title: Distinct clinical and metabolic deficits in PCA and AD are not related to amyloid distribution.
abstract: OBJECTIVE
  Patients with posterior cortical atrophy (PCA) often have Alzheimer disease (AD) at autopsy, yet are cognitively and anatomically distinct from patients with clinical AD. We sought to compare the distribution of β-amyloid and glucose metabolism in PCA and AD in vivo using Pittsburgh compound B (PiB) and FDG-PET.
  
  
  METHODS
  Patients with PCA (n = 12, age 57.5 ± 7.4, Mini-Mental State Examination [MMSE] 22.2 ± 5.1), AD (n = 14, age 58.8 ± 9.6, MMSE 23.8 ± 6.7), and cognitively normal controls (NC, n = 30, age 73.6 ± 6.4) underwent PiB and FDG-PET. Group differences in PiB distribution volume ratios (DVR, cerebellar reference) and FDG uptake (pons-averaged) were assessed on a voxel-wise basis and by comparing binding in regions of interest (ROIs).
  
  
  RESULTS
  Compared to NC, both patients with AD and patients with PCA showed diffuse PiB uptake throughout frontal, temporoparietal, and occipital cortex (p < 0.0001). There were no regional differences in PiB binding between PCA and AD even after correcting for atrophy. FDG patterns in PCA and AD were distinct: while both groups showed hypometabolism compared to NC in temporoparietal cortex and precuneus/posterior cingulate, patients with PCA further showed hypometabolism in inferior occipitotemporal cortex compared to both NC and patients with AD (p < 0.05). Patients with AD did not show areas of relative hypometabolism compared to PCA.
  
  
  CONCLUSIONS
  Fibrillar amyloid deposition in PCA is diffuse and similar to AD, while glucose hypometabolism extends more posteriorly into occipital cortex. Further studies are needed to determine the mechanisms of selective network degeneration in focal variants of AD.
authors.affiliation: HealthPartner Specialty Center, Center for Dementia and Alzheimer's Care, 401 Phalen Boulevard, Mail Stop: 41104C, St. Paul, MN 55130, USA. Michael.H.Rosenbloom@HealthPartners.com
authors.forename: M H
authors.initials: MH
authors.lastname: Rosenbloom
authors.forename: A
authors.initials: A
authors.lastname: Alkalay
authors.forename: N
authors.initials: N
authors.lastname: Agarwal
authors.forename: S L
authors.initials: SL
authors.lastname: Baker
authors.forename: J P
authors.initials: JP
authors.lastname: O'Neil
authors.forename: M
authors.initials: M
authors.lastname: Janabi
authors.forename: I V
authors.initials: IV
authors.lastname: Yen
authors.forename: M
authors.initials: M
authors.lastname: Growdon
authors.forename: J
authors.initials: J
authors.lastname: Jang
authors.forename: C
authors.initials: C
authors.lastname: Madison
authors.forename: E C
authors.initials: EC
authors.lastname: Mormino
authors.forename: H J
authors.initials: HJ
authors.lastname: Rosen
authors.forename: M L
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.forename: M W
authors.initials: MW
authors.lastname: Weiner
authors.forename: B L
authors.initials: BL
authors.lastname: Miller
authors.forename: W J
authors.initials: WJ
authors.lastname: Jagust
authors.forename: G D
authors.initials: GD
authors.lastname: Rabinovici
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D013577:Syndrome
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019788:Fluorodeoxyglucose F18; D005947:Glucose