PT - JOURNAL ARTICLE AU - Marnane, Michael AU - Al-Jawadi, Osama O. AU - Mortazavi, Shervin AU - Pogorzelec, Kathleen J. AU - Wang, Bing Wei AU - Feldman, Howard H. AU - Hsiung, Ging-Yuek R. AU - , TI - Periventricular hyperintensities are associated with elevated cerebral amyloid AID - 10.1212/WNL.0000000000002352 DP - 2016 Feb 09 TA - Neurology PG - 535--543 VI - 86 IP - 6 4099 - http://n.neurology.org/content/86/6/535.short 4100 - http://n.neurology.org/content/86/6/535.full SO - Neurology2016 Feb 09; 86 AB - Objective: To 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.Methods: The 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.Results: Increased 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.Conclusions: Increased 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.Aβ=β-amyloid; AD=Alzheimer disease; ADNI=Alzheimer's Disease Neuroimaging Initiative; CAA=cerebral amyloid angiopathy; CI=confidence interval; CMB=cerebral microbleed; FDG=fluorodeoxyglucose; FLAIR=fluid-attenuated inversion recovery; ICC=intraclass correlation coefficient; MCI=mild cognitive impairment; NC=normal cognition; NINCDS-ADRDA=National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association; OR=odds ratio; PVWMH=periventricular white matter hyperintensities; ROI=region of interest; SVD=small vessel disease; volTWMH=volumetric measurements of total white matter hyperintensity burden; WMH=white matter hyperintensity