학술논문

Lower White Matter Volume and Worse Executive Functioning Reflected in Higher Levels of Plasma GFAP among Older Adults with and Without Cognitive Impairment
Document Type
article
Source
Journal of the International Neuropsychological Society. 28(6)
Subject
Biological Psychology
Psychology
Clinical Research
Brain Disorders
Neurodegenerative
Alzheimer's Disease
Aging
Acquired Cognitive Impairment
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Neurosciences
Dementia
Neurological
Mental health
Aged
Aged
80 and over
Alzheimer Disease
Biomarkers
Cognitive Dysfunction
Executive Function
Glial Fibrillary Acidic Protein
Humans
Intermediate Filaments
Middle Aged
Neurodegenerative Diseases
Neurofilament Proteins
White Matter
Glial fibrillary acidic protein
Astrocyte
Alzheimer's
Alzheimer’s
Medical and Health Sciences
Psychology and Cognitive Sciences
Experimental Psychology
Biomedical and clinical sciences
Health sciences
Language
Abstract
ObjectiveThere 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.MethodsWe 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.ResultsHigher 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.ConclusionsPlasma 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.