White matter hyperintensities and CSF Alzheimer disease biomarkers in preclinical Alzheimer disease.
Adult
Age of Onset
Aged
Aged, 80 and over
Alzheimer Disease
/ cerebrospinal fluid
Amyloid beta-Peptides
/ cerebrospinal fluid
Biomarkers
/ cerebrospinal fluid
Brain
/ pathology
Cognitive Dysfunction
/ complications
Disease Progression
Female
Humans
Longitudinal Studies
Magnetic Resonance Imaging
Male
Middle Aged
Neuroimaging
Neuropsychological Tests
Peptide Fragments
/ cerebrospinal fluid
Phosphorylation
Prodromal Symptoms
White Matter
/ pathology
Young Adult
tau Proteins
/ cerebrospinal fluid
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
03 03 2020
03 03 2020
Historique:
received:
15
01
2019
accepted:
30
08
2019
pubmed:
1
1
2020
medline:
15
7
2020
entrez:
1
1
2020
Statut:
ppublish
Résumé
Recent studies suggest that white matter hyperintensities (WMH) on MRI, which primarily reflect small vessel cerebrovascular disease, may play a role in the evolution of Alzheimer disease (AD). In a longitudinal study, we investigated whether WMH promote the progression of AD pathology, or alter the association between AD pathology and risk of progression from normal cognition to mild cognitive impairment (MCI). Two sets of analyses were conducted. The relationship between whole brain WMH load, based on fluid-attenuated inversion recovery MRI, obtained in initially cognitively normal participants (n = 274) and time to onset of symptoms of MCI (n = 60) was examined using Cox regression models. In a subset of the participants with both MRI and CSF data (n = 204), the interaction of WMH load and CSF AD biomarkers was also evaluated. Baseline WMH load interacted with CSF total tau (t-tau) with respect to symptom onset, but not with CSF β-amyloid 1-42 or phosphorylated tau (p-tau) 181. WMH volume was associated with time to symptom onset of MCI among individuals with low t-tau (hazard ratio [HR] 1.35, confidence interval [CI] 1.06-1.73, These results suggest that WMH primarily affect the risk of progression when CSF measures of neurodegeneration or neuronal injury (as reflected by t-tau) are low. However, CSF biomarkers of amyloid and p-tau and WMH appear to have largely independent and nonsynergistic effects on the risk of progression to MCI.
Identifiants
pubmed: 31888969
pii: WNL.0000000000008864
doi: 10.1212/WNL.0000000000008864
pmc: PMC7238945
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
Peptide Fragments
0
amyloid beta-protein (1-42)
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e950-e960Subventions
Organisme : NIA NIH HHS
ID : P30 AG066507
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005146
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG033655
Pays : United States
Informations de copyright
© 2019 American Academy of Neurology.
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