title: Periventricular hyperintensities are associated with elevated cerebral amyloid.
abstract: 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.
authors.affiliation: From the Clinic for Alzheimer Disease and Related Disorders, Djavad Mowafaghian Center for Brain Health (M.M., O.O.A.-J., S.M., K.J.P., B.W.W., H.H.F., G.-Y.R.H.), and Department of Medicine, Division of Neurology (M.M., H.H.F., G.-Y.R.H.), University of British Columbia, Vancouver, Canada. michael.marnane@vch.ca.
authors.forename: Michael
authors.initials: M
authors.lastname: Marnane
authors.affiliation: From the Clinic for Alzheimer Disease and Related Disorders, Djavad Mowafaghian Center for Brain Health (M.M., O.O.A.-J., S.M., K.J.P., B.W.W., H.H.F., G.-Y.R.H.), and Department of Medicine, Division of Neurology (M.M., H.H.F., G.-Y.R.H.), University of British Columbia, Vancouver, Canada.
authors.forename: Osama O
authors.initials: OO
authors.lastname: Al-Jawadi
authors.affiliation: From the Clinic for Alzheimer Disease and Related Disorders, Djavad Mowafaghian Center for Brain Health (M.M., O.O.A.-J., S.M., K.J.P., B.W.W., H.H.F., G.-Y.R.H.), and Department of Medicine, Division of Neurology (M.M., H.H.F., G.-Y.R.H.), University of British Columbia, Vancouver, Canada.
authors.forename: Shervin
authors.initials: S
authors.lastname: Mortazavi
authors.affiliation: From the Clinic for Alzheimer Disease and Related Disorders, Djavad Mowafaghian Center for Brain Health (M.M., O.O.A.-J., S.M., K.J.P., B.W.W., H.H.F., G.-Y.R.H.), and Department of Medicine, Division of Neurology (M.M., H.H.F., G.-Y.R.H.), University of British Columbia, Vancouver, Canada.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Pogorzelec
authors.affiliation: From the Clinic for Alzheimer Disease and Related Disorders, Djavad Mowafaghian Center for Brain Health (M.M., O.O.A.-J., S.M., K.J.P., B.W.W., H.H.F., G.-Y.R.H.), and Department of Medicine, Division of Neurology (M.M., H.H.F., G.-Y.R.H.), University of British Columbia, Vancouver, Canada.
authors.forename: Bing Wei
authors.initials: BW
authors.lastname: Wang
authors.affiliation: From the Clinic for Alzheimer Disease and Related Disorders, Djavad Mowafaghian Center for Brain Health (M.M., O.O.A.-J., S.M., K.J.P., B.W.W., H.H.F., G.-Y.R.H.), and Department of Medicine, Division of Neurology (M.M., H.H.F., G.-Y.R.H.), University of British Columbia, Vancouver, Canada.
authors.forename: Howard H
authors.initials: HH
authors.lastname: Feldman
authors.affiliation: From the Clinic for Alzheimer Disease and Related Disorders, Djavad Mowafaghian Center for Brain Health (M.M., O.O.A.-J., S.M., K.J.P., B.W.W., H.H.F., G.-Y.R.H.), and Department of Medicine, Division of Neurology (M.M., H.H.F., G.-Y.R.H.), University of British Columbia, Vancouver, Canada.
authors.forename: Ging-Yuek R
authors.initials: GY
authors.lastname: Hsiung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002552:Cerebral Ventricles / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers