USA
John Olichney
Affiliation:
Department of Neurology, University of California, Davis, USA
David Johnson
Affiliation:
Department of Neurology, University of California, Davis, USA
Dan Mungas
Affiliation:
Department of Neurology, University of California, Davis, USA
*
*Correspondence and reprint requests to: Michelle L. Chan, 4860 Y Street, Suite 3900, Sacramento, CA 95817, USA. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

This study evaluated: (1) apolipoprotein E (APOE) ϵ4 prevalence among Black, Latino, and White older adults, (2) associations of APOE ϵ4 status with baseline level and change over time of cognitive outcomes across groups, and (3) combined impact of APOE ϵ4 prevalence and magnitude of effect on cognitive decline within each racial/ethnic group.

Method:

Participants included 297 White, 138 Latino, and 149 Black individuals from the longitudinal UC Davis Diversity Cohort who had APOE genotyping and ≥2 cognitive assessments. Magnitude of associations of ϵ4 with cognitive baseline and change across racial/ethnic groups was tested with multilevel parallel process longitudinal analyses and multiple group models.

Results:

ϵ4 prevalence in Black (46%) and White participants (46%) was almost double that of Latino participants (24%). ϵ4 was associated with poorer baseline episodic memory only in White participants (p = .001), but had a moderately strong association with episodic memory change across all racial/ethnic groups (Blacks= −.061 SD/year, Latinos = −.055,Whites= −.055). ϵ4 association with semantic memory change was strongest in White participants (−.071), intermediate in Latino participants (−.041), and weakest in Black participants (−.022).

Conclusion:

Calculated cognitive trajectories across racial/ethnic groups were influenced in an additive manner by ϵ4 prevalence and strength of association with cognitive decline within the group. Group differences in ϵ4 prevalences and associations of ϵ4 with cognition may suggest different pathways from APOE to cognitive decline, and, AD possibly having less salient impact on cognitive decline in non-White participants. Differential effects of APOE on episodic memory and non-memory cognition have important implications for understanding how APOE influences late life cognitive decline.

Keywords

Alzheimer’s diseaseCognitionMemoryExecutive functioningCognitive agingNeuropsychology
Type
Research Article
Information
Journal of the International Neuropsychological Society , Volume 29 , Issue 2 , February 2023 , pp. 126 - 135
Copyright
Copyright © INS. Published by Cambridge University Press, 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Alzheimer’s Association. (2021). Alzheimer’s disease facts and figures. Alzheimer’s and Dementia, 17(3), 327–406.Google Scholar
American Psychiatric Association. (1987). Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: APA Press.Google Scholar
Barnes, L.L., Arvanitakis, Z., Yu, L., Kelly, J., De Jager, P.L., & Bennett, D.A. (2013). Apolipoprotein E and change in episodic memory in blacks and whites. Neuroepidemiology, 40(3), 211–219. https://doi.org/10.1159/000342778 CrossRefGoogle ScholarPubMed
Blom, G. (1958). Statistical estimates and transformed beta-variables. Biometrical Journal, 3(4), 285–285. https://doi.org/10.1002/bimj.19610030410 Google Scholar
Brewster, P.W., Melrose, R.J., Marquine, M.J., Johnson, J.K., Napoles, A., MacKay-Brandt, A., Farias, S., Reed, B., & Mungas, D. (2014). Life experience and demographic influences on cognitive function in older adults. Neuropsychology, 28(6), 846–858. https://doi.org/10.1037/neu0000098 CrossRefGoogle ScholarPubMed
Campos, M., Edland, S.D., & Peavy, G.M. (2013). Exploratory study of apolipoprotein E ϵ4 genotype and risk of Alzheimer’s disease in Mexican Hispanics. Journal of the American Geriatrics Society, 61(6), 1038–1040. https://doi.org/10.1111/jgs.12292 CrossRefGoogle Scholar
Carmichael, O., Mungas, D., Beckett, L., Harvey, D., Tomaszewski Farias, S., Reed, B., Olichney, J., Miller, J., & Decarli, C. (2012). MRI predictors of cognitive change in a diverse and carefully characterized elderly population. Neurobiology of Aging, 33(1), 83–95. https://doi.org/10.1016/j.neurobiolaging.2010.01.021 CrossRefGoogle Scholar
Early, D.R., Widaman, K.F., Harvey, D., Beckett, L., Park, L.Q., Farias, S.T., Reed, B.R., Decarli, C., & Mungas, D. (2013). Demographic predictors of cognitive change in ethnically diverse older persons. Psychology and Aging, 28(3), 633–645. https://doi.org/10.1037/a0031645 CrossRefGoogle ScholarPubMed
Farrer, L.A., Cupples, L.A., Haines, J.L., Hyman, B., Kukull, W.A., Mayeux, R., Myers, R.H., Pericak-Vance, M.A., Risch, N., & van Duijn, C.M. (1997). Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA, 278(16), 1349–1356.CrossRefGoogle ScholarPubMed
Fillenbaum, G.G., Landerman, L.R., Blazer, D.G., Saunders, A.M., Harris, T.B., & Launer, L.J. (2001). The relationship of APOE genotype to cognitive functioning in older African-American and Caucasian community residents. Journal of the American Geriatrics Society, 49(9), 1148–1155. https://doi.org/10.1046/j.1532-5415.2001.49230.x CrossRefGoogle ScholarPubMed
Fletcher, E., Gavett, B., Harvey, D., Farias, S.T., Olichney, J., Beckett, L., DeCarli, C., & Mungas, D. (2018). Brain volume change and cognitive trajectories in aging. Neuropsychology, 32(4), 436–449. https://doi.org/10.1037/neu0000447 CrossRefGoogle ScholarPubMed
Gavett, B.E., Fletcher, E., Harvey, D., Farias, S.T., Olichney, J., Beckett, L., DeCarli, C., & Mungas, D. (2018). Ethnoracial differences in brain structure change and cognitive change. Neuropsychology, 32(5), 529–540. https://doi.org/10.1037/neu0000452 CrossRefGoogle ScholarPubMed
Haan, M.N. & Mayeda, E.R. (2010). Apolipoprotein E genotype and cardiovascular diseases in the elderly. Current Cardiovascular Risk Reports, 4(5), 361–368. https://doi.org/10.1007/s12170-010-0118-4 CrossRefGoogle ScholarPubMed
Haan, M.N., Miller, J.W., Aiello, A.E., Whitmer, R.A., Jagust, W.J., Mungas, D.M., Allen, L.H., & Green, R. (2007). Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging. The American Journal of Clinical Nutrition, 85(2), 511–517. https://doi.org/10.1093/ajcn/85.2.511 CrossRefGoogle Scholar
Hinton, L., Carter, K., Reed, B.R., Beckett, L., Lara, E., DeCarli, C., & Mungas, D. (2010). Recruitment of a community-based cohort for research on diversity and risk of dementia. Alzheimer Disease and Associated Disorders, 24(3), 234–241. https://doi.org/10.1097/WAD.0b013e3181c1ee01 CrossRefGoogle ScholarPubMed
Kaup, A.R., Nettiksimmons, J., Harris, T.B., Sink, K.M., Satterfield, S., Metti, A.L., Ayonayon, H.N., Yaffe, K., & Health, Aging, and Body Composition (Health ABC) Study (2015). Cognitive resilience to apolipoprotein E ϵ4: contributing factors in black and white older adults. JAMA Neurology, 72(3), 340–348. https://doi.org/10.1001/jamaneurol.2014.3978 CrossRefGoogle ScholarPubMed
Knopman, D.S., Mosley, T.H., Catellier, D.J., & Coker, L.H. (2009). Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: the ARIC MRI Study. Alzheimer’s & Dementia, 5(3), 207–214. https://doi.org/10.1016/j.jalz.2009.01.027 CrossRefGoogle ScholarPubMed
Lockhart, S.N., Mayda, A.B., Roach, A.E., Fletcher, E., Carmichael, O., Maillard, P., Schwarz, C.G., Yonelinas, A.P., Ranganath, C., & Decarli, C. (2012). Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging. Frontiers in Human Neuroscience, 6, 56. https://doi.org/10.3389/fnhum.2012.00056 CrossRefGoogle ScholarPubMed
Mehta, K.M. & Yeo, G.W. (2017). Systematic review of dementia prevalence and incidence in United States race/ethnic populations. Alzheimer’s & Dementia, 13(1), 72–83. https://doi.org/10.1016/j.jalz.2016.06.2360 CrossRefGoogle ScholarPubMed
Melrose, R.J., Brewster, P., Marquine, M.J., MacKay-Brandt, A., Reed, B., Farias, S.T., & Mungas, D. (2015). Early life development in a multiethnic sample and the relation to late life cognition. Journals of Gerontology. Series B, 70(4), 519–531. https://doi.org/10.1093/geronb/gbt126 CrossRefGoogle Scholar
Morris, J.C., Schindler, S.E., McCue, L.M., Moulder, K.L., Benzinger, T., Cruchaga, C., Fagan, A.M., Grant, E., Gordon, B.A., Holtzman, D.M., & Xiong, C. (2019). Assessment of racial disparities in biomarkers for Alzheimer disease. JAMA Neurology, 76(3), 264–273. https://doi.org/10.1001/jamaneurol.2018.4249 CrossRefGoogle ScholarPubMed
Morris, J.C., Weintraub, S., Chui, H.C., Cummings, J., Decarli, C., Ferris, S., Foster, N.L., Galasko, D., Graff-Radford, N., Peskind, E.R., Beekly, D., Ramos, E.M., & Kukull, W.A. (2006). The Uniform Data Set (UDS): clinical and cognitive variables and descriptive data from Alzheimer Disease Centers. Alzheimer Disease and Associated Disorders, 20(4), 210–216. https://doi.org/10.1097/01.wad.0000213865.09806.92 CrossRefGoogle ScholarPubMed
Mungas, D., Beckett, L., Harvey, D., Farias, S.T., Reed, B., Carmichael, O., Olichney, J., Miller, J., & DeCarli, C. (2010). Heterogeneity of cognitive trajectories in diverse older persons. Psychology and Aging, 25(3), 606–619. https://doi.org/10.1037/a0019502 CrossRefGoogle ScholarPubMed
Mungas, D., Gavett, B., Fletcher, E., Farias, S.T., DeCarli, C., & Reed, B. (2018). Education amplifies brain atrophy effect on cognitive decline: implications for cognitive reserve. Neurobiology of Aging, 68, 142–150. https://doi.org/10.1016/j.neurobiolaging.2018.04.002 CrossRefGoogle ScholarPubMed
Mungas, D., Reed, B.R., Crane, P.K., Haan, M.N., & González, H. (2004). Spanish and English Neuropsychological Assessment Scales (SENAS): further development and psychometric characteristics. Psychological Assessment, 16(4), 347–359. https://doi.org/10.1037/1040-3590.16.4.347 CrossRefGoogle ScholarPubMed
Mungas, D., Reed, B.R., Farias, S., & DeCarli, C. (2005). Criterion-referenced validity of a neuropsychological test battery: equivalent performance in elderly Hispanics and non- Hispanic Whites. Journal of the International Neuropsychological Society, 11(5), 620–630. https://doi.org/10.1017/S1355617705050745 CrossRefGoogle ScholarPubMed
Mungas, D., Reed, B.R., Haan, M.N., & González, H. (2005). Spanish and English neuropsychological assessment scales: relationship to demographics, language, cognition, and independent function. Neuropsychology, 19(4), 466–475. https://doi.org/10.1037/0894-4105.19.4.466 CrossRefGoogle ScholarPubMed
Mungas, D., Reed, B.R., Marshall, S.C., & González, H.M. (2000). Development of psychometrically matched English and Spanish language neuropsychological tests for older persons. Neuropsychology, 14(2), 209–223. https://doi.org/10.1037//0894-4105.14.2.209 CrossRefGoogle ScholarPubMed
Mungas, D., Widaman, K.F., Reed, B.R., & Tomaszewski Farias, S. (2011). Measurement invariance of neuropsychological tests in diverse older persons. Neuropsychology, 25(2), 260–269. https://doi.org/10.1037/a0021090 CrossRefGoogle ScholarPubMed
Muthen, L. & Muthen, B. (1998). Mplus User’s Guide.Google Scholar
Nelson, P.T., Braak, H., & Markesbery, W.R. (2009). Neuropathology and cognitive impairment in Alzheimer disease: A complex but coherent relationship. Journal of Neuropathology and Experimental Neurology, 68(1), 1–14. https://doi.org/10.1097/NEN.0b013e3181919a48 CrossRefGoogle ScholarPubMed
Petersen, R.C. (2004). Mild cognitive impairment as diagnostic entity. Journal of Internal Medicine, 256(3), 183–194. https://doi.org/10.1111/j.1365-2796.2004.0133.x CrossRefGoogle ScholarPubMed
Rajan, K.B., Barnes, L.L., Wilson, R.S., Weuve, J., McAninch, E.A., & Evans, D.A. (2019). Apolipoprotein E genotypes, age, race, and cognitive decline in a population sample. Journal of the American Geriatrics Society, 67(4), 734–740. https://doi.org/10.1111/jgs.15727 CrossRefGoogle Scholar
Satorra, A., & Bentler, P.M. (2001). A scaled difference chi-square test statistic for moment structure analysis. Psychometrika, 66(4), 507–514. https://doi.org/10.1007/BF02296192 CrossRefGoogle Scholar
Satorra, A., & Bentler, P.M. (2010). Ensuring positiveness of the scaled difference Chi-square test statistic. Psychometrika, 75(2), 243–248. https://doi.org/10.1007/s11336-009-9135y CrossRefGoogle ScholarPubMed
Sawyer, K., Sachs-Ericsson, N., Preacher, K.J., & Blazer, D.G. (2009). Racial differences in the influence of the APOE epsilon 4 allele on cognitive decline in a sample of community- dwelling older adults. Gerontology, 55(1), 32–40. https://doi.org/10.1159/000137666 CrossRefGoogle Scholar
Schilling, S., DeStefano, A.L., Sachdev, P.S., Choi, S.H., Mather, K.A., DeCarli, C.D., Wen, W., Høgh, P., Raz, N., Au, R., Beiser, A., Wolf, P.A., Romero, J.R., Zhu, Y.C., Lunetta, K.L., Farrer, L., Dufouil, C., Kuller, L.H., Mazoyer, B., Seshadri, S., … Debette, S. (2013). APOE genotype and MRI markers of cerebrovascular disease: systematic review and meta-analysis. Neurology, 81(3), 292–300. https://doi.org/10.1212/WNL.0b013e31829bfda4 CrossRefGoogle ScholarPubMed
Tang, M.X., Cross, P., Andrews, H., Jacobs, D.M., Small, S., Bell, K., Merchant, C., Lantigua, R., Costa, R., Stern, Y., & Mayeux, R. (2001). Incidence of AD in African-Americans, caribbean hispanics, and caucasians in northern manhattan. Neurology, 56(1), 49–56. https://doi.org/10.1212/wnl.56.1.49 CrossRefGoogle ScholarPubMed
Tang, M.X., Stern, Y., Marder, K., Bell, K., Gurland, B., Lantigua, R., Andrews, H., Feng, L., Tycko, B., & Mayeux, R. (1998). The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA, 279(10), 751–755. https://doi.org/10.1001/jama.279.10.751 CrossRefGoogle ScholarPubMed
Weuve, J., Barnes, L.L., Mendes de Leon, C.F., Rajan, K.B., Beck, T., Aggarwal, N.T., Hebert, L.E., Bennett, D.A., Wilson, R.S., & Evans, D.A. (2018). Cognitive aging in black and White Americans: cognition, cognitive decline, and incidence of Alzheimer disease dementia. Epidemiology (Cambridge, Mass.), 29(1), 151–159. https://doi.org/10.1097/EDE.0000000000000747 CrossRefGoogle ScholarPubMed