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BRIEF RESEARCH REPORT article

Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
Volume 16 - 2024 | doi: 10.3389/fnagi.2024.1406394
This article is part of the Research Topic Biological Markers of Healthy Aging View all articles

Cortical lobar volume reductions associated with homocysteine-related subcortical brain atrophy and poorer cognition in healthy aging

Provisionally accepted
Hyun Song Hyun Song 1,2Pradyumna K. Bharadwaj Pradyumna K. Bharadwaj 1,2David A. Raichlen David A. Raichlen 3*Christian G. Habeck Christian G. Habeck 4Matthew D. Grilli Matthew D. Grilli 1,2,5Matthew J. Huentelman Matthew J. Huentelman 2,6,7Georg A. Hishaw Georg A. Hishaw 5*Theodore P. Trouard Theodore P. Trouard 2,7,8Gene E. Alexander Gene E. Alexander 1,10,2,7,9*
  • 1 Department of Psychology, University of Arizona, Tucson, AZ, United States
  • 2 Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, Arizona, United States
  • 3 Human and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, United States
  • 4 Cognitive Neuroscience Division, Department of Neurology and Taub Institute, Columbia University, New York, NY, United States
  • 5 Department of Neurology, College of Medicine, University of Arizona, Tucson, United States
  • 6 Translational Genomics Research Institute (TGen), Phoenix, United States
  • 7 Arizona Alzheimer's Consortium (AAC), Phoenix, United States
  • 8 Department of Biomedical Engineering, University of Arizona, Tucson, AZ, United States
  • 9 Department of Psychiatry, College of Medicine, University of Arizona, Tucson, United States
  • 10 Neuroscience and Physiological Sciences Graduate Interdisciplinary Programs, University of Arizona,, Tucson, AZ, United States

The final, formatted version of the article will be published soon.

    Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer's disease. In 160 healthy older adults (mean age=69.66±9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcyrelated multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging.

    Keywords: cognitive aging, vascular risk, scaled subprofile model, White matter hyperintensity, gray matter atrophy

    Received: 25 Mar 2024; Accepted: 24 Jul 2024.

    Copyright: © 2024 Song, Bharadwaj, Raichlen, Habeck, Grilli, Huentelman, Hishaw, Trouard and Alexander. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    David A. Raichlen, Human and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, United States
    Georg A. Hishaw, Department of Neurology, College of Medicine, University of Arizona, Tucson, United States
    Gene E. Alexander, Department of Psychology, University of Arizona, Tucson, AZ, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.