title: Cerebral perfusion alterations and cerebral amyloid in autosomal dominant Alzheimer disease.
abstract: OBJECTIVE
  To evaluate alterations in cerebral blood flow (CBF) using arterial spin-labeled MRI in autosomal dominant Alzheimer disease (ADAD) mutation carriers (MCs) in relation to cerebral amyloid and compared with age-matched healthy controls.
  
  
  BACKGROUND
  Recent work has identified alterations in CBF in elderly subjects with mild cognitive impairment and Alzheimer dementia using MRI. However, similar studies are lacking in ADAD. Subjects with ADAD are generally free of significant vascular disease and offer the opportunity to measure CBF early in the pathologic process before significant symptom onset when unique markers might be identified.
  
  
  METHODS
  Fourteen MCs (presenilin-1 and amyloid beta precursor protein) (Clinical Dementia Rating [CDR] 0 = 9, CDR 0.5 = 4, CDR 1 = 1) and 50 controls underwent 3-tesla pulsed arterial spin-labeled MRI. SPM8 was used to test the effect of MC status at the voxel level on CBF before and after controlling for age and CDR.
  
  
  RESULTS
  MCs had decreased perfusion in the caudate and inferior striatum bilaterally even after controlling for age and CDR. In MCs, separate areas of decreased CBF were associated with increasing cerebral amyloid and to decreased performance of attention and executive function.
  
  
  CONCLUSIONS
  Early CBF changes were identified in asymptomatic and mildly symptomatic subjects with ADAD, particularly in the anterior striatum. Furthermore, amyloid deposition was associated with decreased CBF in a number of regions including anterior and posterior cortical areas. Both amyloid and decreased CBF were associated with declines primarily in executive cognitive function.
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta. mcdadee@upmc.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: McDade
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Albert
authors.initials: A
authors.lastname: Kim
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: James
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Lei K
authors.initials: LK
authors.lastname: Sheu
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Dora Chieh-Hsin
authors.initials: DC
authors.lastname: Kuan
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Davneet
authors.initials: D
authors.lastname: Minhas
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gianaros
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Snezana
authors.initials: S
authors.lastname: Ikonomovic
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Oscar
authors.initials: O
authors.lastname: Lopez
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Beth
authors.initials: B
authors.lastname: Snitz
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Julie
authors.initials: J
authors.lastname: Price
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Jim
authors.initials: J
authors.lastname: Becker
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: Chet
authors.initials: C
authors.lastname: Mathis
authors.affiliation: From the Departments of Neurology (E.M., S.I., O.L., B.S.), Psychiatry (A.K., J.B., W.K.), and Radiology (J.J., D.M., J.P., C.M., W.K.), School of Medicine, and Department of Psychology (L.K.S., D.C.-H.K., P.J.G.), School of Arts and Sciences, University of Pittsburgh, PA; and Medical College of Georgia (A.K.), Augusta.
authors.forename: William
authors.initials: W
authors.lastname: Klunk
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D053764:Presenilin-1 / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D053764:Presenilin-1