White matter damage due to vascular, tau, and TDP-43 pathologies and its relevance to cognition.
Aged
Aged, 80 and over
Alzheimer Disease
/ complications
Brain
/ diagnostic imaging
Cerebrovascular Disorders
/ complications
Cognitive Dysfunction
/ diagnostic imaging
Cohort Studies
Diffusion Magnetic Resonance Imaging
/ methods
Female
Humans
Male
Neuroimaging
/ methods
Positron-Emission Tomography
/ methods
TDP-43 Proteinopathies
/ complications
Tauopathies
/ complications
White Matter
/ diagnostic imaging
Cerebrovascular disease
Diffusion tensor imaging
Neurite dispersion density imaging
TAR DNA binding protein of 43 kDa
Tau positron emission tomography
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
05 02 2022
05 02 2022
Historique:
received:
14
01
2022
accepted:
19
01
2022
entrez:
6
2
2022
pubmed:
7
2
2022
medline:
8
3
2022
Statut:
epublish
Résumé
Multi-compartment modelling of white matter microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) can provide information on white matter health through neurite density index and free water measures. We hypothesized that cerebrovascular disease, Alzheimer's disease, and TDP-43 proteinopathy would be associated with distinct NODDI readouts of white matter damage which would be informative for identifying the substrate for cognitive impairment. We identified two independent cohorts with multi-shell diffusion MRI, amyloid and tau PET, and cognitive assessments: specifically, a population-based cohort of 347 elderly randomly sampled from the Olmsted county, Minnesota, population and a clinical research-based cohort of 61 amyloid positive Alzheimer's dementia participants. We observed an increase in free water and decrease in neurite density using NODDI measures in the genu of the corpus callosum associated with vascular risk factors, which we refer to as the vascular white matter component. Tau PET signal reflective of 3R/4R tau deposition was associated with worsening neurite density index in the temporal white matter where we measured parahippocampal cingulum and inferior temporal white matter bundles. Worsening temporal white matter neurite density was associated with (antemortem confirmed) FDG TDP-43 signature. Post-mortem neuropathologic data on a small subset of this sample lend support to our findings. In the community-dwelling cohort where vascular disease was more prevalent, the NODDI vascular white matter component explained variability in global cognition (partial R
Identifiants
pubmed: 35123591
doi: 10.1186/s40478-022-01319-6
pii: 10.1186/s40478-022-01319-6
pmc: PMC8817561
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16Subventions
Organisme : NIA NIH HHS
ID : R01 AG056366
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG034676
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054449
Pays : United States
Organisme : NCRR NIH HHS
ID : C06 RR018898
Pays : United States
Organisme : NIA NIH HHS
ID : R33 AG058738
Pays : United States
Organisme : NIH HHS
ID : NS097495
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG006786
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS097495
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG037491
Pays : United States
Informations de copyright
© 2022. The Author(s).
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