학술논문

Periventricular hyperintensities are associated with elevated cerebral amyloid
Document Type
article
Author
Marnane, MichaelAl-Jawadi, Osama OMortazavi, ShervinPogorzelec, Kathleen JWang, Bing WeiFeldman, Howard HHsiung, Ging-Yuek RWeiner, MichaelAisen, PaulPetersen, RonaldJack, Clifford RJagust, WilliamTrojanowki, John QToga, Arthur WBeckett, LaurelGreen, Robert CSaykin, Andrew JMorris, JohnLiu, EnchiMontine, TomGamst, AnthonyThomas, Ronald GDonohue, MichaelWalter, SarahGessert, DevonSather, TamieHarvey, DanielleKornak, JohnDale, AndersBernstein, MatthewFelmlee, JoelFox, NickThompson, PaulSchuff, NorbertAlexander, GeneDeCarli, CharlesBandy, DanKoeppe, Robert AFoster, NormReiman, Eric MChen, KeweiMathis, ChetCairns, Nigel JTaylor-Reinwald, LisaTrojanowki, JQShaw, LesLee, Virginia MYKorecka, MagdalenaCrawford, KarenNeu, ScottForoud, Tatiana MPotkin, StevenShen, LiKachaturian, ZavenFrank, RichardSnyder, Peter JMolchan, SusanKaye, JeffreyQuinn, JosephLind, BettyDolen, SaraSchneider, Lon SPawluczyk, SoniaSpann, Bryan MBrewer, JamesVanderswag, HelenHeidebrink, Judith LLord, Joanne LJohnson, KrisDoody, Rachelle SVillanueva-Meyer, JavierChowdhury, MunirStern, YaakovHonig, Lawrence SBell, Karen LMorris, John CAnces, BeauCarroll, MariaLeon, SueMintun, Mark ASchneider, StacyMarson, DanielGriffith, RandallClark, DavidGrossman, HillelMitsis, Effie
Source
Neurology. 86(6)
Subject
Biomedical and Clinical Sciences
Clinical Sciences
Prevention
Aging
Clinical Research
Alzheimer's Disease
Neurosciences
Brain Disorders
Acquired Cognitive Impairment
Neurodegenerative
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Dementia
2.1 Biological and endogenous factors
Aetiology
Neurological
Adult
Aged
Aged
80 and over
Amyloid beta-Peptides
Biomarkers
Cerebral Ventricles
Cognitive Dysfunction
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Positron-Emission Tomography
Prospective Studies
Alzheimer's Disease Neuroimaging Initiative
Cognitive Sciences
Neurology & Neurosurgery
Clinical sciences
Language
Abstract
ObjectiveTo investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral β-amyloid (Aβ) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study.MethodsThe burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Aβ, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET.ResultsIncreased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p < 0.01) and low CSF-Aβ (p < 0.01). In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p < 0.05). In a similar logistic regression model, parietal and occipital (p < 0.05) but not frontal (p = 0.05) PVWMH were independently associated with CSF-Aβ. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p < 0.05) and occipital PVWMH and elevated CSF-phospho-tau (p < 0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Aβ levels (p < 0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements.ConclusionsIncreased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified.