Paradoxical cognitive trajectories in men from earlier to later adulthood

Graham M L Eglit¹, Jeremy A Elman², Mathew S Panizzon², Mark Sanderson-Cimino³, McKenna E Williams³, Anders M Dale⁴, Lisa T Eyler⁵, Christine Fennema-Notestine⁶, Nathan A Gillespie⁷, Daniel E Gustavson², Sean N Hatton⁸, Donald J Hagler Jr⁹, Richard L Hauger¹⁰, Amy J Jak¹¹, Mark W Logue¹², Linda K McEvoy⁹, Ruth E McKenzie¹³, Michael C Neale⁷, Olivia Puckett², Chandra A Reynolds¹⁴, Rosemary Toomey¹⁵, Xin M Tu², Nathan Whitsel², Hong Xian¹⁶, Michael J Lyons¹⁷, Carol E Franz¹⁷, William S Kremen¹⁸

Affiliations

¹ Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA. Electronic address: geglit@health.ucsd.edu.
² Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.
³ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA; San Diego State University/University of California, San Diego Joint Doctoral Program, San Diego, CA, USA.
⁴ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Department of Radiology, University of California, San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
⁵ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA; Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
⁷ Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA, USA.
⁸ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
⁹ Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
¹⁰ Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.
¹¹ Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.
¹² National Center for PTSD, Behavioral Sciences Division, VA Boston Healthcare System, Boston, MA, USA; Psychiatry and Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
¹³ Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA; School of Education and Social Policy, Merrimack College, North Andover, MA, USA.
¹⁴ Department of Psychology, University of California Riverside, Riverside, CA, USA.
¹⁵ Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
¹⁶ Department of Epidemiology and Biostatistics, St. Louis University, St. Louis, MO, USA.
¹⁷ Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
¹⁸ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.

PMID: 34785406
PMCID: PMC8715388
DOI: 10.1016/j.neurobiolaging.2021.10.002

Paradoxical cognitive trajectories in men from earlier to later adulthood

Graham M L Eglit et al. Neurobiol Aging. 2022 Jan.

. 2022 Jan:109:229-238.

doi: 10.1016/j.neurobiolaging.2021.10.002. Epub 2021 Oct 14.

Authors

Affiliations

¹ Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA. Electronic address: geglit@health.ucsd.edu.
² Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.
³ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA; San Diego State University/University of California, San Diego Joint Doctoral Program, San Diego, CA, USA.
⁴ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Department of Radiology, University of California, San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
⁵ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA; Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
⁷ Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA, USA.
⁸ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
⁹ Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
¹⁰ Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.
¹¹ Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.
¹² National Center for PTSD, Behavioral Sciences Division, VA Boston Healthcare System, Boston, MA, USA; Psychiatry and Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
¹³ Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA; School of Education and Social Policy, Merrimack College, North Andover, MA, USA.
¹⁴ Department of Psychology, University of California Riverside, Riverside, CA, USA.
¹⁵ Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
¹⁶ Department of Epidemiology and Biostatistics, St. Louis University, St. Louis, MO, USA.
¹⁷ Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
¹⁸ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.

PMID: 34785406
PMCID: PMC8715388
DOI: 10.1016/j.neurobiolaging.2021.10.002

Abstract

Because longitudinal studies of aging typically lack cognitive data from earlier ages, it is unclear how general cognitive ability (GCA) changes throughout the life course. In 1173 Vietnam Era Twin Study of Aging (VETSA) participants, we assessed young adult GCA at average age 20 and current GCA at 3 VETSA assessments beginning at average age 56. The same GCA index was used throughout. Higher young adult GCA and better GCA maintenance were associated with stronger specific cognitive abilities from age 51 to 73. Given equivalent GCA at age 56, individuals who had higher age 20 GCA outperformed those whose GCA remained stable in terms of memory, executive function, and working memory abilities from age 51 to 73. Thus, paradoxically, despite poorer maintenance of GCA, high young adult GCA still conferred benefits. Advanced predicted brain age and the combination of elevated vascular burden and APOE-ε4 status were associated with poorer maintenance of GCA. These findings highlight the importance of distinguishing between peak and current GCA for greater understanding of cognitive aging.

Keywords: Cognitive aging; Dementia; General cognitive ability; Longitudinal studies; Neuropsychology.

Published by Elsevier Inc.

PubMed Disclaimer

Conflict of interest statement

Disclosure statement L.K. McEvoy has stock options in CorTechs Laboratories, Inc. A.M. Dale is a founder of and holds equity in CorTechs Laboratories, Inc and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc. The terms of these arrangements have been reviewed and approved by University of California, San Diego in accordance with conflict of interest policies. The remaining authors disclose no conflicts.

Figures

**Figure 1.. Derivation of general cognitive ability residual scores**
*Notes*. a) Scatterplot with regression line predicting VETSA baseline general cognitive ability from age 20 general cognitive ability; b) random sample of 100 participants depicting change in general cognitive ability from age 20 to VETSA baseline assessment in the context of derived GCA residual scores. Arrows point to cases with similar change scores, but different residual scores, demonstrating adjustment for regression to the mean; Age 20 GCA and age 56 GCA were correlated .73, p < .001. GCA = General Cognitive Ability.

**Figure 2.. Timeline of analyzed measures**
Notes. Points represent age at assessment for each participant and text boxes describe analyzed measures from each assessment. VETSA = Vietnam Era Twin Study of Aging; PBAD = Predicted brain age difference; AFQT = Armed Forces Qualification Test

**Figure 3.. General cognitive ability maintenance score by *APOE* genotype and elevated vascular risk burden**
*Notes. APOE*-ε4 genotype significantly moderated the association between vascular burden and general cognitive ability maintenance (b = −.27, t = −2.071, p = .030). There was a significant effect of vascular burden among ε4 carriers (b = −.32, t = −2.972, p = .003), but not among ε4 non-carriers (b = −.05, t = −0.725, p = .468). All models adjusted for white race/ethnicity. Error bars reflect 95% confidence intervals.

See this image and copyright information in PMC

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Paradoxical cognitive trajectories in men from earlier to later adulthood

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Paradoxical cognitive trajectories in men from earlier to later adulthood

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