Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13195-017-0292-4
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dc.titleDistinct white matter microstructural abnormalities and extracellular water increases relate to cognitive impairment in Alzheimer's disease with and without cerebrovascular disease
dc.contributor.authorJi F.
dc.contributor.authorPasternak O.
dc.contributor.authorLiu S.
dc.contributor.authorLoke Y.M.
dc.contributor.authorChoo B.L.
dc.contributor.authorHilal S.
dc.contributor.authorXu X.
dc.contributor.authorIkram M.K.
dc.contributor.authorVenketasubramanian N.
dc.contributor.authorChen C.L.-H.
dc.contributor.authorZhou J.
dc.date.accessioned2020-09-01T00:52:06Z
dc.date.available2020-09-01T00:52:06Z
dc.date.issued2017
dc.identifier.citationJi F., Pasternak O., Liu S., Loke Y.M., Choo B.L., Hilal S., Xu X., Ikram M.K., Venketasubramanian N., Chen C.L.-H., Zhou J. (2017). Distinct white matter microstructural abnormalities and extracellular water increases relate to cognitive impairment in Alzheimer's disease with and without cerebrovascular disease. Alzheimer's Research and Therapy 9 (1) : 63. ScholarBank@NUS Repository. https://doi.org/10.1186/s13195-017-0292-4
dc.identifier.issn17589193
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/173776
dc.description.abstractBackground: Mixed 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. Methods: We 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. Results: The 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. Conclusions: Our 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. © 2017 The Author(s).
dc.sourceUnpaywall 20200831
dc.subjectaged
dc.subjectAlzheimer disease
dc.subjectArticle
dc.subjectattention
dc.subjectbrain water
dc.subjectcerebrovascular disease
dc.subjectcognition assessment
dc.subjectcognitive defect
dc.subjectcontrolled study
dc.subjectdementia
dc.subjectdiffusion tensor imaging
dc.subjectdisease association
dc.subjectdisease classification
dc.subjectdisease course
dc.subjectdisease severity
dc.subjectexecutive function
dc.subjectextracellular fluid
dc.subjectfemale
dc.subjecthuman
dc.subjectimage analysis
dc.subjectlanguage disability
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectmotor performance
dc.subjectmultiinfarct dementia
dc.subjectneurologic examination
dc.subjectpriority journal
dc.subjecttissue structure
dc.subjectvisual stimulation
dc.subjectvoxel based morphometry
dc.subjectwhite matter lesion
dc.subjectAlzheimer disease
dc.subjectbody water
dc.subjectbrain
dc.subjectcerebrovascular disease
dc.subjectcognition
dc.subjectcognitive defect
dc.subjectcohort analysis
dc.subjectcomplication
dc.subjectdementia assessment
dc.subjectdiagnostic imaging
dc.subjectdiffusion weighted imaging
dc.subjectextracellular space
dc.subjectprocedures
dc.subjectpsychology
dc.subjectseverity of illness index
dc.subjectwhite matter
dc.subjectAged
dc.subjectAlzheimer Disease
dc.subjectBody Water
dc.subjectBrain
dc.subjectCerebrovascular Disorders
dc.subjectCognition
dc.subjectCognitive Dysfunction
dc.subjectCohort Studies
dc.subjectDiffusion Magnetic Resonance Imaging
dc.subjectDiffusion Tensor Imaging
dc.subjectExtracellular Space
dc.subjectFemale
dc.subjectHumans
dc.subjectMale
dc.subjectMental Status and Dementia Tests
dc.subjectSeverity of Illness Index
dc.subjectWhite Matter
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.contributor.departmentDEPT OF OPHTHALMOLOGY
dc.contributor.departmentDEPT OF MEDICINE
dc.description.doi10.1186/s13195-017-0292-4
dc.description.sourcetitleAlzheimer's Research and Therapy
dc.description.volume9
dc.description.issue1
dc.description.page63
dc.description.redepositcompleted
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