ArticleJAMA neurology2025
White Matter Abnormalities and Cognition in Aging and Alzheimer Disease.
Article in JAMA neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed.
- Review
- Lesion-Level Subtypes of White Matter Hyperintensity Evolution Beyond Spatial Location.Neurology · 2026Observational
- Oligodendrocyte-Targeted SGK1.1 Inhibition Alleviates White Matter Injury and Cognitive Impairment in Alzheimer's Disease via Modulation of HDAC2 Phosphorylation.CNS neuroscience & therapeutics · 2026Article
- Corpus callosum fractional anisotropy from routine diffusion tensor imaging predicts dementia in older adults beyond clinical risk factors.GeroScience · 2026Article
- The role of vascular risk factors in white matter tract microstructure: a multi-cohort study in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Regional juxtacortical microstructural changes and gene expression provide insights into neurodegeneration in Alzheimer's disease.Translational psychiatry · 2026Article
- Genetic architecture of the limbic white matter microstructure in aging and Alzheimer's Disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Genetically linked brain imaging markers of memory decline in aging and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Superficial white matter and gray matter jointly support cognition among older adults in India.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Lecanemab in practice: AI-derived MRI predictors of benefit and Amyloid Related Imaging Abnormalities (ARIA).Alzheimer's research & therapy · 2026Article
- Short T1 Fraction as a Marker of Myelin Content: Evidence from Postmortem MRI and Histology.bioRxiv : the preprint server for biology · 2026Article
- Predicting Autopsy-Confirmed Neuropathology across Clinical, Neuroimaging, and CSF Biomarkers using Machine Learning.bioRxiv : the preprint server for biology · 2026Article
- Dysregulated oligodendrocyte and myelin dynamics as an early pathological feature of neuropil degeneration in Alzheimer's disease: an ultrastructural study.Acta neuropathologica communications · 2026Article
- SIRT1 Activators as Geroprotective Agents in Brain Aging: Mechanisms and Therapeutic Potential.Neuromolecular medicine · 2026Review
- Contributions of Gray Matter Microstructure to Differences in Fluid Cognition and Episodic Memory Across the Healthy Adult Lifespan.Human brain mapping · 2026Article
- Cross-sectional and longitudinal cognitive trajectories associated with dementia comorbidity clusters: Results from a 10-year follow-up real-world outpatient memory clinic in Brazil.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Independent and interactive contributions of white matter hyperintensities and Alzheimer's disease imaging and plasma biomarkers to cognitive decline in older adults without dementia.Alzheimer's research & therapy · 2026Article
- Divergent white matter metabolic signature patterns indicate impending cognitive decline in aging and dementia.Nature communications · 2026Article
- Free water changes and their correlations with multimodal biomarkers in frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neuroimaging PheWAS and molecular phenotyping implicate PSMC3 in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
Corrections and comments
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Authors and funding
60 authors.
Funding
Abstract
Importance: There has yet to be a large-scale study quantifying the association between white matter microstructure and cognitive performance and decline in aging and Alzheimer disease (AD). Objective: To investigate the associations between tract-specific white matter microstructure and cognitive performance and decline in aging and AD-related cognitive impairment. Design Setting and Participants: This prognostic study of aging and AD, a secondary data analysis of multisite cohort studies, acquired data from 9 cohorts between September 2002 and November 2022. Participants were eligible if they had diffusion-weighted magnetic resonance imaging (dMRI) data, domain-specific cognitive composite Exposures: White matter microstructure and cognitive performance and decline. Main Outcomes and Measures: Clinical diagnosis, imaging measures (dMRI, T1-weighted MRI, and amyloid and tau positron emission tomography), and cognitive tests. Results: Of 4467 participants who underwent 9208 longitudinal cognitive sessions, 2698 (60.4%) were female, and the mean age (SD) was 74.3 (9.2) years; 3213 were cognitively unimpaired, 972 had mild cognitive impairment, and 282 had AD dementia. White matter free water (FW) showed the strongest associations with cross-sectional cognitive performance and longitudinal cognitive decline across all domains, particularly memory. FW in limbic tracts, such as the cingulum, presented the strongest associations with both memory performance (cingulum: β = -0.718; Conclusions and Relevance: White matter microstructural changes, particularly FW, play a critical role in cognitive decline in aging and AD-related cognitive impairment. These findings highlight the importance of FW correction in dMRI studies and highlight the limbic system, especially the cingulum and fornix, as key regions associated with cognitive decline; the interaction models highlight that integrating FW-corrected metrics with other AD biomarkers may further elucidate the biological mechanisms of neurodegeneration in aging.
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Registered trials
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