ArticleNeurology2023
Associations of Blood Cardiovascular Biomarkers With Brain Free Water and Its Relationship to Cognitive Decline: A Diffusion-MRI Study.
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Article in Neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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20citing papers in PubMed, 1 pooled it
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20 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- A systematic review of the neuroprotective role and biomarker potential of GDF15 in neurodegeneration.Frontiers in immunology · 2024Pooled it
- Heart Meets Brain: Insights into Neurocardiac Pathophysiology.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Early identification of vascular cognitive impairment from a multimodal perspective: a combined diagnosis from targeted cognitive assessments, imaging biomarkers, and molecular fluid biomarkers to ecological behavioral characteristics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Divergent Glymphatic Dysfunction and Free Water Pathology Underpin Distinct Mechanisms and Enable Differential Diagnosis in Parkinson's Disease and Multiple System Atrophy.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Association of glymphatic dysfunction, free water, white matter integrity and long-term memory performance in aging autistic adults.Molecular autism · 2026Article
- Plasma proteomics identifies proteins and pathways associated with incident epilepsy.Cell reports. Medicine · 2025Article
- Multimodal neuroimaging unveils basal forebrain-limbic system circuit dysregulation in cognitive impairment with depression: a pathway to early diagnosis and intervention.The journal of prevention of Alzheimer's disease · 2025Article
- Mapping Alzheimer's disease pathology using free water through integrated analysis of plasma biomarkers, microstructural DTI metrics, and macrostructural MRI measures.Scientific reports · 2025Article
- Aging of gray matter microstructure: A brain-wide characterization of age group differences using NODDI.Neurobiology of aging · 2025Article
- A point-based cognitive impairment scoring system for southeast Asian adults.The journal of prevention of Alzheimer's disease · 2025Article
- Associations of ischemic heart disease with brain glymphatic MRI indices and risk of Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Article
- Characterizing Brain-Cardiovascular Aging Using Multiorgan Imaging and Machine Learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Free-water imaging of the nucleus basalis of Meynert in apolipoprotein E4 carriers.Frontiers in aging neuroscience · 2025Article
- Cardiovascular Information and Health Engineering Medicine.Research (Washington, D.C.) · 2025Review
- The heart-brain axis: unraveling the interconnections between cardiovascular and Alzheimer's diseases.Frontiers in cardiovascular medicine · 2025Review
- Increased GDF-15 in chronic male patients with schizophrenia: correlation with body mass index and cognitive impairment.Schizophrenia (Heidelberg, Germany) · 2024Article
- Additive effects of cerebrovascular disease functional connectome phenotype and plasma p-tau181 on longitudinal neurodegeneration and cognitive outcomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Bidirectional Crosstalk between the Heart and Brain in Alzheimer's Disease.Aging and disease · 2024Review
- Heart-brain mapping: Cardiac atrial function is associated with distinct cerebral regions with high free water in older adults.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Mapping the interplay of atrial fibrillation, brain structure, and cognitive dysfunction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Fang JiFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore.ORCID 0000-0002-7471-0115
Yuek Ling ChaiFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore.
Siwei LiuFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore.ORCID 0000-0003-1277-484X
Cheuk Ni KanFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore.
Marcus OngFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore.ORCID 0000-0002-6784-3542
Arthur Mark RichardsFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore.
Boon Yeow TanFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore.
Narayanaswamy VenketasubramanianFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore.
Ofer PasternakFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore.
Christopher ChenFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore.
Mitchell K P LaiFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore. helen.zhou@nus.edu.sg mitchell.lai@dementia-research.org.ORCID 0000-0001-7685-1424
Juan Helen ZhouFrom the Centre for Sleep and Cognition (F.J., S.L., M.O., J.H.Z.), Yong Loo Lin School of Medicine, National University of Singapore; Memory Aging & Cognition Centre (Y.L.C., C.N.K., N.V., C.C., M.K.P.L.), National University Health System; Department of Pharmacology (Y.L.C., C.N.K., C.C., M.K.P.L.), Yong Loo Lin School of Medicine, and Cardiovascular Research Institute (A.M.R.), National University of Singapore; Christchurch Heart Institute (A.M.R.), University of Otago, New Zealand; St Luke's Hospital (B.Y.T.); Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Departments of Psychiatry and Radiology (O.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Centre for Translational MR Research (S.L., J.H.Z.), Yong Loo Lin School of Medicine, Duke-NUS Medical School (J.H.Z.), and Integrative Sciences and Engineering Programme (ISEP) (J.H.Z.), National University of Singapore. helen.zhou@nus.edu.sg mitchell.lai@dementia-research.org.ORCID 0000-0002-0180-8648
National University Health System · SGNational University of Singapore · SGRaffles Institution · SG
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThere is an increasing awareness of the "Heart-Brain Connection," whereby cardiovascular function is connected with cognition. Diffusion-MRI studies reported higher brain free water (FW) was associated with cerebrovascular disease (CeVD) and cognitive impairment. In this study, we investigated whether higher brain FW was related to blood cardiovascular biomarkers and whether FW mediated the associations between blood biomarkers and cognition.
methodsParticipants recruited from 2 Singapore memory clinics between 2010 and 2015 underwent collection of blood samples and neuroimaging at baseline and longitudinal neuropsychological assessments up to 5 years. We examined the associations of blood cardiovascular biomarkers (high-sensitivity cardiac troponin-T [hs-cTnT], N-terminal pro-hormone B-type natriuretic peptide [NT-proBNP], and growth/differentiation factor 15 [GDF-15]) with brain white matter (WM) and cortical gray matter (GM) FW derived from diffusion MRI using whole brain voxel-wise general linear regression. We then assessed the relationships among baseline blood biomarkers, brain FW, and cognitive decline using path models.
resultsA total of 308 older adults (76 with no cognitive impairment, 134 with cognitive impairment no dementia, and 98 with Alzheimer disease dementia and vascular dementia; mean [SD] age: 72.1 [8.3]) were included. We found that blood cardiovascular biomarkers were associated with higher FW in widespread WM regions and in specific GM networks including the default mode, executive control, and somatomotor networks at baseline ( DISCUSSION: Results suggested a role of brain FW in linking cardiovascular dysfunction to cognitive decline. These findings provide new evidence for brain-heart interactions, paving the way for prediction and monitoring of domain-specific cognitive trajectory.
Indexed as
Cognitive DysfunctionGrowth Differentiation Factor 15AgedBiomarkersDiffusion Magnetic Resonance ImagingHumansNatriuretic Peptide, BrainPeptide FragmentsWaterBiomarkersGrowth Differentiation Factor 15Natriuretic Peptide, BrainPeptide FragmentsWater
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