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Lower White Matter Volume and Worse Executive Functioning Reflected in Higher Levels of Plasma GFAP among Older Adults with and Without Cognitive Impairment

Published online by Cambridge University Press:  22 June 2021

Breton M. Asken Open the ORCID record for Breton M. Asken [Opens in a new window] ,
Lawren VandeVrede ,
Julio C. Rojas ,
Corrina Fonseca ,
Adam M. Staffaroni ,
Fanny M. Elahi ,
Cutter A. Lindbergh Open the ORCID record for Cutter A. Lindbergh [Opens in a new window] ,
Alexandra C. Apple ,
Michelle You  and
Sophia Weiner-Light
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Breton M. Asken*
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Lawren VandeVrede
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Julio C. Rojas
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Corrina Fonseca
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Adam M. Staffaroni
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Fanny M. Elahi
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Cutter A. Lindbergh
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Alexandra C. Apple
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Michelle You
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Sophia Weiner-Light
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Nivetha Brathaban
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Nicole Fernandes
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Adam L. Boxer
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Bruce L. Miller
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Howie J. Rosen
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Joel H. Kramer
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
Kaitlin B. Casaletto
Affiliation:
Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
*
*Correspondence and reprint requests to: Breton M. Asken, 675 Nelson Rising Lane, Suite 190, San Francisco, CA 94158, USA. E-mail: breton.asken@ucsf.edu
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Abstract

Objective:

There are minimal data directly comparing plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in aging and neurodegenerative disease research. We evaluated associations of plasma NfL and plasma GFAP with brain volume and cognition in two independent cohorts of older adults diagnosed as clinically normal (CN), mild cognitive impairment (MCI), or Alzheimer’s dementia.

Methods:

We studied 121 total participants (Cohort 1: n = 50, age 71.6 ± 6.9 years, 78% CN, 22% MCI; Cohort 2: n = 71, age 72.2 ± 9.2 years, 45% CN, 25% MCI, 30% dementia). Gray and white matter volumes were obtained for total brain and broad subregions of interest (ROIs). Neuropsychological testing evaluated memory, executive functioning, language, and visuospatial abilities. Plasma samples were analyzed in duplicate for NfL and GFAP using single molecule array assays (Quanterix Simoa). Linear regression models with structural MRI and cognitive outcomes included plasma NfL and GFAP simultaneously along with relevant covariates.

Results:

Higher plasma GFAP was associated with lower white matter volume in both cohorts for temporal (Cohort 1: β = −0.33, p = .002; Cohort 2: β = −0.36, p = .03) and parietal ROIs (Cohort 1: β = −0.31, p = .01; Cohort 2: β = −0.35, p = .04). No consistent findings emerged for gray matter volumes. Higher plasma GFAP was associated with lower executive function scores (Cohort 1: β = −0.38, p = .01; Cohort 2: β = −0.36, p = .007). Plasma NfL was not associated with gray or white matter volumes, or cognition after adjusting for plasma GFAP.

Conclusions:

Plasma GFAP may be more sensitive to white matter and cognitive changes than plasma NfL. Biomarkers reflecting astroglial pathophysiology may capture complex dynamics of aging and neurodegenerative disease.

Keywords

BiomarkersGlial fibrillary acidic proteinAstrocyteAgingAlzheimer’sDementia
Type
Research Article
Information
Journal of the International Neuropsychological Society , Volume 28 , Issue 6 , July 2022 , pp. 588 - 599
Copyright
Copyright © INS. Published by Cambridge University Press, 2021

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