ArticleNeuroImage2020
The association of white matter free water with cognition in older adults.
Article in NeuroImage, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Effects of aerobic exercise and cardiorespiratory fitness on white matter free water fraction in older adults: a 1-year randomized controlled trial.GeroScience · 2026Trial
- Exploring the effect of multi-modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the AgeWell.de imaging study.NeuroImage. Clinical · 2025Trial
- White matter microstructure of sensorimotor projection fibers in chronic low back pain.Pain reports · 2026Article
- Association of glymphatic dysfunction, free water, white matter integrity and long-term memory performance in aging autistic adults.Molecular autism · 2026Article
- Practical judgment in aging: examining behavioral vulnerabilities and neurobiological correlates.Frontiers in psychology · 2026Article
- Multimodal MRI insights into glymphatic clearance and blood-brain barrier integrity in healthy aging.Imaging neuroscience (Cambridge, Mass.) · 2026Article
- Association of Superficial White Matter Microstructure With Cortical Pathology Deposition Across Early Stages of the AD Continuum.Neurology · 2025Article
- Article
- Free Water as a Marker of Early Small Vessel Disease in Healthy Aging.European journal of neurology · 2025Article
- Substantia nigra and locus coeruleus microstructural abnormalities in isolated rapid eye movement sleep behaviour disorder and Parkinson's disease.Brain communications · 2025Article
- Changes of in vivo electrical conductivity in the brain and torso related to age, fat fraction and sex using MRI.Scientific reports · 2024Article
- MRI free water mediates the association between water exchange rate across the blood brain barrier and executive function among older adults.Imaging neuroscience (Cambridge, Mass.) · 2024Article
- Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Comparative analysis of glymphatic system alterations in multiple sclerosis and neuromyelitis optica spectrum disorder using MRI indices from diffusion tensor imaging.Human brain mapping · 2024Article
- Longitudinal evaluation of structural brain alterations in two established mouse models of Gulf War Illness.Frontiers in neuroscience · 2024Article
- Quantifying neuroinflammation within deep gray matter in small vessel disease using diffusion tensor based free-water imaging: a longitudinal study.Frontiers in aging neuroscience · 2024Article
- Microstructural and Microvascular Alterations in Psychotic Spectrum Disorders: A Three-Compartment Intravoxel Incoherent Imaging and Free Water Model.Schizophrenia bulletin · 2023Article
- Automated three-dimensional major white matter bundle segmentation using diffusion magnetic resonance imaging.Anatomical science international · 2023Review
- Biomarkers for rapid H-reflex operant conditioning among females.Journal of neurophysiology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundExtracellular free water within cerebral white matter tissue has been shown to increase with age and pathology, yet the cognitive consequences of free water in typical aging prior to the development of neurodegenerative disease remains unclear. Understanding the contribution of free water to cognitive function in older adults may provide important insight into the neural mechanisms of the cognitive aging process.
methodsA diffusion-weighted MRI measure of extracellular free water as well as a commonly used diffusion MRI metric (fractional anisotropy) along nine bilateral white matter pathways were examined for their relationship with cognitive function assessed by the NIH Toolbox Cognitive Battery in 47 older adults (mean age = 74.4 years, SD = 5.4 years, range = 65-85 years). Probabilistic tractography at the 99th percentile level of probability (Tracts Constrained by Underlying Anatomy; TRACULA) was utilized to produce the pathways on which microstructural characteristics were overlaid and examined for their contribution to cognitive function independent of age, education, and gender.
resultsWhen examining the 99th percentile probability core white matter pathway derived from TRACULA, poorer fluid cognitive ability was related to higher mean free water values across the angular and cingulum bundles of the cingulate gyrus, as well as the corticospinal tract and the superior longitudinal fasciculus. There was no relationship between cognition and mean FA or free water-adjusted FA across the 99th percentile core white matter pathway. Crystallized cognitive ability was not associated with any of the diffusion measures. When examining cognitive domains comprising the NIH Toolbox Fluid Cognition index relationships with these white matter pathways, mean free water demonstrated strong hemispheric and functional specificity for cognitive performance, whereas mean FA was not related to age or cognition across the 99th percentile pathway.
conclusionsExtracellular free water within white matter appears to increase with normal aging, and higher values are associated with significantly lower fluid but not crystallized cognitive functions. When using TRACULA to estimate the core of a white matter pathway, a higher degree of free water appears to be highly specific to the pathways associated with memory, working memory, and speeded decision-making performance, whereas no such relationship existed with FA. These data suggest that free water may play an important role in the cognitive aging process, and may serve as a stronger and more specific indicator of early cognitive decline than traditional diffusion MRI measures, such as FA.
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