ArticleAlzheimer's research & therapy2017
Distinct white matter microstructural abnormalities and extracellular water increases relate to cognitive impairment in Alzheimer's disease with and without cerebrovascular disease.
Article in Alzheimer's research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- White matter hyperintensities and the risk of vascular dementia: a systematic review and meta-analysis.PeerJ · 2025Pooled it
- Effects of aerobic exercise and cardiorespiratory fitness on white matter free water fraction in older adults: a 1-year randomized controlled trial.GeroScience · 2026Trial
- Free water: A marker of age-related modifications of the cingulum white matter and its association with cognitive decline.PloS one · 2020Trial
- "Morphological, Functional, and Molecular Progression of Blood-Brain Barrier Dysfunction in Alzheimer's Disease".Journal of molecular neuroscience : MN · 2026Review
- Regional juxtacortical microstructural changes and gene expression provide insights into neurodegeneration in Alzheimer's disease.Translational psychiatry · 2026Article
- Peripheral inflammation impairs glymphatic function, contributing to neurodegeneration in Alzheimer's disease.iScience · 2026Article
- Free Water Elevation in Alzheimer's Disease: Influence of Amyloid-Beta Deposition Beyond Brain Cell Loss.Journal of Korean medical science · 2026Article
- Perilesional white matter gradients reveal microstructural differences in cerebral amyloid angiopathy versus Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Associations of cardiorespiratory fitness with brain white matter microstructural integrity and white matter hyperintensity volume across the adult lifespan.GeroScience · 2026Article
- Synergistic effects of cerebral small vessel disease burden and plasma phosphorylated tau 181 on white matter microstructure and cognition in a Chinese cohort.Brain communications · 2026Article
- Evaluating regional and global diffusion measures as biomarkers for vascular contributions to cognitive impairment and dementia.Cerebral circulation - cognition and behavior · 2026Article
- Glymphatic dysfunction as an imaging biomarker for cognitive impairment in patients with β-thalassemia major: A multimodal MRI study.European journal of radiology open · 2025Article
- Decreased diffusivity along the perivascular spaces in bipolar disorder: an MRI-based cross-sectional and Mendelian randomization study.Translational psychiatry · 2025Article
- Article
- White matter free water and depressive symptoms in medication-free depressed adolescents: moderation by peripheral inflammation.Translational psychiatry · 2025Article
- Abnormalities of thalamus and thalamocortical pathways in patients with refractory epilepsy caused by focal cortical dysplasia - MRI study.Epilepsia open · 2025Article
- Association of Superficial White Matter Microstructure With Cortical Pathology Deposition Across Early Stages of the AD Continuum.Neurology · 2025Article
- Relation of Alzheimer's disease-related TDP-43 proteinopathy to metrics from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI).Neurobiology of aging · 2025Article
- WMH-DualTasker: A Weakly Supervised Deep Learning Model for Automated White Matter Hyperintensities Segmentation and Visual Rating Prediction.Human brain mapping · 2025Article
- White matter alterations in episodic migraine without aura patients assessed with diffusion MRI: effect of free water correction.The journal of headache and pain · 2025Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundMixed vascular and neurodegenerative dementia, such as Alzheimer's disease (AD) with concomitant cerebrovascular disease, has emerged as the leading cause of age-related cognitive impairment. The brain white matter (WM) microstructural changes in neurodegeneration well-documented by diffusion tensor imaging (DTI) can originate from brain tissue or extracellular free water changes. The differential microstructural and free water changes in AD with and without cerebrovascular disease, especially in normal-appearing WM, remain largely unknown. To cover these gaps, we aimed to characterize the WM free water and tissue microstructural changes in AD and mixed dementia as well as their associations with cognition using a novel free water imaging method.
methodsWe compared WM free water and free water-corrected DTI measures as well as white matter hyperintensity (WMH) in patients with AD with and without cerebrovascular disease, patients with vascular dementia, and age-matched healthy control subjects.
resultsThe cerebrovascular disease groups had higher free water than the non-cerebrovascular disease groups. Importantly, besides the cerebrovascular disease groups, patients with AD without cerebrovascular disease also had increased free water in normal-appearing WM compared with healthy control subjects, reflecting mild vascular damage. Such free water increases in WM or normal-appearing WM (but not WMH) contributed to dementia severity. Whole-brain voxel-wise analysis revealed a close association between widespread free water increases and poorer attention, executive functioning, visual construction, and motor performance, whereas only left hemispheric free water increases were related to language deficits. Moreover, compared with the original DTI metrics, the free water-corrected DTI metric revealed tissue damage-specific (frontal and occipital) microstructural differences between the cerebrovascular disease and non-cerebrovascular disease groups. In contrast to both lobar and subcortical/brainstem free water increases, only focal lobar microstructural damage was associated with poorer cognitive performance.
conclusionsOur findings suggest that free water analysis isolates probable mild vascular damage from WM microstructural alterations and underscore the importance of normal-appearing WM changes underlying cognitive and functional impairment in AD with and without cerebrovascular disease. Further developed, the combined free water and tissue neuroimaging assays could help in differential diagnosis, treatment planning, and disease monitoring of patients with mixed dementia.
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