title: Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.
abstract: OBJECTIVE
  To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease.
  
  
  BACKGROUND
  Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible.
  
  
  METHODS
  Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach.
  
  
  RESULTS
  Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Cerebral Function Unit, Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Christopher
authors.identifier: http://orcid.org/0000-0002-7797-0756
authors.initials: C
authors.lastname: Kobylecki
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Cathleen
authors.initials: C
authors.lastname: Haense
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Cerebral Function Unit, Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Harris
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Cerebral Function Unit, Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Stopford
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|INSERM-EPHE-Université de Caen de Basse-Normandie, Caen, France.
authors.forename: Shailendra H
authors.initials: SH
authors.lastname: Segobin
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Cerebral Function Unit, Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Jones
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Manchester Medical School, University of Manchester, Manchester, UK.
authors.forename: Anna M T
authors.initials: AMT
authors.lastname: Richardson
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Cerebral Function Unit, Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gerhard
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: José
authors.initials: J
authors.lastname: Anton-Rodriguez
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Cerebral Function Unit, Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Thompson
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: Herholz
authors.affiliation: Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Cerebral Function Unit, Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Julie S
authors.initials: JS
authors.lastname: Snowden
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D007802:Language; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D019788:Fluorodeoxyglucose F18
keywords: Alzheimer's disease; FDG-PET; neuropsychology; working memory