Hostname: page-component-848d4c4894-wg55d Total loading time: 0 Render date: 2024-05-18T05:23:27.781Z Has data issue: false hasContentIssue false

Comparison of Education and Episodic Memory as Modifiers of Brain Atrophy Effects on Cognitive Decline: Implications for Measuring Cognitive Reserve

Published online by Cambridge University Press:  18 January 2021

Dan Mungas*
Department of Neurology, University of California, Davis, 4860 Y Street, Sacramento, CA95817, USA
Evan Fletcher
Department of Neurology, University of California, Davis, 1544 Newton Court, Davis, CA95616, USA
Brandon E. Gavett
Department of Psychology, University of Western Australia, School of Psychological Science (M304), 35 Stirling Hwy, Perth, WA6009, Australia
Keith Widaman
Graduate School of Education, University of California, Riverside, 1207 Sproul Hall, 900 University Avenue, Riverside, CA92521, USA
Laura B. Zahodne
Department of Psychology, University of Michigan, 530 Church Street, Ann Arbor, MI48109, Australia
Timothy J. Hohman
Department of Neurology, Vanderbilt University, Vanderbilt Memory & Alzheimer’s Center, 1207 17th Ave South, Suite 204F, Nashville, TN37212, USA
Elizabeth Rose Mayeda
Department of Epidemiology, University of California, Los Angeles, UCLA Pub Hlth - Epidemiology, BOX 951772, 46-070B CHS, Los Angeles, CA90095, USA
N. Maritza Dowling
Department of Acute & Chronic Care, The George Washington School of Nursing, 1919 Pennsylvania Street NW, Suite 500, Washington, DC20006, USA
David K. Johnson
Department of Neurology, University of California, Davis, 100 N. Wiget Lane, Suite 150, Walnut Creek, CA94598, USA
Sarah Tomaszewski Farias
Department of Neurology, University of California, Davis, 4860 Y Street, Sacramento, CA95817, USA
*Correspondence and reprint requests to: Dan Mungas, Department of Neurology, UC Davis Medical Center, 4860 Y Street, Suite 3900, Sacramento, CA 95817, USA. E-mail:



This study compared the level of education and tests from multiple cognitive domains as proxies for cognitive reserve.


The participants were educationally, ethnically, and cognitively diverse older adults enrolled in a longitudinal aging study. We examined independent and interactive effects of education, baseline cognitive scores, and MRI measures of cortical gray matter change on longitudinal cognitive change.


Baseline episodic memory was related to cognitive decline independent of brain and demographic variables and moderated (weakened) the impact of gray matter change. Education moderated (strengthened) the gray matter change effect. Non-memory cognitive measures did not incrementally explain cognitive decline or moderate gray matter change effects.


Episodic memory showed strong construct validity as a measure of cognitive reserve. Education effects on cognitive decline were dependent upon the rate of atrophy, indicating education effectively measures cognitive reserve only when atrophy rate is low. Results indicate that episodic memory has clinical utility as a predictor of future cognitive decline and better represents the neural basis of cognitive reserve than other cognitive abilities or static proxies like education.

Regular Research
Copyright © INS. Published by Cambridge University Press, 2021

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.)



Amieva, H., Mokri, H., Le Goff, M., Meillon, C., Jacqmin-Gadda, H., Foubert-Samier, A., … Dartigues, J.F. (2014). Compensatory mechanisms in higher-educated subjects with Alzheimer’s disease: A study of 20 years of cognitive decline. Brain, 137(Pt 4), 11671175. CrossRefGoogle ScholarPubMed
Ashburner, J. & Friston, K.J. (2000). Voxel-based morphometry – The methods. Neuroimage, 11(6 Pt 1), 805821. CrossRefGoogle ScholarPubMed
Barulli, D. & Stern, Y. (2013). Efficiency, capacity, compensation, maintenance, plasticity: Emerging concepts in cognitive reserve. Trends in Cognitive Sciences, 17(10), 502509. CrossRefGoogle ScholarPubMed
Blom, G. (1958). Statistical Estimates and Transformed Beta-Variables. New York: Wiley.Google Scholar
Brewster, P.W.H., Melrose, R.J., Marquine, M.J., Johnson, J.K., Napoles, A., MacKay-Brandt, A., … Mungas, D. (2014). Life experience and demographic influences on cognitive function in older adults. Neuropsychology, 28(6), 846858. CrossRefGoogle ScholarPubMed
Carmichael, O., Mungas, D., Beckett, L., Harvey, D., Tomaszewski Farias, S., Reed, B., … Decarli, C. (2012). MRI predictors of cognitive change in a diverse and carefully characterized elderly population. Neurobiology of Aging, 33(1), 8395. CrossRefGoogle Scholar
DeCarli, C., Fletcher, E., Ramey, V., Harvey, D., & Jagust, W. (2005). Anatomical mapping of white matter hyperintensities (WMH) exploring the relationships between periventricular WMH, deep WMH, and total WMH burden. Stroke, 36, 5055.CrossRefGoogle ScholarPubMed
Dowling, N.M., Tomaszewski Farias, S., Reed, B.R., Sonnen, J.A., Strauss, M.E., Schneider, J.A., … Mungas, D. (2011). Neuropathological associates of multiple cognitive functions in two community-based cohorts of older adults. Journal of the International Neuropsychological Society: JINS, 17(4), 602614. CrossRefGoogle ScholarPubMed
Early, D.R., Widaman, K.F., Harvey, D., Beckett, L., Park, L.Q., Farias, S.T., … Mungas, D. (2013). Demographic predictors of cognitive change in ethnically diverse older persons. Psychology and Aging, 28(3), 633645. CrossRefGoogle ScholarPubMed
Fletcher, E. (2014). Using prior information to enhance sensitivity of longitudinal brain change computation. In Chen, C.H. (Ed.), Frontiers of medical imaging (pp. 6381). Singapore; Hackensack, NJ: World Scientific.CrossRefGoogle Scholar
Fletcher, E., Carmichael, O., Pasternak, O., Maier-Hein, K.H., & DeCarli, C. (2014). Early brain loss in circuits affected by Alzheimer’s disease is predicted by Fornix microstructure but may be independent of gray matter. Frontiers in Aging Neuroscience, 6, 19. CrossRefGoogle ScholarPubMed
Fletcher, E., Gavett, B., Harvey, D., Farias, S.T., Olichney, J., Beckett, L., … Mungas, D. (2018). Brain volume change and cognitive trajectories in aging. Neuropsychology, 32(4), 436449. CrossRefGoogle Scholar
Fletcher, E., Knaack, A., Singh, B., Lloyd, E., Wu, E., Carmichael, O., & DeCarli, C. (2013). Combining boundary-based methods with tensor-based morphometry in the measurement of longitudinal brain change. IEEE Transactions on Medical Imaging, 32(2), 223236. CrossRefGoogle ScholarPubMed
Fletcher, E., Villeneuve, S., Maillard, P., Harvey, D., Reed, B., Jagust, W., & Decarli, C. (2016). Beta-amyloid, hippocampal atrophy and their relation to longitudinal brain change in cognitively normal individuals. Neurobiology of Aging, 40, 173180. CrossRefGoogle ScholarPubMed
Gavett, B.E., Fletcher, E., Harvey, D., Farias, S.T., Olichney, J., Beckett, L., … Mungas, D. (2018). Ethnoracial differences in brain structure change and cognitive change. Neuropsychology, 32(5), 529540. CrossRefGoogle ScholarPubMed
Gross, A.L., Mungas, D.M., Crane, P.K., Gibbons, L.E., MacKay-Brandt, A., Manly, J.J., … Jones, R.N. (2015). Effects of education and race on cognitive decline: An integrative study of generalizability versus study-specific results. Psychology and Aging, 30(4), 863880. CrossRefGoogle ScholarPubMed
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’s Disease and Associated Disorders, 24(3), 234241. CrossRefGoogle ScholarPubMed
Jones, R.N., Manly, J., Glymour, M.M., Rentz, D.M., Jefferson, A.L., & Stern, Y. (2011). Conceptual and measurement challenges in research on cognitive reserve. Journal of the International Neuropsychological Society, 17(4), 593601. CrossRefGoogle ScholarPubMed
Lee, D.Y., Fletcher, E., Martinez, O., Zozulya, N., Kim, J., Tran, J., … DeCarli, C. (2010). Vascular and degenerative processes differentially affect regional interhemispheric connections in normal aging, mild cognitive impairment, and Alzheimer disease. Stroke, 41(8), 17911797. CrossRefGoogle ScholarPubMed
Masel, M.C., & Peek, M.K. (2009). Ethnic differences in cognitive function over time. Annals of Epidemiology, 19(11), 778783. CrossRefGoogle ScholarPubMed
McKenzie, C., Bucks, R.S., Weinborn, M., Bourgeat, P., Salvado, O., & Gavett, B.E. (2020). Cognitive reserve predicts future executive function decline in older adults with Alzheimer’s disease pathology but not age-associated pathology. Neurobiology of Aging, 88, 119127. CrossRefGoogle Scholar
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. The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences, 70(4), 519531. CrossRefGoogle Scholar
Mungas, D., Beckett, L., Harvey, D., Farias, S.T., Reed, B., Carmichael, O., … DeCarli, C. (2010). Heterogeneity of cognitive trajectories in diverse older persons. Psychology and Aging, 25(3), 606619. CrossRefGoogle ScholarPubMed
Mungas, D., Early, D.R., Glymour, M.M., Zeki Al Hazzouri, A., & Haan, M.N. (2018). Education, bilingualism, and cognitive trajectories: Sacramento Area Latino Aging Study (SALSA). Neuropsychology, 32(1), 7788. CrossRefGoogle Scholar
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, 142150. CrossRefGoogle ScholarPubMed
Mungas, D., Reed, B.R., Crane, P.K., Haan, M.N., & Gonzalez, H. (2004). Spanish and English Neuropsychological Assessment Scales (SENAS): Further development and psychometric characteristics. Psychological Assessment, 16(4), 347359. CrossRefGoogle ScholarPubMed
Mungas, D., Reed, B.R., Farias, S.T., & Decarli, C. (2009). Age and education effects on relationships of cognitive test scores with brain structure in demographically diverse older persons. Psychology and Aging, 24(1), 116128. CrossRefGoogle ScholarPubMed
Mungas, D., Reed, B.R., Haan, M.N., & Gonzalez, H. (2005a). Spanish and English Neuropsychological Assessment Scales: Relationship to demographics, language, cognition, and independent function. Neuropsychology, 19(4), 466475.CrossRefGoogle ScholarPubMed
Mungas, D., Reed, B.R., Marshall, S.C., & Gonzalez, H.M. (2000). Development of psychometrically matched English and Spanish language neuropsychological tests for older persons. Neuropsychology, 14(2), 209223.CrossRefGoogle ScholarPubMed
Mungas, D., Reed, B.R., Tomaszewski Farias, S., & DeCarli, C. (2005b). Criterion-referenced validity of a neuropsychological test battery: Equivalent performance in elderly Hispanics and Non-Hispanic Whites. Journal of the International Neuropsychological Society, 11, 620630.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), 260269. CrossRefGoogle ScholarPubMed
Muthén, L.K., & Muthén, B.O. (1998). Mplus User’s Guide (8th ed.). Los Angeles, CA: Muthén & Muthén.Google Scholar
Park, D.C., & Reuter-Lorenz, P. (2009). The adaptive brain: Aging and neurocognitive scaffolding. Annual Review of Psychology, 60, 173196. CrossRefGoogle ScholarPubMed
Reed, B.R., Dowling, M., Tomaszewski Farias, S., Sonnen, J., Strauss, M., Schneider, J.A., … Mungas, D. (2011). Cognitive activities during adulthood are more important than education in building reserve. Journal of the International Neuropsychological Society, 17(4), 615624. CrossRefGoogle ScholarPubMed
Reed, B.R., Mungas, D., Farias, S.T., Harvey, D., Beckett, L., Widaman, K., … DeCarli, C. (2010). Measuring cognitive reserve based on the decomposition of episodic memory variance. Brain, 133(Pt 8), 21962209. CrossRefGoogle ScholarPubMed
Scarmeas, N., Albert, S.M., Manly, J.J., & Stern, Y. (2006). Education and rates of cognitive decline in incident Alzheimer’s disease. Journal of Neurology, Neurosurgery and Psychiatry, 77(3), 308316.CrossRefGoogle ScholarPubMed
Steffener, J., Barulli, D., Habeck, C., O’Shea, D., Razlighi, Q., & Stern, Y. (2014). The role of education and verbal abilities in altering the effect of age-related gray matter differences on cognition. PloS One, 9(3), e91196. CrossRefGoogle ScholarPubMed
Stern, Y. (2002). What is cognitive reserve? Theory and research application of the reserve concept. Journal of the International Neuropsychological Society, 8(3), 448460.CrossRefGoogle ScholarPubMed
Stern, Y. (2006). Cognitive reserve and Alzheimer disease. Alzheimer’s Disease and Associated Disorders, 20(2), 112117.CrossRefGoogle ScholarPubMed
Stern, Y. (2009). Cognitive reserve. Neuropsychologia, 47(10), 20152028. CrossRefGoogle ScholarPubMed
Stern, Y., Albert, S., Tang, M.X., & Tsai, W.Y. (1999). Rate of memory decline in AD is related to education and occupation: Cognitive reserve? Neurology, 53(9), 19421947.CrossRefGoogle ScholarPubMed
Stern, Y., Arenaza-Urquijo, E.M., Bartres-Faz, D., Belleville, S., Cantilon, M., Chetelat, G., … Conceptual Frameworks Workgroup (2018). Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimers Dement. Google Scholar
Ye, B.S., Seo, S.W., Cho, H., Kim, S.Y., Lee, J.S., Kim, E.J., … Na, D.L. (2013). Effects of education on the progression of early- versus late-stage mild cognitive impairment. International Psychogeriatrics, 25(4), 597606. CrossRefGoogle ScholarPubMed
Zahodne, L.B., Manly, J.J., Brickman, A.M., Siedlecki, K.L., Decarli, C., & Stern, Y. (2013). Quantifying cognitive reserve in older adults by decomposing episodic memory variance: Replication and extension. Journal of the International Neuropsychological Society, 19(8), 854862. CrossRefGoogle Scholar
Supplementary material: File

Mungas et al. supplementary material

Mungas et al. supplementary material

Download Mungas et al. supplementary material(File)
File 24.8 KB